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: 3.71). 10/2012; 144(3). DOI: 10.1016/j.jad.2012.07.038
Source: PubMed

ABSTRACT 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.

  • [Show abstract] [Hide abstract]
    ABSTRACT: The use of combination therapy with mood stabilizers and antipsychotics in acute mania in bipolar disorder (BD) is widespread, although most treatment guidelines recommend monotherapy as the first option, and reserve combination therapy, which is associated with more frequent and more severe side effects, for when patients do not respond to the former treatment option. Reasons to prescribe combination therapy include the lack of efficacy of the current treatment (either real or due to undisclosed poor adherence), psychiatric comorbidities, severe previous course of illness, slow cross-tapering during treatment switching, and potential benefits from particular combinations. The decision to start with monotherapy or combination therapy may depend on the patient characteristics, and is still under debate. Clinical trials designed to ascertain whether combination therapy or monotherapy is more advantageous for patients in acute mania and beyond, according to illness severity, are urgently needed. Adding a third monotherapy arm to the conventional two-arm, adjunctive-design trials or initiating combination therapy from the beginning may help to shed some light on the issue.
    CNS Drugs 02/2015; DOI:10.1007/s40263-015-0235-1 · 4.38 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Loxapine is an antipsychotic used in psychiatry for over 40 years with a well-established profile. Loxapine is a dibenzoxazepine tricyclic antipsychotic agent, available for oral, intramuscular and inhalatory administration. In the light of the recent approval by the regulatory agencies of inhaled loxapine for use in the acute treatment of mild-to-moderate agitation in adults affected with schizophrenia or bipolar disorder, this article aims to critically review the available literature on loxapine, irrespective of its formulation. This review examines the efficacy and tolerability of the various formulations of loxapine in the treatment of agitation and aggression in patients affected with schizophrenia, bipolar disorder and other psychiatric conditions. A comprehensive and systematic literature search of PubMed/MEDLINE was conducted, and relevant pharmacodynamic and pharmacokinetic data was included. The findings from the literature were critically reviewed and synthesized. The available data suggests that the antipsychotic efficacy of loxapine is similar to the efficacy of other typical or atypical antipsychotics, with an adverse effects profile comparable to that of the typical antipsychotics at high doses for chronic treatment. As an acute treatment in agitation associated with schizophrenia or bipolar disorder, inhaled loxapine was developed as an innovative and rapid option which appears to be efficacious and tolerable. Electronic supplementary material The online version of this article (doi:10.1186/s12991-015-0053-3) contains supplementary material, which is available to authorized users.
    Annals of General Psychiatry 04/2015; 14:15. DOI:10.1186/s12991-015-0053-3 · 1.53 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    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.
    Journal of Affective Disorders 06/2014; 162:120-7. DOI:10.1016/j.jad.2014.03.040 · 3.71 Impact Factor