What is the starting dosage and maximum dose of Pristiq (desvenlafaxine)?

Pristiq (Desvenlafaxine) Dosing Guidelines

The recommended starting dose for Pristiq (desvenlafaxine) is 50 mg once daily, which is both the starting and therapeutic dose, with a maximum recommended dose of 400 mg daily. 1

Starting Dosage

• 50 mg once daily is the standard starting dose
• Can be taken with or without food
• Should be taken at approximately the same time each day
• Tablets must be swallowed whole with fluid and not divided, crushed, chewed, or dissolved

Maximum Dosage

• 400 mg per day has been studied in clinical trials
• No additional benefit was demonstrated at doses greater than 50 mg per day
• Adverse reactions and discontinuations were more frequent at higher doses 1
• The 50 mg dose is considered both the starting and therapeutic dose for most patients

Special Dosing Considerations

Renal Impairment

• Moderate renal impairment (CrCl 30-50 mL/min): Maximum 50 mg per day
• Severe renal impairment (CrCl 15-29 mL/min): Maximum 25 mg every day or 50 mg every other day
• End-stage renal disease (CrCl <15 mL/min): Maximum 25 mg every day or 50 mg every other day
• Supplemental doses should not be given after dialysis 1

Hepatic Impairment

• Moderate to severe hepatic impairment (Child-Pugh score 7-15): 50 mg per day
• Dose escalation above 100 mg per day is not recommended in these patients 1

Discontinuation

• Gradually reduce the dosage rather than stopping abruptly
• The 25 mg per day dose is intended for gradual reduction when discontinuing treatment
• Abrupt discontinuation can lead to withdrawal symptoms including dizziness, nausea, headache, irritability, insomnia, diarrhea, anxiety, fatigue, and hyperhidrosis 1

Pharmacological Considerations

• Desvenlafaxine is a serotonin-norepinephrine reuptake inhibitor (SNRI)
• It is the active metabolite of venlafaxine
• Has linear pharmacokinetics, low protein binding, and a half-life of approximately 10 hours
• Primarily metabolized via glucuronidation, with minor metabolism through CYP3A4 2
• Lower potential for CYP2D6-mediated drug interactions compared to venlafaxine 3

Clinical Efficacy

• Response rates at 8 weeks for the 50 mg dose range from 51-63%
• Remission rates at 8 weeks for the 50 mg dose range from 31-45% 3
• These rates are comparable to those seen with venlafaxine (58% response and 45% remission)

Common Side Effects

• Most common: nausea, insomnia, somnolence, and dizziness
• Less common but more serious: hypertension, QTc interval prolongation, elevated lipids, and elevated liver enzymes 2

Important Considerations

• When switching from other antidepressants to desvenlafaxine, tapering of the initial antidepressant may be necessary to minimize discontinuation symptoms 1
• Allow at least 14 days after discontinuing an MAOI before starting desvenlafaxine
• Allow at least 7 days after stopping desvenlafaxine before starting an MAOI 1

Pristiq offers the advantage of once-daily dosing at effective doses with minimal drug-drug interactions due to its limited CYP450 metabolism, making it potentially beneficial for patients on multiple medications.