Do the New Antipsychotics
Make A Difference?

cont. (page 2)

ECG=electrocardiography

Acutely ill patients who have behavioural disturbances may refuse oral treatment. Until parenteral forms of the newer antipsychotic medications become available, the parenteral administration of a traditional antipsychotic (for example, haloperidol 5-10 mg) plus a benzodiazepine for sedation may be required.

Who should receive the new antipsychotics?

Patients experiencing their first episode of schizophrenia should be considered for treatment with the new antipsychotic drugs (except clozapine). The comparative lack of side effects of these drugs makes them the first choice for drug treatment in patients with schizophrenia of recent onset. Hopefully, this advantage will translate into improved compliance with drug treatment during maintenance and reduce the risk of relapse. For those patients who do not respond to treatment with the new antipsychotics, a trial of a traditional antipsychotic should be offered.

Patients who have responded to traditional antipsychotics but who have persistent extrapyramidal side effects should also be offered a trial of a new antipsychotic. Patients who have not responded to other antipsychotics should be offered a trial of clozapine.

Points to consider when prescribing

Switching between antipsychotics

When switching a patient to a newer antipsychotic, it is important to educate patients and their caregivers about the risks (for example, the risk of relapse and temporary exacerbation of side effects) and potential benefits (for example, a reduction in symptoms and side effects). A crossover phase of one to two weeks is recommended, during which the dose of the first drug is reduced (or, in the case of depot preparations, ceased) and the dose of the second drug is gradually increased. During the crossover, patients, their clinicians, and caregivers should look for early signs of breakthrough psychosis. It is also helpful to set predetermined goals for treatment (such as a reduction in the severity or number of symptoms or a decrease in the severity or number of side effects) to help in deciding whether to continue.[18]

Dosage strategies

To reduce the severity and number of side effects, it is important to start new drugs at a low dose and increase the dose slowly. The new drug should be started at as low a dose as possible and then be increased over several weeks in response to changes in symptoms and side effects. Doses in the lower part of the recommended range may be adequate for patients in the early phases of their illness and very young or elderly patients. In acutely ill patients, agitation usually resolves within days, but it may be several weeks before the positive symptoms respond to treatment. Evidence shows that giving higher doses of antipsychotics than recommended increases side effects without increasing relief from symptoms[19] Maintenance treatment needs to be continuous and if possible at the lower end of the reference range. Intermittent treatment is not recommended.

Duration of maintenance treatment

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After one to two years of treatment, those patients who have had only one acute psychotic episode and who have had a good response to drug treatment--that is, their symptoms are in remission--may be suitable for a trial of time without drug treatment. For those patients who have had two or more acute episodes, treatment should be continued for at least five years; many of these patients, however, may require prolonged treatment. For patients undergoing withdrawal from drug treatment or a reduction in dose, a review by a psychiatrist is recommended, as is frequent clinical review.

Coprescription of psychotropic agents

Ideally, the newer antipsychotic drugs should be used alone. Short term use of benzodiazepines may assist agitated or anxious patients and can be particularly useful during acute episodes. Depression is common in schizophrenia, with a lifetime prevalence of up to 80%, and antidepressants may need to be added to treatment with antipsychotics. The depressed patient needs to be monitored closely for any risk of self harm. Those with extrapyramidal symptoms, whose symptoms persist despite a lowered dose and trying newer antipsychotics, may require treatment with anticholinergic drugs.

Prompt diagnosis and treatment

Recently there has been a growing awareness of the association between a longer duration of untreated psychosis and worse outcomes in the medium term and the long term.[20 21] Obviously, there will be a greater impact on the psychosocial networks (including those of work, family, education, and friends) of people who are psychotic and who remain untreated; one school of thought suggests that prolonged, untreated psychosis can result in a poorer long term prognosis because of altered neurobiological mechanisms.[1] Just as prolonged coma and lengthy periods of post-traumatic amnesia are associated with poorer clinical outcomes, so is prolonged psychosis.

As a consequence, many agencies providing mental health services are attempting to reduce the duration of untreated psychosis. For example, health education programmes can teach the general public about psychosis and the need for prompt self referral and the prompt referral of potential patients by caregivers. Close ties need to be developed between key agencies in contact with adolescents and young adults (for example, teachers and healthcare workers) to facilitate the pathway to care for those experiencing psychosis of recent onset. In particular, general practitioners have an important role in the prompt identification of psychosis. General practitioners should monitor closely patients who are at risk to identify the onset or evolution of frank psychosis. Prodromal features of psychosis may include depression, anxiety, suspiciousness, social isolation, and bizarre behaviour. Those with a family history of psychosis or with a schizoid or schizotypal personality are at an increased risk of psychosis. Specialised services for patients with recent onset psychoses have been developed by many centres (see box for information).[22]

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