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Unipolar depression in adults: Treatment with lithium

Michael Gitlin, MD
Section Editor
Peter P Roy-Byrne, MD
Deputy Editor
David Solomon, MD


Lithium is mainly used to treat bipolar disorder, which is characterized by recurrent episodes of depression, mania, and hypomania. However, lithium is also used as an adjunctive medication in patients who have inadequately responded to an antidepressant for treatment of unipolar depression (ie, depression with no lifetime history of mania or hypomania) [1]. In addition, lithium is used as monotherapy to treat acute episodes of unipolar depression and as maintenance treatment to prevent recurrence of unipolar depressive episodes.

Lithium was first used by psychiatrists in the mid-1800s [2]. The first controlled trial of lithium for unipolar depression was in 1968.

This topic reviews the use of lithium as adjunctive treatment and as monotherapy for acute episodes and maintenance treatment of unipolar depression. Treatment resistant depression and the use of lithium to treat bipolar disorder are discussed separately. (See "Unipolar depression in adults: Treatment of resistant depression" and "Bipolar disorder in adults: Choosing pharmacotherapy for acute mania and hypomania", section on 'General principles' and "Bipolar disorder in adults: Choosing maintenance treatment", section on 'Lithium'.)


The most common use of lithium in patients with unipolar depression is to augment an antidepressant that does not adequately treat a depressive syndrome. Lithium or an alternative adjunctive agent is often necessary because remission with antidepressant monotherapy occurs in only 28 to 47 percent of patients, even with an optimal trial [3-5]. It is commonly thought that augmentation is more effective for patients who initially have a partial response to antidepressant monotherapy, compared with patients who do not respond at all, but this is not established [6].

Efficacy — Results from many studies support using lithium for depressed patients who do not fully respond to an antidepressant [7]:

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Literature review current through: Nov 2017. | This topic last updated: Jul 17, 2017.
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