Long-Term Real-World Effectiveness of Pharmacotherapies for Schizoaffective Disorder

Jonne Lintunen; Heidi Taipale; Antti Tanskanen; Ellenor Mittendorfer-Rutz; Jari Tiihonen; Markku Lähteenvuo


Schizophr Bull. 2021;47(4):1099-1107. 

In This Article

Abstract and Introduction


Objective: To investigate the long-term real-world effectiveness of antipsychotics and other psychopharmacotherapies in the treatment of schizoaffective disorder (SCHAFF).

Method: Two nationwide cohorts of SCHAFF patients were identified from Finnish and Swedish registers. Within-individual design was used with stratified Cox regression. The main exposure was use of antipsychotics. Adjunctive pharmacotherapies included mood stabilizers, antidepressants, and benzodiazepines and benzodiazepine-related drugs. The main outcome was hospitalization due to psychosis.

Results: The Finnish cohort included 7655 and the Swedish cohort 7525 patients. Median follow-up time was 11.2 years (IQR 5.6–11.5) in the Finnish and 7.6 years (IQR 3.8–10.3) in the Swedish cohort. Clozapine and long-acting injectable (LAI) antipsychotics were consistently associated with a decreased risk of psychosis hospitalization and treatment failure (psychiatric hospitalization, any change in medication, death) in both cohorts. Quetiapine was not associated with a decreased risk of psychosis hospitalization. Mood stabilizers used in combination with antipsychotics were associated with a decreased risk of psychosis hospitalization (Finnish cohort HR 0.76, 95% CI 0.71–0.81; Swedish cohort HR 0.84, 0.78–0.90) when compared with antipsychotic monotherapy. Combination of antidepressants and antipsychotics was associated with a decreased risk of psychosis hospitalization in the Swedish cohort (HR 0.90, 0.83–0.97) but not in the Finnish cohort (1.00, 0.94–1.07), and benzodiazepine use was associated with an increased risk (Finnish cohort HR 1.07, 1.01–1.14; Swedish cohort 1.21, 1.13–1.30).

Conclusions: Clozapine, LAIs, and combination therapy with mood stabilizers were associated with the best outcome and use of quetiapine and benzodiazepines with the worst outcome in the treatment of SCHAFF.


Schizoaffective disorder (SCHAFF) is a common diagnosis in psychiatry, even though the nosological status of SCHAFF remains controversial.[1,2] SCHAFF symptoms include both schizophrenic (hallucinations, delusions) and affective (depression, mania) symptoms[3] and both ICD-10 and DSM-5 separate manic/bipolar and depressive subtypes of SCHAFF.[4,5] ICD-11 aims to improve the differential diagnosis and diagnostic accuracy of SCHAFF.[6] It has been debated whether SCHAFF represents an independent illness, an atypical form of schizophrenia or a mood disorder, a form of schizophrenia combined with a mood disorder, a heterogeneous group of both schizophrenia and mood disorder patients, or if SCHAFF is on the continuum of schizophrenia and mood disorder spectrum.[1] A systematic review and meta-analysis concluded that SCHAFF may be closer to schizophrenia than bipolar disorder but it shares features of both disorders.[7] Also, from a genetic perspective, SCHAFF seems to be related to both bipolar disorder and schizophrenia.[8] Conducting formal meta-analyses and giving specific guidelines for SCHAFF pharmacotherapy have been challenging due to the small number and heterogeneity of studies focusing purely on SCHAFF patients.[9–11] Pharmacotherapy recommendations for SCHAFF are mostly derived from studies on schizophrenia and bipolar disorder, and thus patients with SCHAFF are commonly treated with antipsychotics, mood stabilizers, and/or antidepressants.[3,9,12] Of specific antipsychotics, the Food and Drug Administration (FDA) and European Medicines Agency (EMA) have approved the use of paliperidone for SCHAFF.[10,13] Combining antipsychotics with adjunctive psychopharmacotherapies, namely mood stabilizers and/or antidepressants, in SCHAFF is common compared with schizophrenia[14,15] and bipolar disorder.[14]

This study compares the long-term real-world effectiveness of psychopharmacotherapies for SCHAFF in two nationwide cohorts in order to observe whether the results are consistent in both countries, indicating that they may be generalizable to other populations as well. Sixteen most commonly used antipsychotics in both countries were reported, and drug formulation information was utilized to further categorize antipsychotics to oral and long-acting injectables (LAIs). Other pharmacotherapy categories included mood stabilizers, antidepressants, benzodiazepines and benzodiazepine-related, so-called Z-drugs (BZDR).