Pristiq (Desvenlafaxine) Dosing
The recommended dose of Pristiq is 50 mg once daily, which serves as both the starting dose and the therapeutic dose, with no additional benefit demonstrated at higher doses. 1
Standard Dosing Regimen
- Take 50 mg once daily with or without food at approximately the same time each day 1
- Swallow tablets whole—do not divide, crush, chew, or dissolve 1
- The 50 mg dose is both the initial and therapeutic dose; no titration is required 1
- While doses of 50-400 mg/day have been studied and shown effective, no additional therapeutic benefit occurs above 50 mg/day, and adverse reactions plus discontinuations increase significantly at higher doses 1, 2, 3
Dose Adjustments for Special Populations
Renal Impairment
- Moderate renal impairment (CrCl 30-50 mL/min): Maximum 50 mg daily 1
- Severe renal impairment (CrCl 15-29 mL/min) or end-stage renal disease (CrCl <15 mL/min): Maximum 25 mg daily OR 50 mg every other day 1
- Do not give supplemental doses after dialysis 1
Hepatic Impairment
- Moderate to severe hepatic impairment (Child-Pugh score 7-15): 50 mg daily 1
- Do not escalate dose above 100 mg/day in hepatic impairment 1
Treatment Duration and Monitoring
- Continue treatment for 4-9 months after satisfactory response in first-episode major depressive disorder 4, 5
- For patients with 2 or more depressive episodes, consider years to lifelong therapy 4, 5
- Assess patient status within 1-2 weeks of initiation for therapeutic response, adverse effects, and emergence of suicidal thoughts or behaviors 4, 5
- Monitor closely during the first 1-2 months when suicide risk is highest 4, 5
- Modify treatment if inadequate response after 6-8 weeks 4, 5
Discontinuation Protocol
- Gradually reduce the dose rather than stopping abruptly to minimize discontinuation symptoms 1
- The 25 mg daily dose is intended specifically for gradual dose reduction when discontinuing 1
- Discontinuation symptoms have been reported and should be anticipated 1
MAOI Interactions and Timing
- Allow at least 14 days between stopping an MAOI and starting desvenlafaxine 1
- Allow at least 7 days after stopping desvenlafaxine before starting an MAOI 1
- Do not start desvenlafaxine in patients receiving linezolid or IV methylene blue due to serotonin syndrome risk 1
- If urgent treatment with linezolid or IV methylene blue is required in a patient on desvenlafaxine, stop desvenlafaxine promptly and monitor for serotonin syndrome for 7 days or until 24 hours after the last dose of linezolid/methylene blue 1
Key Clinical Pearls
- The 50 mg dose achieves response rates of 51-63% and remission rates of 31-45% at 8 weeks, comparable to venlafaxine 6
- Most common adverse event is transient, mild-to-moderate nausea 7
- Discontinuation due to adverse events at the 50 mg dose is similar to placebo (4%), but increases substantially at higher doses (18% at 400 mg) 7
- Desvenlafaxine has lower risk of drug-drug interactions compared to venlafaxine due to minimal CYP2D6 involvement 6, 3