Does paroxetine (Paxil) or amitriptyline (Elavil) cause more somnolence?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: April 19, 2025View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

From the Guidelines

Amitriptyline typically causes more lethargy than paroxetine. Amitriptyline is a tricyclic antidepressant with strong antihistamine and anticholinergic properties, which contribute significantly to its sedating effects 1. Many patients experience drowsiness, fatigue, and lethargy, especially during the initial weeks of treatment. In contrast, paroxetine, a selective serotonin reuptake inhibitor (SSRI), can also cause lethargy but generally to a lesser degree. Some key points to consider when comparing these two medications include:

  • The sedating effects of amitriptyline are so pronounced that it's often prescribed at lower doses (10-25mg) at bedtime for conditions like insomnia or chronic pain 1.
  • Paroxetine, on the other hand, is less likely to cause somnolence compared to other antidepressants like trazodone 1.
  • Individual responses vary considerably, and some patients may experience significant fatigue with either medication.
  • Starting with lower doses and gradually increasing can help minimize lethargy with both medications.
  • If lethargy becomes problematic, discussing dosage adjustments or alternative medications with your healthcare provider is recommended.

From the Research

Comparison of Lethargy Caused by Paroxetine and Amitriptyline

  • The studies provided do not directly compare the lethargy caused by paroxetine and amitriptyline, but they do report on the adverse event profiles of both drugs 2, 3, 4, 5.
  • Paroxetine is reported to cause somnolence, a symptom related to lethargy, in 18-25% of patients in short-term clinical trials 2.
  • Amitriptyline, on the other hand, is known to cause sedation and lethargy due to its anticholinergic and antihistaminic properties 6.
  • A study comparing paroxetine and amitriptyline in the treatment of depression in general practice found that paroxetine was better tolerated than amitriptyline, with fewer adverse events reported 4.
  • Another study comparing the two drugs in the treatment of depression associated with rheumatoid arthritis found that paroxetine was better tolerated than amitriptyline, with fewer anticholinergic adverse events reported 5.

Adverse Event Profiles

  • The adverse event profiles of paroxetine and amitriptyline are reported in several studies 2, 3, 4, 5.
  • Paroxetine is reported to cause nausea, headache, somnolence, dry mouth, and insomnia, among other adverse events 2.
  • Amitriptyline is reported to cause anticholinergic adverse events, such as dry mouth and constipation, as well as sedation and lethargy 6.
  • The studies suggest that paroxetine may be better tolerated than amitriptyline, with fewer adverse events reported 4, 5.

Mechanism of Action

  • The mechanism of action of paroxetine and amitriptyline may contribute to their adverse event profiles 2, 6.
  • Paroxetine is a selective serotonin reuptake inhibitor (SSRI), which may contribute to its relatively favorable adverse event profile 2.
  • Amitriptyline is a tricyclic antidepressant (TCA), which may contribute to its anticholinergic and sedative adverse events 6.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.