Real-World Effectiveness of Antipsychotics

• Observational studies can overcome some limitations of RCTs via nationwide electronic databases but are subject to potential selection bias
• Tiihonen and colleagues[2] aimed to overcome this limitation of observational studies by within-individual analysis, in which each patient serves as his/her own control by comparing periods of (antipsychotic) exposure and non-exposure
• The study objective was to determine the effectiveness of antipsychotics for prevention of psychiatric rehospitalization and treatment failure

• The authors included all individuals in Sweden age 16 to 64 in 2006 who received a diagnosis of schizophrenia (both new and existing diagnoses) from July 2006 to December 2013

• They used the Prescribed Drug Register, which included antipsychotics prescribed from 2005 to 2013 in outpatient care

• Antipsychotics were subdivided by (1) first- and second-generation agents and (2) oral and long-acting injectable (LAI) formulations

• The primary outcome measures were psychiatric rehospitalization (inpatient stay for at least 24 hours) and treatment failure

• Treatment failure was defined as psychiatric rehospitalization, antipsychotic discontinuation/switch, or death

• All-cause health care visits were the secondary outcome measure

• Outcomes were analyzed using Cox proportional hazards regression models, controlling for several time-dependent factors

• 28,823 Patients with schizophrenia met the inclusion criteria (prevalent cohort), including 4603 with a new diagnosis (incident cohort); the mean follow-up period was 6 years

• Olanzapine was the most frequently used oral antipsychotic

• Zuclopenthixol was the most frequently used LAI antipsychotic

• In the prevalent cohort, 44% experienced psychiatric rehospitalization and 72% had treatment failure

• The lowest risk of rehospitalization was found with clozapine (hazard ratio [HR] = 0.58) and LAI paliperidone, zuclopenthixol, perphenazine, and olanzapine (HRs = 0.51 - 0.58)

• The highest risk of rehospitalization was seen with flupentixol (HR = 0.92) and quetiapine (HR = 0.91)

• The pattern of the results was the same after adjusting for concomitant antidepressant and benzodiazepine use

• Clozapine also had the lowest risk of all-cause inpatient or outpatient visits (HR = 0.87)

• The lowest risk of treatment failure was found with clozapine (HR = 0.58) and all LAI antipsychotics (HRs = 0.65 - 0.80)

• The highest risk of treatment failure was seen with levomepromazine (HR = 0.92) and quetiapine (HR = 1.15)

• The pattern of the results was the same after adjusting for concomitant antidepressant and benzodiazepine use

• The risk of rehospitalization was 22% lower during use of LAI compared with corresponding oral formulations

• The authors performed the first study of comparative antipsychotic effectiveness using a within-individual approach, which corrects for selection bias

• They found evidence for the superior efficacy of clozapine and LAI antipsychotics in reducing risks of rehospitalization and treatment failure (22% lower risk)

• They also found evidence that in first-episode schizophrenia, use of a LAI antipsychotic was associated with lower relapse risk compared with its oral formulation

• The authors concluded that there are substantial differences between antipsychotic agents and routes of administration regarding risks of rehospitalization and treatment failure

1. Leucht S, Cipriani A, Spineli L, et al. Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis. Lancet. 2013;382:951-962.

2. Tiihonen J, Mittendorfer-Rutz E, Majak M, et al. Real-world effectiveness of antipsychotic treatments in a nationwide cohort of 29 823 patients with schizophrenia. JAMA Psychiatry. 2017 Jun 7. In press. doi:10.1001/jamapsychiatry.2017.1322.