Dr Miller is Associate Professor, Department of Psychiatry and Health Behavior, Augusta University, Augusta, GA. He is the Schizophrenia Section Editor for Psychiatric Times.
An important question that patients might ask clinicians is, “How long should I continue antipsychotic treatment after the first episode of schizophrenia?” Many current treatment guidelines recommend 1 to 5 years of antipsychotic treatment if relapse does not occur.1 A classic study found that antipsychotic discontinuation was associated with a 5-fold higher risk of relapse over 5 years following a first episode of psychosis.2 However, it is not known whether relapse risk remains elevated after 2 to 5 years of stability.
Tiihonen and colleagues3 used a large electronic database to assess risk of treatment failure (rehospitalization or death) as a function of the duration of antipsychotic treatment prior to discontinuation in a nationwide cohort of patients with first-episode schizophrenia. They first identified all persons hospitalized for schizophrenia (ICD-8, -9, and -10 diagnoses) in Finland from 1972 to 2014 using the Finnish Hospital Discharge register.
Next, they identified 8719 persons with a first hospitalization for schizophrenia between 1996 and 2014, based on no previous hospitalizations and no antipsychotic exposure in the year preceding hospitalization (from the Finnish Prescription register). After hospital discharge, a 30-day definition period was applied to identify users (n = 4217) and non-users (n = 3217), based on initiation of antipsychotic use. A total of 1714 subjects discontinued antipsychotic use during the follow-up period because of rehospitalization, death, or the end of the study period, and were considered discontinuers. Clozapine was used as a proxy for treatment resistance, and long-acting injectable medication as a proxy for poor treatment adherence.
Subjects were followed until the outcome event (rehospitalization or death), until they started using antipsychotics, or until the end of the follow-up period. Patients who discontinued antipsychotic treatment were matched to an antipsychotic user. For mortality analyses, antipsychotic nonusers were matched with patients who discontinued use after less than 1 year. Antipsychotic use was modeled with the PRE2DUP method from purchases recorded in the Finnish Prescription register.4
The composite measure, “treatment failure,” which included psychiatric rehospitalization or death, was the primary outcome to evaluate the net effect of antipsychotic use. Secondary outcome measures were rehospitalization (as a proxy for relapse) and mortality. Covariates included age, sex, and duration of index hospitalization (as a proxy for illness severity). Data were analyzed using Cox proportional hazards models, comparing risk of treatment failure between discontinuers (stratified by 0; 1-2; 2-5; and > 5 years) and matched users, adjusting for age and sex. In separate Cox analyses, nonusers were compared with antipsychotic users.
1. Takeuchi H, Suzuki T, Uchida H, et al. Antipsychotic treatment for schizophrenia in the maintenance phase: a systematic review of the guidelines and algorithms. Schizophr Res. 2012;134:219–225.
2. Robinson D, Woerner MG, Alvir JM, et al. Predictors of relapse following response from a first episode of schizophrenia or schizoaffective disorder. Arch Gen Psychiatry. 1999;56:241–247.
3. Tiihonen J, Tanskanen A, Taipale H. 20-Year Nationwide Follow-Up Study on Discontinuation of Antipsychotic Treatment in First-Episode Schizophrenia. Am J Psychiatry. 2018;175:765-773.
4. Tanskanen A, Taipale H, Koponen M, et al: From prescription drug purchases to drug use periods: a second generation method (PRE2DUP). BMC Med Inform Decis Mak. 2015;15:21.