A device that stimulates the vagus nerve was approved by the FDA in July 1997 for treatment of refractory epilepsy and is now considered "approvable" for treatment-resistant depression.

The FDA has approved the oral, once-daily, second-generation antipsychotic brexpiprazole (Rexulti – Otsuka/Lundbeck) for treatment of schizophrenia and as an adjunct to antidepressants for treatment of major depressive disorder (MDD). Aripiprazole (Abilify), a structurally similar second-generation antipsychotic also comarketed by Otsuka (with BMS), recently became available generically.

L-methylfolate (Deplin — Pamlab) is a “medical food” marketed for adjunctive use in depression or schizophrenia in patients with suboptimal folate levels. It is available only by prescription.

Duloxetine hydrochloride (Cymbalta - Lilly), a selective serotonin and norepinephrine reuptake inhibitor (SNRI), has been approved by the FDA for treatment of major depressive disorder in adults, and more recently for diabetic peripheral neuropathy as well. The Medical Letter will review its role in diabetic neuropathy in a future issue.

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 levomilnacipran (lee" voe mil na' si pran; Fetzima – Forest), a serotonin and norepinephrine reuptake inhibitor (SNRI), for treatment of major depressive disorder. Levomilnacipran is the more active enantiomer of milnacipran (Savella), which was approved in 2009 for management of fibromyalgia. Fetzima has not been studied in fibromyalgia.

The FDA has approved the marketing of an extended-release formulation of trazodone (Oleptro – Angelini Labopharm) for treatment of major depressive disorder in adults. Immediate-release trazodone has been available for treatment of depression for many years, but is used mostly in low doses for its sedating effects.

The fixed-dose combination of olanzapine and fluoxetine (Symbyax - Lilly) has been approved by the FDA for treatment of depressive episodes associated with bipolar disorder. Olanzapine alone (Zyprexa), which is mainly used as an antipsychotic (Medical Letter 2003; 45:102), is FDA-approved for treatment of acute manic episodes and for maintenance treatment of bipolar disorder. Fluoxetine alone (Prozac, and others), which is mainly used as an antidepressant (Medical Letter 2003; 45:93), has no specific approval for use in bipolar...

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.

The FDA has approved esketamine (Spravato – Janssen), an N-methyl-D-aspartate (NMDA) receptor antagonist, for intranasal treatment (in conjunction with an oral antidepressant) of adults with treatment-resistant depression (TRD). This is the first FDA approval for esketamine, which is the S-enantiomer of the intravenous anesthetic ketamine (Ketalar, and generics). In recent years, IV ketamine has been increasingly used (off-label) for treatment of TRD.