Short Term Rescue Study of Olanzapine
Condition: Bipolar Disorder
MeSH terms: Bipolar Disorder
Study type: Interventional
Phase: Phase 4

Summary: 
      We will assess the effect of olanzapine compared to placebo added to prior treatment on CGI-S
      in a one-week randomized double-blind study. We will also assess the effect of olanzapine
      added to prior treatment on CGI-S in an eight-week open treatment study. In addition, we will
      assess the effect of olanzapine on Young Mania Rating Scale (YMRS), Hamilton and
      Montgomery-Asberg Depression Rating Scales (HDRS, and MADRS), and Hamilton Anxiety Rating
      Scales (HARS) in the above paradigms. We will also assess the influence of presentation
      severity (CGI-S) and polarity (mood elevation versus depression) on olanzapine response.
      Finally, we will assess safety and tolerability of olanzapine in the above paradigms.

      We hypothesize that in diverse mild syndromal and subsyndromal exacerbations of BD in
      outpatients, randomized double-blind flexibly dosed olanzapine added to prior treatment
      (including no treatment) will yield greater CGI-S improvement than placebo by the end of one
      week, and that such improvement will persist over one week of open continuation treatment.
    

Detailed description: 
      Development and marketing of new therapies for bipolar disorders (BD) has typically entailed
      performing double-blind placebo-controlled trials in acute mania maintenance studies and more
      recently acute depression studies. Such an approach addresses BD primarily in terms of
      episodes and has the strength of studying levels of pathology sufficiently high to permit
      detection of treatment effects, and guiding clinicians when they encounter syndromal mood
      episodes. However, this approach has the important limitation of not addressing an important
      unmet clinical need, namely the management of subsyndromal symptoms. Indeed, emerging data
      suggest that in BD subsyndromal symptoms compared to syndromal episodes are far more
      pervasive. Also such an approach runs the risk of not paying sufficient attention to the
      disorder construct, in a sense permitting preoccupation with syndromal episodes to carry more
      importance than the disorder.

      We will assess the effect of olanzapine compared to placebo added to prior treatment on CGI-S
      in a one-week randomized double-blind study. We will also assess the effect of olanzapine
      added to prior treatment on CGI-S in an eight-week open treatment study. In addition, we will
      assess the effect of olanzapine on Young Mania Rating Scale (YMRS), Hamilton and
      Montgomery-Asberg Depression Rating Scales (HDRS, and MADRS), and Hamilton Anxiety Rating
      Scales (HARS) in the above paradigms. We will also assess the influence of presentation
      severity (CGI-S) and polarity (mood elevation versus depression) on olanzapine response.
      Finally, we will assess safety and tolerability of olanzapine in the above paradigms.
    

Intervention name(s): Olanzapine/Zyprexa
Intervention type(s): Drug
Intervention description(s): Olanzapine was started at 2.5-10mg/day and adjusted by 2.5-5mg/day on a daily basis with a maximum dose of 20mg/day.
Other intervention name(s): Zyprexa
Intervention MeSH terms: Olanzapine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment