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(p. 271) Pharmacological Treatments for Unipolar Depression 

(p. 271) Pharmacological Treatments for Unipolar Depression
(p. 271) Pharmacological Treatments for Unipolar Depression

Charles B. Nemeroff

and Alan F. Schatzberg

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date: 23 October 2021

The treatment of unipolar major depression with antidepressant medication is well established on the basis of scores of randomized placebo-controlled trials involving thousands of patients. Tricyclic antidepressants (TCAs) were the first to be studied extensively; meta-analyses of placebo-controlled trials show them to be consistently and significantly more efficacious than a placebo. Because of a narrow safety margin and significant drug-induced adverse side effect problems, TCAs have now largely been replaced as the first-line treatment of depression by selective serotonin reuptake inhibitors (SSRIs)—fluoxetine, sertraline, paroxetine, citalopram, and escitalopram; serotonin norepinephrine reuptake inhibitors (SNRIs)—venlafaxine and duloxetine; as well as other compounds, including, for example, bupropion and mirtazapine. Each of these agents has been shown to be superior to a placebo and as effective as comparator TCAs or SSRIs in controlled trials. Clinical trials consistently show them to be better tolerated than TCAs, and they clearly have a wider margin of safety. However, there is a controversy concerning whether TCAs are more effective than SSRIs for the treatment of the most severely ill depressed patients. Monoamine oxidase inhibitors (MAOIs), while also more effective than placebo, have generally been reserved for treatment-refractory patients; however, a recently released transdermally delivered selegiline may be used in less refractory patients. It is now generally recognized that patients with recurrent major depression benefit from continued antidepressant treatment, and there is evidence that TCAs, SSRIs, SNRIs, and so forth are all effective for the long-term management of recurrent major depression. An important issue in evaluating the antidepressant literature is to distinguish between response rated as a reduction in the level of symptoms on a rating scale and response rated as true remission from illness.

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