EVectiveness bulletin Drug treatments for schizophrenia

Background Schizophrenia is an illness or a group of illnesses aVecting language, planning, emotion, perceptions, and movement. In the UK, approximately 250 000 people suVer from schizophrenia or a schizophrenia-like illness. A quarter of those who have experienced an episode of schizophrenia recover and the illness does not recur. Another 25% experience an unremitting illness. The remaining 50% have a recurrent illness, but with long episodes of considerable recovery from positive symptoms such as delusions, hallucinations, disordered thinking, and catatonic movements. Many with recurrent illness have enduring problems from schizophrenia such as persistent psychotic symptoms, but, for most people, the problems consist of negative symptoms such as loss of enthusiasm and emotional responsiveness, apathy, and social withdrawal. These negative symptoms, though intrinsic to schizophrenia, are compounded by the adverse eVects of drugs, living in impoverished circumstances, and by the social stigma associated with mental illness. Recovery from episodes of schizophrenia for some people is often complicated by episodes of depression, substance abuse, and anxiety. People with schizophrenia have a shortened life expectancy due to physical illness, accidents, and other causes of violent death, especially suicide. Treatments for schizophrenia are divided into the so-called “physical interventions” of drugs, psychological and social managements and, rarely in the UK, electroconvulsant treatment. This article draws upon evidence from systematic reviews undertaken by the Cochrane Schizophrenia Group, and summarises the evidence on the eVectiveness of the main drugs used in the treatment of schizophrenia. More detailed information is available on each treatment within the referenced reviews. These reviews are regularly updated in the Cochrane Library. The main class of drugs used to treat or manage schizophrenia is antipsychotics (also known as neuroleptics, anti-schizophrenia drugs, and, inaccurately, as major tranquillisers). The antipsychotic action of these drugs is more than just the promotion of sedation and probably depends upon specific receptors in the brain. The advent of antipsychotic drugs in the 1950s was revolutionary. Countless people for whom little hope then existed were, at least partially, freed from the constraints of an insidious and unpredictable illness that would have kept them out of touch with reality for large periods of their lives. Adverse eVects associated with antipsychotics are common, however. These include troublesome and socially disabling movement disorders that resemble the symptoms of Parkinson’s disease. Involuntary facial movements (tardive dyskinesia) also occur in over 20% of those using older drugs and do not necessarily recede once the antipsychotic is stopped or reduced. Other distressing side eVects include sedation, dry mouth, blurred vision, constipation, weight gain, and, occasionally, impotence. Although conventional drugs are generally an eVective treatment for many of the symptoms of schizophrenia, the above side eVects can limit their use for a significant portion of people with schizophrenia. Continual medication is often necessary during periods of relative wellness, and poor compliance can precipitate relapse and necessitate (costly) readmission to hospital. It has been felt that the side eVect profile of older drugs has contributed to poor patient compliance and relapsing illness after discharge into the community (“revolving door” patients). Over a decade ago, with the re-introduction of the drug clozapine into common use, older drugs began to be labelled as “typical” in their propensity to cause movement disorders. Clozapine was “atypical” in that it did not seem to cause these side eVects as readily. In truth, rather than such a dichotomy of typical and atypical, there is a continuum and some inexpensive, older, drugs may have an atypical profile. 10 The claims being made for the newer atypical compounds are exciting, but take place in the context of ever greater conflicts of interest, both academic and monetary. 14 Yet the quality of trials, as measured by clear reporting and clinical applicability, is poor, and has not increased during the past 50 years—in fact there is some evidence it has declined. Trials are, on average, small, short in duration, include participants that are not typical of everyday practice, randomise care regimens that are diYcult to generalise, have high attrition rates, and report outcomes that are of dubious cliniQuality in Health Care 2000;9:73–79 73