Robert Whitaker in his latest posting on his Mad in America blog (to which I have referred before) elaborates on the work of Giovanna Fava about the vulnerability to relapse created by taking antidepressants. Fava has produced a recent review in which he builds on his hypothesis that the neurobiological mechanism underlying the increased vulnerability is due to oppositional tolerance. By this he means that the effects of the drug are opposed or counteracted by homeostatic changes in the brain, and when drug treatment ends, these processes may operate unopposed.
I am cautious about calling the effect 'tolerance'. Unlike, for example, alcohol, there is no evidence of the need to increase the dose or concentration of antidepressants to produce the desired effect. Maybe what Fava means is a tolerance-like effect.
More fundamentally, I'm not convinced that looking for an underlying neurobiological explanation is the real way to look at the issue. Surely the problem is psychological dependence. As I've said in a previous post, doctors concentrate too much on the physiological explanation of drug effects. People form attachments to their medication more because of what they mean to them than what they do. It's an identity-altering experience taking antidepressants. Discontinuing them is going to cause all sorts of problems which take time to make sense of.
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