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Antidepressant Medications: Drug Dosing and Interactions with ARVs

for Health Care Providers

Table 1. Antidepressant Medications: Drug Dosing and Interactions with ARVs

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Generic Drug NameUsual Starting Dosage/Dosage TitrationComments/Drug Interactions
SSRIs
  • Pros: Favored by some experts because of low potential for fatal overdose
  • Cons: Risk of discontinuation symptoms (see above) with certain agents if discontinued abruptly
  • Increased risk of suicidality among children and young adults with depression during first month of taking SSRIs
  • Most common side effects: sexual dysfunction, nausea, sweating, sleep disturbance
  • Contraindicated for use with monoamine oxidase inhibitors (MAOIs) or triptans because of risk of serotonin syndrome
  • Interactions with ARVs incompletely studied
CitalopramStart at 10-20 mg QD; may increase daily dosage after 7 days, if no adverse effects; maximum dosage: 60 mg QDMetabolized by CYP 3A4; however, no significant change in citalopram levels when coadministered with RTV, and no dosage adjustment required
EscitalopramStart at 5-10 mg QD; may increase daily dosage after 7 days, but no evidence of increased efficacy; maximum dosage: 20 mg QDMetabolized by mixture of enzymes, including CYP 3A4; however, no significant change in citalopram levels when coadministered with RTV, and no dosage adjustment required
FluoxetineStart at 10-20 mg QD; not to exceed 80 mg QD

Also available in weekly dose formulation: 90 mg once weekly
Metabolized by CYP 2D6; may increase RTV AUC by 20% but no adjustment required when coadministered with RTV
ParoxetineStart at 10-20 mg QD; may increase daily dosage by 10 mg every 7 days to maximum of 50 mg QD
  • DRV and FPV decrease paroxetine levels; titrate paroxetine to effect
  • Must be tapered slowly when discontinuing to avoid rebound depression symptoms and discontinuation symptoms
  • Slightly more sedating than other SSRIs
SertralineStart at 50 mg QD; may increase daily dosage by 25-50 mg every 7 days to maximum of 200 mg QDDRV decreases sertraline levels; titrate sertraline to effect
SNRIs
  • Increased presynaptic levels of serotonin and norepinephrine
  • Also approved for treatment of neuropathic pain and peripheral neuropathy
  • Most common side effects: GI events (nausea, diarrhea, constipation), dry mouth
  • Other side effects: somnolence, insomnia, dizziness, nervousness, headache; sexual dysfunction can occur
DuloxetineStart at 20 mg QD; may increase to BID, then to 60 mg QD or divided as 30 mg BID
  • Hepatically metabolized; not recommended for use in patients with hepatic impairment
  • To discontinue, taper gradually
Venlafaxine Formulations
Venlafaxine immediate releaseStart at daily dosage of 75 mg divided BID (ie, 37.5 mg BID) or TID (ie, 25 mg TID) with food; may increase total daily dosage by up to 25 mg per dose every 4 days; maximum daily dosage: 375 mg divided TID (ie, 125 mg TID)
  • Metabolized by CYP 2D6
  • When stopping venlafaxine, it is essential to taper slowly to avoid discontinuation symptoms
  • Postmarketing studies suggest that venlafaxine overdoses are more associated with fatal outcomes than are SSRI overdoses, but less than TCA overdoses; use lowest effective dosage of venlafaxine
Venlafaxine extended release (XR)Start at 75 mg venlafaxine XR QD with food; may increase daily dosage by up to 75 mg every 4 days; maximum daily dosage: 225 mg
Other
Bupropion Formulations
Bupropion
  • Inhibits CYP 2D6
  • EFV, KaletraLPV/-r, and TPV decrease bupropion levels; titrate bupropion to effect
  • Side effects: restlessness, agitation, insomnia
  • Bupropion increases seizure incidence (0.4% at 300 mg/day or higher); contraindicated in patients with elevated risk of seizures
  • Sexual dysfunction unlikely
Bupropion immediate releaseStart at 75-100 mg BID for 3 days, increase to 100 mg TID on day 4; maximum daily dosage: 450 mg divided TID
  • No single dose should exceed 150 mg, and doses should be taken at least 6 hours apart
  • Dosage escalation should be delayed for agitation, motor restlessness, or insomnia
Bupropion SRStart at 100-150 mg QAM; increase to usual dosage of 150 mg BID no earlier than day 4; maximum daily dosage: 400 mg divided BID (ie, 200 mg BID)
  • Doses of bupropion SR should be taken at least 8 hours apart
  • Dosage escalation should be delayed for agitation, motor restlessness, or insomnia
Bupropion XRStart at 150 mg QAM; increase to usual dose of 300 mg QAM no earlier than day 4; maximum dosage: 450 mg QD
  • Doses should be taken at least 24 hours apart
  • Dosage escalation should be delayed in the event of agitation, motor restlessness, or insomnia

From Depression
Primary Care of Veterans with HIV
Office of Clinical Public Health Programs
Veterans Health Administration, 2009