Useful to group according to known actions on CNS monoaminergic systems (Table 200-1). The selective serotonin reuptake inhibitors (SSRIs) have predominant effects on serotonergic neurotransmission, also reflected in side-effect profile. The TCAs, or tricyclic ADs, affect noradrenergic and, to a lesser extent, serotonergic neurotransmission but also have anticholinergic and antihistaminic effects. Venlafaxine, desvenlafaxine, duloxetine, mirtazapine, vilazodone, vortioxetine, and levomilnacipran have mixed noradrenergic and serotonergic effects. Bupropion is a novel AD that enhances noradrenergic function. Trazodone and amoxapine have mixed effects on serotonin receptors and on other neurotransmitter systems. The monoamine oxidase inhibitors (MAOIs) inhibit monoamine oxidase, the primary enzyme responsible for the degradation of monoamines in the synaptic cleft.

TABLE 200-1: Antidepressants

 Fluoxetine (Prozac)

 Sertraline (Zoloft)

 Paroxetine (Paxil)

 Fluvoxamine (Luvox)

 Citalopram (Celexa)

 Escitalopram (Lexapro)







Headache; nausea and other GI effects; jitteriness; insomnia; sexual dysfunction; can affect plasma levels of other medicines (except sertraline); akathisia rareOnce-daily dosing, usually in the morning; fluoxetine has very long half-life; must not be combined with MAOIs
TCAs and tetracyclics

 Amitriptyline (Elavil)

 Nortriptyline (Pamelor)

 Imipramine (Tofranil)

 Desipramine (Norpramin)

 Doxepin (Sinequan)

 Clomipramine (Anafranil)

 Maprotiline (Ludiomil)








Anticholinergic (dry mouth, tachycardia, constipation, urinary retention, blurred vision); sweating; tremor; postural hypotension; cardiac conduction delay; sedation; weight gain

Once-daily dosing, usually qhs; blood levels of most TCAs available; can be lethal in overdose (lethal dose = 2 g); nortriptyline best tolerated, especially by elderly

FDA approved for OCD

Mixed norepinephrine/serotonin reuptake inhibitors (SNRI) and receptor blockers
 Venlafaxine (Effexor)75–375Nausea; dizziness; dry mouth; headaches; increased blood pressure; anxiety and insomniaBid-tid dosing (extended release available); lower potential for drug interactions than SSRIs; contraindicated with MAOIs
 Desvenlafaxine (Pristiq)50–400Nausea, dizziness, insomniaPrimary metabolite of venlafaxine; no increased efficacy with higher dosing
 Duloxetine (Cymbalta)40–60Nausea, dizziness, headache, insomnia, constipationMay have utility in treatment of neuropathic pain and stress incontinence
 Mirtazapine (Remeron)15–45Somnolence, weight gain; neutropenia rareOnce-a-day dosing
 Vilazodone (Viibryd)40Nausea, diarrhea, headache; dosage adjustment if given with CYP3A4 inhibitor/stimulatorAlso 5-HT1a receptor partial agonist
 Vortioxetine (Brintellix)5–20Nausea, diarrhea, sweating, headache; low incidence of sedation or weight gainNo specific p450 effects; 5-HT3a and 5-HT7 receptor antagonist, 5-HT1b partial agonist, and 5-HT1a agonist
 Levomilnacipran (Fetzima)40–120Nausea, constipation, sweating; rare increase in blood pressure/pulseMost noradrenergic of SNRIs
Mixed-action drugs
 Bupropion (Wellbutrin)250–450Jitteriness; flushing; seizures in at-risk pts; anorexia; tachycardia; psychosisTid dosing, but sustained release also available; fewer sexual side effects than SSRIs or TCAs; may be useful for adult ADD
 Trazodone (Desyrel)200–600Sedation; dry mouth; ventricular irritability; postural hypotension; priapism rareUseful in low doses for sleep because of sedating effects with no anticholinergic side effects
 Trazodone extended release (Oleptro)150–375Daytime somnolence, dizziness, nausea 
 Amoxapine (Asendin)200–600Sexual dysfunctionLethality in overdose; EPS possible

 Phenelzine (Nardil)

 Tranylcypromine (Parnate)



Insomnia; hypotension; edema; anorgasmia; weight gain; neuropathy; hypertensive crisis; toxic reactions with SSRIs; narcoticsMay be more effective in pts with atypical features or treatment-refractory depression
 Isocarboxazid (Marplan)20–60 Less weight gain and hypotension than phenelzine
 Transdermal selegiline (Emsam)6–12Local skin reaction hypertensionNo dietary restrictions with 6-mg dose
Abbreviations: ADD, attention deficit disorder; EPS, extrapyramidal symptoms; FDA, U.S. Food and Drug Administration; GI, gastrointestinal; MAOIs, monoamine oxidase inhibitors; OCD, obsessive-compulsive disorder; SSRIs, selective serotonin reuptake inhibitors; TCAs, tricyclic antidepressants.

ADs are effective against major depression, particularly when neurovegetative symptoms and signs are present. Despite the widespread use of SSRIs, there is no convincing evidence that they are more efficacious than TCAs, although their safety profile in overdose is more favorable than that of the TCAs. ADs are also useful in treatment of panic disorder, posttraumatic stress disorder, chronic pain syndromes, and generalized anxiety disorder. The TCA clomipramine and the SSRIs successfully treat obsessive-compulsive disorder.

All ADs require at least 2 weeks at a therapeutic dose before clinical improvement is observed. All ADs also have the potential to trigger a manic episode or rapid cycling when given to a pt with bipolar disorder. The MAOIs must not be prescribed concurrently with other ADs or with narcotics, as potentially fatal reactions may occur. “Withdrawal syndromes” usually consisting of malaise can occur when ADs are stopped abruptly.

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