Tranquilizers: Therapeutic use, Treatment. Tranquilizers rehab.

Last modified: Saturday, 20. June 2009 - 3:44 pm

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); triflu-operazine (Stelazine); trifuluopromazine (Vesprin); ziprasidone (Geodon).
Street names: Major tranquilizers: antipsychotics, neu-roleptics.
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); mephobarbital (Mebaral); methohexital (Brevital); pentobarbital (Nembutal); phenobarbital (Luminal); secobarbital (Seconal)
Drug classifications: Barbiturates: Amobarbital (Amytal); butabarbital (Butisol); pentobarbital (Nembutal); secobarbital (Seconal), Schedule II, narcotic analgesics; mephobarbital (Mebaral); methohexital (Brevital); phenobarbital (Luminal), Schedule IV, narcotic analgesics
Official names: Minortranquilizers/Nonbarbiturate sedative-hypnotics: Chloral hydrate (AquachloralSupprettes, 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

 

Key terms

ANESTHETIC: An agent that causes loss of sensation or consciousness.
ANXIOLYTIC: A drug that decreases anxiety.
HYPNOTIC: A drug that induces sleep by depressing the central nervous system.
OPIOID: A drug, hormone, or other chemical substance having sedative or narcotic effects similar to those containing opium or its derivatives; a natural brain opiate.
PSYCHOTHERAPEUTICS: Drugs that have an effect on brain function; often used to treat psychiatric disorders
SEDATIVE: A drug that decreases CNS activity; a calming agent.

 

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 (sedative-hypnotics/anxiolytics)
Like the neuroleptics, all of the commonly used minor tranquilizers — with the possible exception of bus-pirone (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 GAB A 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 substance 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^-0 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. Nonbarbiturate 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 nonbarbiturate 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. Overdose 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, overdose 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 GAB A. 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 syn-ergistic 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.

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