Quetiapine for Depression in Bipolar Disorders
From MindLinc Wiki
Depression in Bipolar Disorders
Background: Depression in Bipolar disorders is difficult to treat; the first line agents for Bipolar depression, lithium and lamictal, generally show an inadequate response to treating depression. We need more options in treating depression in bipolar 1, 2.
Methods:
Design- Double-blind, randomized, fixed-dose, placebo-controlled trial.
Setting-39 centers in US from Sept 2002-Oct 2003
Inclusion Criteria- DSM-IV for Bipolar 1, 2 and MDD as determined by score >20 HAM-D and not manic based on Young Mania Scale score <12.
Exclusion Criteria-Axis 1 other than bipolar, current episode of depression > 12 mnths or < 4 weeks, non-response to adequate trial of two classes of antidepressants during the current episode of depression, substance dependence/use (except nicotine), a severe medical illness, suicidal, homicidal
Medication- Quetiapine 300 mg or 600 vs placebo
Population- Outpatients 18-65 yrs old, randomized and stratified by voice-response central randomization service, see Table 2
Treatment Protocol-pts continued their nonpsychotropic meds. Zolpidem, ativan allowed three weeks. Quetiapine initiated at 50 mg/QHS, administered to target dose of 300mg by day 4 or 600mg by week 1.
Primary Outcome -weekly, clinical assessments conducted for 8 wks w/ MADRAS measuring the change from baseline scores. Different variables were calculated: the % of pts who achieved response, time to response, those who achieved remission, the time to remission. Secondary Outcomes were measured by the Hamilton Anxiety Rating Scale, Pittsburg Sleep Qual Index, Quality of Life Enjoyment scale. Safety Eval looked at EPS, EKG, akathesia, FSBS, VSs, and mania.
Analysis-Intent to Treat-last observation carried forward in the analysis, ANCOVA for the scores on the rating scales, Chi-Square, and Power Analysis demonstrating an adequately powered sample size.
Validity:
- Pts randomized? Yes and stratified
- Randomization Blinded? Yes, meds looked same but who was blinded was not specified.
- Analyzed in groups to which randomized? Yes
- Similar pts w/ respect to known prognostic factors? Yes
- Groups treated equally? Yes
- F/U complete? Yes but 44 lost to follow-up
Results:
- Primary Outdome- MADRAS: Both 300 and 600 Quetiapine demonstrated significantly greater improvements in depression. Effect size large for both doses (600mg=.81 and 300mg=.67). Responders: both Quetiapine groups together demonstrated that 58% responded vs 36% in the placebo group. NNT=5. Remission: 53% of Quetiapine Group vs 28.4% of placebo. NNT 5.
- HAM-D: 600mg effect size 0.93 and 300mg effect size 0.74
- CGI, Anxiety, Quality of Sleep, and Quality of Life all showed statistically significant improvement in Quetiapine vs Placebo
Comments: Strengths-first randomized, placebo-controlled trial to eval use of quetiapine in bipolar depression. Evidence illustrates early and sustained efficacy in the treatment of bipolar depression. Quetiapine was NOT associated with treatment-emergent mania. Inclusive of both Bipolar 1 and 2 disorders makes data more generalizeable.
Weaknesses- Not large enough sample of bipolar 2 pts. Mod sedation occurred in Quetiapine groups. No guidelines in choosing doseage selection.
Presented by Jennifer Farmer, MD, on March 13, 2006
