Does antipsychotic combination therapy reduce the risk of hospitalization in schizophrenia?

ABSTRACT

Introduction

: Despite treatment with antipsychotic medication, approximately 1/3 of individuals with schizophrenia will fail to have an adequate response. To treat these patients, a commonly utilized approach is antipsychotic combination therapy. Antipsychotic combination therapy is controversial with mixed efficacy and tolerability results. It is also unclear if antipsychotic combination therapy reduces or increases the risk of psychiatric hospitalization.

Areas Covered

: The authors review the prevalence, efficacy and tolerability concerns, and rationale behind antipsychotic combination therapy. Evidence comparing antipsychotic monotherapy vs polypharmacy using hospitalization as an outcome measure is summarized.

Expert opinion

: Psychiatric rehospitalization is a useful measure of treatment effectiveness, incorporating aspects of treatment efficacy and tolerability. The evidence comparing the impact of antipsychotic monotherapy vs combination therapy on rehospitalization is mixed. Evidence is primarily retrospective in nature, and there is high heterogeneity between studies, which could partially explain the mixed results. There is likely a subset of patients for whom antipsychotic combination therapy reduces the risk of hospitalization greater than antipsychotic monotherapy. Patients should be treated individually taking into account their specific pattern of response.

KEYWORDS:

• Antipsychotic combination therapy
• antipsychotic monotherapy
• antipsychotic polypharmacy
• hospitalization
• rehospitalization

Article highlights

• Approximately 1/3 of patients will fail to respond adequately to antipsychotic monotherapy, and there is limited guidance on how next to proceed.

• Despite limited evidence, the worldwide pooled median rate of antipsychotic combination therapy is approximately 20%.

• Some potential benefits of antipsychotic combination therapy include ameliorating antipsychotic induced side-effects such as galactorrhea, weight gain, and drug-induced parkinsonism, and/or improving positive symptoms and/or reducing aggressive behavior.

• Risks of antipsychotic combination therapy include worsening treatment adherence, overall increase in total antipsychotic dosage, increased drug interactions, and/or worsening side-effects.

• Psychiatric rehospitalization can be considered a proxy of treatment effectiveness, incorporating aspects of efficacy, tolerability, and adherence.

• Although a recent large observational study (n=62,250) showed that antipsychotic combination therapy reduced the risk of rehospitalization, the overall evidence on whether antipsychotic combination therapy vs monotherapy reduces the risk of psychiatric rehospitalization is mixed, possibly secondary to the heterogeneity in study design and the variety of specific antipsychotics used. There is an absence of prospective randomized controlled trials addressing antipsychotic combination therapy and rehospitalization.

• Nonetheless, there is likely a subgroup of patients that respond well to antipsychotic combination therapy, and thus treatment should be personalized for the individual patient.

This box summarizes key points contained in the article.

Declaration of interest

L Citrome has, in the past 5 years, engaged in collaborative research with or has received consulting and/or speaking fees from AbbVie, Acadia, Alexza, Alkermes, Allergan, AstraZeneca, Avanir, Axsome, BioXcel, Boehringer Ingelheim, Bristol-Myers Squibb, Cadent Therapeutics, Eisai, Eli Lilly and Company, Forum, Genentech, Impel, Indivior, Intra-Cellular Therapies, Janssen Pharmaceuticals, Jazz Pharmaceuticals, Karuna, Lundbeck, Luye Pharma, Meiji Seika, Merck & Co, Medivation, Mylan, Neurocrine, Novartis, Noven, Osmotica, Otsuka, Pfizer, Reckitt Benckiser, Reviva, Sage, Shire, Sunovion, Takeda, Teva, Valeant and Vanda. L Citrome also has stocks in Bristol-Myers Squibb, Eli Lilly and Company, Johnson and Johnson, Merck and Co and Pfizer all purchased over 10 years ago. He has also received royalties from John Wiley and Sons, UpToDate, Springer Healthcare and Elsevier. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

One reviewer declares having received, in the past 5 years, honoraria or consultation fees from Angelini, Eli Lilly and Company, Gedeon Richter, Janssen Pharmaceuticals/Janssen Cilag and Sun Pharma. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This manuscript was not funded.