Although continuous use of antipsychotics by individuals with schizophrenia is associated with lower mortality than those who discontinue use, the risk for relapse in this follow-up study cohort does not decrease as a function of treatment duration. This points to the benefits of long-term antipsychotic treatment in patients with first-episode schizophrenia, according to a comprehensive study published in The American Journal of Psychiatry.

This study sought to assess the risk of individuals diagnosed with schizophrenia in relation to their continued use or non-use of antipsychotics during a 20-year follow-up period using Finnish databases. Study investigators conducted a prospective nationwide cohort study of 23,499 individuals who were hospitalized for schizophrenia (defined as ICD-10 codes F20 or F25, or ICD-9 and ICD-8 codes 295.x) for the first time between 1996–2014. This cohort was further identified as not having any previous exposure to antipsychotics in the year prior to hospitalization (N=8738).

Following first hospitalization, patients were defined as continuous antipsychotic users (4217) or non-users (3217). Patients who discontinued use during the follow-up period were categorized by treatment duration before discontinuation (<1 year, 1–<2 years, 2– <5 years, and ≥ 5 years) and matched to users who continued with treatment at the same point in time to control for duration of illness.

Risk for treatment failure was compared between users, non-users, and discontinuers measured by outcome events (psychiatric rehospitalization or death), end of antipsychotic use in users, restart of antipsychotic use in non-users and discontinuers, or end of study (December 31, 2015). Though non-users and early discontinuers demonstrated a higher risk for death (214% and 174%) than continuous users, a comparison of the 4 discontinuation groups showed the risk for treatment failure was greatest in the group with the longest continuous use of antipsychotics. These findings may be explained by the modification of brain from long-term exposure to antipsychotics making discontinuation more difficult, greater treatment resistance, or severity of illness in late discontinuers.

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Study limitations included a lack of data supporting patient adherence and whether the decision to discontinue antipsychotic use was a suggestion of the treating physician or made by the patient.

No safe time for discontinuation can be defined from the results of this study. Although the risk for treatment failure increases the longer antipsychotics are used, continued treatment substantially lowers mortality rates in patients diagnosed with schizophrenia. This indicates that long-term antipsychotic use for treating first-episode schizophrenia for the majority of patients is a beneficial practice.

Reference

Tiihonen J, Tanskanen A, Taipale H. 20-Year nationwide follow-up study on discontinuation of antipsychotic treatment in first-episode schizophrenia [published online April 6, 2018]. Am J Psychiatry. doi: 10.1176/appi.ajp.2018.17091001