Effectiveness of Switching From Antipsychotic Polypharmacy to Monotherapy

Susan M. Essock, PhD; Nancy H. Covell, PhD; Nina R. Schooler, PhD; T. Scott Stroup, MD, MPH; and Joseph P. McEvoy, MD
New York State Psychiatric Institute, New York (Drs Essock and Covell); Columbia University, New York, New York (Dr Essock); Georgetown University and the Veterans Affairs VISN 5 MIRECC, Washington, DC (Dr Schooler); the University of North Carolina, Chapel Hill (Dr Stroup); and John Umstead Hospital and Duke University Medical Center, Butner, North Carolina (Dr McEvoy)

This poster presentation was supported by funding from the National Institute of Mental Health.

Background: Absent data, clinical guidelines discourage antipsychotic polypharmacy either by omission or recommending it only after evidence-based approaches have failed.¹ We provide data from a randomized controlled trial addressing the relative risks and benefits of staying on two antipsychotic medications versus switching to monotherapy.

Methods: Fifteen study sites in the NIMH Schizophrenia Trials Network and five sites in the public mental health system in Connecticut recruited adults (18 and older) with a SCID diagnosis of schizophrenia or schizoaffective disorder who were currently taking two prescribed antipsychotics, defined by a plasma level greater than zero. One hundred twenty-seven participants were randomly assigned to stay on both antipsychotic medications or to discontinue one for six months. The choice of which to discontinue was made by the participant and physician. Treatment was open label with assessment by blinded raters. Paralleling CATIE Phase 1 and post-hoc stay or switch analyses of CATIE, we used Kaplan-Meier and Cox regression to examine the impact of staying on polypharmacy compared to switching to monotherapy on time to all-cause treatment discontinuation.^2,3 Similarly, we applied mixed models to examine the effect of stay or switch on changes in total Positive and Negative Syndrome Scale (PANSS) score, weight, and prolactin through the first six study months. We examined intent-to-treat and two as treated models, one where treatment crossovers were excluded entirely and one where data from treatment crossovers were excluded only following crossover.

Results: Individuals randomized to Switch from antipsychotic polypharmacy to monotherapy had significantly shorter times to all-cause discontinuation than those who were randomized to Stay on polypharmacy (p<0.05) in both intent-to-treat and as-treated models. Groups did not differ over time for total PANSS, though there were significant effects for both time (p<0.05) and time squared (p<0.05). Those randomized to switch to monotherapy lost weight compared to those randomized to stay on polypharmacy who gained weight, a difference that was significant when crossovers were excluded entirely and marginally significant in other models. There were no significant group-by time or time effects for prolactin.

Conclusions: While discontinuing one of two antipsychotics was followed by an additional medication change more often than if both antipsychotics had been continued, individuals switched to monotherapy had equivalent symptom control compared to those who continued on polypharmacy. Additionally, individuals who switched to monotherapy experienced weight loss, while those who continued on polypharmacy experienced weight gain. More prospective studies of adding a second antipsychotic are needed.

References

1. Moore TA, Covell NH, Essock SM, et al. Real-world antipsychotic treatment practices. Psychiatr Clin North Am. 2007;30(3):401–416.
2. Lieberman JA, Stroup TS, McEvoy JP, et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Eng J Med. 2005;353(12):1209–1223.
3. Essock SM, Covell NH, Davis SM, et al. Effectiveness of switching antipsychotic medications. Am J Psychiatry. 2006;163(12):2090–2095.

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