Paroxetine (Paxil) versus ...

Based on "Essential Psychopharmacology"
written by Stephen M. Stahl, MD, PhD

During taper and cessation of treatment paroxetine (Paxil) is associated with significantly more discontinuation symptoms than other SSRI antidepressants.

Paroxetine vs. Amitriptyline (Elavil)

Major depressive disorder
Amitriptyline and paroxetine appear to have similar antidepressive efficacy. However, in clinical study amitriptyline showed a greater degree of retardation reduction 12, 13, 14.

Amitriptyline is associated with a significantly higher incidence of anticholinergic effects, whereas nausea, agitation and insomnia occur more often with paroxetine 12, 13.

Paroxetine vs. Mirtazapine (Remeron)


Mirtazapine and paroxetine are equally effective for the treatment of depression after 6 weeks of therapy 1.

Mirtazapine has faster onset of overall therapeutic efficacy than paroxetine. In particular mirtazapine has an earlier onset of improvement of anxiety symptoms in depressed patients 3.

In comparative study of mirtazapine and paroxetine in elderly depressed patients the median time to response was 26 days for mirtazapine and 40 days for paroxetine. Patients treated with mirtazapine showed more reduction in Ham-D Factor I (Anxiety/Somatization) and Factor VI (Sleep Disturbance) scores 2.

Results of comparison of mirtazapine and paroxetine in major depression 1 Paroxetine Mirtazapine
Regimen 20-40 mg/day for 6 weeks 15-45 mg/day for 6 weeks
Mean HAM-D-17 total score at week 1
HAM-D-17 responders (> or = 50% decrease from baseline) at week 1
HAM-D-17 responders at week 4
Most common side effects Nausea, vomiting, tremor, and sweating weight increase and influenza-like symptoms
Conclusion: Mirtazapine and paroxetine were equally effective after 6 weeks of therapy


Paroxetine vs. Trazodone

Major depressive disorder

Trazodone and paroxetine show equal effectiveness at reducing symptoms of depression and promoting remission. Paroxetine has slightly faster onset of efficacy. Trazodone provides extra advantage in depressed patients with sleep difficulties 5.

Side effects: Adverse reactions with trazodone are mainly of the nervous system, and with paroxetine mainly gastrointestinal 5.

Paroxetine vs. Clonazepam (Klonopin)

Panic disorder

Clonazepam is a benzodiazepine with anxiolytic, anticonvulsant, muscle relaxant, and hypnotic properties.

Both clonazepam and paroxetine effectively reduce the number of panic attacks and severity of anxiety6, however clonazepam better reduces anxiety symptoms 7.

Clonazepam is superior to paroxetine with respect to the frequency and nature of side effects.

Results of randomized trial with clonazepam and paroxetine in panic disorder 7 Paroxetine Clonazepam
Weekly panic attacks at week 4
Clinical improvements at week 8 on Clinical global impression improvement scale
Anxiety severity significantly reduced with clonazepam versus paroxetine at weeks 1 and 2, with no difference in panic disorder severity
Adverse events rate
Most common side effects drowsiness/fatigue (81%), sexual dysfunction (70%), nausea/vomiting (61%) drowsiness/fatigue (57%), memory/concentration difficulties (24%), sexual dysfunction (11%)

Further reading


  • 1. Benkert O, Szegedi A, Kohnen R. Mirtazapine compared with paroxetine in major depression. J Clin Psychiatry. 2000 Sep;61(9):656-63. PubMed
  • 2. Schatzberg AF, Kremer C, Rodrigues HE, Murphy GM Jr. Double-blind, randomized comparison of mirtazapine vs. paroxetine in elderly depressed patients. Am J Geriatr Psychiatry. 2002 Sep-Oct;10(5):541-50. PubMed
  • 3. Kim JE, Yoon SJ, Kim J, Jung JY, Jeong HS, Cho HB, Shin E, Lyoo IK, Kim TS. Efficacy and tolerability of mirtazapine in treating major depressive disorder with anxiety symptoms: an 8-week open-label randomised paroxetine-controlled trial. Int J Clin Pract. 2011 Mar;65(3):323-9 PubMed
  • 4. Wade A, Crawford GM, Angus M, Wilson R, Hamilton L. A randomized, double-blind, 24-week study comparing the efficacy and tolerability of mirtazapine and paroxetine in depressed patients in primary care. Int Clin Psychopharmacol. 2003 May;18(3):133-41. PubMed
  • 5. Kasper S, Olivieri L, Di Loreto G, Dionisio P. A comparative, randomised, double-blind study of trazodone and paroxetine in the treatment of major depressive disorder. Curr Med Res Opin. 2005 Aug;21(8):1139-46. PubMed
  • 6. Nardi AE, Freire RC, Mochcovitch MD, et al. A randomized, naturalistic, parallel-group study for the long-term treatment of panic disorder with clonazepam or paroxetine. J Clin Psychopharmacol. 2012 Feb;32(1):120-6. PubMed
  • 7. Nardi AE, Valença AM, Freire RC, et al. Psychopharmacotherapy of panic disorder: 8-week randomized trial with clonazepam and paroxetine. Braz J Med Biol Res. 2011 Apr;44(4):366-73. PubMed
  • 12. Stuppaeck CH, Geretsegger C, Whitworth AB, Schubert H, Platz T, Ko"nig P, Hinterhuber H, Fleischhacker WW. Paroxetine versus amitriptyline in depressed inpatients. J Clin Psychopharmacol. 1994 Aug;14(4):241-6. PubMed
  • 13. Bignamini A, Rapisarda V. Paroxetine and amitriptyline in depressed outpatients. Int Clin Psychopharmacol. 1992 Jun;6 Suppl 4:37-41. PubMed
  • 14. Moller HJ, Berzewski H, Eckmann F, Gonzalves N, Kissling W, Knorr W, Ressler P, Rudolf GA, Steinmeyer EM, Magyar I, et al. Double-blind multicenter study of paroxetine and amitriptyline in depressed inpatients. Pharmacopsychiatry. 1993 May;26(3):75-8. PubMed

Published: March 31, 2008
Last reviewed: February 22, 2017


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