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.

S-adenosyl-methionine (SAM; SAMe; ademetionine; adomet), an endogenous compound synthesized from methionine and adenosine-triphosphate (ATP), has been marketed in stores and on the internet as a dietary supplement to promote "emotional well being."

Bupropion (Wellbutrin - Burroughs Wellcome) was recently marketed in the USA for treatment of depression. First approved by the Food and Drug Administration in late 1985, the drug was withdrawn from the market in early 1986 because of a high incidence of seizures in one study.

Fluoxetine (Prozac - Dista), a phenylpropylamide, is the first serotonin-reuptake blocker introduced in the USA for treatment of . It is being promoted as causing fewer adverse effects than other antidepressants. Claims of greater safety and patient tolerability have often been made for new non-tricyclic antidepressants in recent years, but unpredicted adverse effects have emerged with widespread use, including priapism with trazodone (Desyrel - Medical Letter, 26:35, 1984) and fatal hemolytic anemia with nomifensine (Merital - Medical Letter, 27:73, 1985).

Citalopram hydrobromide (Celexa - Forest/Parke-Davis), a selective serotonin reuptake inhibitor (SSRI) available in Europe since 1989, has now been approved by the US Food and Drug Administration (FDA) for treatment of depression. It is being advertised as having a 'favorable side-effect profile.'

The FDA has approved the marketing of desvenlafaxine (Pristiq - Wyeth), the main active metabolite of venlafaxine (Effexor, and others - Wyeth), for treatment of major depressive disorder. Venlafaxine, a norepinephrine and serotonin reuptake inhibitor (SNRI), is available generically as an immediate-release tablet. Venlafaxine extended-release capsules (Effexor XR) are scheduled to go off-patent in 2010.

Nefazodone (Serzone - Bristol-Myers Squibb) was recently approved by the US Food and Drug Administration for treatment of depression. A phenylpiperazine, nefazodone is chemically related to trazodone (Desyrel, and others).

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.

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.

Escitalopram (Lexapro - Forest), the active S-enantiomer of racemic citalopram (Celexa - Forest), a selective serotonin reuptake inhibitor (SSRI), was recently approved by the FDA for treatment of depression. The manufacturer plans to stop promoting Celexa in favor of Lexapro; Celexa will continue to be available for patients already taking it.