Depressive Disorder Needs an Evidence Base Commensurate with its Public Health Importance

(Can J Psychiatry 2007;52:543-544) For several decades, antidepressant drugs have been routinely recommended for the treatment of depressive disorders. Newer drugs such as the selective serotonin reuptake inhibitors (SSRIs) avoided some of the problems associated with the older tricyclic antidepressants (TCAs), particularly the sedation effects and toxicity in overdose, and the priority became to improve the diagnosis and treatment of depressive disorders in general clinical practice, where they were often underrecognized.1,2 The prescription of antidepressant drugs has increased dramatically over the last decade, and this demonstrates the increasing acceptance by patients and doctors of drug therapy for depression.3·4 Greater willingness to prescribe and to take antidepressant drugs has led to increased treatment of less severely ill patients-the subgroup more likely to be missed in primary care.5 Increased prescribing will almost inevitably lead to a greater incidence and reporting of adverse events, especially as SSRIs are used more in less severely ill patients, for whom the balance of harms and benefits is less clear. The evidence for the efficacy of antidepressants is strongest for patients who have at least moderately severe illness. It is the increased recognition of antidepressants' adverse effects in patients with a less clear capacity to benefit from them that has provided fertile ground for the recent controversy about induction of suicide by antidepressants. The perspective has altered. Rather than calling for greater diagnosis and treatment because there is uncertainty about the balance between benefits and risks in less severely ill patients, some recent clinical practice guidelines recommend that antidepressant drugs should not be used as a first-line therapy in mild major depressive episodes.6 Of course, the problem is that soundly evidence-based, cost-effective alternatives are not abundant, and so antidepressant drugs are likely to remain the main treatment for individuals presenting to doctors with symptoms of depressive disorder. Nonetheless, perceptions about antidepressants have probably changed, and the very public controversy concerning their risks means that, at the very least, patients are more likely to ask clinicians questions about the benefits and risks of drug therapy. Our own unpublished research suggests that some clinicians are likely to avoid prescribing certain antidepressants because the recent publicity has been so negative. It is therefore more important than ever for clinical practice to be soundly and explicitly based on the best currently available evidence. In this issue of The Canadian Journal of Psychiatry, we present 2 articles that attempt to summarize the evidence in several current areas of controversy about pharmacologie treatments for major depression. In the first article, Dr Toshi Furukawa and colleagues7 undertake a narrative review of long-term treatment of depression with antidepressants. In the second article, Dr Andrea Cipriani and colleagues8 review the evidence for the short-term effectiveness and safety of antidepressants. Our conclusions suggest that the evidence for antidepressant drugs is reasonably secure in only 1 or 2 areas. Most obviously, the best currently available evidence suggests that antidepressants are reasonably efficacious in the short term and that long-term therapy with antidepressant drugs can substantially reduce the risk of relapse in patients who have benefited from treatment in the acute phase.9 Evidence that some antidepressants may be modestly more effective than others and that monoamine oxidase inhibitors are more effective than TCAs in treating atypical depression is less convincing. SSRIs appear to increase suicidal ideation during early-phase therapy, but there is no evidence of an increase in suicide rates. There is little evidence about what to do for patients with limited or partial response to initial acute-phase therapy. …

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