In our article on Drugs for Chronic Insomnia, we said there is little evidence that antidepressants such as trazodone, mirtazapine, or amitriptyline are effective in treating insomnia not associated with depression. We received a comment from a reader who has prescribed the tricyclic antidepressant amitriptyline for insomnia, particularly for patients with headache disorders, and finds that most patients are satisfied with the treatment.

A selective serotonin reuptake inhibitor (SSRI) is generally used for initial treatment of major depressive disorder (MDD). A serotonin-norepinephrine reuptake inhibitor (SNRI), bupropion (Wellbutrin SR, and others), and mirtazapine (Remeron, and others) are reasonable alternatives. Improvement in symptoms can occur within the first two weeks of treatment with these drugs, but a substantial benefit may not be achieved for 4-8 weeks.

The FDA has approved an oral extended-release formulation of gepirone (Exxua – Fabre-Kramer), a selective 5-HT_1A receptor agonist, for treatment of major depressive disorder (MDD) in adults. Gepirone was originally developed decades ago for treatment of anxiety and depression, but it was not approved by the FDA for such use. Gepirone is structurally related to buspirone, which is FDA-approved for treatment of anxiety.

The FDA has approved an extended-release fixed-dose combination of dextromethorphan and bupropion (Auvelity – Axsome) for treatment of major depressive disorder (MDD) in adults.

The FDA has approved the second-generation antipsychotic drug cariprazine (Vraylar — Abbvie) for adjunctive treatment of major depressive disorder (MDD) in adults. Cariprazine was previously approved for treatment of schizophrenia and bipolar depression, and for acute treatment of manic or mixed episodes associated with bipolar I disorder.

The FDA has approved the oral GABA_A receptor modulator zuranolone (Zurzuvae – Sage Therapeutics/Biogen) for treatment of postpartum depression (PPD). Zuranolone is the second drug to be approved for this indication; brexanolone (Zulresso), another GABA_A receptor modulator, was approved for IV treatment of PPD in 2019.

Esketamine (Spravato – Janssen), an intranasal N-methyl-D-aspartate (NMDA) receptor antagonist that was previously approved by the FDA for treatmentresistant depression,1 has now been approved for treatment of depressive symptoms in adults with major depressive disorder (MDD) and acute suicidal ideation or behavior. Esketamine is the S-enantiomer of the anesthetic ketamine (Ketalar, and generics). It is the first drug to be approved for this indication. Most clinical trials of antidepressants have excluded patients with acute suicidal ideation.

View Figure: Treatments for Irritable Bowel Syndrome (IBS) in Adults

View the Comparison Chart: Safety of Drugs for IBS in Pregnancy and Lactation

The FDA has approved lemborexant (Dayvigo – Eisai), an orexin receptor antagonist, for treatment of sleep-onset and/or sleep-maintenance insomnia in adults. It is the second orexin receptor antagonist to be approved for this indication; suvorexant (Belsomra) was the first.