Drugs in Treatment of Schizophrenia

By | February 24, 2012


The introduction of chlorpromazine (Thorazine), the first of the antipsychotic drugs (also known as neuroleptics), in 1952 revolutionized the treatment of schizophrenia. Since then, these drugs have become the mainstay of treatment for people with schizophrenia. Before these drugs were discovered, many who suffered from this illness spent most of their lives in hospitals, experiencing active psychotic symptoms. In 1955 state hospitals in the United States had 552,000 patients; in 1990 they had 119,000. With antipsychotic medication, there are decreases in agitation and in psychotic thinking (hallucinations and delusions), and while impaired functioning remains, many people are able to leave hospitals and function in a range of settings with perhaps intermittent, short hospitalizations. Thus medication is vital in the active stage of schizophrenia as well as for maintenance. The medication helps with feelings of disintegration and of being overwhelmed. These drugs are not without liabilities, however; there are serious, sometimes unpleasant side effects. Because of the side effects, there is growing awareness of the need to keep the dosage as low as possible and to give people “vacations” from medication in order to evaluate ongoing need. Although social workers cannot prescribe medication, they are frequently the professionals most in contact with people who have schizophrenia, and they may be aware of side effects that they can bring to the attention of the prescribing psychiatrist. The social worker can possibly affect the adjustment of the dosage, based on the person’s social and vocational functioning as assessed by the social worker and relayed to the psychiatrist. It must be cautioned that although medication has helped the majority of people with schizophrenia, some do not respond, and some symptoms are not ameliorated.

Until 1990, when clozapine (Clozaril) was introduced, none of the antipsychotic drugs developed after chlorpromazine had proved to be more effective. Decisions on which to prescribe are based on the person’s reported tolerance, past history with the medication, and, often, on the provider’s preference. There are at least two dozen antipsychotic drugs, often classified as high-potency (therapeutic effects require relatively small doses) or low-potency drugs (therapeutic effects require larger doses). The low-potency drugs are more sedating, cause dry mouth, constipation, and dizziness but have fewer neurological side effects. Chlorpromazine (Thorazine), thioridazine (Mellaril), and mesoridazine (Serentil) are low-potency drugs; fluphenazine (Prolixin) and haloperidol (Haldol) are high-potency drugs. Mid-potency drugs include perphenazine (Trilafon), trifluoperazine (Stelazine), thiothixene (Navane), chlorprothixene (Taractan), molindone (Moban), and trifluopromazine (Vesprin). Most drugs are administered in pill form, but some are given as liquids. Liquid forms of medication are frequently used in hospitals, because it is easier to administer them to noncompliant patients. When outpatients cannot be relied on to follow their medication regime, fluphenazine and haloperidol may be administered by intramuscular injection, because their effects last from two weeks to a month.

Medications begun in the acute phase of schizophrenia may not reach full effectiveness for about six weeks, although some response should be evidenced in three to four weeks. If there is no improvement, a different drug should be tried. Once there is a response, the dosage is lowered to a maintenance level that will control the return of symptoms.

Clozapine (Clozaril), approved by the FDA in 1989 and considered an atypical antipsychotic, has proved highly effective for people who do not respond to other antipsychotic drugs, and it appears not to cause neurological side effects. It is believed to affect the neurotransmitters serotonin and norepinephrine more than dopamine. It does, however, have one serious nonneurological side effect: it may cause bone marrow to stop making white blood cells. These cells are important for warding off infections; thus frequent blood tests are indicated, adding to patient inconvenience and treatment expense. Like most neuroleptic drugs, it affects positive symptoms but also relieves negative symptoms.

A newer drug, risperidone (Risperdal), affects dopamine and serotonin and appears to be safer than clozapine. It works faster and affects both positive and negative symptoms. Other new and promising drugs that affect both positive and negative symptoms are olanzapine (Zyprexa) with fewer extrapyramidal effects, but with the side effects of sedation and weight gain; quetiapine (Seroquel), which has side effects similar to those of olanzapine; sertindole (Serlect), which has a fairly long half-life and thus is useful for uncompliant persons; and ziprasidone (Zeldox), which is helpful not only with symptoms of schizophrenia but also with affective and anxiety symptoms.

The presence of side effects often causes people to stop taking medication. Most of them — drowsiness, dizziness, dry mouth, constipation, blurred vision, and sexual dysfunction, especially in males — are temporary or will eventually diminish in severity. Weight gain also presents a problem, espedaily for women. The most distressing side effects are the neurological symptoms resembling Parkinsonian symptoms. These symptoms can sometimes be relieved by lowering the dosage, as long as psychotic symptoms do not reappear, or by adding anti-Parkinsonian drugs such as trihexyphenidyl (Artane) or benztropine (Cogentin).

Tardive dyskinesia is the most persistent side effect, with symptoms appearing months or years after medication is started. Twenty to thirty percent of people in long-term medication treatment for schizophrenia will develop its symptoms, ranging from mild to severe, beginning with involuntary facial tics, jaw movements, lip smacking, tongue thrusting, sucking, eye blinking; over time, the person develops spasmodic and writhing hand, arm, leg, and neck movements. Tardive dyskinesia is more common in women than men and more often seen in older people. Since these symptoms will disappear for many when the antipsychotic medication is discontinued, although for some they are irreversible, it is recommended that the dosage be stopped when symptoms appear. Should psychotic symptoms reappear, the person and family must be helped to accept tardive dyskinesia as a side effect of needed treatment.

Other side effects are similar to those of Parkinson’s disease and may be hard to recognize. Akinesia is a state of reduced voluntary, spontaneous movement, such as arm swinging or crossing one’s legs. There are few spontaneous facial expressions, and walking may appear rigid. Other symptoms are similar to the negative symptoms of schizophrenia and depression, and the best way to determine if the person is suffering from this side effect is to add anti-Parkinsonian medication in high doses. Akathisia, in contrast, is a state of motor restlessness. The sufferer moves constantly, shifting around when seated, crossing or uncrossing legs, shifting from foot to foot, and has a stated inability to relax, which may be confused with anxiety. Although anti-Parkinsonian medication may be given, it has been found that the beta-blocker propranolol is also useful.

Finally, the least common but most serious side effect is neuroleptic malignant syndrome, whose symptoms are fever, high blood pressure, muscular rigidity, confusion, and stupor. It most frequently occurs after antipsychotic drugs are begun or after raising the dosage. The person must be hospitalized medically and the medication discontinued. Though most recover in days or weeks, this side effect is potentially fatal.

Clearly, people need to be observed for signs of side effects, yet also helped to understand the need for medication. A large number of those suffering from schizophrenia relapse because they do not follow their drug regimen after discharge from a hospital. Since remaining on antipsychotic drugs for long periods of time is so problematic, however, trials on lower doses or periods without medication should be undertaken if they can be monitored.

Since depression may follow the acute phase of schizophrenia, there are times when adding an antidepressant is indicated. Lithium is sometimes prescribed for people with schizophrenia, but it is not clear why it is effective. It also may be prescribed because of an inaccurate diagnosis. Electro-convulsive therapy (electroconvulsive therapy) is sometimes used when catatonic or affective symptoms are present or when the person fails to respond to high doses of medication. Acute, rather than chronic, schizophrenia appears to respond better to electroconvulsive therapy.