The brain processes sensory information in neuronal networks that are shaped by experience,
particularly during early life, to optimally represent the internal and external milieu. Recent
surprising findings have revealed that antidepressant drugs reactivate a window of juvenile-like
plasticity in the adult cortex. When antidepressant-induced plasticity was combined with appropriate
rehabilitation, it brought about a functional recovery of abnormally wired neuronal networks. These
observations suggest that antidepressants act permissively to facilitate environmental influence on
neuronal network reorganization and so provide a plausible neurobiological explanation for the
enhanced effect of combining antidepressant treatment with psychotherapy. The results emphasize that
pharmacological and psychological treatments of mood disorders are closely entwined: the effect of
antidepressant-induced plasticity is facilitated by rehabilitation, such as psychotherapy, that
guides the plastic networks, and psychotherapy benefits from the enhanced plasticity provided by the
drug treatment. Optimized combinations of pharmacological and psychological treatments might help
make best use of existing antidepressant drugs and reduce the number of treatment-resistant
patients. The network hypothesis of antidepressant action presented here proposes that recovery from
depression and related mood disorders is a gradual process that develops slowly and is facilitated
by structured guidance and rehabilitation.
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