Drug Class/Generic Name (Proprietary Name)/Dosagesa		Side Effects/Comments
TRICYCLIC ANTIDEPRESSANTS (TCAs)		All TCAs can cause cardiac arrhythmias.
		EKG at baseline to evaluate for preexisting cardiac conduction abnormalities. Therapeutic drug concentration ranges in plasma have been identified for all agents, but dosage adjustments should be based on a patient's clinical response and not solely on plasma concentrations.b
		In responding patients, decrease daily dosages to the lowest effective amount needed to sustain a response.c TCAs can cause sexual dysfunction.
		Treatment may be associated with weight gain.d
amitriptyline (Elavil)		Marked sedation; dizziness; headache; weight gain; anticholinergic effects;e orthostatic blood pressure (BP) changes (postural hypotension); may produce sexual dysfunction. Therapeutic plasma concentrations (parent drug + active metabolite) = 110–250 ng/mL.
	initial: 10–25 mg as a single daily dose, preferably at bedtime
	maintenance: 150–300 mg/day
clomipramine (Anafranil)		Anticholinergic effects; dizziness; drowsiness; headache; weight gain; orthostatic hypotension.
	initial: 25 mg/day and gradually increase to 100 mg/day the first 2 weeks; may be given at bedtime
	maintenance: 100–250 mg/day maximum
desipramine (Norpramin)		Mild sedation; increased appetite; nausea; minimal anticholinergic effects;e orthostatic BP changes. Therapeutic plasma concentrations = 125–300 ng/mL.
	initial: 25–50 mg/day as a single daily dose, preferably at bedtime
	maintenance: 100–300 mg/day as a single daily dose; In elderly patients, daily doses >150 mg are not recommended
doxepin (Sinequan)		Moderately to very sedating; dizziness; headache; weight gain; moderate anticholinergic effects;e postural hypotension. Optimal antidepressant effect is characteristically delayed by 2–3 weeks; however, onset of antianxiety effect is comparatively rapid. Therapeutic plasma concentrations (parent drug + active metabolite) = 100–200 ng/mL.
	initial: 10–25 mg/day as a single daily dose, preferably at bedtime
	maintenance: 75–300 mg/day as a single daily dose, preferably at bedtime
imipramine (Tofranil)		Moderately to very sedating; dizziness; headache; weight gain; moderate anticholinergic effects;e moderate-marked orthostatic BP changes; may produce sexual dysfunction (both genders). Therapeutic plasma concentrations (parent drug + active metabolite) = 200–350 ng/mL.
	initial: 25–50 mg/day as a single daily dose, preferably at bedtime
	maintenance: 75–200 mg/day as a single daily dose, preferably at bedtime
nortriptyline (Pamelor, Aventyl)		Mild-moderate sedation; constipation; nausea; increased appetite; mild-moderate anticholinergic effects;e the TCA least likely to produce postural hypotension. Therapeutic plasma concentrations = 50–150 ng/mL.
	initial: 10–25 mg, 3–4 times daily
	maintenance: 30–50 mg, 3 times daily, daily doses >150 mg are not recommended
SELECTIVE SEROTONIN REUPTAKE INHIBITORS (SSRIs)		SSRIs have few anticholinergic and cardiovascular adverse effects. Life-threatening and fatal reactions have occurred in patients who receive SSRIs within 2 weeks of using monoamine oxidase inhibitor antidepressants. Sexual dysfunction has been reported to be associated with SSRI use. There is limited experience with long-term use.
citalopram (Celexa)		Ejaculation disorder; other sexual dysfunctions; insomnia; dry mouth; nausea; somnolence. In vitro studies indicated that CYP3A4 and CYP2C19 are the primary enzymes involved in the metabolism of citalopram. Citalopram is a relatively weak inhibitor of CYP2D6.
	initial: 10 mg/day
	maintenance: 10–40 mg/day
fluoxetine (Prozac)		Anxiety; nervousness; insomnia; anorexia; mild bradycardia; sinoatrial node slowing; weight loss; solar photosensitivity; hyponatremia; sexual dysfunction; may alter glycemic control in diabetic patients. Fluoxetine substantially inhibits CYP2D6 and may inhibit the clearance of other drugs metabolized by cytochrome P450 CYP2D6 isozymes.[15] Fluoxetine probably inhibits CYP2C9/10, moderately inhibits CYP2C19, and mildly inhibits CYP3A4;[15] fluoxetine metabolism is impaired in elderly patients.
	initial: 10–20 mg/day
	maintenance: 20–80 mg/day
escitalopram (Lexapro)		Nausea, vomiting, diarrhea, constipation, upset stomach, loss of appetite, dizziness, drowsiness, trouble sleeping, back pain, or dry mouth.
	initial: 10 mg/day
	maintenance: 10–20 mg/day
fluvoxamine (Luvox)		Nausea; sexual dysfunction; headache; nervousness; insomnia; drowsiness.
	initial: 50 mg at bedtime, adjust in 50 mg increments at 4- to 7-day intervals
	maintenance: 100–300 mg/day
paroxetine (Paxil)		Anxiety; nervousness; insomnia; mild weight loss; headache; solar photosensitivity; hyponatremia; sexual dysfunction. Paroxetine substantially inhibits and may interact with other drugs metabolized by cytochrome P450 CYP2D6 isozyme.[15] Paroxetine metabolism is impaired in elderly patients.
	initial: 10–20 mg/day
	maintenance: 20–50 mg/day
sertraline (Zoloft)		Anxiety; nervousness; insomnia; mild weight loss; headache; solar photosensitivity; hyponatremia; sexual dysfunction. Produces mild inhibition of and may interact with drugs metabolized by cytochrome P450 CYP2D6 isozymes with little, if any, effect on CYP1A2, CYP2C9/10, CYP2C19, or CYP3A3/4.[15]
	initial: 25–50 mg/day
	maintenance: 50–200 mg/day
MONOAMINE OXIDASE INHIBITORS (MAOIs)
tranylcypromine (Parnate)		Orthostatic hypotension; drowsiness; hyperexcitability; headache. Low-tyramine diet required.
	initial: 10 mg twice daily, increase by 10 mg increments at 1- to 3-week intervals
	maintenance: 10–40 mg/day
phenelzine (Nardil)		Orthostatic hypotension; drowsiness; hyperexcitability; headache. Low-tyramine diet required.
	initial: 15 mg 3 times a day
	maintenance: 15–90 mg/day
selegiline (EMSAM)		Application site reaction; orthostatic hypotension; diarrhea; headache; insomnia; dry mouth. Any dosages higher than 6 mg/24 h require low-tyramine diet.
	initial: 6-mg patch/24 h (20-mg patch topically every 24 h)
	maintenance: 6-mg patch/24 h (20-mg patch topically every 24 h). May increase at increments of 3 mg/24 h at 2-week intervals up to 12 mg/24 h.
ATYPICAL ANTIDEPRESSANTS		In general, serum drug concentrations do not correlate with antidepressant response.
bupropion (Wellbutrin, also approved for the treatment of smoking cessation as Zyban)		Initially activating dose-related seizure-inducing potential; contraindicated in patients with CNS involvement, with a history of seizure, in those with concomitant conditions predisposing to seizure, and in patients taking other drugs that lower seizure threshold. Mild-moderate sedation; mild-moderate anticholinergic effects;e mild orthostatic BP changes; agitation; insomnia; headache; confusion; dizziness; seizures; weight loss.
	initial: 75 mg/day
	maintenance: 200–450 mg/day not to exceed 150 mg/dose
trazodone (Desyrel)		Mild-moderate sedation; negligible anticholinergic effects; mild-moderate orthostatic BP changes, particularly in elderly patients; dizziness; headache; confusion; muscle tremors; may produce priapism; taking trazodone with food can decrease gastrointestinal upset. Therapeutic plasma concentrations = 800–1,600 ng/mL.
	initial: 50 mg/day
	maintenance: 150–600 mg/day
nefazodone (Serzone)		Postural hypotension (although <TCAs); less sexual dysfunction than is reported with SSRIs. Headache; drowsiness; insomnia; agitation; confusion; nausea; tremor. Potential interaction with drugs metabolized by cytochrome P450 isozymes, CYP2D6 and CYP3A4. Check liver function tests at baseline and periodically during therapy. May cause fatal hepatotoxicity.
	initial: 100 mg twice daily
	maintenance: 300–600 mg/day
mirtazapine (Remeron)		A tetracyclic antidepressant. Mirtazapine elimination is decreased in elderly persons. Somnolence; dizziness; increased appetite and weight gain; constipation; hypertension; edema; confusion; increased nonfasting triglycerides and cholesterol; significantly increased hepatic ALT; orthostatic hypotension. When used concomitantly with drugs that reduce the seizure threshold (e.g., phenothiazines), mirtazapine may increase the risk of seizure.
	initial: 7.5–15 mg/day
	maintenance: 15–45 mg/day
venlafaxine (Effexor)		Dose-related sustained hypertension. Headache; dizziness; insomnia; nausea; constipation; abnormal ejaculation. Life-threatening and fatal reactions have occurred in patients who received venlafaxine within 2 weeks of using monoamine oxidase antidepressants.
	initial: 75 mg/day
	maintenance: 150–375 mg/day
duloxetine (Cymbalta)		Nausea, dry mouth, constipation, decreased appetite, fatigue, sleepiness, and increased sweating; decreased sexual drive or ability; urinary hesitation.
	initial: 30 mg/day
	maintenance: 30–60 mg/day
Psychostimulants		Psychostimulants may cause restlessness, agitation, insomnia, nightmares, psychosis, anorexia; and may exacerbate preexisting cardiac disease. Psychostimulants should be administered early in a patient's daily waking cycle. Psychostimulants are sometimes used adjuvantly to antagonize opioid analgesics' sedative effects.
dextroamphetamine (Dexedrine)		Drug tolerance, abuse, and dependence liability. Arrhythmia; nervousness; restlessness; insomnia. Contraindicated in patients with advanced arteriosclerosis, symptomatic cardiovascular disease, moderate-severe hypertension, and glaucoma.
	initial: 2.5–5 mg/day
	maintenance: 10–30 mg/day
methylphenidate (Ritalin, Methylin)		Drug tolerance, abuse, and dependence liability. Hypertension; may decrease the convulsive threshold in patients with a history of seizure disorders. Tachycardia; nervousness; insomnia; anorexia; drowsiness; dizziness.
	initial: 2.5–10 mg/day
	maintenance: 20–60 mg/day
dexmethylphenidate (Focalin)		Dry mouth, tremor or muscle spasms, nervousness, trouble sleeping, headache, drowsiness, nausea, insomnia, increased sweating, dizziness, lightheadedness, changes in sexual function.
	initial: 10 mg/day
	maintenance: 10–20 mg/day

aConsult complete prescribing information for appropriate administration schedules.

bTCAs prolong cardiac conduction through His-Purkinje system similar to Type IA antiarrhythmic agents (e.g., quinidine). They are specifically contraindicated in patients with bundle-branch disease and second- or third-degree heart block. Their effects on conduction correlate with dosage and serum concentrations and for those agents with positive chronotropic and adrenergic-stimulating properties, TCAs can cause reentry arrhythmias. Persons at greatest risk are those with preexisting cardiac conduction defects and those who have taken an overdose.

cPlasma concentrations are most useful for guiding treatment in elderly patients who are (1) experiencing signs and symptoms of toxicity, (2) unresponsive to treatment, (3) suspected of being noncompliant with planned treatment, or (4) receiving other medications that may interact or otherwise alter antidepressant medication pharmacokinetics.

dTCAs and other antidepressants may cause sexual dysfunction characterized as decreased libido, penile erectile dysfunction, and decreased sensation during orgasm and ejaculation. Management consists of waiting for spontaneous resolution with continued therapy, decreasing the antidepressant dose, selecting an alternative antidepressant, or concomitant treatment with medications that treat the dysfunction (e.g., bethanechol for antidepressants with prominent anticholinergic effects).

eCommon antimuscarinic or anticholinergic effects include dry mouth, blurred vision, constipation, and urinary retention. Although patients may eventually develop tolerance to these effects with repeated medication use, symptoms may not completely resolve until the drug is discontinued.

References

15. Preskorn SH: Clinically relevant pharmacology of selective serotonin reuptake inhibitors. An overview with emphasis on pharmacokinetics and effects on oxidative drug metabolism. Clin Pharmacokinet 32 (Suppl 1): 1-21, 1997.  [PUBMED Abstract]