The SNRI duloxetine (Cymbalta) is reasonable first-line choice for depressed patients with comorbid pain syndromes. Among antidepressants, it stands out as being particularly effective for generalized anxiety disorder (GAD).
Side effects may include nausea (22%), dry mouth (16%), fatigue (11%), dizziness (11%), somnolence, constipation, diarrhea, insomnia, agitation, sweating, headaches, and sexual dysfunction. Duloxetine is not expected to cause appreciable weight gain. Hypertension (1%) due to duloxetine does not appear to be dose dependent. The discontinuation rate of duloxetine due to side effects was 15% (versus 5% for placebo).
Compared to the SNRI venlafaxine (Effexor), duloxetine is more likely to cause nausea but less likely to elevate blood pressure. Duloxetine is less likely than venlafaxine to cause serotonin withdrawal symptoms upon discontinuation.
Duloxetine is more likely to be involved in clinically significant CYP interactions than venlafaxine.
Serious liver damage is possible with duloxetine, although rare. It is not considered necessary to closely monitor liver enzymes (beyond routine screening labs for all patients).
Avoid prescribing duloxetine to alcoholics or those with known liver problems.
Risk of death from a single-drug overdose with duloxetine is about 1 in 3,500, making it safer than venlafaxine (1 in 800).
Peak plasma levels are achieved at 3 hours. Half-life is 12 hours, so steady-state concentrations are achieved within 3 days of oral dosing (5 x 12 hours). Upon discontinuation, duloxetine is cleared from the body within 3 days (also 5 x 12 hours) and there are no active metabolites.
For depression, the FDA maximum of 120 mg was found no more effective than 60 mg. For pain, the 120 mg dose (divided 60 mg BID) can be more effective.
Dosing: Duloxetine can be dosed BID or QD, either AM or HS. Consider starting 30 mg QD x 1 wk, then increase to target dose of 60 mg QD or 30 mg BID. For depression, the FDA maximum of 120 mg is rarely more effective than 60 mg. Doses over 60 mg may be more effective for pain. 120 mg dose is usually divided to 60 mg BID. Taper gradually to discontinue to avoid serotonin withdrawal symptoms.
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