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

Main Article Content

Scott B Patten

Keywords

Antidepressive agent, longitudinal studies, epidemiology, methods

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.

Abstract 114 | PDF Downloads 88

References

1. CANMAT Working Group. Clinical guidelines for the treatment of depressive disorders. Can J Psychiatry 2001;46(Suppl. 1):1S-92S.
2. Moncrieff J. Are antidepressants overrated? A review of methodological problems in antidepressant clinical trials. J Nerv Ment Dis 2001;189:288-95.
3. Turner EH, Matthews AM, Linardatos E, et al. Selective Publication of Antidepressant Trials and Its Influence on Apparent Efficacy. New Eng J Med 2008;358:252-60.
4. Fava GA. Can long-term treatment with antidepressant drugs worsen the clinical course of depression? J Clin Psychiatry 2003;64:123-33.
5. Patten SB. The impact of antidepressant treatment on population health: Synthesis of data from two national data sources in Canada. Population Health metrics 2004;2/1/9.
6. Brugha TS, Bebbington PE, MacCarthy B, et al. Antidepressants may not assist recovery in practice: a naturalistic prospective survey. Acta Psychiatr Scand 1992;86:5- 11.
7. Moncrieff J. Are antidepressants as effective as claimed? No, they are not effective at all. Can J Psychiatry 2007;52:96-7.
8. Patten SB. In debate: Are antidepressants as effective as claimed? ( Letter). Can J Psychiatry 2007;52:750.
9. Spitzer RL, Kroenke K, Williams JBW, et al. Validation and utility of a self-report version of the PRIME-MD. The PHQ Primary Care Study. JAMA 1999;282:1737-44.
10. Spitzer RL, Williams JBW, Kroenke K, et al. Validity and utility of the PRIME-MD Patient Health Questionnaire in assessment of 3000 obstetric- gynecologic patients: The PRIME- MD Patient Health Questionnaire Obstetric- Gynecology Study. Am J Obstet Gynecol 2000;183:759-69.
11. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders(DSM- IV-TR). Washington: American Psychiatric Association; 2000.
12. Kroenke K, Spitzer RL, Williams JBW. The PHQ-9. Validity of a brief depression severity measure. J Gen Intern Med 2001;16:606 -13.
13. Patten SB. A visual depiction of major depression epidemiology. BMC Psychiatry 2007;7:23.
14. Löwe B, Spitzer RL, Gräfe K, et al. Comparative validity of three screening questionnaires for DSM-IV depressive disorders and physicians' diagnosis. J Affect Disord 2004;78:131-41.