Pharmacological prevention of relapse.

Relapse is the "return of a disease after partial recovery", and is a major feature of schizophrenia disorder. It can be defined in terms of need for change in treatment, including rehospitalization or crisis intervention, the re-emergence of florid psychotic features, or gross social decompensation. Relapse is best viewed as continuum of severity rather than as discrete "attacks". Factors influencing relapse include major life events and the family constellation. Antipsychotic drugs protect against the latter but not the former, and relapse may be mediated by non-specific arousal mechanisms. The efficacy of drug treatment in postponing rather than preventing relapse is well established. The interval between relapses is prolonged at least two-fold, but in the long run most patients relapse. Unwanted effects of antipsychotic drugs can be a burden to patients, impairing quality of life. In particular, movement disorders and subjective dysphoria may be marked, as may compliance. Of these EPS, tardive dyskinesia is the most serious on long term use. Non-EPS long term effects include weight gain and endocrine changes. Depot medication has advantages over oral medication in the more ill, less compliant patients. Side effects may, however, be more marked. The greatest pain is in improved compliance but the regular supervision of the patient is also helpful. Pharmacokinetic issues are poorly understood. High and mega-dose strategies have been advocated. High doses may be needed in some patients, but megadoses are rarely justified and may be hazardous. Low dose and intermittent therapy have been evaluated but are not as successful as hoped. Some less ill patients may benefit. These schedules depend on the identification of prodromata of relapse which is not always easy, nor are relapses necessarily preceded by prodromata. Newer drugs are being developed rapidly in the search for a safer clozapine, the only antipsychotic with definitely enhanced efficacy. Other drugs which have been re-evaluated include the benzodiazepines. However, the area of greatest priority in research is that of interactions, particularly potentiation, between drug and non-drug treatments.