Reasons for discontinuation and continuation of antipsychotics in the treatment of schizophrenia from patient and clinician perspectives

Abstract

Objective:

To identify reasons for discontinuation and continuation of antipsychotic medications in the treatment of schizophrenia from the patients’ and their clinicians’ perspectives.

Research design and methods:

Two measures were previously developed to assess the Reasons for Antipsychotic Discontinuation/Continuation (RAD), one from the patient's perspective and another from the clinician's perspective. These measures were administered to acutely ill schizophrenia patients enrolled in a 12-week study of antipsychotic medications (N = 596) and to their clinicians. The RAD was assessed at baseline and at endpoint. Reasons were rated on a 5-point scale from ‘primary reason’ to ‘not a reason.’ The single most important reason was also identified. The ‘single most important reason’ and the ‘primary reasons’ for discontinuing the drug used prior to enrollment, and for discontinuing or continuing the study drug were identified. Levels of concordance between patients’ and clinicians’ reasons were assessed.

Clinical trial registration:

The data source for this study is a clinical trial registered at www.clinicaltrials.gov (NCT00337662).

Main outcome measures:

Reasons for Antipsychotic Discontinuation/Continuation (RAD).

Results:

Patients and clinicians identified several reasons for medication discontinuation and continuation (2.3 to 6.3 reasons, on average). The top ‘single most important’ reason for discontinuing the drug used prior to enrollment and for discontinuing the study drug was ‘positive symptoms not sufficiently improved or made worse,’ followed by ‘medication-related adverse events.’ The most frequent ‘single most important’ reason for medication continuation was ‘improved positive symptoms,’ followed by ‘patient's perception of improvement,’ and ‘functional improvement.’ A high level of concordance was observed between patients’ and clinicians’ ratings.

Conclusions:

Medication efficacy appears to be the core driver of medication discontinuation and continuation, especially with regard to positive symptoms. There was a high level of concordance between patients’ and clinicians’ perspectives. Limitations include the study requirement that patients be at least moderately ill and experiencing acute psychotic exacerbation, a potential selection bias in the readiness to respond to measures, and small sample sizes for some analyses. Further research is needed to replicate findings in patients who are not acutely ill.

Key words::

• Antipsychotic
• Concurrent validity
• RAD scale
• Schizophrenia

Transparency

Declaration of funding

This work was supported by Eli Lilly and Company.

Declaration of financial/other relationships

H.A-S., V.S., B.J.K., D.E.F., G.A.P., K.S. and A.W.N. have disclosed that they are employees and minor shareholders of Eli Lilly and Company or Lilly USA, LLC, a wholly owned subsidiary of Eli Lilly and Company. A.G.A. has disclosed that he served as a research consultant to a number of psychopharmaceutical companies including Lilly, Pfizer, AstraZeneca and Janssen-Ortho. R.K. has disclosed that he currently or in the past 12 months has received investigator-initiated research funding support from the National Institute of Mental Health, Allon, Novartis and the Singapore National Medical Research Council; has received an unrestricted educational grant from AstraZeneca; and that he currently or in the past 12 months has received honoraria or served as a consultant or advisory board member for Abbott, AstraZeneca, BiolineRx, Bristol Myers Squibb, Cephalon, Dainippon Sumitomo Pharma, Lilly, Johnson & Johnson, Lundbeck, Memory Pharmaceuticals, Merck, Neurosearch, Orion, Orexigen, Otsuka, Pfizer, Roche, Targacept, sanofi-aventis, Shire, Wyeth and Xenoport. In addition, in the past, he has received honoraria or served as a consultant or advisory board member for Acadia, Cortex, Cyberonics, Forest, Gabriel, GlaxoSmithKline, Repligen, Saegis and Schering-Plough; and has received research funding from AstraZeneca, Lilly, Janssen and Pfizer. R.K. also has disclosed that he receives royalties from the Brief Assessment of Cognition in Schizophrenia (BACS) testing battery and the MATRICS Battery (BACS Symbol Coding). D.N. has disclosed that he has received honoraria from, and/or acted as consultant for, AstraZeneca, Bristol-Myers Squibb, Lilly, Janssen-Cilag, Pfizer, Schering-Plough, Servier and Wyeth.

Acknowledgments

Lilly contracted the technical editing of this manuscript with i3 Statprobe. The authors thank Ms. Teri Tucker, i3Statprobe, for editorial assistance.

Data in this paper were presented at the American Psychiatric Association Annual Meeting, San Francisco, CA, USA, May 16–21, 2009.