CONFOUNDING BY SEVERITY AND INDICATION IN OBSERVATIONAL STUDIES OF ANTIDEPRE SSANT EFFECTIVENESS

Abstract

Background

It   has   been   suggested   that   antidepressants   worsen   the   course   of   major   depressive   disorder. Epidemiological data have sometimes been cited in support of this idea, but such estimates are vulnerable to confounding. The objective of this study was to assess episode incidence and recovery in relation to antidepressant use, adjusting for symptom severity.

 Methods

Random digit dialing was used to select a sample of n=3304 community residents. Each respondent was then assessed with a baseline interview followed by a series of six subsequent interviews spaced two weeks apart. The brief Patient Health Questionnaire  (PHQ-9)  was used to detect depressive  episodes during follow-up and to provide ratings of symptom severity. Grouped time proportional hazards models were used to assess confounding by producing estimates of the association between antidepressant use and major depression incidence and prognosis adjusted for baseline symptom severity.

 Results

Antidepressant  use  in  initially  non-depressed  respondents  was  associated  with  a  markedly  higher incidence of depression (Hazard Ratio, HR = 3.9, 95% CI 1.8 – 8.5). With adjustment for the depression severity  score  in  the  two  weeks  preceding  the  emergence  of  a  new  episode,  this  effect  diminished markedly  and  was  no  longer  statistically  significant  (HR  =  1.2,  95%  CI  0.6  –  2.7,  p  =  0.57). Antidepressant use was also associated with a lower rate of recovery from major depression (HR = 0.8, 95% CI 0.5 – 1.2, p = 0.27), but this effect also moved towards  the null value after adjustment  for baseline severity (HR = 0.9, 95% CI 0.6 – 1.5).

 Conclusions

Antidepressant medication use is confounded with symptom severity. Observational studies seeming to show harmful effects of antidepressants are subject to bias as a result.