Harrison's Manual of Medicine
ANTIDEPRESSANTS
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.
| NAME | USUAL DAILY DOSE, mg | SIDE EFFECTS | COMMENTS |
|---|---|---|---|
| SSRIs | |||
Fluoxetine (Prozac) Sertraline (Zoloft) Paroxetine (Paxil) Fluvoxamine (Luvox) Citalopram (Celexa) Escitalopram (Lexapro) | 10–80 50–200 20–60 100–300 20–60 10–30 | Headache; nausea and other GI effects; jitteriness; insomnia; sexual dysfunction; can affect plasma levels of other medicines (except sertraline); akathisia rare | Once-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) | 150–300 50–200 150–300 150–300 150–300 150–300 25–150 | 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) | 75–375 | Nausea; dizziness; dry mouth; headaches; increased blood pressure; anxiety and insomnia | Bid-tid dosing (extended release available); lower potential for drug interactions than SSRIs; contraindicated with MAOIs |
| Desvenlafaxine (Pristiq) | 50–400 | Nausea, dizziness, insomnia | Primary metabolite of venlafaxine; no increased efficacy with higher dosing |
| Duloxetine (Cymbalta) | 40–60 | Nausea, dizziness, headache, insomnia, constipation | May have utility in treatment of neuropathic pain and stress incontinence |
| Mirtazapine (Remeron) | 15–45 | Somnolence, weight gain; neutropenia rare | Once-a-day dosing |
| Vilazodone (Viibryd) | 40 | Nausea, diarrhea, headache; dosage adjustment if given with CYP3A4 inhibitor/stimulator | Also 5-HT1a receptor partial agonist |
| Vortioxetine (Brintellix) | 5–20 | Nausea, diarrhea, sweating, headache; low incidence of sedation or weight gain | No specific p450 effects; 5-HT3a and 5-HT7 receptor antagonist, 5-HT1b partial agonist, and 5-HT1a agonist |
| Levomilnacipran (Fetzima) | 40–120 | Nausea, constipation, sweating; rare increase in blood pressure/pulse | Most noradrenergic of SNRIs |
| Mixed-action drugs | |||
| Bupropion (Wellbutrin) | 250–450 | Jitteriness; flushing; seizures in at-risk pts; anorexia; tachycardia; psychosis | Tid dosing, but sustained release also available; fewer sexual side effects than SSRIs or TCAs; may be useful for adult ADD |
| Trazodone (Desyrel) | 200–600 | Sedation; dry mouth; ventricular irritability; postural hypotension; priapism rare | Useful in low doses for sleep because of sedating effects with no anticholinergic side effects |
| Trazodone extended release (Oleptro) | 150–375 | Daytime somnolence, dizziness, nausea | |
| Amoxapine (Asendin) | 200–600 | Sexual dysfunction | Lethality in overdose; EPS possible |
| MAOIs | |||
Phenelzine (Nardil) Tranylcypromine (Parnate) | 45–90 20–50 | Insomnia; hypotension; edema; anorgasmia; weight gain; neuropathy; hypertensive crisis; toxic reactions with SSRIs; narcotics | May 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) | 6–12 | Local skin reaction hypertension | No dietary restrictions with 6-mg dose |
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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