Over the past 30 years psychiatry has made a paradigm shift within a medical model from a psychological to a biological explanation for mental disorder. Depression is attributed to an imbalance of monoamines in the brain caused by depletion of neurotransmitters at receptor sites. The standard of care for treating depression is prescription of antidepressant medications alleged to correct this chemical imbalance. Research results testing the chemical imbalance theories for depression have been contradictory to the theories. Analyses of data from studies and meta-analyses of the efficacy of antidepressants indicate selective publication fostering an inflated impression of effectiveness and that antidepressants offer little more than placebos. Several sources of error, particularly breaking of the blind, may have determined outcome in studies showing drug/placebo differences. Despite negative results regarding the theory and pharmacotherapy for depression, the frequency of diagnoses of depression and prescription of antidepressant drugs have increased enormously. Economic interests more than science appear to be determining the treatment of depression. Prescription of antidepressant drugs as the standard of care for depression warrants reconsideration. A biopsychosocial model may be more useful than a disease model for conceptualizing and treating depression.

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