33.2 EARLY INTERVENTION FOR SCHIZOPHRENIA: THE RISK-BENEFIT RATIO OF ANTIPSYCHOTIC TREATMENT IN THE PRODROMAL PHASE

Abstract

In schizophrenia, once psychosis and negative symptoms have manifested, most patients will suffer from persistent illness and declining social and vocational functioning; hence prevention has been contemplated for many years. In the early 1990s, the perception that second-generation antipsychotics improved the risk-benefit ratio of antipsychotic treatment was the impetus for investigators to attempt to treat the illness before the appearance of full-blown psychosis.In order to identify these future patients, diagnostic criteria for this prodromal phase of the illness were developed, and initial results indicated that 40% of patients who met these criteria transitioned to full-blown psychosis within a year. However, as time went by the rates of transition from prodrome to schizophrenia dropped and are currently under 10% after one year. The reasons for this are unknown and might include publicity and increased awareness leading to earlier referrals, and increased exposure of putative prodromal patients to pharmacological and psychosocial interventions. These data are further confounded by the finding that that attenuated psychotic symptoms are quite frequent in the nontreatment-seeking general population, and about 10% of persons in the community endorse having attenuated, but generally transient positive symptoms, and a person with attenuated positive symptoms might be misclassified as being in the prodromal phase of the illness. In addition, over time it has become clear that the second-generation antipsychotics are marginally if at all more efficacious than the old drugs and have significant metabolic side effects. These factors have led to a re-shifting of the risk-benefit ratio of suggested prevention strategies.The relatively low rates of transition mean that while persons meeting criteria for the prodrome will have to be exposed to preventive low-dose antipsychotic treatment, but only 1 out of 10 will transition. In addition, while anti-psychotics are proven to be efficacious in treating some, but not all patients with established schizophrenia, there are no data showing that anti-psychotic treatment decreases onset, while there are ample data showing that even low dose treatment causes side effects. Such preventive strategies also might stigmatize a person as a future schizophrenia patient, while in fact the vast majority will not have the illness.In conclusion, based on the date available today, our lack of diagnostic accuracy in predicting schizophrenia, together with the side effects of all currently marketed drugs, votes against antipsychotic treatment in persons in the putative prodrome of schizophrenia. Hopefully, in the future, when we have a better understanding of the biology of these disorders, more precise prediction will enable attempts at prevention with a more beneficial risk-benefit ratio.