National Brain Research Program (Nemzeti Agykutatási Program, NAP2)(2017-1.2.1-NKP-2017-0002)
Funder: Ministry of Human Capacities
Subjects:
Psychiatry
Background Summarizing evidence from clinical trials of patients with schizophrenia
with predominant or prominent negative symptoms (NS), a prior meta-analysis reported
a large placebo effect in negative symptoms (Cohen's d = 2.909). Assuming that such
an effect was clinically not plausible, we performed a critical re-assessment and
an update of the previous results with newly available data from add-on and monotherapy
studies. Study Design Random-effect meta/regression analysis of trials that focused
on predominant or prominent NS; and adopted a double-blind, randomized, placebo-controlled
design. The final pooled meta-analytic database, based on the available add-on and
monotherapy studies combined, included 24 publications containing data on a total
of 25 studies (21 add-on, 4 monotherapy). Study Results The pooled overall estimate
for the placebo effect from the primary analysis for all included studies had a medium
effect size, with a Cohen's d value of 0.6444 (SE = 0.091). The estimates were similar
in the add-on and monotherapy studies. Meta-regression indicated that the high placebo
response was significantly associated with clinical trial characteristics, including
the high ratio of patients assigned to active vs. placebo treatment and short trial
duration. Conclusions These results represent a major downward correction for a current
effect size estimate of the placebo response in the negative symptoms of schizophrenia.
Our findings also pinpoint certain clinical trial characteristics, which may serve
as important predictors of the placebo response. The knowledge of these factors can
have important implications for drug development and trial design for new drugs for
negative symptoms of schizophrenia.
