Since the introduction of fluoxetine (Prozac - Medical Letter, 30:45, 1988), bupropion (Wellbutrin - Medical Letter, 31:97, 1989), sertraline (Zoloft - Medical Letter, 34:47, 1992) and paroxetine (Paxil - this issue), the choice of an antidepressant has become more difficult. Should these widely prescribed new drugs replace tricyclic antidepressants such as amitriptyline (Elavil, and others), imipramine (Tofranil, and others), or nortriptyline (Aventyl, and others) for treatment of most patients with depression?

Mirtazapine (mir taz a peen; Remeron - Organon) has been approved by the US Food and Drug Administration for treatment of depression. A tetracyclic piperazinoazepine, it is an analog of mianserin, an antidepressant available in Europe, but is structurally unrelated to antidepressants previously available in the USA.

Venlafaxine hydrochloride (Effexor - Wyeth-Ayerst) was recently approved by the US Food and Drug Administration for treatment of depression. An aminomethyl-benzyl- cyclohexanol, it is chemically related to bupropion (Wellbutrin).

Vilazodone (Viibryd – Forest), a selective serotonin reuptake inhibitor (SSRI) and partial 5-HT_1A receptor agonist, has been approved by the FDA for treatment of depression. It has been claimed to have no sexual side effects and not to cause weight gain.

The 1990 labeling for Norpramin, the Merrell Dow brand of the tricyclic antidepressant desipramine, reports the occurrence of sudden death in an eight-year-old child treated with the drug. Desipramine is also available as Pertofrane (Rorer) and generically.

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.

Sertraline (Zoloft - Roerig), a serotonin reuptake inhibitor, was recently approved for marketing by the US Food and Drug Administration for treatment of depression. Another serotonin reuptake inhibitor, fluoxetine (Prozac), is prescribed more frequently in the USA than any other antidepressant (Medical Letter, 32:83, 1990).

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.

The FDA has approved vortioxetine (vor" tye ox' e teen; Trintellix – Takeda/Lundbeck), a new serotonergic drug, for treatment of major depressive disorder. Like vilazodone (Viibryd), another serotonergic antidepressant, it has been claimed to have a low incidence of sexual side effects and no significant effect on weight.

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.