Psychotropic Medications for Patients With Bipolar Disorder in the United States: Polytherapy and Adherence

Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
Psychiatric services (Washington, D.C.) (Impact Factor: 2.41). 10/2008; 59(10):1175-83. DOI: 10.1176/
Source: PubMed


Because treatments for bipolar disorder include a growing number of psychotropic agents, the authors evaluated psychotropic polytherapy and adherence to treatment among U.S. patients with bipolar disorder.
National health plan claims data (2000-2004) were used to identify patients diagnosed as having bipolar disorder who had continuous benefits and had not been prescribed medication for bipolar disorder for six months or more. The study compared drugs dispensed to these patients initially and at one year and characterized patients who were adherent to mood-stabilizers.
A total of 7,406 patients had a bipolar disorder: bipolar I (55%), bipolar II (15%), or bipolar disorder not otherwise specified (30%). Women represented 57% of the sample; mean+/-SD age was 35.4+/-12.4 years. Initial prescription fills involved one psychotropic agent in 67% of patients, and two or more psychotropics (polytherapy) in 33%. Initial prescription drug selections involved: antidepressants > anticonvulsants >or= antipsychotics > sedatives > lithium; initial mood stabilizer use ranked: valproate > lithium > carbamazepine or oxcarbazepine > lamotrigine; antipsychotics ranked: olanzapine > quetiapine >or= risperidone > ziprasidone > aripiprazole > clozapine. Rankings were similar at one year, when only 31% of patients received monotherapy (a 2.2-fold decline), 32% received polytherapy, and 37% received no psychotropics. Initially patients received 1.42 psychotropic drugs per person; at one year, patients received 175, and at both times polytherapy was less likely with lithium than with anticonvulsants. In multivariate modeling, one-year mood stabilizer use was greater with the following: older age, type of mood stabilizer (lamotrigine > valproate > carbamazepine or oxcarbazepine > lithium) and was associated with more psychiatric office and emergency visits, clinician type (more common with psychiatrists than with primary care physicians), and nonuse of off-label anticonvulsants.
Polytherapy was used by one-third of patients initially and at one year, antidepressant use was highly prevalent initially and later, but lack of treatment was prevalent at one year. Plausible clinical and treatment factors were associated with sustained mood stabilizer adherence.

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    • "Specifically, there is evidence of the presence of cognitive dysfunction , even in asymptomatic patients, particularly in the domains of executive function and declarative memory (Arts et al., 2008; Robinson et al., 2006). Despite a growing body of research, it is still difficult to determine whether cognitive complaints reflect intrinsic aspects of the disease, lasting subclinical symptoms, comorbid conditions (e.g., ADHD, substance abuse, or cerebrovascular disease), or adverse side effects of the prescribed drug therapy (Baldessarini et al., 2008). In particular, the adverse effect of drug treatments on cognition has especially received attention because BD is treated Contents lists available at ScienceDirect journal homepage: "
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    ABSTRACT: Background: The aim of choosing a mood-stabilizing drug (lithium or anticonvulsants) or a combination of them with minimal neurocognitive effects is to stimulate the development of criteria for a therapeutic adequacy, particularly in Bipolar Disorder (BD) patients who are clinically stabilized. Method: Three groups of BD patients were established according to their treatment: i) lithium monotherapy (n = 29); ii) lithium together with one or more anticonvulsants (n = 28); and iii) one or more anticonvulsants (n = 16). A group of healthy controls served as the control (n = 25). The following tests were applied: Wechsler Adult Intelligence Scale, Trail Making Test, Wechsler Memory Scale, Rey Complex Figure Test, Stroop color-word test, Wisconsin Card Sorting Test, Tower of Hanoi, Frontal Assessment Battery, and Reading the Mind in the Eyes Test. Results. Relative to healthy controls, BD patients showed the following: i) those on lithium monotherapy, but not other BD groups, had preserved short-term auditory memory, long-term memory, and attention; ii) those who took only anticonvulsants showed worse findings in short-term visual memory, working memory, and several executive functions; and iii) all BD patients showed worse performance in processing speed, resistance to interference, and emotion recognition. Limitations: Medication alone cannot explain why all BD patients showed common cognitive deficits despite different pharmacological treatment. Conclusion: The impairment on some executive functions and emotion recognition is an inherent trait in BD patients, regardless of their pharmacological treatment. However, while memory, attention, and most of the executive functions are preserved in long-term stable BD patients, these cognitive functions are impaired in those who take anticonvulsants.
    Journal of Affective Disorders 10/2015; DOI:10.1016/j.jad.2015.10.008 · 3.38 Impact Factor
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    • "Some clinicians have expressed skepticism about these findings (Rasmussen). Such skepticism may reflect insufficient appreciation of the importance of randomized data as opposed to observational data, and insufficient knowledge of prior studies regarding the nature of rapid cycling bipolar disorder, as found in the standard text in the field (Goodwin and Jamison, 2007), prospective outcome studies (Schneck et al., 2008), and comprehensive review articles (Baldessarini et al., 2008). In bipolar disorder—including rapid-cycling—depressive episodes are more frequent and lengthy than manic episodes (e.g., Nierenberg et al., 2010). "
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    ABSTRACT: The use of antidepressants in rapid-cycling bipolar disorder has been controversial. We report the first randomized clinical trial with modern antidepressants on this topic. As part of the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) study, we analyzed, as an a priori secondary outcome, rapid cycling as a predictor of response in 68 patients randomized to continue vs. discontinue antidepressant treatment, after initial response for an acute major depressive episode. Outcomes assessed were percent time well and total number of episodes. All patients received standard mood stabilizers. In those continued on antidepressants (AD), rapid cycling (RC) subjects experienced 268% (3.14/1.17) more total mood episodes/year, and 293% (1.29/0.44) more depressive episodes/year, compared with non-rapid cycling (NRC) subjects (mean difference in depressive episodes per year RC vs. NRC was 0.85±0.37 (SE), df=28, p=0.03). In the AD continuation group, RC patients also had 28.8% less time in remission than NRC patients (95% confidence intervals (9.9%, 46.5%), p=0.004). No such differences between RC and NRC subjects were seen in the AD discontinuation group (Table 1). Analyses within the rapid-cycling subgroup alone were consistent with the above comparisons between RC and NRC subjects, stratified by maintenance antidepressant treatment, though limited by sample size. In an a priori analysis, despite preselection for good antidepressant response and concurrent mood stabilizer treatment, antidepressant continuation in rapid-cycling was associated with worsened maintenance outcomes, especially for depressive morbidity, vs. antidepressant discontinuation. Copyright © 2015 Elsevier B.V. All rights reserved.
    Journal of Affective Disorders 06/2015; 184. DOI:10.1016/j.jad.2015.04.054 · 3.38 Impact Factor
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    • "Antidepressants in bipolar depression 1677 Goldberg et al., 2007 ; Sachs et al., 2007 ; Ghaemi et al., 2008, 2010 ; Baldessarini et al., 2010d ; Frye et al., 2011). Evidence for prophylactic effects of sustained antidepressant treatment, even in non-bipolar recurrent depressive illnesses, remains limited and ambiguous, with risk of confounding effects of discontinuing ongoing antidepressant treatment (Altshuler et al., 2003 ; Baldessarini et al., 2007a, 2008, 2010c ; Vieta, 2008 ; Vö hringer and Ghaemi, 2011 ; Baldessarini, 2013). "

    03/2015; 13(1):102-112. DOI:10.1176/appi.focus.130119
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