Placebo response in bipolar disorder trials is more likely to occur in patients who are mildly ill , bipolar II , mixed-episode , first-episode , rapid cycling , atypical , non-psychotic , substance abusers and medically ill .
The use of concomitant medication such as benzodiazepines , a high frequency of visits , a high number of treatment groups and sites , fixed-dose design s , and the concomitant use of psychotherapy are likely to increase placebo response .
There are a number of clinical and method ological variables that are associated with placebo response
Background :  Placebo response is high in bipolar disorder trials .
This is a challenge for research ers and an enigma for clinicians .
This article will attempt to aid in the comprehension of the ethical questions and method ologies related to the use of placebo in bipolar disorder .
Results : Placebo has a very important role in the study of bipolar disorders .
From a method ological point of view , and given the limitations of non-inferiority design s , the use of placebo is necessary to evaluate the sensitivity of the study and ensure that the drug under investigation is really effective .
Olanzapine versus placebo in the treatment of acute mania
OBJECTIVE The primary intent of this study was to compare the efficacy and safety of olanzapine and placebo in the treatment of acute mania . METHOD The design involved a r and om-assignment , double-blind , placebo-controlled parallel group study of 3 weeks ' duration . After a 2- to 4-day screening period , qualified patients were assigned to either olanzapine ( N = 70 ) or placebo ( N = 69 ) . Patients began double-blind therapy with either olanzapine , 10 mg , or placebo given once per day . After the first day of treatment , the daily dose could be adjusted upward or downward , as clinical ly indicated , by one capsule ( olanzapine , 5 mg/day ) within the allowed range of one to four capsules . The primary efficacy measure in the protocol was defined as a change from baseline to endpoint in total score on the Young Mania Rating Scale . Clinical response was defined a priori as a decrease of 50 % or more from baseline in Young Mania Rating Scale total score . RESULTS The olanzapine group experienced significantly greater mean improvement in Young Mania Rating Scale total score than the placebo group . On the basis of the clinical response criteria , significantly more olanzapine-treated patients ( 48.6 % ) responded than those assigned to placebo ( 24.2 % ) . Somnolence , dizziness , dry mouth , and weight gain occurred significantly more often with olanzapine . There were no statistically significant differences between the olanzapine-treated and placebo-treated patients with respect to measures of parkinsonism , akathisia , and dyskinesias . No discontinuations of treatment due to adverse events occurred in the olanzapine treatment group . CONCLUSIONS The results from this study suggest that compared with placebo , olanzapine has superior efficacy for the symptoms of acute mania
Placebo response in bipolar disorder trials is more likely to occur in patients who are mildly ill , bipolar II , mixed-episode , first-episode , rapid cycling , atypical , non-psychotic , substance abusers and medically ill .
The use of concomitant medication such as benzodiazepines , a high frequency of visits , a high number of treatment groups and sites , fixed-dose design s , and the concomitant use of psychotherapy are likely to increase placebo response .
There are a number of clinical and method ological variables that are associated with placebo response
Background :  Placebo response is high in bipolar disorder trials .
This is a challenge for research ers and an enigma for clinicians .
This article will attempt to aid in the comprehension of the ethical questions and method ologies related to the use of placebo in bipolar disorder .
Results : Placebo has a very important role in the study of bipolar disorders .
From a method ological point of view , and given the limitations of non-inferiority design s , the use of placebo is necessary to evaluate the sensitivity of the study and ensure that the drug under investigation is really effective .