The feasibility of a randomised, placebo-controlled clinical trial of homeopathic treatment of depression in general practice
21 June 2004
revised 19 July 2004
accepted 06 April 2005
29 December 2017 (online)
Depression is common in general practice and lack of concordance is an important problem in its treatment. Homeopathy has few side effects and is generally associated with good compliance. We report a study investigating the feasibility of a trial to compare the effectiveness of homeopathy with a conventional antidepressant and placebo.
Objectives To assess the feasibility of a general practice-based clinical trial comparing the effectiveness of individualised homeopathic treatment vs Fluoxetine (Prozac) vs placebo in the treatment of major depressive episodes of moderate severity.
Design Randomised, double-dummy, double-blind parallel group clinical trial.
Setting Lower Clapton Group Practice, East London.
Method Patients were recruited through their general practitioners as they presented during a 9 month period. Recruitment target was 30 patients. Eligibility was confirmed by a consultant psychiatrist using standard criteria (DSM-IV) and instruments Hamilton Depression Scale (HAMD). Suicidal and psychotic patients were excluded, additional precautions against suicide were incorporated. There was a 1 week run-in period and patients showing spontaneous improvement were excluded. Homeopathic treatment was prescribed by a GP qualified in homeopathy, from a ‘limited list’ of 30 homeopathic medicines, with the help of decision support software. Patients were randomised to receive verum Fluoxetine and placebo homeopathy, or verum homeopathy and placebo Fluoxetine, or placebo homeopathy and placebo Fluoxetine. Treatment duration was 12 weeks. The outcomes were: adverse drug reactions, clinical global impression (CGI); HAMD; mini international psychiatric Interview; Pittsburgh sleep quality index; Side-effects checklist; Short Form 12; treatment credibility questionnaire; work and social disability scale. The primary outcome measures were HAMD and CGI.
Results A recruitment calculation indicated that over 230 suitable patients would be expected to attend the practice during the recruitment phase. Thirty one patients were referred for possible inclusion in the trial by their GPs. Twenty three met the entry criteria, 11 were randomised and 6 completed the study. Of the completers, one received homeopathy, 2 placebo and 3 Fluoxetine.
Conclusions A trial of this design in general practice is not feasible, because of recruitment difficulties, many of them linked to patient preference. Different approaches are required to recruit adequate patient numbers to trials of this sort.
- 1 Mann A.. Depression and anxiety in primary care: the epidemiological evidence. in: Jenkins R., Newton J., Young R.. The Prevention of Depression and Anxiety. 1992. London: HMSO;
- 2 Hale A.S.. ABC of mental health: depression. BMJ 1997; 315: 43-46.
- 3 Freeling T.A.. Depression in general practice. In: Paykel E.S.. Handbook of Affective Disorders. 2nd edn. 1992. Edinburgh: Churchill Livingstone;
- 4 Boyer W.F., Feighner J.P.. The financial implications of starting treatment with a selective serotonin reuptake inhibitor or tricyclic antidepressant in drug-naive depressed patients. In: Jonsson B., Rosenbaum J.F.. Health Economics of Depression. 1993. Chichester: J Wiley;
- 5 The treatment of depression in primary care. Effective Health Care Bulletin 1993; 1 (5). Centre for Reviews and Dissemination. University of York, York.
- 6 Kleijnen J., Knipschild P., ter Riet G.. Clinical trials of homeopathy. Br Med J 1991; 302: 316-323.
- 7 Linde K., Clausius N., Ramirez G.. et al. Are the clinical effects of Homeopathy placebo effects? A meta-analysis of placebo-controlled trials. Lancet 1997; 350 9081 834-843.
- 8 Mathie R.T.. The research evidence base for homeopathy: a fresh assessment of the literature. Homeopathy 2003; 92: 84-91.
- 9 Dantas F., Rampes H.. Do homeopathic medicines provoke adverse effects? A systematic review. Br Hom J 2000; 89: S35-S38.
- 10 Sharples F., Van Haselen R., Fisher P.. NHS Patients’ perspective on complementary medicine. Complement Ther Med 2003; 11: 243-248.
- 11 Khan A., Detke M., Khan S.R., Mallinckrodt C.. Placebo response and antidepressant clinical trial outcome. J Nerv Ment Dis 2003; 191: 211-218.
- 12 American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 3rd edn. Washington DC: American Psychiatric Association; 1987.
- 13 Spitzer R.L., Endicott J., Robins E.. Research diagnostic criteria: rationale and reliability. Arch Gen Psychiatry 1978; 35: 773-782.
- 14 Hamilton M.. A rating scale for depression. J Neurol Neurosurg Psychiatry 1960; 23: 56.
- 15 Paykel E.S.. The Background: extent and nature of the disorder. in: Herbst K., Paykel E.S.. Depression: An Integrative Approach. 1989. Heinemann: Oxford; 3-17.
- 16 Sheehan D, Janavas J, Knapp E, et al. Mini International Neuropsychiatric Interview Version 4.4. University of South Florida, Tampa.
- 17 Dahlke F., Lohaus A., Gutzmann H.. Reliability and clinical concepts underlying clinical judgements in dementia: Implications for clinical research. Psychopharmaco Bull 1992; 28 (04) 430-452.
- 18 Ware J., Sherbourne C.. The MOS 36-item Short-form health Survey (SF-36). Med Care 1992; 30 (06) 473-483.
- 19 Buysse D., Reynolds C., Monk T.. et al. The Pittsburgh sleep quality index: a new instrument for psychiatric practice and research. Psychiatry Res 1989; 28: 193-213.
- 20 RADAR Homeopathic Software. Archibel SA Assesse Belgium, 1995.
- 21 Moher D., Schulz K.F., Altman D.G.. The CONSORT statement: revised recommendations for improving the quality of reports of parallel-group randomised trials. Lancet 2001; 357: 1191-1194.
- 22 Hunt C., Shepherd L., Andrews G.. Do doctors know best? Comments on a failed trial. Med J Australia 2001; 174: 144-146.
- 23 Gore S.M.. Assessing clinical trials: first steps. BMJ 1981; 282: 1605-1607.
- 24 Wilson S., Delaney C., Roalfe A.. et al. Randomised trials in primary care: case study. Br Med J 2000; 321: 24-27.
- 25 Bell-Syer S., Moffett J.. Recruiting patients to randomised trials in primary care: principles and case study. Fam Practice 2000; 17 (02) 187-191.
- 26 Halbert J., Silagy C., Finucane P.. et al. Recruitment of older adults for a randomised, controlled trial of exercise advice in a general practice setting. J Am Geriatr Soc 1999; 47 (04) 477-481.
- 27 Peto V., Coulter A., Bond A.. Factors affecting general practitioners’ recruitment of patients into a prospective study. Fam Practice 1993; 10: 207-211.
- 28 Margitie S., Sevick M., Miller M.. et al. Challenges faced in recruiting patients from primary care practices into a physical activity intervention trial. Prev Med 1999; 29: 277-286.
- 29 Chilvers C., Dewey M., Fielding K.. et al. Antidepressant drugs and generic counselling for treatment of major depression in primary care: randomised trial with patient preference arms. Br Med J 2001; 322: 772-775.
- 30 Ross S., Grant A., Counsell C.. et al. Barriers to participation in randomised controlled trials: a systematic review. J Clin Epidem 1999; 52 (12) 1143-1156.
- 31 Tognoni G., Alli C., Avanzini F.. et al. Randomised controlled trials in general practice: lessons from a failure. Br Med J 1991; 303: 969-971.
- 32 Van der Windt. Koes B., Van Aarst M.. et al. Practical aspects of conducting a pragmatic randomised controlled trial in primary care: patient recruitment and outcome assessment. Br J Gen Pract 2000; 50: 371-374.
- 33 Ward E., King M., Lloyd M., Bower P., Friedli K.. Conducting randomised trials in general practice: methodological and practical issues. Br J Gen Pract 1999; 49: 919-922.
- 34 Silverman W.A., Altman D.G.. Patient's preferences and randomised trials. Lancet 1996; 347: 171-174.
- 35 Concato J., Shah N., Horwitz R.I.. Randomized, controlled trials, observational studies, and the hierarchy of research designs. N Eng J Med 2000; 342: 1887-1892.
- 36 McCarney R., Fisher P., van Haselen R.. Accruing large numbers of patients in primary care trials by retrospective recruitment methods. Complement Ther Med 2002; 10: 63-68.
- 37 Aickin M.. Participant-centered analysis in complementary and alternative medicine comparative trials. J Altern Complement Med 2003; 9: 949-957.