Quetiapine for acute bipolar depression: a systematic review and meta-analysis

Putthisri

et al. 2017

NDT

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BackgroundSome studies have indicated the efficacy of quetiapine in the treatment of bipolar depression in adult patients. However, its efficacy has been not shown in child and adolescent patients.ObjectiveThis systematic review purposefully determined the efficacy and acceptability of quetiapine in the treatment of children and adolescents with bipolar depression.Data sourcesA database search of EMBASE, PubMed, CINAHL, and Cochrane Controlled Trials Register was carried out in March 2016. All randomized controlled trials (RCTs) of bipolar depression in children and adolescents were considered for inclusion in this review.Study eligibility criteria, participants, and interventionsRCTs of quetiapine in the treatment of child and adolescent patients with bipolar depression with end point outcomes were included in this study. Languages were not limited.Study appraisal and synthesis methodsThe full-text versions of relevant clinical studies were thoroughly examined and extracted. The primary efficacy of outcome was measured by using the pooled mean-changed scores of the rating scales for bipolar depression. However, the response and remission rates were also measured.ResultsA total of 251 randomized patients in the three RCTs of quetiapine versus placebo in the treatment of bipolar depression for children and adolescents were eligible in this review. The pooled mean-changed score of the quetiapine-treated group was not greater than that of the placebo-treated group. Similarly, the pooled response and remission rates were not different between the two groups. The pooled overall discontinuation rate and the discontinuation rate due to adverse events were not different between the two groups.LimitationsLimited studies were eligible in this review.ConclusionAccording to the findings in this review, quetiapine may not be efficacious in the treatment of bipolar depression in children and adolescents. Its acceptability, however, was comparable to a placebo. Therefore, the use of quetiapine in children and adolescents with bipolar depression is not recommended. Further well-defined clinical studies should be performed to confirm these outcomes.

Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Quetiapine monotherapy versus placebo in the treatment of children and adolescents with bipolar depression: a systematic review and meta-analysis

Putthisri

et al. 2017

NDT

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“…Thirty-five reviews, including 179 trials with adult and 117 with pediatric participants, were finally analyzed (15, (Supplementary Table S1 online). From these reviews, 19 assessed the risk of bias (18,20,22,25,26,28,29,32,35,(37)(38)(39)(40)(41)44,46,(49)(50)(51), 6 reported only the Jadad score (15,19,21,36,45,48), 4 assessed only the allocation concealment (34,42,43,47), and 6 did not assess quality (23,24,27,30,31,33). Overall, 13 382 adult and 5 417 pediatric participants were enrolled in the placebo groups.…”

Section: Resultsmentioning

confidence: 99%

Is the perceived placebo effect comparable between adults and children? A meta-regression analysis

et al. 2016

Background: A potential larger perceived placebo effect in children compared with adults could influence the detection of the treatment effect and the extrapolation of the treatment benefit from adults to children. This study aims to explore this potential difference, using a meta-epidemiological approach. Methods: A systematic review of the literature was done to identify trials included in meta-analyses evaluating a drug intervention with separate data for adults and children. The standardized mean change and the proportion of responders (binary outcomes) were used to calculate the perceived placebo effect. A meta-regression analysis was conducted to test for the difference between adults and children of the perceived placebo effect. results: For binary outcomes, the perceived placebo effect was significantly more favorable in children compared with adults (β = 0.13; P = 0.001). Parallel group trials (β = −1.83; P < 0.001), subjective outcomes (β = −0.76; P < 0.001), and the disease type significantly influenced the perceived placebo effect. conclusion: The perceived placebo effect is different between adults and children for binary outcomes. This difference seems to be influenced by the design, the disease, and outcomes. Calibration of new studies for children should consider cautiously the placebo effect in children.

“…Despite the clinical challenge that anxious bipolar depression presents, some positive findings exist in the literature. A review of 11 RCTs found that quetiapine (monotherapy or in combination) was associated with significant improvements in anxiety [measured by the Hamilton Anxiety Rating Scale (HAM‐A)] in bipolar depression . Similarly, patients with bipolar depression and high levels of anxiety (a score of ≥ 18 on the HAM‐A) experienced significant reductions in symptoms of both depression and anxiety following treatment with olanzapine or olanzapine–fluoxetine combination versus placebo; however, weight gain and increased cholesterol levels were also significant .…”

mentioning

confidence: 99%

A single infusion of ketamine improves depression scores in patients with anxious bipolar depression

et al. 2014

Objective Patents with anxious bipolar disorder have worse clinical outcomes and are harder to treat with traditional medication regimens compared to those with non-anxious bipolar disorder. Ketamine has been shown to rapidly and robustly decrease symptoms of depression in depressed patients with bipolar disorder. We sought to determine whether baseline anxiety status reduced ketamine’s ability to decrease symptoms of depression. Methods Thirty-six inpatients with anxious (n = 21) and non-anxious (n = 15) treatment-resistant bipolar depression (types I and II; concurrently treated with either lithium or valproate) received a single infusion of ketamine (0.5 mg/kg) over 40 minutes. Post-hoc analyses compared changes in the Montgomery–Åsberg Depression Rating Scale (MADRS) and Hamilton Depression Rating Scale (HDRS) in anxious versus non-anxious depressed patients with bipolar disorder through 14 days post-infusion. Anxious bipolar depression was defined as DSM-IV bipolar depression plus ≥ 7 on the HDRS Anxiety/Somatization Factor Score. Results A linear mixed model revealed a significant effect of anxiety group on the MADRS (p = 0.04) and HDRS (p = 0.04). Significant drug effects (all p < 0.001) suggested both anxious and non-anxious groups had an antidepressant response to ketamine. The drug by anxiety interactions were not significant (all p > 0.28). Conclusions Both anxious and non-anxious patients with bipolar depression had significant antidepressant responses to ketamine, though the anxious depressed group did not show a clear antidepressant response disadvantage over the non-anxious group. Given that anxiety has been shown to be a predictor of poor treatment response in bipolar depression when traditional treatments are used, our findings suggest the need for further investigations into ketamine’s novel role in the treatment of anxious bipolar depression.