Psychotherapeutic Medications

Chapter 13

Historical Overview

Psychoactive substances have been used to treat mental illness for centuries

In the 1840s, a French physician working in a mental hospital, attempted to treat mental illness with marijuana. He found that depressed patients became happy and talkative while manic patients calmed down and relaxed. The effects tended to be only temporary

Manic – Relating to mania, a mood disturbance that typically includes hyperactivity, agitation, excessive elation, and pressured speech

Amphetamines were used in the treatment of depression and narcolepsy and carbon dioxide inhalation for various psychotic and neurotic conditions

Narcoleptic – A state characterized by brief but uncontrollable episodes of sleep

Neuroses – Nonpsychotic emotional disturbance, pain, or discomfort beyond what is appropriate in the conditions of one’s life

Antihistamines, insulin shock, and psychosurgery were also used to treat psychosis

Psychosurgery – Surgery that entails the cutting of fibers connecting particular parts of the brain or the removal or destruction of areas of brain tissue with the goal of modifying severe behavioral or emotional disturbances

Electroshock therapy was used to treat severe depression and is still used on a limited basis today

It is important to remember that in the past the motivation to administer psychopharmacological agents to the mentally ill was largely to subdue them.

Thus many of the approaches were actually cruel, including bloodletting, hot irons, flogging, revolving chairs, starvation, and sneezing powder

The intention today is to provide persons with some relief and ideally with the opportunity to function better in their environments

In 1949, John Cade, an Australian physician, discovered the alkali metal lithium and it became one of the first of what are now called psychotropic drugs

Psychotropic – Exerting a special or unique action on psychological functioning

Lithium was found to successfully moderate manic conditions and remains a mainstay in the treatment of bipolar illnesses today

The greatest advance in psychopharmacology was the use, starting around 1950 in Paris, of the drug chlorpromazine (Thorazine). Initially used as an anesthetic due to its calming effects

Chlorpromazine was adopted throughout the world and prompted the deinstitutionalization movement, thus significantly decreasing the number of hospitalized psychiatric patients

In 1955 there were 600,000 and today despite an increase in the mentally ill population, there are approximately 150,000 hospitalized psychiatric patients

Unfortunately, there have been downsides to this deinstitutionalization. What are they ?

A host of other drugs were introduced in the years following including antidepressant and antianxiety medications

Epidemiology

Most prevalent mental disorders are anxiety disorders (18%), mood disorders (10%), impulse-control disorders (9%), and substance abuse (15%)

About 25% of the U.S. population experience some form of mental disorder in any given year. Most have symptoms associated with anxiety, depression, or alcohol abuse

An additional 15% seek clinical services for various symptoms that affect their life-functioning but may not meet the diagnostic criteria for a particular disorder

Almost half of U.S. adults met the criteria for a mental illness at some point in their lives. Most of these cases were mild and did not require treatment

Comorbidity was common as (45%) of adults with one mental disorder met the criteria for at least one other disorder

Fewer than half in need get treatment, and those who do often wait many years before doing so

Half with a mental disorder showed signs of the disease by age 14 and three quarters by age 24. Few sought help

Prevalence rates may be underestimates of mental illness in the U.S. because sample did not draw from homeless or institutionalized individuals and did not assess less common psychiatric disorders as schizophrenia and autism.

Most mental health disorders are treated with prescription medications, most commonly antianxiety and antidepressant medications, and three fourths of people who receive these medications report some degree of symptomatic relief

More than 200 million prescriptions for the lawful use of psychotherapuetics are written yearly

Approximately 10-15% of the general population in any given year are given a prescription for some psychotropic drug, usually an antidepressant or antianxiety agent

Psychotropic drug use is more likely among women, older persons, persons living alone, the more educated, and those with higher incomes

Abuse of psychiatric drugs and Illicit use of such prescription medications is a serious problem. Abuse can range from exceeding recommended dosages, not taking drugs as prescribed, taking multiple prescriptions to street sale and diversion

Prescription drugs are a factor in a large number of drug-related emergency room cases and drug-related deaths

Drugs most often abused or misused in Western cultures are depressants and stimulants

Classes of Drugs and Their Actions

Like other drugs, psychiatric drugs can be classified in different ways but the most common way is by therapeutic use

The four major categories are: antipsychotics which include the phenothiazines such as chlorpromazine and fluphenazine and nonphenothiazines such as haloperidol (See Table 13.1 for complete list); antidepressants which include cyclic antidepressants and MAOIs (See Table 13.2 for complete list); antianxiety agents such as barbiturates and nonbarbiturate sedatives, benzodiazepines, and general anesthetics (See Tables 13.3 & 13.4), and antimanic medications or mood-stabilizers

Antipsychotics

Antipsychotic medications, also known as neuroleptics or major tranquilizers, are used to treat schizophrenia and other disorders such as mania, agitated depression, toxic (drug-induced) psychosis, emotionally unstable personalities, and psychosis associated with old age.

Neuroleptic – Tranquilizing drugs used to treat psychoses; a synonym is major tranquilizer

Agitated Depression – Depressed mood accompanied by a state of tension or restlessness. Person shows excessive motor activity, as he or she may, for example, be unable to sit still, pace, wring the hands, or pull at his or her clothes

Schizophrenia – An array of thought disorders, including disturbances in areas of functioning such as language, affect, perception, and behavior. Disturbances may include distortions of reality (such as delusions and hallucinations), profoundly blunted mood, and withdrawn or bizarre behavior

Symptoms most likely to respond to antipsychotic medications are agitation, mania, hallucinations, delusions, fury, and accelerated and disorganized thinking processes

Paranoid Schizophrenia – A type of schizophrenia distinguished by systematic delusions or auditory hallucinations related to one theme

Antipsychotic medications affect primarily the reticular activating system by moderating spontaneous activity and decreasing reactivity to stimuli, the limbic system by moderating or blunting emotional arousal, and the hypothalamus by modulating metabolism, alertness, and muscle tone

The dopamine hypothesis is the most accepted explanation for the action of antipsychotic medications. Two core elements of the dopamine hypothesis are: psychosis is caused by increased levels of dopamine in the brain, and most antipsychotics block dopamine receptors inhibiting their transmission

Although the antipsychotics have produced many positive effects in the treatment of mental disorders, their use comes with significant side effects

Chief among the acute side effects are motor disturbances which give the appearance of a Parkinsonian syndrome

Extrapyramidal symptoms are the most apparent motor disturbances and include dyskinesia and akinesia,

Extrapyramidal – Outside the pyramidal tracts, with origin in the basal ganglia. These cell bodies are involved with starting, stopping, and smoothing out movements

Dyskinesia – Disordered movements Akinesia – Slowness of movement and underactivity The most common side effect assocaited with long-

term use (2 years or more) of antipsychotics is tardive dyskinesia

Tardive Dyskinesia – An extrapyramidal complication characterized by involuntary movements of the mouth and tongue, trunk, and extremities; a side effect of long-term (two or more years) use of antipsychotic drugs

Such effects can be controlled or eliminated now with medications such as Cogentin designed to treat them

Antidepressants

Depression is one of the most common psychiatric disorders in the United States with 20% of the U.S. population experiencing a major depressive episode in their lifetime.

It is often classified as one of two major types: endogenous or exogenous

Endogenous – Developed from within. When applied to depression, the term means that depressive symptoms seem to be due to genetic factors

Exogenous – Developed from without. When applied to depression, the term means that depressive symptoms seem to be in reaction to a particular situation or event

Two major classes of antidepressant medications now are prescribed: cyclic antidepressants and monoamine oxidase inhibitors (MAOIs).

The cyclics are prescribed more frequently in the united States and include SSRIs such as Paxil, Prozac, and Zoloft

A newer group of antidepressants have mechanisms of action that are not yet well understood or have therapeutic effects that mirror both the tricyclis and SSRIs and include Wellbutrin, Celexa, Effexor, and Desyrel

The biochemical hypothesis for depression is that it results from a deficiency in catecholamines, specifically norepinephrine, and serotonin

One disadvantage in the use of antidepressants is that their clinical action frequently takes two to three weeks to be apparent in the patient’s functioning. Unfortunately it is during this initial period when most of the undesired side effects are experienced and patients terminate their use

Common side effects of the cyclics are drowsiness, dry mouth, constipation, difficulty urinating, blurred vision, dizziness, weight gain, and rapid heart rate

Side effects for the MAOIs are the same as above but may also include temporay low blood pressure when changing positions and impaired sexual functioning

Antidepressants and Suicide Risk

An area of recent concern regarding some antidepressants, primarily SSRIs (Paxil, Zolft, Prozac, Luvox), is the possibility of suicide, especially in children, and when dosages are being increased or decreased

FDA urged manufacturers of 10 popular antidepressants (listed in the text) to revise warning labels to identify these concerns

Great Britain markedly increased restrictions on the prescribing of antidepressants for children and in 2003, declared certain antidepressants as too risky for any children under 18

History of Depressant Drugs

Depressant drugs are often classified by their most common use but this can be misleading as the same drug can have multiple effects depending on the dose

For example, benzodiazepines such as Valium and Librium reduce anxiety at moderate doses, they produce sedative-hypnotic effects (calm and induce sleep) in larger doses

Barbiturates are usually prescribed for sleep but are anxiety-reducing in lower doses and can produce surgical anesthesia in higher doses

Barbiturates – Depressant drugs formerly used as sleeping pills; currently used in anesthesia and treatment for epilepsy

All depressant drugs (including alcohol) produce similar effects. At low doses they relieve anxiety, at moderate doses they induce sleep, and at higher doses they produce general anesthesia and eventually coma and death.

The first depressants were drugs used for general anesthesia such as nitrous oxide and ether.

Development of the barbiturates in 1862 led to the use of depressants as sleeping pills and as treatment of anxiety and epilepsy

Effects of barbiturates are generally similar, differing primarily in potency and duration of action.

Pentobarbital and secobarbital are considered potent and short-acting (2-4 hours), amobarbital is intermediate (6-8 hours), and phenobarbital longer-acting(8-10 hours)

Barbiturates with a rapid onset and short duration of action such as pentobarbital are used as anesthetics, whereas those with slower onset and longer duration of action such as phenobarbital are preferred for the treatment of epilepsy

Barbiturate use was limited when adverse effects were discovered such as rapid development of tolerance, severe withdrawal symptoms, high risk of overdose, and high abuse potential

Antianxiety Agents

The discovery of benzodiazepines revolutionized the medical use of depressant drugs because they relieve anxiety with fewer side effects than previous depressants

Librium and Valium were the first drugs in this group marketed and they quickly came to dominate the market as treatments for anxiety and insomnia

Because alcohol shows cross-dependence with benzodiazepines, they are commonly used to withdraw alcoholics from alcohol

They are believed to act at the GABA receptor site in the central nervous system

The anxiolytic effects of benzodiazepines are more selective than those of other depressants because they relieve anxiety at doses that produce minimal sedation and motor impairment

Although less problematic than barbiturates, benzodiazepines may produce tolerance and dependence and withdrawal symptoms may occur

Because the lethal dose is so high, suicide and accidental overdose are far less of a risk than with other depressant drugs. However, because of potentiation with alcohol and other drugs, fatal overdoses are not uncommon with such drug combinations.

Benzodiazepines may interfere with the storage of memories, a phenomenon called anterograde amnesia

Anterograde Amnesia – Loss or limitation of the ability to form new memories

The drug Rohypnol (street name “roofies”) is called the “date rape” drug due cases where men have slipped the drug into a woman’s drink without her knowledge and then raped her after the drug has “knocked her out”. The drug has the ability to produce significant memory loss and blackouts in its users

Barbiturates and methaqualone also produce blackouts, which suggest some type of memory deficit may be characteristic of any depressant drug

Mood-Stabilizing Drugs

The most specific treatment for the mood disorders of mania and bipolar disorder is lithium

Mania is a state with pronounced elevations in mood and increased activity

It is believed bipolar disorder is the result of overactivity of neurotransmitters in the brain. Serotonin, norepinephrine, and dopamine are all affected

Other drugs available for the treatment of mania include the antiepileptic drug Tegretol, and anticonvulsants Klonopin and Depakote

Psychotropic Drugs and Pregnancy

No psychotropic drug is totally safe for use during pregnancy

The best approach is that they be given only when necessary and when nondrug therapies, such as counseling, have been tried and failed

There are risks to both mother and fetus with the fetus facing various teratogenic, neurobehavioral, and toxic consequences

Teratogenic – Producing abnormalities in the fetus The most widely recognized effect is the association of

lithium use during the first trimester and risk of cardiovascular system impairment