TRANQUILIZERS

OFFICIAL NAMES: Major tranquilizers (neuroleptics/antipsychotics): Chlorpromazine (Thorazine); chlorprothixene (Taractan); clozaril (Clozapine); fluphenazine (Permitil, Prolixin); haloperidol (Haldol); loxapine (Daxolin, Loxitane); mesoridazine (Serentil); molindone (Lidone, Moban); olanzapine (Zyprexa); perphenazine (Trilafon); pimozide (Orap); quetiapine (Seroquel); risperidone (Risperdal); thioridazine (Mellaril); thiothixene (Navane); trifluoperazine (Stelazine); trifuluopromazine (Vesprin); ziprasidone (Geodon).

STREET NAMES: Major tranquilizers: antipsychotics, neuroleptics.

DRUG CLASSIFICATIONS: Major tranquilizers: Not scheduled

OFFICIAL NAMES: Minor tranquilizers (sedative-hypnotics/anxiolytics)/Benzodiazepines: Alprazolam (Xanax); chlordiazepoxide (Librium, Novopoxide); clonazepam (Klonopin); clorazepate (Azene, Tranxene); diazepam (Valium); estazolam (ProSom); flunitrazepam (Rohypnol/illegal in the United States); flurazepam (Dalmane); halazepam (Paxipam); lorazepam (Ativan); midazolam (Versed); oxazepam (Serax); prazepam (Centrax); quazepam (Doral); temazepam (Restoril); triazolam (Halcion)

STREET NAMES: Minor tranquilizers: (benzodiazepines: BZDs, tranks, downers, benzos, goofballs, happy pills, sedative-hypnotics, anxiolytics); (barbiturates: Amys, barbs, blues, downers, yellow jackets, rainbows, red devils); (nonbarbiturate sedative-hypnotics: ludes, Sopors)

DRUG CLASSIFICATIONS: Benzodiazepines: Schedule IV, depressants

OFFICIAL NAMES: Minor tranquilizers (sedative-hypnotics/anxiolytics)/Nonbenzodiazepines: Zaleplon (Sonata); zolpidem (Ambien); Buspirone (BuSpar)

DRUG CLASSIFICATIONS: Nonbenzodiadepine hypnotics: Zaleplon (Sonata); zolpidem (Ambien), Schedule IV, depressants; Buspirone (Buspar): Not scheduled

OFFICIAL NAMES: Minor tranquilizers (sedative-hypnotics/anxiolytics)/ Barbiturates: Amobarbital (Amytal); butabarbital (Butisol); butalbital (Fiorinal, Sedapap); mepho-barbital (Mebaral); methohexital (Brevital); pentobarbital (Nembutal); phenobarbital (Luminal); secobarbital (Seconal)

DRUG CLASSIFICATIONS: Barbiturates: Amobarbital (Amytal); butabarbital (Butisol); pentobarbital (Nembutal); secobarbital (Seconal), Schedule II, narcotic analgesics; mepho-barbital (Mebaral); methohexital (Brevital); phenobarbital (Luminal), Schedule IV, narcotic analgesics

OFFICIAL NAMES: Minor tranquilizers/Nonbarbiturate sedative-hypnotics: Chloral hydrate (Aquachloral Supprettes, Noctec, Somnos); ethchlorvynol (Placidyl); glutethimide (Doriden); meprobamate (Miltown, Equanil); methaqualone (Quaalude); methyprylon (Noludar)

DRUG CLASSIFICATIONS: Nonbarbiturate sedative-hypnotics: Chloral hydrate (Noctec, Somnos), ethchlorvynol (Placidyl), Schedule IV, depressants; glutethimide (Doriden), Schedule II, depressant; meprobamate (Miltown, Equanil), Schedule IV, depressant; methaqualone (Quaalude); methyprylon (Noludar), Schedule I, depressant

OVERVIEW

Tranquilizers are agents that suppress or inhibit some aspects of central nervous system (CNS) activity—the brain, spinal cord, and the nerves from both—and are thus referred to as CNS depressants. Used primarily to treat insomnia as well as a wide variety of anxiety disorders, tranquilizers are among the most commonly prescribed—and abused—psychiatric medications in the United States. According to Food and Drug Administration (FDA) estimates, over 60 million people receive prescriptions for tranquilizers every year.

As a group, tranquilizers act mostly on the brain by affecting the neurotransmitter gamma-aminobutyric acid (GABA). Neurotransmitters are brain chemicals that facilitate communication between brain cells (neurons). Although the various classes of CNS depressants work in different ways, ultimately it is through their ability to increase GABA activity (thereby decreasing brain activity) that they produce a drowsy or calming effect that is beneficial to those suffering from anxiety or sleep disorders.

Although a wide variety of substances can have tranquilizing effects, historically, the term "major tranquilizer" was applied to the category of drugs used to treat severe mental illnesses such as schizophrenia. This term, however, arose from the inaccurate belief that the major positive action of the earliest drugs used to treat this illness was sedating and that these drugs were on a continuum with other, less powerful, antianxiety drugs.

However, these drugs are now more commonly—and more accurately—called neuroleptics or antipsychotics. As opposed to medications prescribed for sedation, the neuroleptics often produce signs of neurological dysfunction, such as extrapyrimidal effects (involuntary movements such as Parkinson-like tremors and other abnormal movements). The term "antipsychotics" is sometimes used because these drugs are generally used to treat symptoms of paranoia, psychosis, or serious distortions in the perception of reality, such as hallucinations or delusions. The neuroleptics are not typically drugs of abuse.

The term "minor tranquilizer" (which has been replaced by the more precise terms "sedative-hypnotic" or "anxiolytic") refers to drugs used to treat conditions such as insomnia and anxiety. Because they reduce anxiety and produce pleasantly sedating or "tranquilizing" effects, these drugs are more subject to abuse than the neuroleptics.

History

Since antiquity, people of virtually every culture have used chemical substances to induce sleep, relieve stress, alleviate anxiety, and manage the crippling symptoms of severe mental illness. Although clinical descriptions of psychotic patients—especially schizophrenics—date back to at least 1400 b.c., prior to 1950, effective drugs for the treatment of psychotic patients were virtually nonexistent.

Reserpine, an alkaloid, and the active ingredient of Rauwolfia serpentina, the Indian snakeroot, was the basis of the first major tranquilizer. Reserpine was used in the treatment of snake bites, high blood pressure, and anxiety. Rauwolfia was long used in India for the treatment of mental illness (especially paranoia and schizophrenia) and known to medicine men and locals as the "insanity herb." And although the plant was well known in India—Ghandi sometimes sipped tea made from its leaves—Westerners paid little attention to it until an Indian physician wrote an article about it in 1943.

After a U.S. physician named Wilkins demonstrated the positive effects of reserpine in 1952, the drug gained instant notoriety. Reserpine rapidly replaced induced insulin shock therapy (injecting patients with insulin until their blood sugar levels fall so low that the they become comatose), electroconvulsive (ECT) therapy (inducing seizures by passing an electric current through the brain), and lobotomy (making an incision in the lobe of the brain) as treatments for certain types of mental illness. Moreover, knowledge about the chemistry of this natural plant stimulated the synthesis of other similar alkaloids that were later used as major tranquilizers.

The advent of neuroleptics is sometimes identified as a turning point in the practice of psychiatry because it made possible for the first time the treatment and control of mentally ill people outside an institutional setting. In most developed countries, a large percentage of the people suffering, or in remission, from psychosis are treated in the community. This community-based treatment depends almost entirely on dosing with neuroleptics.

However, since their discovery, the use of neuroleptics has fueled an ongoing debate within the mainstream psychiatric community. This discussion arises primarily as a result of the serious nature and unpredictability of side effects associated with these drugs.

The first sedative-hypnotic, or minor tranquilizer, bromide, originated in the 1860s. Bromides are long-acting sedatives that were rarely used past the turn of the nineteenth century; however, bromide can still be found in Bromo Seltzer. The bromides are gastric irritants with a narrow safety margin and may cause a chronic toxicity known as bromism.

Barbiturates (a class of drugs with more effective sedative-hypnotic effects) replaced bromides in 1903. Depending on the dose, frequency, and duration of use, however, tolerance, physical dependence, and psychological dependence on barbiturates can occur relatively rapidly. With the development of tolerance, the margin of safety between the effective dose and the lethal dose becomes very narrow. That is, in order to obtain the same level of intoxication, the tolerant abuser may raise his or her dose to a level that can produce coma and death.

Major tranquilizers (neuroleptics/antipsychotics)

The most frequently cited possible cause of mental illnesses is an abnormal hyperactivity of the dopamine neurotransmitter system in the brain. Neuroleptics inhibit dopamine nerve transmission in the frontal lobes and in the limbic system—the emotion-regulating brain structures. Inhibiting this portion of the brain causes diffuse CNS depression and disrupts an individual's behavior entirely—reducing psychotic thoughts, perceptions, and agitation.

Neuroleptics are used primarily in managing the symptoms of schizophrenia, although they are also used to treat a variety of conditions, including autism, attention deficit hyperactivity disorder (ADHD), bipolar disorder, and even to alleviate severe pain.

Neuroleptics are sometimes placed into two categories, typical and atypical. The typical neuroleptics are those that were marketed before 1990. The atypical or "new generation" neuroleptics work on different neurotransmitters than the older medications. The most common typical or conventional neuroleptic drugs include:

• haloperidol (Haldol)
• thiothixene (Navane)
• trifluoperazine (Stelazine)
• mesoridazine (Serentil)
• thioridazine (Mellaril)
• chlorpromazine (Thorazine)

This list ranks the neuroleptics in increasing order of causing sedation and in decreasing order of causing abnormal involuntary muscle movements and potency. All are equally effective in treating the symptoms of schizophrenia.

The atypical neuroleptics—or "new generation" neuroleptics—cause fewer adverse side effects, are more effective in managing the symptoms of schizophrenia, and are effective for the treatment of bipolar disorder with or without psychosis. However, these drugs are cost more than the older medications. The five approved in the United States as of 2002 are:

• clozaril (Clozapine)
• olanzapine (Zyprexa)
• quetiapine (Seroquel)
• risperidone (Risperdal)
• ziprasidone (Geodon)

The atypical neuroleptics also cause less sedation than the low-potency older neuroleptics such as chlorpromazine (Thorazine) and thioridazine (Mellaril), and fewer movement disorders than the older high-potency neuroleptics fluphenazine (Permitil, Prolixin) and haloperidol (Haldol). Although they often improve the symptoms of psychosis more effectively than the older drugs, the atypical neuroleptics are not without adverse side effects.

Clozaril (Clozapine), for example, can cause agranulocytosis (a potentially lethal suppression of white blood cells by the bone marrow). Parkinsonian symptoms and weight gain occur with risperidone (Risperdal) and olanzapine (Zyprexa). In addition, quetiapine (Seroquel) has been associated with an increased incidence of cataracts.

As researchers have pointed out, well-controlled, rigorous studies of the neuroleptics have been rare. One analysis of seven studies showed improvement of behavioral symptoms in 59% of patients, but there was also improvement in 41% of those taking placebo (sugar pill). Patients with psychosis but without signs of movement disorder are often started on 0.5–1 mg of haloperidol (Haldol), with a subsequent increase in the dosage, trading off between adverse side effects and benefits.

Minor tranquilizers (sedativehypnotics/anxiolytics)

Like the neuroleptics, all of the commonly used minor tranquilizers—with the possible exception of buspirone (BuSpar)—are CNS depressants. Unlike the neuroleptics, however, these drugs are called sedative-hypnotics because they produce relaxation (sedation) at lower doses and sleep (hypnosis) and eventually coma at higher ones. The anxiolytic (antianxiety) effect is merely an early stage of CNS depression.

The sedative-hypnotics, which include all prescription sleep medications and nearly all antianxiety medications, are sometimes prescribed for other conditions, such as preventing or alleviating epileptic seizures. Benzodiazepines are the most commonly prescribed forms of all the major and minor tranquilizers and among the most abused. Unlike most other classes of drugs of abuse, however, CNS depressants such as the barbiturates or the BZDs are rarely manufactured in clandestine laboratories. Instead, legal pharmaceutical products are usually diverted to the black market.

Several motivating factors are involved in sedative-hypnotic misuse and abuse. Abusers may seek to

• sleep
• relieve stress
• feel euphoria or pleasurable sensations
• escape/avoidance—unpleasant sensations, tension, fear, or anxiety
• enhance effects of other narcotic drugs or alcohol
• offset effects of stimulant drugs

Benzodiazepines. The first benzodiazepine—chlordiazepoxide (Librium)—was developed as an antianxiety agent in 1957. BZDs largely replaced the barbiturates because they were safer, since the margin between the therapeutic and toxic level is wider than the barbiturates. In addition, the BZDs were also found to be less-sedating alternatives for treating anxiety and effective for sleep problems, muscle strains, and seizures. Quickly rising in popularity, in the 1970s, diazepam (Valium) was the most widely prescribed drug in North America; in 1986, alprazolam (Xanax) moved to the top of the list. As of 2001, alprazolam (Xanax) was the most widely prescribed BZD in the United States.

Although the BZDs are CNS depressants, they differ from other depressant drugs in that they target specific receptors in the limbic region of the brain instead of depressing activity throughout the entire CNS. Thus, these drugs, if taken as indicated, produce their intended effects without many of the side effects—such as impaired thinking and judgment, and serious respiratory depression—linked to, for example, the neuroleptics.

Most of the minor tranquilizers in the BZD exhibit similar clinical effects; they differ primarily in their duration of action and in the dosage required to achieve the same effect. The BZDs are classified as short-(triazolam [Halcion]), intermediate-(alprazolam [Xanax] and lorazepam [Ativan]), and long-acting (chlordiazepoxide [Librium] and diazepam [Valium]). Of the various BZDs available in the United States in 2002, those primarily prescribed as anxiolytics and hypnotics include the intermediate-and long-acting variety.

Benzodiazepines are highly lipid (fat) soluble—they are stored in body fat and may be toxic if taken in large amounts. They also easily cross the blood-brain barrier and rapidly travel into the CNS. Tolerance builds rapidly to the sedative and the euphoric effects of the BZDS, sometimes within a few days. In contrast, tolerance to the antianxiety and antipanic effects of these drugs is almost nonexistent.

Although the BZDs have minimal depressant effects on respiration, when combined with other CNS depressants (alcohol, opioids), BZDs can cause fatal respiratory suppression. However, most non-BZD sedatives may also cause death by suppression of breathing and heart failure if taken in sufficient quantity. Benzodiazepines can also cause some degree of memory loss called anterograde amnesia—a form of amnesia that involves the formation of memories after a specific event; a person with anterograde amnesia cannot remember information presented to them after ingesting the BZD, a process similar to an alcohol black-out.

Withdrawal from sedative-hypnotics may be accompanied by a delirium that can be life threatening. In severe withdrawal, seizures, visual, tactile, or auditory hallucinations may occur.

Nonbenzodiazepine sedative-hypnotics. The non-BZD hypnotic zolpidem (Ambien) is a newer sleeping agent that is thought to work on more specific subdivisions of the GABA receptor complex than, for example, some of the older benzodiazepine agents. It is indicated for short-term insomnia and is generally limited to seven to 10 days of use.

Zaleplon (Sonata), as of 2002, was the newest sleep medication on the market. Like zolpidem, it also acts on a subdivision of GABA receptors. It has a very short half-life of approximately one hour. (The half-life is the time it takes for the body to metabolize half the sub-stance taken in.) Therefore, it usually produces no effects the next day, such as sedation or memory impairment.

Both zolpidem and zaleplon have a rapid onset of action and are useful in both initiating and maintaining sleep, as well as in decreasing the number of awakenings per night. These drugs also have been shown to lack withdrawal effects and do not demonstrate rebound insomnia. Another benefit of these two non-BZD sedative-hypnotics over the BZDs is the minimal effect on sleep stages. It does not alter the physiologic sleep architecture, providing a more natural sleep. Both hypnotics have a lower tolerance and abuse potential than the BZDs.

Nonbenzodiazepine anxiolytic. Busprione (Bu-Spar) is the first in a class of drugs that specifically work as anxiolytics. In addition to exerting no sedative effect, this medication poses few of the disadvantages associated with the benzodiazepines—such as physical or psychological dependency—and does not significantly interact with most other compounds.

Barbiturates. Barbiturates—which produce a wide spectrum of CNS depression, from mild sedation to coma—have been used as sedatives, hypnotics, anesthetics, and anticonvulsants since they were first introduced for medical use in the early 1900s.

As a class, the barbiturates are very similar; all are fat soluble. Once barbiturates reach the bloodstream, they distribute throughout the body and affect all body tissues. Barbiturates depress the activity of muscle tissues, including the heart, and have a great impact on the respiratory system.

The barbiturates are classified according to how quickly they produce an effect and how long those effects last: ultrashort-, short-, intermediate-, and long-acting. The ultrashort-acting barbiturates produce anesthesia within about one minute after intravenous (IV) administration. When administered orally, these drugs begin acting within 15–40 minutes and maintain their effects for up to six hours.

Long-acting barbiturates include phenobarbital (Luminal) and mephobarbital (Mebaral). These drugs, which take effect in about one hour and last for about 12 hours, are used primarily for daytime sedation and the treatment of seizure disorders or mild anxiety. Generally, these are not drugs of abuse; rather the short-and intermediate-acting barbiturates—such as amobarbital (Amytal), pentobarbital (Nembutal), and secobarbital (Seconal)—are among those most commonly abused.

Depending on dosage, barbiturates may act as either sedatives or as hypnotics. Subjectively, the effects of barbiturates are very similar to those of alcohol. Like alcohol intoxication, a barbiturate state of intoxication involves slurred speech and unsteady gait. Also, both substances can cause a hangover; the barbiturate hangover is caused by traces of unmetabolized drug remaining in the bloodstream when the medication is discontinued.

Tolerance to many of the effects of barbiturates develops rapidly, but it is a characteristic of this class of drugs that tolerance to the effects does not develop uniformly. Tolerance builds to the euphoric effects but not to the lethal dose; euphoric doses come closer and closer to the lethal dose.

Barbiturate overdose is a factor in nearly one-third of all reported drug-related deaths in the United States. These deaths include suicides and accidental drug poisonings. Accidental deaths sometimes occur when a user takes one dose, becomes confused, and unintentionally takes additional or larger doses. In the case of barbiturates, there is a narrow margin between the amount that induces sleep and the amount that kills.

Barbiturate withdrawal time is related to whether the drug is short or long-lasting. Symptoms accompanying withdrawal include apprehension, weakness, tremors, anorexia, muscle twitches, and possible delirium. However, barbiturate withdrawal is seldom symptom-free and can be more difficult than heroin withdrawal.

Although many individuals have taken barbiturates therapeutically without harmful effects, concern about the degree of drowsiness produced in routine dosage, the potential for addiction, and the growing numbers of fatalities associated with the barbiturates led to the development of alternative medications such as the benzodiazepines. As of 2001, barbiturates comprised only about 20% of all depressant prescriptions written in the United States.

Nonbarbiturate sedative-hypnotics. Nonbarbitu-rate sedative-hypnotics are drugs with chemical or physiological properties similar to barbiturates and are considered barbiturate-like substances. These drugs include:

• chloral hydrate (Noctec, Somnos)
• ethchlorvynol (Placidyl)
• glutethimide (Doriden)
• meprobamate (Miltown, Equanil)
• methaqualone (Quaalude)
• methyprylon (Noludar)

Due to their high potential for abuse, most barbiturate-like substances have been replaced by newer, safer agents—such as the BZDs and non-BZD sedative-hypnotics—that exert a sedative-hypnotic effect.

Chloral hydrate (Noctec, Somnos) is metabolized into trichloroethanol, which in turn produces sleep and anesthesia. Chloral hydrate was used in the "Mickey Finn," an anesthetic cocktail used to lure sailors to the Orient in the 1800s. It has a rapid onset, short duration, and few cardiovascular or respiratory effects. Its side effects include an unpleasant taste, gastric irritation, nausea, vomiting, lightheadedness, and nightmares. It has a low margin of safety.

Ethchlorvynol (Placidyl) is an alcohol derivative indicated for short-term (up to one week) therapy in the management of insomnia. The hypnotic dose induces sleep within 15–60 minutes and usually lasts for about five hours. Prolonged use of ethchlorvynol may result in tolerance and physical and psychological dependence. Abrupt discontinuation may result in withdrawal symptoms. The main adverse effects associated with ethchlorvynol are dizziness, gastrointestinal distress, blurred vision, nausea and vomiting, and mild hangover. Ethchlorvynol also has a narrow margin of safety in comparison to other sedative-hypnotic agents. In 1999, the manufacturer, Abbott Laboratories, notified Placidyl prescribers that the drug would be discontinued.

Glutethimide (Doriden), a highly lipid-soluble drug classified as a sedative-hypnotic, was introduced in 1954 as a safe barbiturate substitute. However, its addiction potential and the severity of withdrawal symptoms were similar to those of barbiturates. In 1991, glutethimide was classified as a Schedule II controlled substance in response to an upsurge in the prevalence of diversion, abuse, and overdose deaths. The drug is illegal in the United States and in several other countries. It is classified as a sedative-hypnotic.

Meprobamate (Miltown, Equanil) was introduced in the 1950s. It had the effect of relieving anxiety without producing sleep. However, regular use produced psychological and physical dependence.

Methaqualone (Quaalude, Sopor) is a nonbarbitu-rate hypnotic that is said to give a heroin-like high without drowsiness. When it was first introduced as a prescription drug to treat anxiety and insomnia in 1965, it already had a reputation as a drug of abuse in other countries. It was banned in the United States in 1984 due to the high incidence of its abuse. Despite its nickname "the love drug," it diminishes sexual performance.

By 1972, "luding out"—taking methaqualone with wine—was popular on college campuses. Excessive use of the drug leads to tolerance, dependence, and withdrawal symptoms similar to those of barbiturates. Over-dose by methaqualone is more difficult to treat than barbiturate overdose, and deaths have frequently occurred. In the United States, the marketing of methaqualone pharmaceutical products was discontinued in 1984, and the drug became a Schedule I controlled substance. However, some level of occasional abuse has continued.

Methyprylon (Nodular) was introduced as a sedative and hypnotic in 1955. Its effects are nearly identical to the barbiturate secobarbital (Seconal); it acts by raising the threshold of arousal centers in the CNS. However, over-dose produces shock, low blood pressure, and water in the lungs more often than respiratory depression.

Antihistamines. Because of their sedating effects, antihistamines are sometimes used to treat insomnia. These drugs include diphenhydramine (Benadryl), an over-the-counter medication, and the prescription drugs hydroxizine (Atarax, Vistaril) and promethazine (Phenergan). Tylenol PM and many similar agents combine a pain medication with an antihistamine.

Beta-blockers. Beta-blocking agents (including atenolol [Tenormin] and metoprol [Lopressor]) are a class of drugs that block substances such as adrenaline (epinephrine), a key agent in the autonomic (involuntary) nervous system and in the activation of heart muscle.

Beta-blockers relieve stress on the heart by slowing the heart beat and reducing blood vessel contraction in the heart, brain, and throughout the body. Generally, these drugs are used to treat abnormal heart rhythms, chest pain, high blood pressure, and certain types of tremors (familial or hereditary essential tremors).

In addition to these uses, beta-blockers are sometimes used to treat a variety of physical symptoms associated with anxiety and tension. The ability of these drugs to relieve anxiety led to their nonmedical use by, for example, students prior to exams, competitors, and performers before going on stage. Beta-blockers are sometimes called "the musician's underground drug."

Herbs and supplements. Increasingly, people with sleep difficulties have been turning to herbal remedies instead of sedative-hypnotic drugs such as the BZDs. Melatonin (5-methoxy-N-acetyltryptamine), a hormone released from the pineal gland (a small pine-cone shaped structure in the brain) is essential in regulating circadian rhythms (approximately 24-hour intervals). In mammals, the melatonin rhythm is generated by an internal circadian clock in the hypothalamus region of the brain that is linked to the light/dark cycle of the 24-hour day.

Melatonin production decreases with advancing age, and in a small number of insomniacs, true melatonin deficiency occurs. Whether melatonin is effective for those who are not melatonin-deficient is not known, and research does not support the indiscriminate use of this supplement.

Valerian root (Valerian officinalis) has also been a popular sleep aid. It is believed to work by stimulating the release of the neurotransmitter GABA. Several trials have shown a 400 mg dose to significantly reduce sleep latency (the time it takes to fall asleep) and improve subjective sleep quality. Some commercial preparations of valerian root also contain hops (Flores humuli) as a synergistic ingredient.

Other supplements having milder effects on sleep include kava, scullcap, chamomile, passion flower, lemon balm, and lavender.

Antidepressants. Although not specifically indicated to treat insomnia, antidepressant compounds are often used for their sedating properties, particularly when coexisting depression or anxiety are present. Newer antidepressants that often help with insomnia include trazodone (Desyrel); nefazodone (Serzone); mirtazapine (Remeron); amytriptyline (Elavil); trimipramine (Surmontil); and doxepin (Sinequan).

Illicit sedative-hypnotic drugs

A number of street drugs have tranquilizing effects and are often associated with sexual assaults in the United States. These so-called "date-rape drugs" include:

• Flunitrazepam (Rohypnol), also known as roofies, is a benzodiazepine with physiological effects similar to diazepam (Valium), although it is about 10 times more potent. The drug produces sedative-hypnotic effects that include muscle relaxation and amnesia; it can also produce physical and psychological dependence. It is illegal and not approved for use in the United States.
• Gamma-hydroxybutyrate (GHB), also called liquid ecstasy, is a clear, odorless, and tasteless liquid whose sedative-hypnotic effects are intensified by alcohol. It has been poured into the drink of an unsuspecting person and used as a "date rape" drug and in "rave" dance clubs and bars. The drug is used illicitly for its sedative and euphoric effects, and it is also claimed to promote muscle development. In 2000, the FDA classified it as a Schedule I controlled substance.
• Ketamine hydrochloride (Ketalar) is primarily used as an animal tranquilizer. When humans use the drug in a nonmedical setting, ketamine can cause hallucinations, amnesia, and dissociation. It is often used with other drugs such as ecstasy, heroin, or cocaine. Due to widespread abuse by young people, the DEA classified this drug as a Schedule III controlled substance in 1999.

CHEMICAL/ORGANIC COMPOSITION

All of the neuroleptics are consumed in their pure form and are rarely abused. Most of the sedative-hypnotics of abuse are diverted from legitimate sources and remain in their pure form. However, occasionally powdered forms of illegal drugs (such as ketamine hydrochloride), which are often manufactured in clandestine laboratories, are mixed with tobacco, marijuana, or other drugs.

INGESTION METHODS

Tranquilizers are usually swallowed as a capsule or tablet but may be injected into the bloodstream or muscle (intramuscularly) as a solution as well. Some are available in rectal suppositories and sublingual (under the tongue) forms. Illicit tranquilizers are also snorted or taken with other drugs, alcohol, or tobacco.

THERAPEUTIC USE

Although the major and minor tranquilizers are used for their ability to depress CNS activity, these classes of drugs are used to manage a variety of specific symptoms and conditions.

Major tranquilizers

Initially, the neuroleptics were used to manage severe anxiety, agitation, and aggression in individuals with severe mental illness such as schizophrenia, a psychotic illness characterized by delusions, hallucinations, and disorganized, illogical thinking. The first neuroleptic used in schizophrenia was chlorpromazine (Thorazine) in 1952. Additional neuroleptics were later developed to treat a variety of other disorders and conditions in children and adults, including autism, attention-deficit hyperactivity disorder (ADHD), bipolar disorder, and Tourette's syndrome. Occasionally, these drugs are also used to manage severe pain.

Minor tranquilizers

BZDs such as chlordiazepoxide (Librium) or diazepam (Valium) may be prescribed to treat anxiety, seizures, acute stress reactions, and panic attacks, or to alleviate the side effects of drug or alcohol withdrawal. Those BZDs with a more sedating effect, such as estazolam (ProSom) or triazolam (Halcion), may be prescribed for short-term treatment of sleep disorders. However, the newer generation of non-BZD agents—zolpidem (Ambien) and (Sonata)—are less potentially addictive hypnotic drugs than the BZDs.

In addition to treating anxiety and insomnia, intra-venous BZDs are used as a sedating agent in outpatient surgical procedures. The most commonly used BZD for this indication is the short-acting agent midazolam (Versed). There is a lower potential for respiratory suppression with midazolam than with the barbiturates.

Barbiturates such as mephobarbital (Mebaral) and pentobarbital (Nembutal), although not prescribed as often as the BZDs, may be used to treat anxiety, tension, and sleep disorders. Veterinarians also use pentobarbital (Nembutal) for anesthesia and euthanasia. In some states, a form of barbiturate is used to execute criminals by lethal injection.

The rapid-acting barbiturates, such as methohexital (Brevital), are used as intravenous anesthetics/induction agents. Advantages are rapid anesthesia and short duration of action. A disadvantage is respiratory suppression with higher doses.

Buspirone (BuSpar) is specifically formulated to reduce the symptoms of anxiety but takes two to four weeks to take effect. Adverse reactions include agitation, nausea, and dizziness.

USAGE TRENDS

The Food and Drug Administration (FDA) estimates that over 60 million people receive prescriptions for tranquilizers every year. In the 1980s, the focus of psychiatric care was on depression and its treatment; in the 1990s, the focus turned to the early identification, diagnosis, and treatment of anxiety disorders. This shift in focus resulted in a corresponding shift in drug usage patterns.

In targeting those suffering from anxiety, pharmaceutical companies generated greater consumer demand for their drugs. Prescriptions for one class of these drugs, the BZDs, already are estimated at nearly 100 million a year in the United States, at a cost of about $500 million. Some estimates place the total cost at $800 million or more.

Scope and severity

Since the early 1960s, the BZDs have accounted for more than half the total world sales of tranquilizers. As of 2002, the BZDs were the most commonly prescribed class of tranquilizers in the United States. According to FDA data, however, there has been a dramatic decline in the use of minor tranquilizers and other antianxiety drugs since 1975, when prescriptions peaked at 103 million. An American Psychiatric Association task force report estimates that annual prescriptions for BZDs have leveled off since the mid-1980s to about 61 million.

Age, ethnic, and gender trends

Although many Americans abuse prescription drugs, certain usage trends can be seen among adolescents, young adults, older adults, and women. National Household Survey on Drug Abuse (2000) statistics indicate that the sharpest increases in new users of prescription drugs for nonmedical purposes occurred in 12–17 and 18–25 year-olds. Among 12–14 year-olds, psychiatric medications (including sedative-hypnotics) and narcotics (opioids) were reportedly the two main classes of drugs used.

The 1999 Monitoring the Future Survey of eighth, tenth, and twelfth graders nationwide showed that general declines in the use of barbiturates, sedative-hypnotics, and opioids other than heroin in the 1980s leveled off in the early 1990s, with modest increases again in the mid-1990s.

According to a number of national surveys, men and women have roughly similar rates of nonmedical use of prescription drugs, with the exception of 12–17 year-olds. In this age group, young women are more likely than young men to use psychiatric drugs nonmedically. Also, among men and women who use either a sedative, antianxiety drug, or hypnotic, women are almost twice as likely to become addicted.

Studies indicate that women who were abused as girls, or who saw their mothers abused by a male partner, are more likely, as adults, to use tranquilizers and also illegal drugs. Also, women who are abused by their partners use more tranquilizers—as well as more alcohol—than other women. Other frequent tranquilizer users are those with only an elementary school education; those in the lowest income group; and those who do not work outside the home (including housewives, students, the disabled, and the retired).

In terms of approved medical use, the neuroleptics are often prescribed for children with autism, attention-deficit hyperactivity disorder (ADHD), and Tourette's syndrome. In addition, the popularity of the newer atypical neuroleptics for childhood bipolar disorder is growing rapidly, and sometimes these drugs are the only treatment offered. The neuroleptics are also commonly prescribed for the elderly in nursing homes or other institutional settings.

MENTAL EFFECTS

The most significant beneficial mental effects of the major and minor tranquilizers include:

• anxiety reduction
• mild euphoria
• panic reduction

PHYSIOLOGICAL EFFECTS

Beneficial physiological effects of the major and minor tranquilizers include:

• anesthesia
• anticonvulsant effects
• blood vessel dilation
• decreased contractability of the heart
• decreased hyperactivity, impulsivity, and aggression
• muscle relaxation
• pain relief
• reduced muscle spasms
• relaxation
• sedation
• slowed heart rate

Harmful side effects

At high doses, both the major and minor tranquilizers are severely toxic and may cause coma, respiratory arrest, convulsions, acute renal failure, speech impairment, or death. However, at therapeutic doses, the neuroleptics have been associated with more severe, long-term side effects than the sedative-hypnotics.

Major tranquilizers. Although long-term studies are few, the adverse side effects of the atypical neuroleptics are thought to be less severe than the typical agents. However, adverse side effects have been reported with all neuroleptics. These side effects include:

• agitation and confusion
• cardiac symptoms (such as irregularities in cardiac rhythm)
• dyskinesias (involuntary movements) of the face and tongue
• extrapyramidal symptoms (tremor, slowing down of the movements, muscle stiffening)
• moderate respiratory depression with increased bronchial secretions
• postural hypotension (drop in blood pressure upon standing up)
• sedation
• weight gain

Minor tranquilizers. Some of the most commonly reported adverse effects of the sedative-hypnotics, particularly when used long-term, include:

• blurred and double vision
• compromised mechanical performance (such as automobile driving)
• depression
• dizziness
• hallucinations
• hostility
• impaired mental alertness, thinking, and memory
• paradoxical reactions (acute agitation, confusion, disorientation, anxiety, and aggression), especially in children, adults with brain disease, and the elderly
• rebound anxiety or insomnia (continued use eventually causes an increase of the very symptoms that the drug is supposed to ameliorate)

Regular use of the sedative-hypnotics may result in tolerance—the need for increasing doses to achieve the same effect. Within two to four weeks, tolerance can develop to the sedative effect of minor tranquilizers taken at night for sleep. Thus, these drugs are not usually used prescribed for more than a few days at a time.

The risk of drug dependence increases if sedative-hypnotics are taken regularly for more than a few months, although problems have been reported within shorter periods. The onset and severity of withdrawal differ between the BZDs that are rapidly eliminated from the body (such as triazolam [Halcion]) and those that are slowly eliminated (such as diazepam [Valium]). In the drugs that are rapidly eliminated, symptoms appear within a few hours after stopping treatment of the drug and may be more severe. In drugs that are eliminated slowly, symptoms usually take several days to appear. The frequency and severity of the withdrawal symptoms—which include gastrointestinal problems, loss of appetite, sleep disturbances, sweating, trembling, weakness, anxiety, and changes in perception (such as increased sensitivity to light, sound, and smells), depends on the dosage, duration of use, and whether usage ceases abruptly or tapers gradually. Obvious withdrawal symptoms typically last two to four weeks; however, the more subtle symptoms may last for months.

Although the barbiturates do not directly cause CNS damage, some individuals with asthma may have a hypersensitive reaction to these drugs. Many individuals who are prescribed barbiturates develop an extreme sensitivity to sunlight known as photosensitivity. In addition, physical dependence on barbiturates can be one of the most dangerous of all drug dependencies; growing tolerance can lead to chronic use close to a lethal level, and abrupt withdrawal can cause symptoms severe enough to lead to death.

Long-term health effects

Both the neuroleptics and the sedative-hypnotics may cause severe, long-term adverse health effects, depending on the dosage and how long the drugs are in use.

Major tranquilizers. Long-term, the most serious side effect of neuroleptics is tardive dyskinesia (TD), a movement disorder that can affect any of the voluntary muscles. The disorder, which strikes usually after six months to two years of treatment, occurs in about 20% to 35% of patients treated with neuroleptics. This incurable condition is most severe in young men and most common in elderly women. Tardive dyskinesia affects the muscles of the mouth and face and causes lip smacking, teeth grinding, rolling or protrusion of the tongue, tics, and diaphragmatic (chest and abdominal) movements that may impair breathing.

All of the major tranquilizers have been implicated in the development of neuroleptic malignant syndrome, a life-threatening disorder that affects multiple organ systems and may result in death in up to 20% of individuals, especially if the symptoms (including extreme muscle rigidity, rapid heart rate, fever, high blood pressure, incontinence, delirium, stupor, coma) are not recognized immediately. The neuroleptics also have the potential to cause brain damage as a result of impairment to the frontal lobes and limbic system. Typical changes are apathy, loss of memory and concentration, and loss of deeper feelings and tenderness.

Minor tranquilizers. There have been very few studies to measure the long-term impact of regular sedative-hypnotic use on overall mental function. Thus, it is impossible to determine how long it is safe for an individual to continue to take BZDs, or at what dosage, before cognitive ability begins to deteriorate. Some researchers have indicated, however, that like alcohol, the minor tranquilizers, when used long-term, may cause brain shrinkage. There is evidence to show that taking a low dose for a short time has little effect, whereas a high intake is almost always certainly harmful.

Tranquilizer overdose, particularly with BZDs, has become increasingly common since the 1960s. Although the sedative-hypnotics are usually safe even when an overdose is taken, they can be fatal in combination with alcohol and other CNS depressants. In addition, the drugs used in suicide attempts—most drug-related suicide attempts are made by women under 30—are those most widely prescribed and available.

REACTIONS WITH OTHER DRUGS OR SUBSTANCES

The major and minor tranquilizers, as CNS depressants, should be used with other medications only under a physician's supervision. Typically, they should not be combined with any other medication or substance that causes CNS depression, including prescription pain medications, some over-the-counter cold and allergy medications, or alcohol. Using CNS depressants with these substances—particularly alcohol—potentiates (amplifies) their effects and can slow breathing, or slow both the heart and respiration, and possibly lead to death from overdose or from driving under the influence. A large percentage of drug-related emergency room visits involve minor tranquilizers.

Although primary abuse of the BZDs is well documented, abuse of these drugs usually occurs as part of a pattern of multiple drug abuse. Heroin or cocaine abusers, for example, use BZDs with other depressants to intensify their "high" or alter the side effects associated with overstimulation or narcotic withdrawal.

TREATMENT AND REHABILITATION

Anyone taking BZDs daily for six to eight weeks may develop dependence and suffer from withdrawal symptoms. Although treatment strategies are usually tailored to the severity of symptoms—a high-dose withdrawal (usually at doses greater than the therapeutic for longer than one month); or low-dose withdrawal (therapeutic doses for more than a few months)—the most effective way to treat dependence is a very gradual tapering (gradual dose reduction) of the drug. If an individual abruptly stops taking the drug, the brain, having become accustomed to sedated activity, can race out of control. This can lead to seizures and other serious or life-threatening consequences. Close monitoring by a qualified physician is critical to the safe use of, and withdrawal from, the sedative-hypnotics. Inpatient or outpatient counseling is also helpful during the detoxification/withdrawal process.

Patients are typically withdrawn from high-dose sedative-hypnotics by gradually reducing the substance of dependence, substituting a longer-acting BZD, which is later tapered, or substituting the barbiturate phenobarbital (Luminal) and subsequently tapering. The chosen method depends on the substance of abuse. Gradual dose reduction is used in a medical setting and requires that the patient use no other drugs of abuse and adhere strictly to the dosing regimen. Substituting a long-acting BZD with subsequent taper is often used to treat BZD withdrawal or mixed BZD-alcohol withdrawal. Substituting phenobarbital may be used for withdrawal from BZDs or other sedative-hypnotics or in patients with multiple drug dependence.

Most individuals who are tapered and withdrawn from therapeutic (low) doses of BZDs experience mild to no withdrawal symptoms that gradually subside and disappear within a few days to a few weeks. For those individuals who experience continued symptoms, a slow, gradual taper from the original BZD dose usually minimizes these symptoms.

PERSONAL AND SOCIAL CONSEQUENCES

The personal cost of dependence on prescription sedative-hypnotics is high. Aside from the short-or long-term health effects, physical or psychological dependence may lead to family discord, job loss, birth defects in infants born to addicted mothers, and even criminal behavior and incarceration in individuals who purchase these drugs illicitly.

Although not often considered, the social cost of prescribing neuroleptics to some groups of people may be enormous. Recent research suggests that an older person living in a nursing home receives four times as many prescription drugs as an older person in their own home. Thus, some healthcare professionals are concerned that the neuroleptics are often overprescribed in the elderly—especially those living in nursing homes and long-term treatment facilities. Critics argue that these medications are often routinely used to suppress emotions and render elderly patients passive and docile, thus easing the workload of caregivers, rather than alleviating the symptoms of dementia.

Some maintain that rather than treating a disease or condition, neuroleptics often create another disease. Although these drugs eliminate or reduce the intensity of psychotic experiences such as delusions and hallucinations, the adverse side effects that may actually worsen the symptoms of dementia.

Dealing with the "problem" behavior of children with autism or ADHD by prescribing neuroleptics, according to some, has much in common with the treatment of the elderly. Although stimulants like methylphenidate (Ritalin) have been reportedly prescribed to large numbers of children and received much media attention, other psychotropic (mind-altering) drugs, such as the neuroleptics, are also prescribed. However, there has been virtually no testing of these drugs conducted on children, and the long-term effects are unknown.

LEGAL CONSEQUENCES

Legal history

Although some sedative-hypnotics such as the nonbarbiturates glutethimide (Doriden) and methaqualone (Quaalude) were once legally prescribed drugs, these substances were banned from use in the United States because of their potential for addiction and abuse. Some sedative-hypnotics such as flunitrazepam (Rohypnol) are illegal in the United States but are legal in Europe and Latin America.

Federal guidelines, regulations, and penalties

The major and minor tranquilizers are legal as manufactured and prescribed and are classified as Schedule II, III, or IV controlled substances under the federal Controlled Substances Act (CSA). However, manufacturing, distributing, and selling these drugs without a prescription are subject to federal and state penalties. The CSA dictates penalties of up to 15 years imprisonment and fines up to $25,000 for unlawful distribution or possession of a controlled substance.

See also Antidepressants; Barbiturates; Benzodiazepines; GHB; Herbal drugs; Ketamine; Melatonin; Methaqualone; Rohypnol

RESOURCES

Books

Bloomfield, Harold. Healing Anxiety With Herbs. New York: HarperCollins, 1998.

Breggin, Peter R. and David Cohen. Your Drug May Be Your Problem: How and Why to Stop Taking Psychiatric Medications. Reading, MA: Perseus Books, 1999.

Gorman, Jack M. The Essential Guide to Psychotropic Drugs. New York: St. Martin's Press, 1998.

Keltner, Norman L. and David G. Folks. Psychotropic Drugs. Philadelphia: Mosby, 2001.

Parker, Jim. The Benzodiazepine Blues: Living With (and Without) Minor Tranquilizers. Tempe, AZ: Do It Now Foundation, 2000.

Periodicals

Garfinkel D., N. Zisapel, J. Wainstein, et al. "Facilitation of Benzodiazepine Discontinuation by Melatonin. A New Clinical Approach." Archives of Internal Medicine 159, no. 20 (November 1999): 2456-60.

Longo, L.P. "Addiction: Part I. Benzodiazepines: Side Effects, Abuse Risk, and Alternatives." American Family Physician 61 (April 1, 2000): 2121-2128.

U.S. National Institute on Drug Abuse Research Report, NIH Pub. # 01-4881. April 2001.

Zito, Julie Magno et al. "Trends in the Prescribing of Psychotropic Medications to Preschoolers." Journal of the American Medical Association 283 (February 23, 2000): 1025-1030.

Organizations

National Clearinghouse for Alcohol and Drug Information (NCADI), P.O. Box 2345, Rockville, USA, (800) 729-6686.

National Council on Alcohol and Drug Dependence, 12 West 21st Street, New York, NY, USA, 10010, (800) 622-2255 or(800) 475-4673, <http://ncadd.org>.

National Institute on Drug Abuse (NIDA), National Institutes of Health, 6001 Executive Boulevard, Room 5213, Bethesda, MD, USA, 20892-9561, (301) 443-1124, (888) 644-6432, information @lists.nida.nih.gov, <http://www.drugabuse.gov>.

Substance Abuse and Mental Health Services Administration (SAMSHA)/Center for Substance Abuse Treatment (CSAT), 5600 Fishers Lane, Rockville, MD, USA, 20857, (301) 443-8956, info@samsha.gov, <http://www.samhsa.gov>.

Genevieve T. Slomski, Ph.D.

Tranquilizers

What Kind of Drug Is It?

Tranquilizing drugs slow normal brain function. For that reason, they are often referred to as depressants. These kinds of drugs work by affecting the neurotransmitter gamma-aminobutyric acid (GABA). Neurotransmitters are brain chemicals that help brain cells communicate with one another by spreading nerve impulses from one nerve cell to another. The higher the level of GABA activity in the brain, the greater the calming effect produced. Tranquilizers are prescribed by doctors only and are usually dispensed as pills or capsules. Some types come in liquid or solution form.

Because tranquilizers slow down normal brain activity and produce a calming or drowsy effect, they are among the most common drugs prescribed to patients suffering from insomnia. Insomniacs are patients who either have trouble falling asleep or cannot fall asleep at all. Tranquilizers are also prescribed to patients diagnosed with anxiety, a type of mental disorder that causes extreme restlessness, uncontrollable feelings of fear, excessive worrying, and panic attacks. According to Jim Parker in Tranx: Minor Tranquilizers, Major Problems, about 70 million prescriptions for tranquilizers are written each year in the United States. Tranquilizers are also among the most commonly abused medications. In 2005, the National Center on Addiction and Substance Abuse (CASA) at Columbia University released a 214-page report titled "Under the Counter: The Diversion and Abuse of Controlled Prescription Drugs in the U.S." That report indicates that in 2003 nearly 6 million Americans abused prescription tranquilizers and sedatives.

Official Drug Name: Major tranquilizers: aripiprazole (ah-rih-PIP-rah-zole; Abilify); chlorpromazine (klorr-PROH-mah-zeen; Thorazine); clozapine (CLAW-zuh-peen; Clozaril); fluphenazine (flu-FENNuh-zeen; Permitil, Prolixin); haloperidol (hal-oh-PEH-rih-dawl; Haldol); loxapine (LOK-suh-peen; Daxolin, Loxitane); mesoridazine (meh-zoh-RY-duh-zeen; Serentil); olanzapine (oh-LANN-zuh-peen; Zyprexa); perphenazine (per-FENN-uhzeen; Trilafon); pimozide (PIMM-oh-zide; Orap); quetiapine (kweh-TY-uh-peen; Seroquel); risperidone (rih-SPER-ih-doan; Risperdal); thioridazine (thy-oh-RY-duh-zeen; Mellaril); thiothixene (thy-oh-THIK-seen; Navane); trifluoperazine (try-FLU-oh-PERR-uh-zeen; Stelazine); triflupromazine (try-flu-PROH-muh-zeen; Vesprin); ziprasidone (zih-PRAY-zih-don; Geodon)

Also Known As: Antipsychotics, neuroleptics

Drug Classifications: Major tranquilizers; not scheduled

Official Drug Name: Minor tranquilizers (benzodiazepines): alprazolam (al-PRAZZ-oh-lam; Xanax); chlordiazepoxide (klor-dye-az-uh-POKS-ide; Librium); clonazepam (kloh-NAZZ-uh-pam; Klonopin); clorazepate (klor-AZZ-uh-pate; Tranxene); diazepam (dye-AZZ-uh-pam; Valium); estazolam (ess-TAH-zoh-lam; ProSom); flunitrazepam (flu-nih-TRAZ-uh-pam; Rohypnol); flurazepam (flor-AZZ-uh-pam; Dalmane); halazepam (huh-LAZZ-uh-pam; Paxipam); lorazepam (lorr-AZZ-uh-pam; Ativan); midazolam (my-DAY-zoh-lam; Versed); oxazepam (oks-AZZ-uh-pam; Serax); prazepam (PRAZZ-uh-pam; Centrax); quazepam (KWAY-zuh-pam; Doral); temazepam (tuh-MAZZ-uh-pam; Restoril); triazolam (try-AY-zoe-lam; Halcion)

Also Known As: Anxiolytics (ANG-zee-oh-LIH-tiks), benzos, BZDs, downers, goofballs, happy pills, sedative-hypnotics, tranks, tranx

Drug Classifications: Benzodiazepines: Schedule IV (except for flunitrazepam, which as of 2005 was a Schedule III drug; change in status to Schedule I possible, according to the Drug Enforcement Administration); depressants

Official Drug Name: Minor tranquilizers (nonbenzodiazepines): buspirone (byoo-SPY-rone; BuSpar); zaleplon (ZAH-leh-plon; Sonata); zolpidem (zole-PIE-dem; Ambien)

Also Known As: Anxiolytics, sedative-hypnotics, tranks, tranx

Drug Classifications: Nonbenzodiazepine hypnotics: buspirone, not scheduled; zaleplon and zolpidem, both Schedule IV, depressants

Official Drug Name: Minor tranquilizers (barbiturates): amobarbital (AMM-oh-BAR-bit-al; Amytal); butabarbital (BYOOT-uh-BAR-bit-al; Butisol); butalbital (byoo-TAHL-bit-al; Fioricet and Fiorinal); mephobarbital (MEFF-oh-BAR-bital; Mebaral); methohexital (meh-thoh-HEK-sih-tal; Brevital); pentobarbital (PENT-oh-BAR-bit-al; Nembutal); phenobarbital (FEEN-oh-BAR-bit-al; Luminal); secobarbital (SEK-oh-BAR-bit-al; Seconal)

Also Known As: Amys, anxiolytics, barbs, blues, downers, rainbows, red devils, sedative-hypnotics, tranks, tranx, yellow jackets

Drug Classifications: Barbiturates: amobarbital, pentobarbital, and secobarbital, all Schedule II, depressants; butabarbital and butalbital, both Schedule III, depressants; mephobarbital, methohexital, and phenobarbital, all Schedule IV, depressants

Official Drug Name: Minor tranquilizers (nonbarbiturate sedative-hypnotics): chloral hydrate (KLORR-uhl HIGH-drate; Aquachloral Supprettes, Noctec); ethchlorvynol (eth-KLORR-vih-nol; Placidyl); glutethimide (glue-TEH-thuh-mide; Doriden); meprobamate (meh-proe-BAM-Mate; Miltown, Equanil); methaqualone (meth-a-KWAY-lone; Quaalude); methyprylon (meth-ih-PRY-lon; Noludar)

Also Known As: Anxiolytics, ludes, sedative-hypnotics, sopors, tranks, tranx

Drug Classifications: Nonbarbiturate sedative-hypnotics: methaqualone, Schedule I, depressant; glutethimide, Schedule II, depressant; methyprylon, Schedule III, depressant; chloral hydrate, ethchlorvynol, and meprobamate, all Schedule IV, depressants

Official Drug Name: Herbals: Rauwolfia serpentina (row-WOLF-ee-uh SER-penn-TEEN-uh; active ingredient in reserpine [Serpasil]); Valeriana officinalis

Also Known As: Indian snakeroot (for Rauwolfia); valerian

Drug Classifications: Not scheduled; dietary supplements

Overview

In general, tranquilizers fall into two categories: major tranquilizers and minor tranquilizers. Major tranquilizers are drugs used to treat severe mental illnesses, such as schizophrenia and psychosis (sy-KOH-sis). A mental disease, schizophrenia causes patients to withdraw from reality and suffer other intellectual and emotional disturbances. Psychosis is a severe mental disorder that often causes hallucinations, or visions, and makes it difficult for people to distinguish what is real from what is imagined. Major

tranquilizers are more commonly called neuroleptics or antipsychotics. These drugs help decrease the symptoms of serious psychiatric disorders by targeting areas of the brain that deal with emotion. They are not typically abused by patients.

Minor tranquilizers, also known as sedative-hypnotic or anxiolytic drugs, are a group of medications that are prescribed to treat sleep and anxiety disorders. Although different sedative-hypnotic and anxiolytic drugs work in the brain in slightly different ways, they all produce a calming effect that is beneficial to patients who cannot sleep or who suffer from severe anxiety attacks. These drugs are among the most abused in the United States.

Minor tranquilizers can also be broken down into two main categories: barbiturates, which are used to treat anxiety, tension, and sleep disorders; and benzodiazepines (BZDs), which can be prescribed to treat anxiety, severe stress reactions, and panic attacks. Panic attacks are unexpected episodes of severe anxiety that can cause shortness of breath, dizziness, sweating, and shaking. (Entries on barbiturates and benzodiazepines are included in this encyclopedia.) The main difference between the two groups is that BZDs target specific receptors (groups of cells that receive stimuli) in the brain instead of affecting the entire brain. Therefore, BZDs do not produce many of the negative side effects associated with major tranquilizers or barbiturates, such as impaired judgment or breathing problems. Most tranquilizers and sleeping pills prescribed as of 2005 belonged to the BZD chemical group because of their higher safety ratings. The best-known examples of BZDs are Ativan, Halcion, Librium, Valium (VAL-eum), and Xanax (ZAN-ex).

History

In some form or another, tranquilizers have been around since ancient times. Virtually every culture discovered the sedative effects of certain herbs and plants growing in nature. (A separate entry on herbal drugs is available in this encyclopedia.) Through years of trial and error, these cultures were able to identify specific plants that—when prepared a particular way—could have a tranquilizing effect. By drying these plants or their roots and grinding them into food or mixing them with liquids, herbalists found that the substances could relieve stress, insomnia, and the symptoms of severe mental disorders in people who consumed them.

Major Tranquilizers

The first major tranquilizer was developed from Rauwolfia serpentina, also known as the Indian snakeroot. Rauwolfia is known for its ability to lower blood pressure. Used for many years in India for the treatment of serious mental illness, it was frequently referred to there as the "insanity herb." Most often, its roots were crushed and consumed in a tea. In 1943 an Indian physician named Rustom Jal Vakil (1911–1974) wrote about the plant's success in treating mental illness. It wasn't long before Western doctors began studying Rauwolfia, hoping that it could help patients with severe psychiatric disorders.

American doctor Robert Wallace Wilkins (1906–2003) of Boston University Medical School conducted extensive research on Rauwolfia serpentina after hearing about its use in India. In 1954, he showed that reserpine, an alkaloid and the active ingredient in Rauwolfia, was successful in treating both high blood pressure and severe psychiatric disorders such as schizophrenia and other psychoses. Almost immediately the new drug (sold under the brand name Serpasil) became the most popular way to treat such disorders.

Wilkins' work inspired further research, which resulted in the development of other drugs used as major tranquilizers. With neuroleptic and antipsychotic drugs came the possibility that mentally ill patients would not have to spend their lives committed

to institutions and under a doctor's strict supervision. Instead, they could return to their homes and families as long as they followed prescribed drug therapy and other treatment.

Minor Tranquilizers

Herbs such as valerian, kava, and lavender produce tranquilizing effects and have been used by various cultures for centuries. There were no alternatives to natural tranquilizers until the 1860s, when the first synthetic minor tranquilizer, bromide, was created. (Synthetic drugs are those created in a laboratory.) But the dangerous side effects it produced made it rather unpopular. The drug caused stomach problems and, if taken for a long time, proved toxic (harmful or poisonous). Bromides were replaced by barbiturates in 1903. Barbiturates are effective in reducing anxiety and causing drowsiness, but can very quickly become addictive or habit-forming. Amytal, Nembutal, and Seconal are all examples of barbiturates.

The danger with barbiturates is the high rate of death connected with overdose. An overdose of barbiturates affects the heart and the respiratory system, causing shortness of breath, extreme drowsiness, and an unusually slow heart rate. The user then slips into a coma and dies. Because of this, chemists knew they had to find an alternative to barbiturates—a drug that could ease anxiety without slowing breathing rates to dangerously low levels. The answer came with the discovery of benzodiazepines.

Drug Therapy Replaces Radical Treatments for Mental Illness

Reserpine was the first drug developed to treat patients with severe psychiatric problems, such as: schizophrenia; paranoia—having abnormal feelings of suspicion and fear; and hallucinations—having visions or seeing things that are not really present. Before reserpine, psychiatric patients suffering from severe mental illnesses had to endure radical treatments. These included: 1) insulin shock therapy, in which a doctor injects the patient with insulin, making blood sugar levels fall so low that the patient becomes comatose, or unconscious; 2) electroconvulsive (ECT) therapy, in which a patient is shocked with electricity; and 3) lobotomy, a surgical procedure that actually removes part of the brain. It is easy to see why the development of reserpine was viewed as a revolutionary treatment for psychiatric patients.

Because of its positive effects in treating not only psychiatric disorders but also high blood pressure, reserpine quickly became a very popular drug. Reserpine lowers high blood pressure in two ways. First, it decreases the heart rate. Second, it opens up blood vessels to improve the flow of blood throughout the body. According to the MedlinePlus Web site, the drug was still being used for this purpose in the early 2000s. However, as of 2005, it was no longer considered the drug of choice for treating patients with mental disorders.

Doctors and researchers soon realized that although the drug was useful in calming upset psychotic patients—those experiencing a dangerous loss of contact with reality that could lead to violence—it caused severe depression in others. There were also other negative side effects, including nightmares, stomach problems, and parkinsonism (PAR-kin-son-izm), which is a disorder of the nervous system that resembles Parkinson's disease. Symptoms of parkinsonism include overall weakness, partial paralysis of the face, trembling hands, and a slowed, shuffling walk. As a result, reserpine has been largely replaced in psychiatric use by other major tranquilizers.

In 1954, Austrian scientist Dr. Leo Sternbach (1908–2005) discovered the first benzodiazepine while conducting research on chemical compounds for the New Jersey-based Hoffmann-La Roche drug company. He did not recognize the importance of his discovery until 1957, when he realized that one of his compounds would make a great tranquilizer. Known as RO 5-0690, the drug eventually became Librium. Sternbach also developed Valium in 1963. Over time, BZDs became popular drugs for the treatment of anxiety and sleep disorders.

What Is It Made Of?

Although all tranquilizers have the same general effects, they vary widely in chemical makeup. Most are synthetic, which means they are made in a lab from chemicals. Other tranquilizing drugs are found naturally in plants and have been used for centuries to cure such troubles as tremors, insomnia, and heart problems. An example of a natural tranquilizer is valerian, which is a plant that grows in mild climates. Other herbal supplements that are thought to decrease stress responses and improve sleep include kava, skullcap, chamomile, passion flower, lemon balm, and lavender.

How Is It Taken?

Most tranquilizers are taken by mouth in pill, capsule, or liquid form. If a pill or capsule is taken, doctors recommend drinking a full glass of water along with each dose. Since most pills or capsules are formulated to release the medication in the body slowly, it is important not to chew or break them. Concentrated liquid forms should be diluted, or mixed with another liquid, such as coffee, milk, tea, water, or fruit juice. Tranquilizers also can be injected into a vein or administered rectally in a suppository. Illegal tranquilizers, like Rohypnol (roh-HIPP-nahl) or ketamine (KETT-uh-meen), are sometimes dissolved in drinks, snorted, or sprinkled on tobacco or marijuana and then smoked. (Entries on Rohypnol and ketamine are included in this encyclopedia.)

A History of Valerian

Valerian (Valeriana officinalis) is a natural herbal remedy that has been popular throughout history for its sedative and hypnotic (sleep-producing) properties. In more contemporary times, it has been used as an anxiolytic drug with mixed success. The rhizomes (RYE-zohmz), or underground stems, of the plant are used to make teas and other herbal remedies for nervous tension and insomnia. Dosages of 300 to 600 milligrams of valerian are said to help people fall asleep faster.

Valerian grows in Europe, North America, and the northern part of Asia. It has been used since the time of the ancient Greeks. The Greek physician Hippocrates (430–370 bce) wrote about valerian, and the renowned Greek physician Galen (131–203 ce) prescribed it for insomnia. It was very popular in the Middle Ages (c. 500– c. 1500), when it was used to treat tremors, nervous conditions, and heart palpitations. In World War II (1939–1945), it was used by the British to relieve the massive stress brought on during nightly air raids by the Germans.

There are more than 150 species of valerian root. All of them contain rare oils that are known to produce nerve-calming, sedative effects on the body. Valerian is also well known for its extremely unpleasant odor, which is described as being similar to sweaty feet and dirty socks.

Are There Any Medical Reasons for Taking This Substance?

Major tranquilizers such as Clozapine, Haldol, or Thorazine are powerful drugs that are prescribed to relieve the symptoms of major psychiatric disorders such as schizophrenia. Some have been developed to treat the following: 1) dementia, a brain disorder that causes a reduction in a person's intellectual functioning, most often affecting memory, concentration, and decision-making skills; 2) autism, a psychological disorder, usually diagnosed in children, that affects emotional development, social interactions, and the ability to communicate effectively; 3) bipolar disorder, a psychological disorder that causes alternating periods of depression and extreme happiness; 4) Tourette's syndrome, a severe tic disorder that causes distress and significant disability to those affected by it; and 5) attention-deficit/hyperactivity disorder (ADHD), a condition characterized by impulsive behavior, difficulty concentrating, and hyperactivity that interferes with social and academic functioning. These drugs may also be used in individuals exhibiting signs of severe agitation, violence, hostility, or paranoid behavior. In rare cases, they have been used to ease severe pain.

There are a number of medical reasons why doctors prescribe tranquilizers. Because minor tranquilizers produce a calming or drowsy effect, the most common reasons are insomnia and anxiety disorders. Minor tranquilizers are also considered effective in treating anxiety in patients suffering from Alzheimer's disease, which is a brain disease that usually strikes older individuals and results in memory loss, impaired thinking, and personality changes. Minor tranquilizers are sometimes prescribed to help with alcohol and drug withdrawal. Others help to prevent epileptic seizures, which are sudden violent spasms or convulsions resulting from epilepsy, a disorder involving the misfiring of electrical impulses in the brain. In some instances, certain types of barbiturates and BZDs have been used as an anesthetic to deaden pain in outpatient procedures. In some states, a form of barbiturate is used to execute criminals by lethal injection.

"Someone Must Have Slipped Him a Mickey"

There are a few stories behind the term "slipping someone a Mickey," which means putting a knockout drug in someone's drink. Some say the original Mickey was a laxative (a drug that helps produce bowel movements) used for horses. Others believe that the phrase began with Mickey Finn, a man who owned a bar named the Lone Star Saloon and Palm Garden in Chicago, Illinois, in 1896. A colorful criminal, Mickey found that when he mixed a little sedative-hypnotic chloral hydrate into an unsuspecting patron's drink, the guy would quickly pass out. Then Mickey and his associates would drag the victim into a back room, rob him, and dump him in an alley. The next morning, the unsuspecting victim would wake up with no memory of what had happened.

The Lone Star Saloon and Palm Garden was shut down in 1903, but Finn was never arrested for his crimes. He even sold his secret drink recipe to other bar owners. The "Mickey Finn" became a popular term for any kind of knockout punch, especially one that comes in a glass.

Usage Trends

By the end of the twentieth century, usage trends for tranquilizers had shifted. In the 1980s, tranquilizers were used mainly to treat depression. In the 1990s, they were prescribed more often for anxiety and stress disorders. As diagnoses of anxiety and stress disorders

increased in the 1990s and early 2000s, so did the demand for tranquilizers. The 2005 CASA report states that prescriptions filled for benzodiazepines alone increased nearly 50 percent between 1992 and 2002. In addition, BZDs account for 20 percent of all prescriptions written for controlled substances in the United States. As the use of BZDs has increased, the demand for barbiturates has decreased dramatically.

Trends in the Use of Major Tranquilizers

According to Parker in Tranx: Minor Tranquilizers, Major Problems, "The major tranquilizers do not produce effects generally experienced as pleasurable, and are thus rarely abused." However, doctors are increasingly prescribing neuroleptics for children with severe cases of autism, ADHD, Tourette's syndrome, and childhood bipolar disorder. Moreover, neuroleptics are also commonly prescribed for elderly patients in nursing homes and other institutions, particularly those who have been diagnosed with Alzheimer's disease.

Trends in the Use of Minor Tranquilizers

The National Survey on Drug Use and Health (NSDUH) is conducted by the U.S. Substance Abuse and Mental Health Services Administration (SAMHSA). This well-known survey obtains information on nine different categories of illicit drug use. One of these categories includes the nonmedical use of prescription-type pain relievers, tranquilizers, stimulants, and sedatives. The NSDUH report refers to these drugs collectively as "any psychotherapeutics" (SY-koh-ther-uh-PYOO-tiks).

The latest NSDUH results available as of mid-2005 covered drug usage trends for the year 2003. NSDUH statistics showed that teenagers and young adults were increasingly turning to prescription drugs to get high. A large number of Americans became "new users" of psychotherapeutic drugs in 2003. Roughly 1.2 million people began using tranquilizers that year, and 225,000 began using sedatives. Among fifteen benzodiazepines, the nonmedical use of two specific drugs—alprazolam (Xanax) and lorazepam (Ativan)—rose the most, from 3.5 percent to 4 percent of those surveyed in 2003. Usage among eighteen to twenty-five year olds was particularly high, increasing from 6.7 to 7.5 percent in 2003.

The results of the 2004 Monitoring the Future (MTF) study, conducted by the University of Michigan (U of M) and sponsored by research grants from the National Institute on Drug Abuse (NIDA), reveal similar findings. MTF data indicate that about 2.5 percent of eighth graders, 5.1 percent of tenth graders, and 7.3 percent of high school seniors reported using drugs such as Xanax between 2003 and 2004. Barbiturate use among twelfth-grade students held steady between 2003 and 2004.

According to the Drug Abuse Warning Network (DAWN), psychotherapeutic agents were "the drugs most frequently involved in overmedication" emergency room visits in the last six months of 2003. More females than males were hospitalized for overmedication cases, and young people age eighteen to twenty were involved in overdose visits more often than any other age group. These statistics were the latest available from DAWN as of mid-2005.

A 2001 NIDA Research Report titled "Prescription Drugs: Abuse and Addiction" indicates that, historically, females are twice as likely as males to become addicted to sedative-hypnotic-type drugs. Furthermore, women who have been abused or have witnessed abuse in their family are more likely to use and be addicted to tranquilizers, alcohol, and illegal drugs. In general, women of all ages, older individuals of both sexes, people with low levels of education, and people with unsatisfying family lives or jobs are most likely to abuse tranquilizing drugs.

Mom's an Addict

In the 1960s, an unusual trend in tranquilizer use emerged: middle-class, suburban homemakers were becoming addicted. Known as "Mother's Little Helpers," these minor tranquilizers were prescribed by doctors to help discontented wives and mothers deal with the pressures of domestic life. Soon, advertisers caught on to the trend and marketed these drugs as a perfectly safe way to relax. Ads for tranquilizers such as Librium and Valium portrayed these drugs as the answer to anxieties about housework and demands from work, school, or family.

Such drugs were also said to help calm anxiety over political and social issues like the sexual revolution and American involvement in the Vietnam war (1954–1975). The trend became so widespread that the rock group the Rolling Stones wrote a song about it in 1966. Titled "Mother's Little Helper," the song talked about the little yellow pill that helped mothers get through the stress of their busy days.

But as use increased, so did the rate of addiction. It wasn't long before the negative effects of that addiction were also being reported. People began to realize that there was a serious downside to "Mother's Little Helper."

Effects on the Body

Tranquilizers act on the brain by affecting the neurotransmitter known as GABA. Although different types of tranquilizers work in different ways, ultimately they all decrease brain activity by increasing GABA activity. This action produces a drowsy, calming effect that helps those suffering from anxiety or sleep disorders. Some tranquilizers are absorbed into the bloodstream very quickly, and others are timed to be released in slower amounts. For example, barbiturate classification is determined by how quickly the drugs start to work and how long the effects last. An ultrashort-acting barbiturate starts working in less than one minute. Long-acting barbiturates take effect in about one hour, and their effects can last for about twelve hours.

Effects on the body also differ depending on what kind of tranquilizer is ingested. Most tranquilizers produce a general calming feeling, a reduction in stress and anxiety, and sometimes a feeling of happiness. Other effects include slowed heart rate, reduced muscle spasms, pain relief, a decrease in convulsions, and even sedation.

Dangerous Side Effects

Depending on the dose, frequency, and duration of use, tolerance and dependence can occur rapidly among users of tranquilizers. Tolerance is a condition in which higher and higher doses of a drug are needed to produce the original effect or high experienced. Dependence occurs when a user has a physical or psychological need to take a certain substance in order to function. As tolerance develops, users may increase their doses to dangerous levels that can result in coma or death.

Other harmful side effects may develop if an individual uses tranquilizers for a long time period. At high doses, both major and minor tranquilizers may cause convulsions, slowed breathing, loss of speech, and kidney problems. Major tranquilizers can also cause confusion, agitation, heart and breathing problems, weight gain, lowered blood pressure, tremors, and muscle stiffening. In the long term, one of the most serious side effects of neuroleptics is tardive dyskinesia (TAR-div diss-kih-NEE-zhuh; TD). TD is a nerve disorder that causes involuntary tics and uncontrollable movements of the face, mouth, tongue, and limbs. It can also interfere with breathing if it affects the chest. The onset of TD usually begins between six months to two years after the use of neuroleptics starts. It occurs in about 20 percent of patients treated with these types of tranquilizers.

Another possible side effect of major tranquilizers is the development of a life-threatening disorder called neuroleptic malignant syndrome. Symptoms of neuroleptic malignant syndrome include a very high fever, sweating, rapid heart rate, high blood pressure, incontinence, stupor (profound drowsiness or lethargy), delirium, extreme muscle rigidity, and coma. Once the syndrome is diagnosed in a patient, steps are taken to minimize the risk of brain damage. The neuroleptic drug is discontinued immediately, and efforts are made to reduce the fever as quickly as possible.

Minor tranquilizers can also have serious side effects, such as dizziness, irritability, confusion, and loss of memory. Some long-term users have also reported blurred and double vision, increased anxiety, insomnia, hallucinations, depression, agitation, and aggression. The ability to drive or operate machinery can be extremely impaired in people taking minor tranquilizers.

The Thalidomide Tragedy and the Woman Who Said "No"

The thalidomide (thuh-LIH-doh-myd) tragedy is a prime example of what can happen when doctors prescribe drugs that have not been thoroughly studied and tested. Created in a West German lab in 1954, the hypnotic drug was sold as a sleep aid in Australia, Europe, Asia, Africa, and North America. It was considered so safe that it was also given to thousands of pregnant women to relieve morning sickness—the nausea and vomiting that often accompany the early stages of pregnancy.

By the end of the 1950s, doctors became alarmed when there was a shocking increase in the number of babies born with disabilities. Some had brain damage. Many were born with very short, flipper-like arms or legs, a condition known as phocomelia (foh-koh-MEE-lee-uh). When doctors began tracing these disabilities back to the mother's use of thalidomide, these children became known as "thalidomide babies." As of 2005, there were approximately 12,000 people dealing with some form of disability caused by their mother's use of thalidomide.

A dangerous drug like thalidomide was so widely prescribed because drug testing procedures in the 1950s were much different than they are in the 2000s. At that time, drug companies did not have to submit testing results to the appropriate government agencies. Also, drug manufacturers were not required to reveal some of the results of the tests, which were conducted on rodents—animals that are very different from humans.

FDA's Kelsey Says "No"

In the United States, the right to distribute thalidomide was bought by the William S. Merrell Company, a division of Richardson-Merrell. The company had to get approval to sell the drug from the U.S. Food and Drug Administration (FDA). The thalidomide approval case was assigned to Canadian-born FDA researcher Dr. Frances Kathleen Oldham Kelsey (1914– ). It was her first case review and was expected to be a simple process, since the drug was already widely available around the world. But Kelsey was not convinced that the drug was safe. Despite intense pressure, she held up approval of thalidomide until further testing was complete. It wasn't long before there were reports from Europe of the serious health problems. The drug was quickly pulled from the market. Thanks to Kelsey's conviction about thalidomide, only seventeen thalidomide babies were born in the United States.

Thalidomide babies are still being born in other parts of the world, however. In 1965 doctors discovered that the drug was a very effective treatment for leprosy (LEPP-ruh-see), a tropical disease that is caused by bacteria and affects both the skin and the nerves. Leprosy may produce sores, scarring, and a loss of feeling, especially in the fingers and toes. Later, doctors began using thalidomide to combat Crohn's disease, a serious intestinal disease that causes inflammation along with severe pain, diarrhea, nausea, and sometimes extreme weight loss. The drug has also been prescribed to fight certain cancers and the ravaging effects of acquired immunodeficiency syndrome (AIDS), an infectious disease that destroys the body's immune system and leads to illness and death.

In underdeveloped and poverty-stricken nations across the world, thalidomide is often given to AIDS and leprosy patients—some of whom are pregnant. Despite the medical community's knowledge of the drug's severely harmful effects on babies, thalidomide is still being given to pregnant women who have few resources and are unaware of the dangers. Just one dose of thalidomide can cause major birth defects in a developing fetus. In 1998 the FDA gave approval for thalidomide to be marketed as a leprosy treatment in the United States, but with special safeguards to protect pregnant women.

Brain Damage?

Other long-term effects have been harder to determine. Some researchers believe that prolonged use of minor tranquilizers affect overall brain function and may cause brain shrinkage. Because very few studies have measured these effects, there is little evidence to support such theories. It is generally agreed that taking a low dose over a long period of time has little impact on a user's brain and nervous system. However, if individuals begin to take these drugs at a higher dosage than prescribed or more frequently than recommended, they run the risk of developing serious health problems.

Reactions with Other Drugs or Substances

Tranquilizers can be used with other medications, but only under a doctor's supervision. A person should not use tranquilizers along with similar drugs that affect the brain and nervous system. These include drugs such as other tranquilizers, prescription pain medications, some over-the-counter cold and allergy medications, and alcohol. Even herbal remedies such as valerian may intensify the sedative effects of barbiturates, so these substances should not be taken together. Combining them can result in an overdose or a serious accident.

Treatment for Habitual Users

Tranquilizers are often abused. Even users who take them at a prescribed dose run the risk of developing an addiction after just six weeks of use. In general, the best way to treat an addiction to tranquilizers is to gradually reduce the dose of the drug under the supervision of a qualified physician. If an individual decides to just stop taking the drug, there can be serious physical consequences, such as seizures, psychosis, paranoia, heart palpitations, and depression. Inpatient or outpatient counseling is also recommended during the detoxification and withdrawal processes.

Doctors match the withdrawal process to the type of tranquilizer the patient is abusing. Patients who are taking high-dose BZDs follow a program that takes one of three approaches: 1) the dosage and amount of the abused drug is gradually decreased over time; 2) another BZD is substituted for the original tranquilizer abused, then the substitute BZD is gradually decreased over time; or 3) the barbiturate phenobarbital (Luminal) is substituted for the original tranquilizer abused and then the withdrawal process begins. The chosen method depends on the substance of abuse. Detoxification and the withdrawal process typically occur in a medical setting and require the patient to follow the doctor's orders exactly.

Consequences

Minor tranquilizers can be effective for short periods of time. However, long-term use can result in the buildup of a tolerance to the drug. This means that the body adjusts to the prescribed dosage and the individual has to take more of the drug to achieve the same effect. Individuals who increase the dose they take are in danger of over-dosing on the drug, which can result in coma and possibly death.

Tranquilizer addiction can have a damaging impact on an individual's life. Marriages may break up; families may go bankrupt; jobs may be lost; and some addicted individuals may turn to criminal behavior to obtain the drugs they crave. Addicts may turn to other drugs to try to achieve the same effects they get from tranquilizers or to ease withdrawal symptoms from tranquilizer use.

Since the 1990s and early 2000s, there has been a great deal of research conducted on the consequences of overprescribing certain major tranquilizers, especially for elderly people living in nursing homes. This research suggests that an older person living in a nursing home receives four times as many prescription drugs as an older person living in his or her own home. Critics argue that drugging these patients may make life easier for caregivers, but it leaves the patients unresponsive and alienated from their surroundings. Rather than just using drugs, they suggest trying other therapies that may result in a better quality of life for the patient. Similar concerns have surfaced for children who suffer extreme cases of autism and ADHD and are heavily medicated with major tranquilizers.

The Law

Tranquilizers are legal drugs that are only available with a prescription from a licensed doctor. In the United States, they are classified as Schedule II, III, or IV controlled substances under the Controlled Substances Act (CSA) of 1970. However, it is not legal to manufacture, distribute, or sell these drugs without a proper license. A person who illegally distributes tranquilizers can face up to fifteen years in prison and fines of up to $25,000.

A few types of minor tranquilizers are so addictive that they have been outlawed. Doriden and Quaaludes are examples of drugs that were once legally prescribed but are now banned from the United States because they were so frequently abused. Rohypnol, known as a "date rape drug," is illegal in the United States as well, but legal in countries in Europe, Central America, and South America.

For More Information

Books

Clayton, Lawrence. Tranquilizers. Springfield, NJ: Enslow Publishers, Inc., 1997.

Drummond, Edward H. The Complete Guide to Psychiatric Drugs: Straight Talk for Best Results. New York: Wiley, 2000.

Gorman, Jack M. The Essential Guide to Psychiatric Drugs. New York: St. Martin's Griffin, 1997.

Houle, Michelle M. Tranquilizer, Barbiturate, and Downer Drug Dangers. Springfield, NJ: Enslow Publishers, Inc., 2000.

Parker, Jim. Tranx: Minor Tranquilizers, Major Problems. Tempe, AZ: Do It Now Foundation, 2000.

Preston, John D., John H. O'Neal, and Mary C. Talaga. Consumer's Guide to Psychiatric Drugs. Oakland, CA: New Harbinger Publications, 1998.

Periodicals

Bonn, Dorothy, and John Bonn. "Anxious Times for the Treatment of Anxiety." The Lancet (October 3, 1998): p. 1126.

Gelenberg, Alan J. "New Antipsychotic Drugs: The Good, the Bad, and the Ugly." Behavioral Health Management (July-August, 2004): p. 9.

Kuchment, Anna. "Get Some Sleep." Newsweek (March 21, 2005): pp. E14-15.

Longo, L. P. "Addiction: Part I. Benzodiazepines: Side Effects, Abuse Risk, and Alternatives." American Family Physician (April 1, 2000): pp. 2121-2128.

Meadows, Michelle. "Prescription Drug Use and Abuse." FDA Consumer (September, 2001): p. 18.

Schlozman, Steven. "Psychiatric Drugs: The New Pharmacopoeia." Newsweek (April 25, 2005): p. 56.

Web Sites

"2003 National Survey on Drug Use and Health (NSDUH)." U.S. Department of Health and Human Services, Substance Abuse and Mental Health Services Administration (SAMHSA).http://www.oas.samhsa.gov/nhsda.htm (accessed August 19, 2005).

"Dr. Frances Kathleen Oldham Kelsey." National Library of Medicine: Changing the Face of Medicine—Physicians' Biographies.http://www.nlm.nih.gov/changingthefaceofmedicine/physicians/biography_182.html (accessed August 19, 2005).

"Drug Abuse Warning Network, 2003: Interim National Estimates of Drug-Related Emergency Department Visits" (December, 2004). U.S. Department of Health and Human Services, Substance Abuse and Mental Health Services Administration (SAMHSA).http://dawninfo.samhsa.gov/files/DAWN_ED_Interim2003.pdf (accessed August 19, 2005).

Gupta, S. P. K. "History of Medicine: Rustom Jal Vakil (1911–1974)—Father of Modern Cardiology." Journal of the Indian Academy of Clinical Medicine, July-September, 2000. http://www.indegene.com/JIACM/JanMar2002/indJIACMHistoryOfMedicine.html (accessed August 19, 2005).

Leshner, Alan. "Prescription Drugs: Abuse and Addiction." National Institute on Drug Abuse (NIDA), Research Report Series, 2001. http://www.drugabuse.gov/ResearchReports/Prescription/ (accessed August 19, 2005).

Monitoring the Future.http://www.monitoringthefuture.org/ and http://www.nida.nih.gov/Newsroom/04/2004MTFDrug.pdf (both accessed August 19, 2005).

National Institute on Drug Abuse (NIDA).http://www.nida.nih.gov/ and http://www.drugabuse.gov (both accessed August 19, 2005).

"NINDS Neuroleptic Malignant Syndrome Information Page" (February 9, 2005). National Institute of Neurological Disorders and Stroke. http://www.ninds.nih.gov/disorders/neuroleptic_syndrome/neuroleptic_syndrome.htm (accessed August 19, 2005).

"Prescription Sedatives and Tranquilizers." The Partnership for a Drug-Free America.http://www.drugfree.org/Portal/Drug_Guide/Prescription%20Sedatives%20and%20Tranquilizers# (accessed August 19, 2005).

"Reserpine: MedlinePlus Drug Information" (April 1, 2003). U.S. National Library of Medicine, National Institutes of Health, MedlinePlus. http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a601107.html (accessed August 19, 2005).

"Robert W. Wilkins Obituary." Lasker Foundation, originally published by the New York Times, April 27, 2003. http://www.laskerfoundation.org/awards/obits/rwilkinsobit.shtml (accessed August 19, 2005).

Schleis, Paula. "'Chill Pill' Eased Nerves across Nation; Leo Sternbach's Invention, Valium, Was Hit, but Addiction Soon Followed." Ledger-Enquirer.com, May 5, 2005. http://www.ledger-enquirer.com/mld/ledgerenquirer/news/nation/11569716.htm (accessed August 19, 2005).

"Under the Counter: The Diversion and Abuse of Controlled Prescription Drugs in the U.S." (July, 2005). National Center on Addiction and Substance Abuse (CASA) at Columbia University.http://www.casacolumbia.org/Absolutenm/articlefiles/380-final_report_not_embargoed.pdf (accessed August 19, 2005).

See also: Alcohol; Barbiturates; Benzodiazepine; Herbal Drugs; Rohypnol

Tranquilizers

Anxiety

Acute anxiety

Chronic anxiety

Treatment for anxiety

Benzodiazepines

Action

Choice of tranquilizers

Resources

The medical use of drugs to reduce or relieve anxiety has given rise to a group of medications called antianxiety agents. These agents include anxiolytics, tranquilizers, and sedatives. The first tranquilizer (chlordiazepoxide hydrochloride [Librium^®]) was approved by the U.S. Food and Drug Administration (FDA) in 1960.

In pharmacology, tranquilizers were formerly grouped as either minor tranquilizers or major tranquilizers. The word major stands for major psychiatric illness, not heavily sedating or tranquilizing. Today, major tranquilizers are more often referred to as neuroleptics or antipsychotic agents and they are used in the treatment of schizophrenia, depression, and bipolar illness. Examples of antipsychotic agents are chlorpromazine (Thorazine^®), synthesized in France in 1950, and the phenothiazines.

Presently, the common use of the term tranquilizer refers to the minor tranquilizers mainly of the benzodiazepine family. This newer group of anti-anxiety agents has tended to replace the use of barbiturates and meprobamate and certain antihistamines that were used as sedatives and anti-anxiety agents. It is these drugs that are prescribed as tranquilizers in the non-psychiatric setting of general medicine that treats anxiety brought on by stress rather than some disorder in the central nervous system.

Anxiety

while anxiety is usually an accompanying state of mind of most psychiatric disorders, it is also a special disorder of its own. Anxiety disorder or reaction is characterized by a chronic state of anxiety that does not have an immediate or visible basis. That is, the individual feels alarmed or uneasy but cannot point to any outside or realistic basis for the fear. There is a general state of unease that may become expressed by acute attacks of anxiety or panic, called panic disorder.

The emotional stress of anxiety may be triggered by impulses and mental images that in turn lead to a number of complex physiological responses. The autonomic nervous system may react to signals from the emotional side of the mind that call forth defense reactions of either fight or flight. An excess of adrenalin may be released that cannot be adequately discharged, thus leading to the symptoms of anxiety.

The psychology of anxiety often entails the repression of certain drives and needs. Sexual feelings, aggression at work, in school, in the family, and dependency on a spouse or other social relationship that is being threatened, or that the anxious person feels apprehensive toward are all examples of the circumstances that can unleash a chronic state of anxiety. The loss of a job or the sudden onslaught of an illness may, likewise, be responsible for anxiety states as the individual attempts to cope with these new conditions.

Acute anxiety

Acute anxiety panic attacks have been described as one of the most painful of life experiences. The condition can last for a few minutes to one or two hours. The individual is cast into a state of terror by some nameless imminent catastrophe. All rational thought processes cease during this time.

There are a number of cardiovascular responses to this state such as palpitations, tachycardia (elevated heartrate), arrhythmias of the heart, and sharp chest pain. Breathing becomes very difficult, almost impossible. The term given for this condition is hyperventilation. The extremities (hands and feet) feel cold, numb, and tingle with a feeling of pins and needles being present in the skin which may turn blue in places.

Other symptoms include fine trembling of the hands when they are stretched out, a feeling of (so-called) butterflies in the stomach, sweating, a general sense of weakness, dizziness, nausea, and sometimes diarrhea. People and the environment and surrounding objects seem remote and unreal. All these symptoms reinforce the anxious patient’s belief that either loss of consciousness or death are nearby.

Chronic anxiety

Many of the symptoms of chronic anxiety are similar to acute anxiety, but they are less intense and more prolonged. They can last for days, weeks, or months. There is a considerable amount of tension and expectation of conflict. There is fear about the future and an inability to deal effectively with other people, especially at home, school, and work. The condition is also characterized by chronic fatigue, insomnia, and headaches along with difficulty in concentration. With chronic anxiety the individual is still able to function on some level, but the ability to deal with life situations is substantially compromised.

Treatment for anxiety

Treatment for anxiety can include psychotherapy for those who are responsive for unearthing unconscious conflicts. Supportive psychotherapy is given by physicians, social workers, and therapists to reassure the individual. Relaxation techniques, meditation, and hypnosis also help to alleviate the condition.

Tranquilizers play a role in the pharmacologic treatment of anxiety. Medications, however, are usually not sufficient to deal with the root causes of anxiety, and it is not certain to what extent they play a placebo role in alleviating feelings of anxiety. The attitude of the taker of the medication along with the belief in the medical authority figure administering the drug are further factors in determining the effectiveness of pharmacologic intervention.

Benzodiazepines

there are about 20 tranquilizers in the benzodiaze-pine family of tranquilizers. Some of the popular ones are diazepam (Valium^®), Fluorazepam (Dalmane^®), oxazepam (Serax^®), and chlordiazepoxide (Librium^®). In addition to being prescribed for anxiety, they are also used as muscle relaxants, sedatives, anesthetics, and as supportive medication for withdrawal from alcohol. These drugs were introduced in the 1960s, and they quickly replaced other drugs that were then being used as tranquilizers. Their popularity seems to be now in decline, partly due to the more cautious attitude physicians have in prescribing them.

The amount of adverse effects is low. There is only a slight depression in respiratory rate and the amount needed for an overdose is very high, at a ratio of 200 (excess) to 1. Used in suicide attempts the results lead more to confusion and drowsiness without damage of a permanent nature. Librium^® (chlordiazepoxide) has some record of causing coma when taken in high dosages. Some people may react to benzodiazepines by losing inhibitions and expressing hostile or aggressive behavior that is not characteristic of their personalities, especially if they have been experiencing a high rate of frustration.

Since benzodiazepines produce less euphoria than other types of tranquilizers there is less chance of a dependency reaction that leads to abuse. Minor tranquilizers are generally not sought after by the illegal drug abuse market, nor are any of the other neuroleptic medications used to treat such mental illnesses as schizophrenia, manic depression, or depression. Some withdrawal symptoms can develop with benzodiazepines if they are used for an extended period of time, such asamonthor more. While there may be such symptoms as increased anxiety, sensitivity to bright lights, twitching of the muscles, nausea, and even convulsions, there is not a craving for the drug itself. Symptoms can be reduced by withdrawing from the drug gradually and phenytoin sodium (Dilantin^®) can be used for convulsions.

Action

tranquilizers act as anti-anxiety agents by depressing the central nervous system without leading to sedation. Barbiturates are seldom used now for managing anxiety or dysphoria because of their addictive potential. The molecules of barbiturate drugs pass through the membranes of the cells in the brain. They are then able to block nerve signals that pass from cell to cell, thus inhibiting the stimulation and conduction of chemical neurotransmitters between the cells. In addition, barbiturates are able to reduce the effect of abnormal electrical activity in the brain which cause seizures, such as in the case of epilepsy. Phenobarbital is a barbiturate that performs this function exceptionally well, therefore it is still useful as an anticonvulsant drug.

Depressant drugs, like alcohol and barbiturates, just as stimulant drugs, like cocaine and amphetamines, all appear to have the ability to stimulate the brain’s reward circuit. The behavioral effect of this action is to increase the need for more of the drug, usually to get the same effect (drug tolerance). If it is being taken for its effect as a euphoric, more of the drug is needed each time it is taken to produce a high or for sleep if it is being used as a sedative. Drugs that stimulate the brain reward centers also have the effect of excluding other types of reward sensations like those from food or sex.

Drugs that stimulate the brain reward centers seem to enhance the presence of a chemical found in the brain called gamma aminobutyric acid (GABA). GABA has the effect of quieting the neurons where the GABA receptors are found.

The newer benzodiazepine tranquilizers reduce neuron sensitivity only for cells that do have the GABA receptor sites, but the barbiturates are able to work the sedating effect elsewhere as well, wherever there are chloride channels. That difference in action may account for the higher degree of sedation afforded by the barbiturates over the benzodiazepines. Both types of drugs are able to affect the brain’s reward center by increasing the amount of dopamine released into the limbic system, the part of the brain that regulates certain biological functions such as sleep and the emotions.

Choice of tranquilizers

Tranquilizers are the most commonly used prescription drugs in the United States. The three major groups of tranquilizers are the benzodiazepines with the brand names of Valium^®,Librium^®, and Alprazolam^®. The second major group are the dephenylmethanes prescribed under the brand names of Vistaril^® and Atarax^®. The third group are the older alcohol-like propanediols that came out in the 1950s, such as tybamate and meprobamate under the brand names of Equanil^® and Miltown^®.

The physician chooses among the various tranquilizers the one that will best serve the patient’s need. Stress is a normal part of daily living for most people and it will produce in each individual a certain range of anxiety. Tranquilizers are prescribed on a non-psychiatric basis by the physician in general practice when the level of anxiety experienced by the individual interferes with the ability to cope with everyday stressful events or when anxiety symptoms have reached clinical proportions.

KEY TERMS

Arrhythmia —Any abnormal rhythm of the heart, which can be too rapid, too slow, or irregular in pace; one of the symptoms of anxiety disorder.

Autonomic nervous system —The part of the nervous system that controls involuntary processes, such as heart beat, digestion, and breathing.

Chronic anxiety —A prolonged period of an abnormal level of anxiety symptoms.

Euphoria —A feeling of intense well being; the opposite of dysphoria.

Gamma aminobutyric acid (GABA) —A chemical in the brain that quiets neuronal activity.

Hyperventilation —An autonomic reaction to anxiety which increases the breathing rate, thereby altering the ratio of the exchange of gases in the lung. That change makes the act of breathing difficult to perform.

Minor tranquilizers —As opposed to major tranquilizers generally used to treat psychoses, minor tranquilizers are used to treat anxiety, irritability, and tension.

Panic disorder —An acute anxiety attack that can last for several minutes to several hours.

Psychotherapy —A broad term that usually refers to interpersonal verbal treatment of disease or disorder that addresses psychological and social factors.

Tachycardia —An elevated heart rate due to exercise or some other physiological response to a particular condition such as an anxiety attack.

Panic attacks respond well with the treatment of alprazolam. Certain antidepressant drugs have also been found useful in treating panic disorder. Other symptoms, such as rapid heart rate, palpitations, involuntary motor reactions, insomnia or other sleep disorders, diarrhea, band-like headaches, increased urination rate, and gastric discomfort can be temporarily relieved by the use of other tranquilizers.

It is, however, necessary for the physician to point out to the patient that the tranquilizers are covering up the symptoms rather than curing them. The hazard in such palliative treatment is that the underlying condition may get worse without the conflict resolution necessary for the nervous system to readjust itself to the demands of reality.

Tranquilizers are not suited for long term use and over a period of time higher dosages may be needed, especially for the mild euphoria that some of them produce. While they do not pose the degree of dependency of other psychoactive drugs, some have been limited for general use because of the potential of overdependence. Valium^® is an example of a benzodiazepine that now is prescribed more cautiously.

Buspirone (BuSpar^®) appears to avoid the problem of possible dependency as well as that of drowsiness. This drug appeared in the mid-1980s. It is reported to be a true tranquilizer in that it does not produce either the slight euphoria of other tranquilizers or the drowsiness which is also characteristic of the sedative effect of other tranquilizers.

Resources

BOOKS

Dworkin, Ronald William. Artificial Happiness: The Dark Side of the New Happy Class. New York: Carroll & Graf, 2006.

Hanson, Glen R. Drugs and Society. Sudbury, MA: Jones and Bartlett, 2004.

Hochadel, Maryanne, ed. The AARP Guide to Pills: Essential information on More than 1,200 Prescription and Nonprescription Medicines, including Generics. New York: Sterling Pub., 2006.

Levinthal, Charles F. Drugs, Behavior, and Modern Society. Boston, MA: Pearson/Allyn and Bacon, 2005.

Malone, Patrick M., Karen L. Kier, and John E. Stanovich, eds. Drug Information: A Guide for Pharmacists. New York: McGraw-Hill Medical Pub. Division, 2006.

Rybacki, James J. The Essential Guide to Prescription Drugs. New York: HarperCollins, 2006.

Jordan P. Richman

Tranquilizers

The medical use of drugs to reduce or relieve anxiety has given rise to a group of medications called an tianxiety agents. These agents include anxiolytics, tranquilizers, and sedatives.

Tranquilizers were formerly grouped as either "minor" tranquilizers or "major" tranquilizers. The word major stands for "major psychiatric illness," not heavily sedating or tranquilizing. Today, major tranquilizers are more often referred to as neuroleptics or antipsychotic agents and they are used in the treatment of schizophrenia , depression , and bipolar illness. Examples of antipsychotic agents are chlorpromazine (Thorazine), synthesized in France in 1950, and the phenothiazines.

Presently, the common use of the term tranquilizer refers to the "minor" tranquilizers mainly of the benzodiazepine family. This newer group of anti-anxiety agents has tended to replace the use of barbiturates and meprobamate and certain antihistamines which were used as sedatives and anti-anxiety agents. It is these drugs that are prescribed as tranquilizers in the non-psychiatric setting of general medicine which treats anxiety brought on by stress rather than some disorder in the central nervous system .

Anxiety

While anxiety is usually an accompanying state of mind of most psychiatric disorders, it is also a special disorder of its own. Anxiety disorder or reaction is characterized by a chronic state of anxiety that does not have an immediate or visible basis. That is, the individual feels alarmed or uneasy but cannot point to any outside or realistic basis for the fear. There is a general state of unease that may become expressed by acute attacks of anxiety or panic, called panic disorder.

The emotional stress of anxiety may be triggered by impulses and mental images that in turn lead to a number of complex physiological responses. The autonomic nervous system may react to signals from the emotional side of the mind which call forth defense reactions of either fight or flight. An excess of adrenalin may be released which cannot be adequately discharged, thus leading to the symptoms of anxiety.

The psychology of anxiety often entails the repression of certain drives and needs. Sexual feelings, aggression at work, in school, in the family, and dependency on a spouse or other social relationship that is being threatened, or that the anxious person feels apprehensive toward are all examples of the circumstances that can unleash a chronic state of anxiety. The loss of a job or the sudden onslaught of an illness may, likewise, be responsible for anxiety states as the individual attempts to cope with these new conditions.

Acute anxiety

Acute anxiety panic attacks have been described as one of the most painful of life experiences. The condition can last for a few minutes to one or two hours. The individual is cast into a state of terror by some nameless imminent catastrophe. All rational thought processes cease during this time.

There are a number of cardiovascular responses to this state such as palpitations, tachycardia (elevated heart rate ), arrhythmias of the heart, and sharp chest pain . Breathing becomes very difficult, almost impossible. The term given for this condition is hyperventilation. The extremities (hands and feet) feel cold, numb, and tingle with a feeling of pins and needles being present in the skin which may turn blue in places.

Other symptoms include fine trembling of the hands when they are stretched out, a feeling of "butterflies" in the stomach, sweating, a general sense of weakness, dizziness, nausea, and sometimes diarrhea. People and the environment and surrounding objects seem remote and unreal. All these symptoms reinforce the anxious patient's belief that either loss of consciousness or death are nearby.

Chronic anxiety

Many of the symptoms of chronic anxiety are similar to acute anxiety, but they are less intense and more prolonged. They can last for days, weeks, or months. There is a considerable amount of tension and expectation of conflict. There is fear about the future and an inability to deal effectively with other people, especially at home, school, and work. The condition is also characterized by chronic fatigue, insomnia , and headaches along with difficulty in concentration. With chronic anxiety the individual is still able to function on some level, but the ability to deal with life situations is substantially compromised.

Treatment for anxiety

Treatment for anxiety can include psychotherapy for those who are responsive for unearthing unconscious conflicts. Supportive psychotherapy is given by physicians, social workers, and therapists to reassure the individual. Relaxation techniques, meditation, and hypnosis also help to alleviate the condition.

Tranquilizers play a role in the pharmacologic treatment of anxiety. Medications, however, are usually not sufficient to deal with the root causes of anxiety, and it is not certain to what extent they play a placebo role in alleviating feelings of anxiety. The attitude of the taker of the medication along with the belief in the medical authority figure administering the drug are further factors in determining the effectiveness of pharmacologic intervention.

Benzodiazepines

There are about 20 tranquilizers in the benzodiazepine family of tranquilizers. Some of the popular ones are diazepam (Valium), Fluorazepam (Dalmane), oxazepam (Serax), and chlordiazepoxide (Librium). In addition to being prescribed for anxiety, they are also used as muscle relaxants , sedatives, anesthetics, and as supportive medication for withdrawal from alcohol . These drugs were introduced in the 1960s, and they quickly replaced other drugs that were then being used as tranquilizers. Their popularity seems to be now in decline, partly due to the more cautious attitude physicians have in prescribing them.

The amount of adverse effects is low. There is only a slight depression in respiratory rate and the amount needed for an overdose is very high, at a ratio of 200 (excess) to 1. Used in suicide attempts the results lead more to confusion and drowsiness without damage of a permanent nature. Librium (chlordiazepoxide) has some record of causing coma when taken in high dosages. Some people may react to benzodiazepines by losing inhibitions and expressing hostile or aggressive behavior that is not characteristic of their personalities, especially if they have been experiencing a high rate of frustration.

Since benzodiazepines produce less euphoria than other types of tranquilizers there is less chance of a dependency reaction that leads to abuse. Minor tranquilizers are generally not sought after by the illegal drug abuse market, nor are any of the other neuroleptic medications used to treat such mental illnesses as schizophrenia, manic depression , or depression. Some withdrawal symptoms can develop with benzodiazepines if they are used for an extended period of time, such as a month or more. While there may be such symptoms as increased anxiety, sensitivity to bright lights, twitching of the muscles, nausea, and even convulsions, there is not a craving for the drug itself. Symptoms can be reduced by withdrawing from the drug gradually and Dilantin can be used for convulsions.

Action

Tranquilizers act as anti-anxiety agents by depressing the central nervous system without leading to sedation. Barbiturates are seldom used now for managing anxiety or dysphoria because of their addictive potential. The molecules of barbiturate drugs pass through the membranes of the cells in the brain . They are then able to block nerve signals that pass from cell to cell, thus inhibiting the stimulation and conduction of chemical neurotransmitters between the cells. In addition, barbiturates are able to reduce the effect of abnormal electrical activity in the brain which cause seizures, such as in the case of epilepsy . Phenobarbital is a barbiturate that performs this function exceptionally well, therefore it is still useful as an anticonvulsant drug.

Depressant drugs, like alcohol and barbiturates, just as stimulant drugs, like cocaine and amphetamines , all appear to have the ability to stimulate the brain's reward circuit. The behavioral effect of this action is to increase the need for more of the drug, usually to get the same effect (drug tolerance). If it is being taken for its effect as a euphoric, more of the drug is needed each time it is taken to produce a high or for sleep if it is being used as a sedative. Drugs that stimulate the brain reward centers also have the effect of excluding other types of reward sensations like those from food or sex.

Drugs that stimulate the brain reward centers seem to enhance the presence of a chemical found in the brain called gamma aminobutyric acid (GABA). GABA has the effect of quieting the neurons where the GABA receptors are found.

The newer benzodiazepine tranquilizers reduce neuron sensitivity only for cells that do have the GABA receptor sites, but the barbiturates are able to work the sedating effect elsewhere as well, wherever there are chloride channels. That difference in action may account for the higher degree of sedation afforded by the barbiturates over the benzodiazepines. Both types of drugs are able to affect the brain's reward center by increasing the amount of dopamine released into the limbic system, the part of the brain that regulates certain biological functions such as sleep and the emotions.

Choice of tranquilizers

Tranquilizers are the most commonly used prescription drugs in the United States. The three major groups of tranquilizers are the benzodiazepines with the brand names of Valium, Librium, and Alprazolam. The second major group are the dephenylmethanes prescribed under the brand names of Vistaril and Atarax. The third group are the older alcohol-like propanediols that came out in the 1950s, such as tybamate and meprobamate under the brand names of Equanil and Miltown.

The physician chooses among the various tranquilizers the one that will best serve the patient's need. Stress is a normal part of daily living for most people and it will produce in each individual a certain range of anxiety. Tranquilizers are prescribed on a non-psychiatric basis by the physician in general practice when the level of anxiety experienced by the individual interferes with the ability to cope with everyday stressful events or when anxiety symptoms have reached clinical proportions.

Panic attacks respond well with the treatment of alprazolam. Certain antidepressant drugs have also been found useful in treating panic disorder. Other symptoms, such as rapid heart rate, palpitations, involuntary motor reactions, insomnia or other sleep disorders , diarrhea, bandlike headaches, increased urination rate, and gastric discomfort can be temporarily relieved by the use of other tranquilizers.

It is, however, necessary for the physician to point out to the patient that the tranquilizers are covering up the symptoms rather than curing them. The hazard in such palliative treatment is that the underlying condition may get worse without the conflict resolution necessary for the nervous system to readjust itself to the demands of reality.

Tranquilizers are not suited for long term use and over a period of time higher dosages may be needed, especially for the mild euphoria that some of them produce. While they do not pose the degree of dependency of other psychoactive drugs, some have been limited for general use because of the potential of overdependence. Valium is an example of a benzodiazepine that now is prescribed more cautiously.

Buspirone (BuSpar) appears to avoid the problem of possible dependency as well as that of drowsiness. This drug appeared in the mid-1980s. It is reported to be a "true" tranquilizer in that it does not produce either the slight euphoria of other tranquilizers or the drowsiness which is also characteristic of the sedative effect of other tranquilizers.

Resources

books

Longenecker, Gesina L. How Drugs Work. Emeryville, CA: Ziff-Davis Press, 1994.

Morgan, Robert. The Emotional Pharmacy. Los Angeles, CA: The Body Press, 1988.

Nicholi, Armand M., Jr. The New Harvard Guide to Psychiatry. Cambridge, MA: Harvard University Press, 1988.

Oppenheim, Mike. 100 Drugs That Work. Los Angeles: Lowell House, 1994.

Jordan P. Richman

KEY TERMS

Arrhythmia

—Any abnormal rhythm of the heart, which can be too rapid, too slow, or irregular in pace; one of the symptoms of anxiety disorder.

Autonomic nervous system

—The part of the nervous system that controls involuntary processes, such as heart beat, digestion, and breathing.

Chronic anxiety

—A prolonged period of an abnormal level of anxiety symptoms.

Euphoria

—A feeling of intense well being; the opposite of dysphoria.

Gamma aminobutyric acid (GABA)

—A chemical in the brain that quiets neuronal activity.

Hyperventilation

—An autonomic reaction to anxiety which increases the breathing rate, thereby altering the ratio of the exchange of gases in the lung. That change makes the act of breathing difficult to perform.

Minor tranquilizers

—As opposed to major tranquilizers generally used to treat psychoses, minor tranquilizers are used to treat anxiety, irritability, and tension.

Panic disorder

—An acute anxiety attack that can last for several minutes to several hours.

Psychotherapy

—A broad term that usually refers to interpersonal verbal treatment of disease or disorder that addresses psychological and social factors.

Tachycardia

—An elevated heart rate due to exercise or some other physiological response to a particular condition such as an anxiety attack.

Tranquilizer

A tranquilizer is a drug that acts on the central nervous system and is used to calm, decrease anxiety, or help a person to sleep. Often called depressants because they suppress the central nervous system and slow the body down, they are used to treat mental illness as well as common anxiety and sleeplessness. Available only by prescription, they can cause dependence and certain ones can easily be abused.

Major and minor tranquilizers

There are two types or classes of tranquilizers: major tranquilizers and minor tranquilizers. The former are antipsychotic drugs and the latter are considered antianxiety drugs. Antipsychotic drugs are used to treat patients with a severe mental illness, like schizophrenia (pronounced skit-zo-FREH-nee-uh). Antianxiety drugs are given to patients with emotional problems, like anxiety. Both types of tranquilizers were first introduced in the 1950s. At the time, they revolutionized psychiatry for they seemed to offer physicians a way to manage psychoses (pronounced sy-KOH-sees), which are severe forms of mental illness, and to make their patients emotionally calm and quiet. They also seemed to offer an alternative to people simply trying to cope or put up with the everyday anxieties, tension, and sleeplessness that many experience in their normal lives.

Major tranquilizers for psychoses

The major tranquilizers were first developed in the very early 1950s when scientists discovered that the organic compound called phenothiazine (pronounced fee-no-THY-uh-zeen) had a strong sedative effect, meaning it calmed or relaxed the person taking it. In 1952, a phenothiazine derivative called chlorpromazine (pronounced klor-PRO-muhzeen) was seen to make highly agitated patients quiet and calm without making them unconscious. However, it also made them much less aware mentally, as they seemed to have little or no interest in anything going on around them. These calming effects led doctors to begin giving this new drug (whose trade name was Thorazine) to severely disturbed, psychotic patients, since for the first time, science had found a drug that specifically targeted the central nervous system.

Words to Know

Anxiety: A feeling of uneasiness and distress about something in the future.

Insomnia: Inability to go to sleep or stay asleep.

Psychosis: A major psychiatric disorder characterized by the inability to tell what is real from what is not real.

Schizophrenia: A serious mental illness characterized by isolation from others and thought and emotional disturbances.

About the same time, another compound called reserpine became useful as a major tranquilizer. It was found to reduce the delusions and hallucinations of schizophrenics. However, it eventually was replaced by another class of drugs since it had several physical side effects. Although antipsychotic drugs or major tranquilizers have side effects—such as increased heart rate, dry mouth, blurred vision, and constipation—they are not addictive and patients seldom build up a tolerance for them. Since they do not give the user any of the good feelings that stimulants do (instead they cause drowsiness), they do not lend themselves to recreational use. They will not make a person feel "high."

Minor tranquilizers for anxiety

Minor tranquilizers are quite different, however, and although these antianxiety drugs are called "minor," there is in fact nothing minor or mild about these drugs. Nor is there anything minor about their effects or their potential for abuse. This class of drugs is the most common type of drug today. More prescriptions are written for these compounds than for any other type of drugs. Minor tranquilizers include the well-known brand names of Valium, Librium, Xanax, and Ativan. Unlike major tranquilizers, which are used by doctors to try and manage severe psychiatric illnesses, minor tranquilizers are given fairly liberally by doctors to patients who complain about anxiety, depression, and sleep disorders. Minor tranquilizers work by reducing tension without heavily sedating the patient. Although they relax tense muscles, they produce less sleepiness during the day than major tranquilizers, although at night they do help with sleep.

Though they should be taken in prescribed doses for short periods of time, many people take these minor tranquilizers regularly, and they can cause dependence and tolerance. This means that the patient may experience unpleasant withdrawal symptoms if they suddenly stop taking them, and that they eventually need to take larger doses to maintain a feeling of well-being. Minor tranquilizers are the most widely abused drug in the United States and are regularly involved in suicide attempts and accidental overdoses. Called "downers" on the street, they can give a feeling of calm and relaxation (some say a "floating" sensation) that can, however, turn into more serious and unpleasant side effects. Over-use of downers can make people hostile and aggressive, and leave them with blurred vision, memory loss, disorganized thinking, headaches, and depression.

Not a cure

Whether major or minor tranquilizers, these two classes of drugs are not a cure for any of the conditions they treat. They are given by doctors to relieve symptoms that are associated with other problems. Neither type of drug should be taken with alcohol, as both are depressants and can therefore compound or exaggerate the effect of the other. People who take tranquilizers also should not drive a car or operate anything mechanical for several hours after taking the pills, since they interfere with the control of a person's movements. Although technically there are major and minor tranquilizers, the word "tranquilizer" has commonly come to refer only to the minor class of drugs that treat anxiety and insomnia—probably because they are the most frequently prescribed type of drug in the world.

[See also Psychosis; Schizophrenia ]