A systematic review of the evidence on the treatment of rapid cycling bipolar disorder

Third Department of Psychiatry, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki First Psychiatric Department, Psychiatric Hospital of Attica, Athens, Greece Department of Pharmacodynamics, Faculty of Medicine, and Department of Clinical and Theoretical Mental Health, Semmelweis University, Budapest, Hungary Department of Psychiatry, University of British Columbia, Vancouver, Canada.
Bipolar Disorders (Impact Factor: 4.97). 03/2013; 15(2):115-37. DOI: 10.1111/bdi.12045
Source: PubMed


Rapid cycling is associated with longer illness duration and greater illness severity in bipolar disorder. The aim of the present study was to review the existing published randomized trials investigating the effect of treatment on patients with rapid cycling bipolar disorder.

A MEDLINE search was conducted using combinations of the following key words: bipolar and rapid or rapid-cycling or rapid cycling and randomized. The search was conducted through July 16, 2011, and no conference proceedings were included.

The search returned 206 papers and ultimately 25 papers were selected for review. Only six randomized, controlled trials specifically designed to study a rapid cycling population were found. Most data were derived from post hoc analyses of trials that had included rapid cyclers. The literature suggested that: (i) rapid cycling patients perform worse in the follow-up period; (ii) lithium and anticonvulsants have comparable efficacies; (iii) there is inconclusive evidence on the comparative acute or prophylactic efficacy of the combination of anticonvulsants versus anticonvulsant monotherapy; (iv) aripiprazole, olanzapine, and quetiapine are effective against acute bipolar episodes; (v) olanzapine and quetiapine appear to be equally effective to anticonvulsants during acute treatment; (vi) aripiprazole and olanzapine appear promising for the maintenance of response of rapid cyclers; and (vii) there might be an association between antidepressant use and the presence of rapid cycling.

The literature examining the pharmacological treatment of rapid cycling is still sparse and therefore there is no clear consensus with respect to its optimal pharmacological management. Clinical trials specifically studying rapid cycling are needed in order to unravel the appropriate management of rapid cycling bipolar disorder.

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    • "However, the patients with bipolar disorder are more likely to have the comorbidities of anxiety, substance use disorder [9] and personality disorder [10] which complicate the treatment and may be associated with a higher recurrence rate [11] and poor prognosis [12-15]. In addition, the different subtypes (bipolar I, II or rapid cycling) [16-18] of bipolar disorder or the gender of the patient [19,20] may lead to different responses to treatments. Therefore, acute and prophylactic pharmacological treatment for bipolar depression is challenging for clinicians as only a few agents have been demonstrated to be efficacious. "
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    ABSTRACT: Bipolar disorder is a highly recurrent disease and has great impact on the function of patients. Depressive symptoms consist of more than 50% of life time during the illness and may lead to self harm or suicidal behaviors. Little is known about the antidepressant effects of olanzapine, an atypical antipsychotic, as monotherapy despite its indication for preventing manic episodes. In contrast, lamotrigine, a mood stabilizer, has been proven to be effective in preventing depression in patients with bipolar disorder. However, no studies have compared the efficacy between lamotrigine and olanzapine in the maintenance treatment of bipolar disorder. This enriched naturalistic study was implemented to assess the effectiveness of olanzapine and lamotrigine as monotherapy in the prevention of recurrence of bipolar disorder. Patients with bipolar disorder in a euthymic state (Young’s Mania Rating Scale (YMRS) score <12, and 21-item Hamilton Depression Rating Scale (HAM-D) score <7) for at least two months, having already received either olanzapine or lamotrigine as the maintenance treatment were recruited. The patients maintained with olanzapine (n = 22) were applied to olanzapine group whereas those maintained with lamotrigine (n = 29) were applied to lamotrigine group. They were followed up for 12 months. Differences in the efficacy between olanzapine and lamotrigine in recurrence prevention were analyzed. The Kaplan-Meier method was used to generate time-to-recurrence curves, and differences between the two groups were compared using the log-rank test. Olanzapine had a significantly lower recurrence rate of depressive episodes than lamotrigine (20.0% vs. 57.7%, χ2 = 6.62, p = .010). However, olanzapine and lamotrigine had similar mania (15.0% vs. 0%, χ2 = 4.17, p = .075, Fisher’s exact test) and any mood episode (35.0% vs. 57.7%, χ2 = 2.33, p = .127) recurrence rates. Olanzapine was significantly superior to lamotrigine in the time to recurrence of depressive episodes (χ2 = 4.55, df = 1, p = .033), but there was no difference in the time to recurrence of any mood episode (χ2 = 1.68, df = 1, p = .195). This prospective naturalistic study suggests that olanzapine is more effective than lamotrigine in the prevention of depressive episodes in patients with bipolar disorder. Future large-scale randomized studies are warranted to validate our results. Trial registration ID NCT01864551.
    BMC Psychiatry 05/2014; 14(1):145. DOI:10.1186/1471-244X-14-145 · 2.21 Impact Factor
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    • "The use of medication may affect the presentation of BD, and thus, it is important to ask how the use of medication may have affected the variables examined in this study. Rapid cycling has been linked to antidepressant use in some studies (Fountoulakis et al. 2013); however, in this sample of euthymic BD subjects, antidepressants were used by a quarter of the participants (n = 31) at baseline, and the use was not correlated to the PSQI score (r = .03, p = .76), "
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    ABSTRACT: Background Poor sleep quality is known to precede the onset of mood episodes and to be associated with poor treatment outcomes in bipolar disorder (BD). We sought to identify modifiable factors that correlate with poor sleep quality in BD independent of residual mood symptoms. Methods A retrospective analysis was conducted to assess the association between the Pittsburgh Sleep Quality Index and clinical variables of interest in euthymic patients with DSM-IV BD (n = 119) and healthy controls (HC; n = 136) participating in the Prechter Longitudinal Study of Bipolar Disorder. Multivariable linear regression models were constructed to investigate the relationship between sleep quality and demographic and clinical variables in BD and HC participants. A unified model determined independent predictors of sleep quality. Results and discussion Euthymic participants with BD and HC differed in all domains. The best fitting unified multivariable model of poor sleep quality in euthymic participants with BD included rapid cycling (β = .20, p = .03), neuroticism (β = .28, p = 2 × 10−3), and stressful life events (β = .20, p = .02). Poor sleep quality often persists during euthymia and can be a target for treatment. Clinicians should remain vigilant for treating subjective sleep complaints independent of residual mood symptoms in those sensitive to poor sleep quality, including individuals with high neuroticism, rapid cycling, and recent stressful life events. Modifiable factors associated with sleep quality should be targeted directly with psychosocial or somatic treatment. Sleep quality may be a useful outcome measure in BD treatment studies.
    09/2013; 1(16):16. DOI:10.1186/2194-7511-1-16
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    ABSTRACT: Treatment of bipolar depression with antidepressants is strongly debated on the basis of the methodologically poor and insufficient data supporting their use and the widely held belief that antidepressants can induce new episodes of abnormal mood elevation or accelerate the rate of cycling. The present study aimed at identifying clinical risk factors for switch into hypomania, mania, or mixed states, within 8 weeks after introduction of an antidepressant or after increasing its dosage, in a prospective, longitudinal design. 221 consecutive DSM-IV-TR depressed bipolar I and II disorder patients were treated with antidepressants, which were added to previously prescribed mood stabilizers and/or atypical antipsychotics. No patient was on antidepressant monotherapy. The patients were enrolled from October 2005 through January 2010. The primary outcome was the assessment of switch to mania or hypomania within 8 weeks after the introduction or dose increase of an antidepressant. Both groups were compared with analysis of variance and χ² procedures. Treatment-emergent affective switch was detected in 54 patients (24.4%) (switch group) while 167 patients (75.6%) (nonswitch group) did not experience a treatment-related switch. The main clinical differences significantly associated with the occurrence of an antidepressant-related switch, after performing logistic regression analysis, were higher rate of previous switches (P < .001) in the switch versus the nonswitch group, lower rate of responses to antidepressants (P < .001) in the switch versus the nonswitch group, and earlier age at onset (P = .026) in the switch versus the nonswitch group. Bipolar patients with an earlier age at onset and an illness course characterized by lower rate of response to antidepressants and higher rate of switches into mania or hypomania were found to be the ones with higher switch risk. Nevertheless, a greater number of previous antidepressant exposures was not associated with the occurrence of an antidepressant-associated switch. Identifier: NCT01503489.
    The Journal of Clinical Psychiatry 02/2012; 73(2):e271-6. DOI:10.4088/JCP.11m07166 · 5.50 Impact Factor
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