Abstract
Jack Kirszenblat, Delmont Private Hospital, Melbourne, Australia:
The Beerworth and Tiller article ‘Liability in prescribing choice: the example of antidepressants’ [1] is marred by the misleading way in which reference material is used, in respect to ‘the example of anti-depressants’, to illustrate the authors' thesis that practitioners must be aware of legal consequences of medical decision-making.
The authors cite a number of references to support their contention that ‘Concern has… been expressed in medical journals since the early 1970s about the use of tricyclic antidepressants (TCAs) with cardiac patients’. Having identified this concern, the authors then proceed to argue that TCAs carry unacceptable risks of cardiac toxicity in all patients (and not merely in overdose) and that TCAs would be contraindicated in cardiac patients.
A closer reading of these references [2–4] actually reveals somewhat less dogmatic conclusions.
Vohra et al. [2] concluded that some patients, notably those with pre-existing left bundle branch block or bifascicular block, could be exposed to hazardous prolongation of conduction by TCAs in therapeutic doses, which might be associated with sudden death.
Glassman et al. [3] concluded that TCAs at normal therapeutic levels are free of clinically adverse cardiovascular effects, except for postural hypotension and that ‘even in those patients with overt heart disease, TCAdrugs do not necessarily pose a threat’. They also found, like Vohra et al. in the earlier study, that the group of cardiac patients at greatest risk were those with pre-existing bundle branch block. They advocated a pre-treatment electocardiogram in any patient over 50 or any patient suspected of having cardiac disease.
Veith et al. [4] found that ‘in the absence of severely impaired myocardial performance, depressed patients with preexisting heart disease can be effectively treated with these agents without an adverse effect on ventricular rhythm or haemodynamic function’.
I have found it useful, and reassuring, to consult the patient's cardiologist in those patients with cardiac disease in whom I am considering the use of a TCA. As it happens, I recently consulted the author of one of these studies, a Melbourne cardiologist, to ask him his opinion regarding the safety of prescribing a TCA to one of his patients with major depression and pre-existing cardiac disease. He did not consider this to present a problem.
The authors repeatedly assert that the newer anti-depressants are more readily tolerated than, and equally efficacious with, the older antidepressants.
They do acknowledge that non-compliance rates and treatment discontinuation rates with the newer antidepressants in clinical practice are unknown, but are prepared to venture the unproven assumption that these rates parallel research findings. Yet patients prescribed selective serotonin re-uptake inhibitors report high rates of sexual dysfunction (higher than previously reported) and also report tolerance difficulties not just because of the more usually recognised serotonergic side effects, but also because of less common but troubling adverse effects such as bleeding and purpura.
In regard to the question of efficacy, the authors are selective in their use of evidence, or use evidence which is questionable in regard to its reliability.
The authors' selective use of reference material is demonstrated by their failure to refer to evidence which suggests that the newer antidepressants may be less effective in some depression subtypes or in some populations [5].
However, the authors' citing of a meta-analysis emanating from the Clinical Research Department of a pharmaceutical manufacturer [6] hardly inspires confidence and has no place in an article with such serious implications for medical practitioners.
I find it disappointing, and disturbing, that an article which may well be quoted in judicial proceedings, should promote a view based, as it is, on misrepresentation of the research studies, selective exclusion of studies, and the use of reference material of dubious merit.