Are antidepressants effective for severe depression?

Since Kuhn’s paper on imipramine, it has been believed that antidepressants are most effective in severe depression. Many people, who are sceptical of their widespread use for milder cases, maintain that antidepressants are nevertheless effective and necessary in severe depression. It has also been suggested that the reason some studies find little difference between antidepressants and placebo is because they are conducted with people with mild depression, who dilute the antidepressant effect (National Institute for Clinical Excellence 2004).

Evidence for disease-centred action of antidepressants

Evidence about serotonin and noradrenalin levels in people with depression is inconsistent and confusing and most studies fail to control for the effects of potential confounders, such as previous drug treatment. Overall, there is little evidence to suggest that there is a characteristic abnormality in either of these systems that is associated with depression. Depression rating scales contain items that are not specific to depression, including sleeping difficulties, anxiety, agitation and somatic complaints.

Selective Serotonin Reuptake Inhibitors, suicide and violence

For well over a decade now there have been suggestions that the selective serotonin reuptake inhibitor and other newer antidepressants might induce suicidal ideas or behaviour in some people. In 1990 details of six patients who had developed intense suicidal thoughts after starting fluoxetine (Prozac) were published in an article in the American Journal of Psychiatry, followed by similar case reports.

Evidence on long-term treatment

The current recommendation is that antidepressants should be continued for 4-6 months after the resolution of an acute episode of depression. This recommendation probably originates with Kuhn’s advice but subsequently several long-term studies appeared to show that people are more likely to relapse after stopping antidepressants compared to if they continue to take them.

Role of the pharmaceutical industry

Subsequent accounts reveal the extent of cooperation between psychiatric researchers and pharmaceutical company personnel in the development of antidepressants. Company scientists were involved in providing new compounds for psychiatrists to try and psychiatrists sometimes suggested leads for companies to follow. Nathan Kline subsequently claimed that the industry was sceptical about the market for antidepressants, and was only persuaded to collaborate in research by his own remonstrations.