Pamphlet #2:
New Treatments for Schizophrenia
New Drugs
The new drugs, already in widespread use are still sometimes called "atypical," a term that may soon become obsolete. In general, they have fewer neurological side effects than the older drugs and are probably more helpful for negative symptoms and cognitive deficiencies. They may also be more effective in reducing depression and preventing relapse. Their higher present cost, research suggests, is probably made up by savings from lower rates of hospitalization and fewer visits to emergency rooms and doctors' offices. Some of these drugs will be still more valuable when they become available in depot ("deposit") form for slow absorption by intramuscular injection once a month -- a technique that can be helpful when patients will not consistently take a daily dose on their own.
- Clozapine (Clozaril) is the first substantial qualitative
advance in the drug treatment of schizophrenia since the 1950s. It
has proved moderately but distinctly superior to conventional drugs
in 14 controlled studies; some patients do so well that they seem
almost to have fully recovered. Clozapine may improve some negative
symptoms and relieve deficiencies in memory and attention. It is the
only drug that has been proved effective for patients who do not respond
to the older drugs. It does not raise prolactin levels. It has little
effect on body movements and may even improve symptoms of tardive
dyskinesia in some patients. Unfortunately, clozapine has many other
side effects, including dizziness, drowsiness, drooling, lowered blood
pressure, weight gain, and occasionally seizures. The greatest danger
is agranulocytosis, a potentially deadly decrease in the capacity
to manufacture white blood cells. With careful monitoring, it occurs
in less than 1% of patients and can be corrected if it is discovered
early. The death rate has been very low -- about one in 10,000 --
but the need for periodic blood testing makes clozapine expensive
and cumbersome to use.
- Risperidone (Risperdal), already one of the most widely prescribed
antipsychotic drugs, has some of the virtues of clozapine without
the risk of agranulocytosis. Like clozapine, it may be useful in the
treatment of positive and negative symptoms as well as thinking deficiencies.
Its most common side effects are dizziness, fatigue, a dry mouth,
a rapid heart beat, and lowered blood pressure. Unlike clozapine,
risperidone raises prolactin levels and has some modest effect on
body movements.
- Olanzapine (Zyprexa) has recently outperformed the traditional
medication haloperidol (Haldol) in two large controlled experiments.
Like risperidone, it appears to be effective for both positive and
negative symptoms, and researchers are now studying its effect on
thinking. Patients often prefer it because of its unusually low rate
of side effects (the most common are drowsiness, constipation, and
weight gain). It affects body movements slightly, does not significantly
raise prolactin levels, and is unlikely to cause seizures. Little
is known about its long-term effectiveness.
- Quetiapine (Seroquel) is useful for both positive and negative
symptoms and has few significant side effects. It does not raise prolactin
levels and has almost no effect on body movements. Some animals given
high doses of quetiapine have developed cataracts. Although it is
not clear that this can occur in human beings at therapeutic doses,
the manufacturer recommends regular eye examinations for patients
taking the drug.
- Ziprasidone (Zeldox) is expected to be available soon as a prescription drug. It has little effect on sexual functions or body movements and does not cause weight gain. The main side effects are headache, nausea, constipation, and insomnia.
The development of new antipsychotic drugs has been stimulated by advances in our knowledge of the brain's chemical transmitters and the receptor sites on neurons where they lodge to regulate the passage of nerve impulses. All the older drugs relieve positive symptoms by preventing the neurotransmitter dopamine from acting at D2 nerve receptors in the limbic region of the brain, which governs emotional responses. They disturb body movements by affecting the same type of receptor in the extrapyramidal system. The new drugs work differently, each in its own way. Some block D2 receptors chiefly in the limbic region
Others may act at D1, D3, or D4 receptors and influence patterns of interaction among receptors for other transmitters, including norepinephrine, serotonin, and gluatmate. Some authorities believe that malfunctioning of neurotransmitter systems in prefrontal cortex, the seat of planning and social judgment, is the ultimate cause of negative schizophrenic symptoms. Low activity in that region may cause positive symptoms by weakening inhibitions against excessive dopamine activity in the limbic system. New drugs that seem to relieve negative symptoms may be acting indirectly on the prefrontal region by altering the balance of neurotransmitters elsewhere in the brain. Their relative lack of extrapyramidal activity presumably explains why they cause fewer abnormal body movements.
When schizophrenic symptoms first appear, drug treatment is often put off because the nature of the illness is unclear or because the patient cannot be persuaded to seek help. A year's delay between the first psychotic symptoms and the first use of antipsychotic drugs is common. Recent studies suggest that delay makes for slower recovery from the first episode and a poorer long-term prognosis. The alienating and isolating effects of prolonged psychotic episodes make it increasingly difficult to recover a normal personal and social life after each one. And each psychotic episode may heighten the brain's vulnerability to further psychosis, in the same way that an epileptic seizure can further irritate its focus (originating point) in the brain and raise the likelihood of later seizures. For these reasons, many authorities are now putting special emphasis on the need to detect and treat schizophrenia early. Psychiatrists have often been reluctant to prescribe antipsychotic drugs immediately because of their concern about side effects, but the new drugs should change that attitude.
Cognitive and Behavioural Support
Although most schizophrenic patients need antipsychotic medication to benefit from any other help, the drugs by themselves are far from sufficient; a psychiatric care and social rehabilitation are just as important. Depending on the severity of their symptoms, patients may need help in understanding the illness, taking their drugs regularly, responding to signs of relapse, securing housing, jobs and medical care, even caring for their basic physical needs and coping with everyday social situations and personal relations.
Behavioral techniques, including social skills training, are one widely used form of help. Schizophrenic patients are coached, prompted, and corrected as they rehearse behaviour and observe others as models. They are shown how to cash cheques, prepare for interviews, sustain a conversation, and even clean and dress themselves. Research has shown that social skills training can be effective. In two recent meta-analyses (combined statistical analyses of many studies), this training has been found to reduce relapse rates for up to a year. But the results are difficult to transfer to real life, and they often dissipate over time.
Some mental health professionals are now trying to teach what could be called thinking and emotional skills. Patients are lectured and coached on how to monitor their thoughts, overcome tendencies to withdraw, paranoia, and loss of concentration, and cope with guilt, sadness, feelings of humiliation, and aggressive impulses. They may also work to improve memory, planning, and decision-making. A cognitive-behavioral program for hospitalized patients, integrated psychological therapy, uses word problems and games to practise conversation and the interpretation of social situations. Cognitive training can be time-consuming and expensive, and there is some question whether its effects carry over into daily life. Some believe that thinking exercises have limited potential for the damaged brains of schizophrenic patients. In one recent study, patients given integrated psychological therapy showed improvement on tests of attention after 18 months, but their capacity for complex thinking remained low, and they still lacked the skills needed for independent living.
Another cognitive approach emphasizes the content of thoughts rather than the process of thinking. Patients are taught to evaluate and correct their delusional ideas and hallucinatory perceptions. The therapist finds out when the most disabling psychotic symptoms occur, how seriously they interfere with the patient's life, and how the patient copes with them. The patient practises these methods and is helped to develop new ones. What little evidence there is, suggests that this technique may be somewhat effective for delusions but does not affect hallucinations or the more common negative symptoms
From The Harvard Mental Health Letter, from Harvard
Medical School (Volume 14, Number 10, April 1998)
