Lower rate of depressive switch following antimanic treatment with second-generation antipsychotics versus haloperidol

Barcelona Bipolar Disorders Program, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain.
Journal of Affective Disorders (Impact Factor: 3.38). 10/2012; 144(3). DOI: 10.1016/j.jad.2012.07.038
Source: PubMed


BACKGROUND: Treatment of acute mania with second-generation antipsychotics has been claimed to involve a lower risk of switch to depression than haloperidol. However, clinical guidelines clearly state that this is not a proven fact. METHODS: Meta-analysis of double-blind randomized controlled trials in acute mania, comparing rates of switch to depression with atypical antipsychotics and with haloperidol. Search was conducted in MEDLINE and CENTRAL databases (last search: September 2011). RESULTS: 8 randomized clinical trials fulfilled inclusion criteria. 2 of them were excluded because of low methodological quality or lack of data. 5 second-generation antipsychotics (aripiprazole, olanzapine, quetiapine, risperidone, and ziprasidone) were compared to haloperidol. In the mixed effects model the Risk Ratio for depressive switch was 0.71 (0.52, 0.96) favouring atypical antipsychotics. In the random effects model the difference did not reach statistical significance. In the heterogeneity analysis, exclusion of an outlying aripiprazole trial yielded a Risk Ratio of 0.58 (0.42, 0.82) with a non-significant heterogeneity test. Although no atypical antipsychotic was individually significantly superior to haloperidol, a trend could be seen favouring olanzapine (RR=0.56 [0.29, 1.08]), quetiapine (RR=0.36 [0.10, 1.33]), and ziprasidone (RR=0.51 [0.22, 1.18]). LIMITATIONS: All trials were industry supported, with some variability in dosage of haloperidol. Switch to depression was not the primary outcome of the trials. Heterogeneity could be explained as a lack of class-effect for atypicals. CONCLUSIONS: Treating acute mania with atypicals is associated to 42% less risk of switch to depression than with haloperidol. Nevertheless, caution should be taken when considering this a class effect, as only olanzapine, quetiapine, and ziprasidone may show a better profile.

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Available from: Juan Undurraga, Dec 11, 2015
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    • "The Brazilian mental health care system is still under development, which may explain the low access to specialized care (Mateus et al., 2008). The high prescription of typical antipsychotics for these patients may promote an aggravation and/or precipitate depressive symptoms in patients with BD (Goikolea et al., 2013). "
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    ABSTRACT: To compare individuals in primary care (PC) who screen positive for bipolar depression to those who screened positive for unipolar depression on mental health care ouctomes, PC service utilization, medical comorbidities, suicidal ideation, health-related quality of life (HRQoL) and psychosocial functioning. In this cross-sectional study, participants (N=1197) answered self-reported measures of depressive symptoms (Center for epidemiologic studies depression scale), HRQoL (World Health Organization Quality of Life instrument-Abbreviated version), medical comorbidity (functional comorbidity index) and functioning (Functional Assessment Short test). Participants were partitioned into 'bipolar' and 'unipolar' depression groups based on a predefined cutoff on the Brazilian mood disorder questionnaire. The prevalence of bipolar depression was in PC was 4.6% (95% CI: 3.4-5.8). Participants with bipolar depression were more likely to endorse suicidal ideation, present with more medical comorbidities, report a worse physical HRQoL and have a higher rate of PC services utilization as compared to participants who screened positive for unipolar depression. Only six (10.9%) participants were recognized by the general practitioner as having a diagnosis of bipolar depression. The cross-sectional design prevents firm causal inferences from being drawn. A positive screen for BD does not substantiate the actual diagnosis. Co-morbid mental disorders were not accessed. Bipolar depression is common and under-recognized in Brazilian PC services. A positive screen for bipolar depression was associated with worse clinical outcomes and greater PC service utilization.
    Full-text · Article · Jun 2014 · Journal of Affective Disorders
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    • "In their metaanalysis , Yildiz et al. (2011) found that mixed features predicted poorer response to both active treatment and placebo. An additional challenge in the treatment of mixed states arises from the mood-switching risk derived from the need to concurrently treat both manic and depressive symptoms; an antipsychotic monotherapy centered on improving only manic symptoms can increase the risk of switching to depression (Goikolea et al., 2013; Vieta, 2005), particularly in the case of conventional antipsychotics and drugs with a high polarity index (Popovic et al., 2012). Conversely, antidepressant treatment to treat only depressive symptoms can induce a manic switch (Baldessarini et al., 2012; Fornaro et al., 2012; Pacchiarotti et al., 2011a; Valenti et al., 2011). "
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    ABSTRACT: The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) nomenclature for the co-occurrence of manic and depressive symptoms (mixed states) has been revised in the new DSM-5 version to accommodate a mixed categorical-dimensional concept. The new classification will capture subthreshold non-overlapping symptoms of the opposite pole using a "with mixed features" specifier to be applied to manic episodes in bipolar disorder I (BD I), hypomanic, and major depressive episodes experienced in BD I, BD II, bipolar disorder not otherwise specified, and major depressive disorder. The revision will have a substantial impact in several fields: epidemiology, diagnosis, treatment, research, education, and regulations. The new concept is data-driven and overcomes the problems derived from the extremely narrow definition in the DSM-IV-TR. However, it is unclear how clinicians will deal with the possibility of diagnosing major depression with mixed features and how this may impact the bipolar-unipolar dichotomy and diagnostic reliability. Clinical trials may also need to address treatment effects according to the presence or absence of mixed features. The medications that are effective in treating mixed episodes per the DSM-IV-TR definition may also be effective in treating mixed features per the DSM-5, but new studies are needed to demonstrate it.
    Full-text · Article · Apr 2013 · Journal of Affective Disorders
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    ABSTRACT: Background: there is a lack of scientific data regarding speed of action of antimanic treatments, a relevant issue in clinical practice. Objective: to assess differences in the speed of onset of antimanic efficacy between haloperidol (as most studied first-generation antipsychotic) and second-generation antipsychotics. Experimental procedures: meta-analysis of double-blind randomized clinical trials in acute mania, comparing treatment with haloperidol and with second-generation antipsychotics. Search was conducted in MEDLINE and CENTRAL databases (last search: September 2011). Differences in mania scale score reduction at week 1 were assessed. Results: 8 randomized clinical trials fulfilled inclusion criteria and 1 of them was excluded due to low methodological quality. 2037 Manic patients had been treated with antipsychotics in the 7 trials. Haloperidol was found to be significantly more efficacious in the reduction of the mania scale score at week 1. The effect size was small, the Standardized Mean Difference (SMD) being 0.17, with a 95% Confidence Interval ranging from 0.01 to 0.32. Haloperidol was significantly more efficacious than olanzapine (SMD: 0.40 [0.21, 0.59]) and ziprasidone (0.39 [0.18, 0.61]). A non-significant trend towards superiority of haloperidol was found over aripiprazole (SMD: 0.13 [-0.02, 0.19]). There were no significant differences between haloperidol and quetiapine (0.17 [-0.11, 0.44]), and haloperidol and risperidone (SMD: -0.10 [0.30, 0.09]). Conclusions: haloperidol shows a faster onset of antimanic action than second-generation antipsychotics. This difference may be related to D2 affinity. Haloperidol may be considered a treatment option in severely ill manic patients who require urgent relief of symptoms.
    Full-text · Article · Jul 2012 · European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology
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