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"Depression clinics" in primary care
- Simon Mullins (7 September 1999)
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Response to article
- B J Baby (9 September 1999)
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Antidepressant drug counselling, information leaflets, and adherence to drug treatment
- Ross J Hamilton (13 September 1999)
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A tailor-made dosage, another way of improving antidepressant treatment effectiveness
- M Mercè Garcia-Barcelo (14 September 1999)
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Limitations of subgroup analyses
- Adam Jacobs (27 September 1999)
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Simon Mullins
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EDITOR- Peveler et al (1) have added to the evidence to justify piloting 'depression clinics' in primary care. They have shown that intervention by practice nurses can significantly improve treatment compliance and subsequent clinical outcome in major depression. Nurse practitioners without a mental health background could provide supportive counselling, compliance therapy and monitor depressive symptoms through questionnaires after modest training. This would provide a model of care that has proved successful in medical illnesses such as hypertension and asthma. Depression is common in primary care but has been shown to respond well to treatment without specialist input (2,3). 'Depression clinics' have the potential to provide a cost-effective and user-friendly way of delivering this service successfully. S D Mullins 1 Peveler et al . Effect of antidepressant drug councelling and information leaflets on adherence to drug treatment in primary care: randomised control trial. BMJ 1999;319:612-5 2 Simon GE. Can depression be managed appropriately in primary care? J Clin Psychiatry 1998;Suppl 2:3-8 ( Review article) 3 Scott et al. A.I.F. Scott and C.P.L. Freeman's "Edinburgh Primary Care Depression Study". B J Psychiatry 1994 Mar; 164(3) ; 410-5. |
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B J Baby, 4th Year Medical Student University of Newcastle
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Sir- Drug adherence is a difficult area to investigate and this paper by Peveler et al highlights a fundamentally important area of research. However, we believe that some of the conclusions on clinical outcome drawn by the authors are inappropriate. In a study that is primarily investigating adherence, the authors are justified in attaching little significance to drug dose. However, this lack of detail on exact drug dose prevents them from linking adherence to clinical benefit. The stated objective of the study was to evaluate several methods of improving adherence to antidepressant drugs. Clinical improvement was and additional aspect that was not identified at the outset. If outcome were to be investigated in relation to adherence, detailed drug doses need to be included in the study. In addition, conclusion reached by the authors were based on small sample sizes (n=52-55) in the four treatment groups. The size of the sample may have diminished the impact of this study. The authors also state that the usual length of treatment for antidepressant medication is six months, yet it is not explained why a study period of three months was chosen. We would suggest that repeating the study with an increased sample size for a minimum period of six months would therefore be worthwhile. By drawing conclusions on clinical outcomes, Peveler et al have overcomplicated what were clear objectives. Benjamin Baby Rubaraj Jayarajasingam Alastair Kidd James McCaslin Helen Spoors
4th Year Medical Students Dept. of Epidemiology and Public Health School of Health Sciences, Medical School. University of Newcastle, Newcastle upon Tyne. NE2 4HH UK Email: Benjamin Baby B.J.Baby@ncl.ac.uk Word Count: 226 |
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Ross J Hamilton
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Editor- Peveler and colleagues' research into improving adherence to antidepressants prescribed in general practice is welcome (1). We would question the significance of the conclusions reached, however, based on the trial's entry criteria. By limiting entry to the trial to patients prescribed one of the two older generation antidepressants, dothiepin and amitriptyline, the counselling intervention improved adherence for drugs that usually require dose titration to reach antidepressant levels and which have a range of unpleasant side-effects. One of the trial's authors has previously acknowledged that side-effect burden is significantly associated with non -compliance (2), and it has been shown repeatedly that tricyclic antidepressants in general practice are often prescribed at doses which are unlikely to be effective (3 and 4). Thus, it would appear from this paper that patients can be persuaded to continue taking unpalatable and, at times, subtherapeutic doses of an antidepressant which can be lethal in overdose. Given the documented trend towards general practitioners prescribing SSRIs first line (5), we believe that an intervention tested in this way is not 'as naturalistic as possible' and that the restriction to these two agents may, in part, explain why the intervention's effect of increasing adherence did not result in significant differences in depressive symptoms between the groups. Ross J Hamilton Simon Naji 1 Peveler R, George C, Kinmonth A, Campbell M, Thompson C. Effect of antidepressant drug counselling and information leaflets on adherence to drug treatment in primary care: randomised control trial. BMJ 1999;319:612 -5. 2 Maddox JC, Levi M, Thompson C. The compliance with antidepressants in general practice. Journal of Psychopharmacology 1994 8(1) 48-53. 3 MacDonald TM, McMahon AD, Reid IC, Fenton GW, McDevitt DG. Antidepressant drug use in primary care: a record linkage study in Tayside Scotland. BMJ 1996;313:860-1. 4 Donoghue JM, Tylee A. The treatment of depression: prescribing patterns of antidepressants in primary care in the UK. Br J Psychiatry 1996; 168:164-8 5 Lawrenson R. Pattern of antidepressant prescription in general practice: lessons from the MediPlus database. Primary Care Psychiatry 1999 5:S3-S7. |
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M Mercè Garcia-Barcelo, Research fellow Department of Psychiatry, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong
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Dear Editor, Compliance with treatment is an essential factor in the successful treatment of depression and other mental illnesses. Any effort to improve adherence to treatment is welcome. Peveler et al show that by providing psychosocial support to the patients, adherence to drug treatment is improved although little clinical benefit is obtained. There are several and diverse reasons for non-compliance such as lack of adequate information, poor psychosocial supports, demoralisation and severe side effects due to drug toxicity. The latter accounts for 80% of people receiving antidepressant medication that fail to comply with treatment (1). While the article proves the importance of psychosocial factors in the treatment of depression, it omits the description of the racial ethnic make-up of the subjects studied, which is an important factor that induces different drug responses leading to poor compliance with treatment in many cases. These variations in response lead to either adverse side effects related to drug toxicity, in which case the patient's compliance is at risk, or to drug inefficacy, which implies lack of response to acute treatment. Either way results in therapeutic failure. Assuming that the subjects included in Peveler et al study are Caucasians, in this race, from 2.9% to 10% of the individuals (2) bear genetic polymorphisms that alter the activity of their tricyclic antidepressant (TCA)-metabolising enzyme and hence their drug response. If the population studied were multiracial, the variation in drug response would be even more noticeable (3). Inter-individual and inter-ethnic diversity in drug response and variation in side effect profiles have been neglected and it presents more clinical and economical relevance than often appreciated (4). Genetic screening of subjects participating in clinical trials should be initiated to further define the impact that genetic variability has upon drug therapy. The possible link between genetics and drug metabolism and its response should be carefully contemplated. Thus, individualised dosage of antidepressant together with counselling should improve not only the adherence to treatment but also the clinical outcome. 1. Brugha TS. Depression undertreatment: Lost cohorts, lost opportunities. Psychol Med 1995; 25:3-6. 2. Lin KM, Anderson D, Poland EP. Ethnicity and psychopharmacology. Cultur Psych 1995 18:635-647. 3. Genetic analysis of the CYP2D6 locus in a Hong Kong Chinese population. M Garcia-Barcelo, LY Chow, HFK Chiu, YK Wing, DTS Lee, KL Lam and MMY Waye. Clinical Chemistry. 1999. (in press). 4. Chen S, Kumar S, Chow WH, Barret JS, Wedlund PJ. A genetic bias in clinical trials? Cytochrome P450-2D6 genotype in general vs selected healthy subjects populations. British J Clin Pharm 1997; 44:303-304. Dr. M.Mercè GARCIA-BARCELO Dr. Susana CASTAN-CAMEO Lok-Yee CHOW Helen FK CHIU |
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Adam Jacobs, Director Dianthus Medical Limited
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Although Peveler et al are to be congratulated for what was mostly a well thought out attempt to get to grips with the difficult problem of adherence, I am concerned about one of their conclusions. They concluded that the clinical benefit of the counselling intervention was apparent only in a subgroup of patients with major depression taking doses above 75 mg. What was the reason for investigating this particular subgroup? Was it a pre-specified analysis, and if so, were other subgroup analyses specified (and done)? If multiple subgroup analyses were done, was any correction made for multiple testing (eg Bonferroni adjustment of p values)? If one can think of 20 subgroups to analyse, it is always likely that one of them will show a significant treatment effect at the p = 0.05 level. The study has certainly demonstrated that counselling can improve adherence, but does not convince me that the intervention has any effect on clinical outcome. |
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