Table.

Clinical Considerations for Individual Drugs Used in the Treatment of Depression and Generalized Anxiety Disorder in Adults²⁸

Drug	Class	Notes
Citalopram (Celexa)	SSRI	Potential benefits •May have particular benefits for those who are excessively activated by other SSRIs
		Considerations •May start 20 mg daily and increase to 40 mg if needed •Doses beyond 40 mg have been associated with QTc prolongation (consider risk factors); lower dosing recommended for those over 60 years of age •Has unique mild antihistamine properties that may contribute to sedation and fatigue in some; consider taking at night if patient experiences daytime sedation
Escitalopram (Lexapro)	SSRI	Potential benefits •Known as S-citalopram, may have faster onset and better efficacy with reduced side effects compared with R,S-citalopram (citalopram) •For those who will use an antidepressant during pregnancy, a large study32 determined that escitalopram had the lowest proportion of elevated adjusted odds ratios (none) for associations between maternal antidepressant use and birth defects; consider benefits and risks and individualize decisions33 using shared decision-making5 •FDA-approved for the treatment of GAD
		Consideration •May start 10 mg daily and increase to 20 mg as needed
Fluoxetine (Prozac, Prozac weekly)	SSRI	Potential benefits: •May be more activating, increasing energy for some; consider administration early in the day •May have particular benefits for those with hypersomnia, fatigue, low energy •Possible weight loss •Has a longer half-life, which has various clinical implications, including being less likely to be associated with discontinuation effects24
		Consideration •May start 20 mg daily and increase after a few weeks by 20 mg increments as needed; typical maximum is 80 mg
Paroxetine (Paxil, Paxil CR)	SSRI	Potential benefits •Also has indication for vasomotor symptoms of menopause •Mild anticholinergic actions may offer potential advantages for those with insomnia or anxiety •FDA-approved for the treatment of GAD
		Considerations •May start 20 mg daily (25 mg CR) and increase by 10-mg increments (12.5-mg increments for CR) as needed; typical maximum is 50 mg (62.5 mg CR) •Mild anticholinergic actions can cause constipation, dry mouth, sedation •Weight gain is not unusual, occurring in a significant minority •Withdrawal effects can be more common or severe than with some SSRIs; if discontinuing, gradually taper over many months; consultation with a mental health expert may be helpful for taper •The American College of Obstetricians and Gynecologists recommended avoiding use in pregnant women and women planning pregnancy when possible33
Sertraline (Zoloft)	SSRI	Potential benefits •May have particular benefits for those with hypersomnia, fatigue, low energy, increased appetite •May be activating, increasing energy for some; consider administration early in the day
		Considerations: •May start 50 mg daily and increase by 25- to 50-mg increments as needed; typical maximum is 200 mg •May have more adverse GI effects (such as diarrhea) than other SSRIs; may not be optimal for those with irritable bowel syndrome
Venlafaxine (Effexor, Effexor XR)	SNRI	Potential benefits •May have particular benefits for those who do not respond or remit on treatment with SSRIs •Lower dose may be more serotonergic for some, with more dual serotonin and norepinephrine effects at higher doses (consider titrating dose before concluding lack of response) •FDA-approved for the treatment of GAD
		Considerations •May start 37.5 mg (extended-release) daily and increase by 75-mg increments as needed up to 225 mg •Withdrawal effects can be more common or severe than with some other antidepressants; if discontinuing, taper the dose over many months to prevent withdrawal symptoms; consultation with a mental health expert may also be helpful when considering strategies for taper •May increase BP, so may not be optimal for those who have hypertension or cardiac disease •There are some concerns with use during pregnancy; a large study32 determined that venlafaxine had meaningfully elevated associations with many specific birth defects (consider benefits and risks and individualize decisions33)
Desvenlafaxine (Pristiq)	SNRI	Potential benefits •Primary metabolite of venlafaxine in an extended-release formulation with once daily dosing and similar efficacy •Less impact on BP is expected
		Consideration •May start 50 mg daily; increase to 100 mg if needed
Duloxetine (Cymbalta)	SNRI	Potential benefits •Well-documented efficacy for the painful physical symptoms of depression •May offer particular benefits for those with neuropathic pain in diabetes, chronic musculoskeletal pain, or fibromyalgia •FDA-approved for the treatment of GAD
		Considerations •May start 30–40 mg daily and increase to 60 mg as needed; typical maximum is 120 mg (studies have not demonstrated increased efficacy at doses beyond 60 mg per day) •May increase BP or urinary retention
Bupropion (Wellbutrin, Wellbutrin SR, Wellbutrin XL)	NDRI	Potential benefits • May have particular benefits for those o who have a partial or suboptimal response to SSRI therapy despite appropriate trial o with unacceptable and persistent sexual dysfunction o with emotional flattening, cognitive slowing, or apathy o seeking additional support for smoking cessation •May be cautiously added as an adjunct to SSRIs to treat partial responders or mitigate SSRI-induced sexual dysfunction •Possible weight loss •May be more activating, increasing energy for some; consider administration early in the day
		Considerations •May start 150 mg (extended-release) daily and increase to 300 mg as needed; typical maximum is 450 mg •May increase BP •May not be optimal for those with comorbid anxiety or insomnia •Seizure risk increased for those with predisposing factors •Avoid for those with bulimia and anorexia, either currently or in the past
Mirtazapine (Remeron)	Serotonin norepinephrine receptor antagonist	Potential benefits •Multifunctional drug with 5 principal mechanisms of action13; affects serotonin, norepinephrine, alpha 2, and histamine receptors •May have particular benefits for those with insomnia, agitation, decreased appetite, persistent GI effects, or sexual dysfunction
		Considerations •May start 15 mg daily and increase by 15-mg increments as needed; typical maximum is 45 mg •Sedation is common and may be pronounced •May cause significant weight gain, which may be desirable for some patients such as older adults with weight loss and/or difficulty with sleep
Vortioxetine (Trintellix)	Multimodal antidepressant	Potential benefits: •May have particular benefits for those who do not respond to other antidepressants with other mechanisms of action •Demonstrated beneficial cognitive effects, such as processing speed, executive and cognitive control24 •May have less sexual dysfunction
		Considerations •May start 10 mg daily and increase to 20 mg as needed •May cause adverse GI effects (such as nausea and constipation, which may be marked) •No generic option currently
Vilazodone (Viibryd)	Multimodal antidepressant; serotonin partial agonist reuptake inhibitor (SPARI)	Potential benefits •May have particular benefits for those with comorbid depression and anxiety •May have less sexual dysfunction
		Considerations •May start 10 mg daily and increase to 20 mg if needed; typical maximum is 40 mg •Must be taken with food to ensure adequate absorption24 •Titrate as directed to avoid adverse GI effects24
Trazodone	Serotonin receptor antagonist and reuptake inhibitor	Considerations •May start 150 mg daily in divided doses for depression; increase in 50-mg increments as needed; typical daily outpatient maximum is 400 mg •Expected to be less efficacious for depression and less tolerable at doses required for depression •Sedation is common, even at lower doses, and can be pronounced; often not tolerated as a monotherapy for moderate to severe depression but may be a helpful for insomnia (a common but off-label use)
Buspirone (Buspar)	Non-benzodiazepine anxiolytic	Considerations •May start 7.5–15 mg twice daily and increase in 5-mg increments as needed; typical daily maximum is 60 mg, divided in 2 or 3 times daily dosing •Not controlled •Not expected to cause sexual dysfunction or weight gain •Sedation is not unusual, occurring in a significant minority •FDA approved for the treatment of GAD
Hydroxyzine (Atarax, Vistaril)	First-generation antihistamine	Considerations: •May take 50–100 mg every 4–6 hours up to 4 times daily, or less frequently on an as-needed basis •Quick onset (15–20 minutes) •May be used for short-term symptoms of anxiety or during transition to a maintenance therapy, then discontinued or used as needed •Sedation is common and can be pronounced, but is usually transient as tolerance develops

BP = blood pressure; GI = gastrointestinal; FDA = US Food and Drug Administration; SNRI = serotonin norepinephrine reuptake inhibitors; SSRI = selective serotonin reuptake inhibitor.