Personal and social functioning in schizophrenia: defining a clinically meaningful measure of maintenance in relapse prevention

Abstract

Background:

Relapse prevention and maintenance of social functioning are important treatment objectives in the long-term management of schizophrenia. However, relatively little is known about measuring maintenance of social functioning to assess treatment benefit in relapse prevention clinical trials or as a tool to predict relapse in clinical practice. This study aims (1) to define a clinically meaningful decrease in the Personal and Social Performance scale (PSP) to assess antipsychotic treatment benefit in terms of maintenance of functioning and (2) to explore the threshold value of PSP decline as a useful tool to predict relapse in clinical practice.

Methods:

This post hoc analysis of two similar placebo-controlled relapse prevention clinical trials consisted of an exploration of change in PSP that would represent a clinically important decrement to measure treatment benefit in terms of time to PSP decrement (ITT analysis set; Study 1: n = 205) and an assessment of predictive value of PSP decrement and relapse status (ITT analysis set; Study 2: n = 408).

Results:

A 10-point decrement in PSP score was the threshold value for a clinically meaningful decline in personal and social functioning in a relapse prevention trial (Study 1). A strong association was found with relapse status: 61% of subjects with at least a 10-point decrease in PSP experienced the decrement prior to (between start of double-blind phase and before day of relapse) or on the day of relapse (Study 2). Kaplan–Meier survival analysis of time to at least a 10-point decrement in PSP showed that the proportion of subjects who did not experience at least a 10-point PSP decrease was statistically significantly greater in the paliperidone palmitate group than in the placebo group (p = 0.0014) (Study 2).

Conclusions:

Findings suggest a 10-point PSP decrement is a clinically relevant measure of maintenance of functioning in patients stabilized with antipsychotic therapy. Paliperidone palmitate demonstrated a statistically significant treatment benefit in terms of maintenance of functioning versus placebo. Furthermore, measuring a clinically relevant PSP decrement may be useful as an early functional indicator of relapse in clinical practice.

Limitations:

The exploration and validation of the threshold value of change in the PSP was designed and conducted post hoc. Predictive value is limited by the frequency in which PSP assessments were carried out in these trials, underscoring the importance of regular assessment.

Key words::

• Functioning
• Minimal important change
• Outcome assessment
• PSP
• Psychiatric status rating scales
• Schizophrenia
• Social behavior

Transparency

Declaration of funding

Funding for editorial support was provided by Johnson & Johnson Pharmaceutical Services, LLC.

Declaration of financial/other relationships

D.N., I.N., K.A., D.D.G. and S.G. have disclosed that they are employees of, and own stock in, Johnson & Johnson Pharmaceuticals. H.N. has disclosed serving on advisory boards, speaker bureaus and as a consultant to Abbott, AstraZeneca, Janssen, Novartis, Pfizer and Merck. He also has received research grants from Forest, GlaxoSmithKline, Janssen, Otsuka, Pfizer, Roche, Sanofi-Aventis and Shire.

The authors received no honoraria or other form of financial support related to the development of this manuscript. Methodological decisions, analysis and interpretation of results in the current article are those of the authors.

Some peer reviewers receive honoraria from CMRO for their review work. The peer reviewers of this paper have disclosed that they have no relevant financial relationships.

Acknowledgment

The authors thank ApotheCom for providing editorial support (for which funding was provided by Johnson & Johnson) in the preparation of this manuscript.