Open-Label Non-Randomized versus Double-Blind Randomized Antidepressive Treatment: What are the Advantages of Clinical Decision over Randomization?

Objective: To study, whether and how the results from open and double-blind randomized trials on antidepressants differ. Methods: Seventy-one patients were included in a study comparing open, non-randomized, standardized treatment with paroxetine (PAROX) and amitriptyline (AMI) after a minimum of six drug-free days (OPEN). A second group of 56 patients received the same treatment under blind-randomized conditions (BLIND-RANDOM). The course of psychopathology as assessed by the Hamilton Depression Rating Scale was compared using repeated measurements ANOVA-(rm). Results: While the rate of adverse events was higher in the BLIND-RANDOM compared to the OPEN condition, completer-analyses revealed no differences in psychopathological outcome. Conclusions: With similar clinical outcome BLIND-RANDOM trials of antidepressants may expose depressed patients to an increased risk of adverse events, when compared to OPEN conditions. However, the clinical outcome in study completers did not differ between the BLIND-RANDOM and the OPEN condition. Thus, the psychiatrist's choice may have impact on adverse events rather than on clinical outcome of antidepressant treatment.

References

• 1 Barbui C, Violante A, Garattini S. Does placebo help establish equivalence in trials of new antidepressants?.  Eur Psychiatry. 2000;  15 268-273
• 2 Danish University Antidepressant G roup. Citalopram: clinical effect profile in comparison with clomipramine: a controlled multicenter study.  Psychopharmacology. 1986;  90 131-138
• 3 Danish University Study G roup. Paroxetine: a selective serotonin reuptake inhibitor showing better tolerance, but weaker antidepressant effect than clomipramine in a controlled multicenter study.  J Affect Disord. 1990;  18 289-299
• 4 Enserik M. Can the placebo be the cure?.  Science. 1999;  284 238-240
• 5 Fritze J, Möller H J. Designs of clinical trials of antidepressants: should a placebo arm be included?.  CNS Drugs. 2001;  15 755-764
• 6 Kaptchuk T J. Powerful placebo: the dark side of the randomised controlled trial.  Lancet. 1998;  351 1722-1725
• 7 Kavale K. The efficacy of stimulant drug treatment for hyperactivity: a meta-analysis.  J Learn Disabil. 1982;  15 280-289
• 8 Kim S YH, Holloway R G. Burdens and benefits of placebos in antidepressant clinical trials: a decision and cost-effectiveness analysis.  Am J Psychiatry. 2003;  160 1272-1276
• 9 Oslin D W, Streim J E, Katz I R, Smith B D, DiFilippo S D, Ten Have T R, Cooper T. Heuristic comparison of sertraline with nortriptyline for the treatment of depression in frail elderly patients.  Am J Geriatr Psychiatry. 2000;  8 141-149
• 10 Pajonk F G, Holsbach R, Naber D. Evaluation of efficacy of neuroleptics in open versus double-blind trials.  Fortschr Neurol Psychiat. 2000;  68 313-320
• 11 Quitkin F M, McGrath P J, Stewart J W, Ocepek-Welikson K, Taylor B P, Nunes E, Delivannides D, Agosti V, Donovan S J, Ross D, Petkova E, Klein D F. Placebo run-in period in studies of depressive disorders.  Br J Psychiatry. 1998;  173 242-248
• 12 Quitkin F M. Placebos, drug effects, and study design: a clinician's guide.  Am J Psychiatry. 1999;  156 829-836
• 13 Roose S P, Glassman A H, Attia E, Woodring S. Comparative efficacy of selective serotonin reuptake inhibitors and tricyclics in the treatment of melancholia.  Am J Psychiatry. 1994;  151 1735-1739
• 14 Sauer H, Huppertz-Helmhold S, Dierkes W. Efficacy and safety of venlafaxine ER vs. amitriptyline ER in patients with major depression of moderate severity.  Pharmacopsychiatry. 2003;  36 169-175
• 15 Schatzberg A F, Kraemer H C. Use of placebo control groups in evaluating efficacy of treatment of unipolar depression.  Biol Psychiatry. 2000;  47 736-744