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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    • "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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    • "A majority of these studies are based on limited and selected study populations, most commonly patients initiating prophylactic pharmacotherapy after acute mania (Strakowski et al., 1998; Keck et al., 1997; DelBello et al., 2007; Tohen et al., 2003), which makes it hard to generalize the findings to the diverse population of patients with a bipolar disorder diagnosis. Among the factors most consistently associated with non-adherence to prophylactic treatment are substance abuse (Baldessarini et al., 2008a, 2008b; Aagaard and Vestergaard, 1990; Strakowski et al., 1998; Sajatovic et al., 2007) and comorbid personality disorder (Colom et al., 2000; Arvilommi et al., 2014). Further, absence of psychotic symptoms and having non-disabling initial episodes have been associated with a greater delay before initiation of prophylactic treatment (Goldberg and Ernst, 2002). "
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    ABSTRACT: Treatment guidelines state that all patients with bipolar disorder should use pharmacological prophylaxis; however the actual use of prophylactic drugs after bipolar disorder diagnosis is unknown. Our aim was to assess the use of, and predictors for, pharmacoprophylaxis in newly diagnosed bipolar disorder patients.Methods Data from three Swedish nationwide registers were obtained. We identified patients aged 18–75 with a first time diagnosis of bipolar disorder between 2006 and 2012 (n=31,770) and reviewed subsequent mood-stabilizer and antipsychotic prescription fills. In multivariable Cox regression models, we studied demographic and illness related factors as predictors of prescription fills after diagnosis.ResultsIn total, 72.2% (95% confidence interval [CI] 71.7–72.7%) of the patients filled a prescription of a prophylactic drug within 3 months after diagnosis. Pharmacological prophylaxis was mainly associated with a longer duration of hospitalization at bipolar disorder diagnosis (adjusted hazard ratio [AHR] 2.18; CI 2.02–2.35 for a hospitalization of ≥28 days compared to <7 days) and previous use of any mood-stabilizer or antipsychotic (inpatients: AHR 1.24; CI 1.17–1.31 and outpatients: AHR 1.78; CI 1.73–1.84).LimitationsWe had no information on drug prescriptions that were never filled.Conclusions The proportion of newly diagnosed bipolar disorder patients without pharmacological prophylaxis is substantial. Patients who are naïve to mood-stabilizers and antipsychotics and are hospitalized for a brief period at diagnosis are the ones least likely to initiate pharmacoprophylaxis, suggesting that this group deserves attention in order to improve the long term prognosis.
    Journal of Affective Disorders 10/2014; 172. DOI:10.1016/j.jad.2014.09.044 · 3.38 Impact Factor
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