Guidelines for treating schizophrenia are mainly based on randomized controlled trials of highly selected patients and limited follow-up. It is unknown how well these data can be applied to representative community settings, nor how the choice of antipsychotic medication affects the long-term outcome.

We evaluated a nation-wide cohort of consecutive subjects (n=2230) hospitalized in Finland for the first time due to schizophrenia or schizoaffective disorder between January 1995 and December 2001. National central registers were used to study all-cause discontinuation rates, re-hospitalization rates, and mortality associated with monotherapy with the 10 most frequently used antipsychotic medications.

Initial use of clozapine (propensity score adjusted relative risk 0.17, 95% confidence interval 0.10 to 0.29), perphenazine depot (0.24, 0.13 to 0.47), and olanzapine (0.35, 0.18 to 0.71) were associated with the lowest rates of discontinuation for any reason when compared with oral haloperidol. Current use of perphenazine depot (0.32, 0.22 to 0.49), olanzapine (0.54, 0.41 to 0.71), and clozapine (0.64, 0.48 to 0.85) were associated with the lowest risk of rehospitalisation. Mortality was markedly raised in patients not taking antipsychotics (12.3, 6.0 to 24.1) and the risk of suicide was high (37.4, 5.1 to 276).

The effectiveness of first and second generation antipsychotics varies greatly in the community. Patients treated with perphenazine depot, clozapine, or olanzapine have a substantially lower risk of rehospitalisation or discontinuation of their initial treatment than do patients treated with haloperidol. Excess mortality is seen mostly in patients not using antipsychotic drugs.