Can Long-Term Treatment With Antidepressant Drugs Worsen the Course of Depression? [CME]
J Clin Psychiatry 2003;64(2):123-133
© Copyright 2015 Physicians Postgraduate Press, Inc.
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Background: The possibility that
antidepressant drugs, while effectively treating depression, may
worsen its course has received inadequate attention.
Method: A review of the literature suggesting
potential depressogenic effects of long-term treatment with
antidepressant drugs was performed. A MEDLINE search was
conducted using the keywords tolerance, sensitization,
antidepressive agents, and switching. This was
supplemented by a manual search of Index Medicus under the
heading "antidepressant agents" and a manual search of
the literature for articles pointing to paradoxical effects of
Results: A number of reported clinical findings
point to the following possibilities: very unfavorable long-term
outcome of major depression treated by pharmacologic means,
paradoxical (depression-inducing) effects of antidepressant drugs
in some patients with mood and anxiety disturbances,
antidepressant-induced switching and cycle acceleration in
bipolar disorder, occurrence of tolerance to the effects of
antidepressants during long-term treatment, onset of resistance
upon rechallenge with the same antidepressant drug in a few
patients, and withdrawal syndromes following discontinuation of
mood-elevating drugs. These phenomena in susceptible individuals
may be explained on the basis of the oppositional model of
tolerance. Continued drug treatment may recruit processes that
oppose the initial acute effects of a drug and may result in loss
of clinical effect. When drug treatment ends, these processes may
operate unopposed, at least for some time, and increase
vulnerability to relapse.
Conclusion: The possibility that antidepressant
drugs may worsen the course of depression needs to be tested,
even though its scientific exploration is likely to encounter
considerable methodological and ideological difficulties. The
clinical implications of this hypothesis in depression are
considerable. Antidepressant drugs are crucial in the treatment
of major depressive episodes. However, appraisal of paradoxical
effects that may occur in susceptible patients during long-term
treatment may lead to more effective use of the drugs.