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Editor, – I refer to the articles on the new antidepressants (Aust Prescr 1999;22:106-8,108-11). I have read elsewhere that antidepressants have not been shown to work better than an active placebo such as benztropine mesylate. Active means a placebo that makes you feel as though you are taking something by producing adverse effects such as a dry mouth.

Could one of the authors of your recent antidepressant articles comment?

Kevin O'Dempsey
General Practitioner
Kallangur, Qld.

Associate Professor T.R. Norman, the author of 'The new antidepressants -mechanisms of action', comments:'Active placebos' have been employed occasionally in controlled evaluations of antidepressant drugs. Most often these have been used in tricyclic antidepressant trials to maintain the 'blind' as these drugs are well known for their anticholinergic effects and can often be distinguished from placebo on this basis. Over the course of evaluation of new antidepressants some trials will show no significant difference from placebo, but the weight of clinical evidence is that the new antidepressants are clearly more effective than placebo. Several reasons for the failure to distinguish a psychotropic medication from placebo can be recognised, such as inclusion of incorrect diagnostic groups, mild forms of depressive illness, failure to include a placebo washout period prior to commencing trial medication, and non-compliance with the study drug. Non-specific factors in treatment are also important and the psychotherapeutic aspect of a patient regularly consulting with someone willing to listen to their problems cannot be ignored. Furthermore, it should be recognised that the natural history of depression is for recovery to eventually take place, without treatment. (Medications can considerably shorten the period to recovery.) Clearly, if patients are at the point of recovery then any treatment, active drug or placebo, will apparently be 'successful'.