What are the chances for personalised treatment with antidepressants? Detection of patient-by-treatment interaction with a variance ratio meta-analysis.
OBJECTIVES
To investigate if the treatment effect of antidepressants in patients with depression substantially varies in each patient (patient-by-treatment interaction or treatment heterogeneity), a necessary but largely unexplored prerequisite of personalised antidepressant treatment.


DESIGN
Meta-analytic variance comparison of treatment outcome between drug arms and placebo arms of clinical trials, based on the assumption that patient-by-treatment interaction should lead to larger variances in drug arms than placebo arms. To put the results into context, we run simple simulations, assuming different definitions and rates of those who respond especially well to antidepressants.


DATA SOURCES
163 randomised, placebo-controlled trials (51 396 patients) with complete results for pre-post differences, selected from a recently published systematic review.


ANALYSIS
Variance ratios (VRs) and coefficients of variance ratios (CVRs) of individual trials were meta-analytically combined. The analysis was repeated for classes of antidepressants and specific antidepressants.


RESULTS
VRs (VR=1.01, CI 0.99 to 1.02) and CVRs (CVR=0.82, CI 0.80 to 0.84) of the antidepressant-treatment arms were comparable or smaller than in placebo arms. Similar results were observed for classes of antidepressants and for specific antidepressants. Our simulation analysis confirmed that equal VRs can only be obtained if they are not more than a few patients who respond slightly above average.


CONCLUSIONS
The lack of increased treatment-outcome variance in the antidepressants versus placebo groups in randomised controlled trials indicates that no or only very small subgroups of patients respond particularly well to antidepressants. Thus, the scope for personalised treatment with antidepressants seems to be limited.
['Plöderl|Martin|M|0000-0003-4659-9314', 'Hengartner|Michael Pascal|MP|0000-0002-2956-2969']
D000928:Antidepressive Agents D003863:Depression D006801:Humans D057285:Precision Medicine D016032:Randomized Controlled Trials as Topic D016896:Treatment Outcome
depression and mood disorders psychiatry statistics and research methods