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Real-World Effectiveness of Antipsychotics

Real-World Effectiveness of Antipsychotics

  • Which of these agents best prevents relapse? A recent study employed a novel approach to find out.
  • • The comparative effectiveness of antipsychotics remains controversial despite extensive research
    • Evidence from randomized clinical trials (RCTs) suggests superior efficacy of clozapine, olanzapine, and amisulpride[1]
    • However, patients in RCTs are “atypical” in terms of voluntary participation, medication adherence, and (the absence of) psychiatric, medical, and/or substance use comorbidity
    • As a result, RCTs do not provide information on “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.


Observational studies are more naturalistic comparing to RCTs very good design of this study.


Good stuff. Thanks

Richard @

Succinct and bite size. Love this kind of presentation.

Timothy @

Succinct and bite size. Love this kind of presentation.

Timothy @

The best antipsychotic is the one that the patient is happy to take regularly. So you have to ask!

Michele @

It's not that simple! What if the one that the patient is happy to take regularly isn't all that effective for that patient's symptoms?


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