Antipsychotic Combination Strategies in Bipolar Disorder: Strategies to Maximize Treatment Adherence

Antipsychotic Combination Strategies in Bipolar Disorder: Strategies to Maximize Treatment Adherence

In This Special Report:

The Art of Psychopharmacology, David S. Janowsky, MD

Hypnotics: How Effective Are They for Insomnia?, Malcolm H. Lader, MD, PhD, LLB

Antidepressants: Brand Name or Generic?, James W. Jefferson, MD

Antipsychotic Combination Strategies in Bipolar Disorder, David J. Muzina, MD and Martha Sajatovic, MD

Optimal management of bipolar disorder (BD) includes the careful selection and regular ingestion of appropriate medication to stabilize mood. Unfortunately, between 40% and 50% of patients with BD in routine clinical settings take breaks or forget to take their medication or even discontinue the drug altogether.1-3 Treatment nonadherence is associated with mood relapse, hospitalization, and suicide.4,5

Adequate adherence can be defined as the taking of the minimum amount of medication required to achieve acceptable control of symptoms and to prevent relapse to an extent that is mutually agreed on by the patient and the clinician. This definition underscores the need for a collaborative treatment approach that takes into account the nature and severity of the illness, associated comorbidities, the patient’s response to medication (including adverse effects and perceived benefits), and patient preference.6

One of the challenges in addressing the issue of nonadherence is that there are a variety of ways to measure adherence, all of which have limitations (Table). Various studies have defined a working concept of what constitutes clinically relevant nonadherence, including serum drug levels (for drugs in which serum levels might be typically monitored), categorical stratification (ie, missing a specific percentage of prescribed medication), medication refill frequencies, and combined/composite definitions.3,7

Recognizing that adherence is rarely an all-or-nothing phenomenon, some groups have defined adherence categories within a range. For example, patients who are adherent take 80% or more of the prescribed medication; partially adherent patients take 51% to 79% of a prescribed medication; and those who are nonadherent take 50% or less of a prescribed drug.8 Such categorization allows for comparison of medication prescription filling across various medication classes, including medication combination therapies, among groups of individuals in a health care network. Whether any one specific compound or class of compounds (either as monotherapy or in combination) might be generally associated with relatively greater adherence among patients with BD has yet to be determined.

The role of antipsychotic drugs

In recent years, the pharmacopeia for BD therapy has expanded substantially to include not only traditional mood-stabilizing compounds (such as lithium and anticonvulsants) but also the atypical antipsychotics. The latter have been associated with antimanic, antidepressant, and mood-stabilizing properties.9,10

Randomized, placebo-controlled trials, which demonstrated the efficacy of atypical antipsychotics (olanzapine, risperidone, quetiapine, ziprasidone, and aripiprazole), led to their approval for the management of acute bipolar mania with or without psychotic features. The differences in antimanic efficacy among these agents are likely to be small.11


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