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Unipolar depression in adults: Treatment with antidepressant combinations

Peter P Roy-Byrne, MD
Section Editor
Murray B Stein, MD, MPH
Deputy Editor
David Solomon, MD


Antidepressant combinations are generally used for unipolar major depression (major depressive disorder) that is resistant to treatment with antidepressant monotherapy. Add-on pharmacotherapy is often necessary because initial treatment with a single antidepressant leads to remission in only 30 to 50 percent of patients [1-3]. Options for adjunctive pharmacotherapy include a second antidepressant, as well as second-generation antipsychotics, lithium, and triiodothyronine. Adjunctive psychotherapy is also an option.

Combining two antidepressants for treatment resistant depression is common [4]. As an example, retrospective studies of patients treated for depression with a single antidepressant (insurance claims database n >134,000; registry database n > 240,000) found that a second antidepressant was added in approximately 10 percent of patients [5,6].  

This topic reviews the indications and efficacy of combining antidepressants for patients with unipolar, nonpsychotic major depression. Choosing a drug regimen for major depression and using a second antidepressant as a hypnotic are discussed separately. (See "Unipolar depression in adults: Treatment of resistant depression" and "Unipolar major depression in adults: Choosing initial treatment" and "Treatment of insomnia", section on 'Antidepressants'.)


Indications for antidepressant combinations include:

Unipolar major depression that does not respond to multiple courses of treatment with antidepressant monotherapy as well as an antidepressant plus adjunctive pharmacotherapy (eg, antidepressant plus a second-generation antipsychotic, lithium, or triiodothyronine). (See "Unipolar depression in adults: Treatment of resistant depression", section on 'Choosing a drug'.)


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Literature review current through: Sep 2016. | This topic last updated: May 27, 2015.
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