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

• Efficacy:
  Panic disorder: Paroxetine and citalopram have similar anti-panic properties and a good tolerability profile 16.

• Efficacy:
• Major depressive disorder: Escitalopram is significantly more effective than paroxetine in the long-term treatment of severely depressed patients 19, 20.
• Generalized anxiety disorder: The results of the study have shown that escitalopram 10 mg is more efficacious than paroxetine 20 mg for reducing symptoms in people with generalised anxiety disorder 18.
• Side effects: The results of the clinical study have shown that the frequency of adverse events are higher with paroxetine vs. escitalopram: overall (88.7% vs. 77.0%), insomnia (25.8% vs. 14.8%), constipation (14.5% vs. 1.6%), ejaculation disorder (30.0% vs. 14.8%), anorgasmia (26.2% vs. 5.9%), and decreased libido (22.6% vs. 4.9%). Conversely, diarrhea and upper respiratory tract infection are higher with escitalopram than paroxetine (21.3% vs. 8.1%, and 14.8% vs. 4.8%, respectively) 17.
• Withdrawal symptoms: Paroxetine treatment is associated with significantly more discontinuation symptoms than escitalopram 19.

• Efficacy:
  Major depressive disorder: Paroxetine has comparable efficacy to fluoxetine in the treatment of depression in elderly. However, as indicated results of the clinical study, paroxetine has a significantly higher response rate than fluoxetine. Paroxetine appears to produce earlier antidepressant effect 22, 23.
• Side effects: Constipation, dyspepsia, tremor, sweating and abnormal ejaculation are more common with paroxetine, whereas nausea and nervousness are more frequent with fluoxetine. Weight loss is more common with fluoxetine 23.
• Withdrawal symptoms: Discontinuation of paroxetine is more often associated with somatic and psychological symptoms than discontinuation of fluoxetine. Patients treated with fluoxetine appear to be protected by its longer half-life 21.

• Efficacy:
• Panic disorder. Both sertraline and paroxetine are equally effective in panic disorder. However, sertraline is associated with significantly less clinical worsening during taper period than paroxetine 4.
• Generalized anxiety disorder: Both paroxetine and sertraline appear similarly effective for the treatment of generalized anxiety disorder 14.
• Tolerability: Sertraline is significantly better tolerated. Paroxetine has a higher rate of treatment discontinuation due to adverse events 4.
• Side effects: Paroxetine has a significantly higher rate of weight gain 4. Also, paroxetine is associated with higher incidence of sexual side-effects like delay of orgasm or ejaculation and impotence 19.
• Discontinuation syndrome: Paroxetine discontinuation is accosiated with the higher degree of emergence of new somatic and psychological symptoms in patients than sertraline 15.
• Drug interactions: Sertraline may have advantages paroxetine in elderly patients because of the comparatively low potential for drug interactions.

• Efficacy:
• Major depressive disorder: In clinical study venlafaxine showed some evidence of superiority to paroxetine in the treatment-resistant depression. In patients with non-chronic treatment-resistant depression the response rate was 51.9% for venlafaxine and 32.7% for paroxetine, and a remission was achieved in 42.3% of venlafaxine-treated and 20.0% of paroxetine-treated patients 10.
  Venlafaxine appears to have a higher rate of response and remission in patients with depressive disorder or dysthymia. In clinical study a response was achieved in 55% of patients on venlafaxine and 29% on paroxetine after 6 weeks of treatment. After 12 weeks, significantly more patients in the venlafaxine group had a HAM-D remission score of 8 or less (59% versus 31%) 11.
• Obsessive-compulsive disorder: Paroxetine is more efficacious than venlafaxine in the treatment of nonresponders to a previous SSRI trial 8.
• Panic disorder: In randomized controlled trial patients treated with venlafaxine ER had significantly greater mean Panic Disorder Severity Scale score improvement than patients treated with the paroxetine and a significantly higher proportion of patients free of full symptom panic attacks (70.0 vs 58.3%) 7.
• Social anxiety disorder: Venlafaxine ER appears to be effective treatment for SAD, with efficacy and tolerability comparable to paroxetine. In clinical study after 12 week of the treatment response rates were 58.6% for the venlafaxine ER and 62.5% for paroxetine 9.
• Bipolar depression: Paroxetine and venlafaxine are both effective and safe in the treatment of depressive breakthrough episodes in bipolar disorder. There is a slightly higher risk for switch to mania or hypomania with venlafaxine 4.

• Efficacy:
  Major depressive disorder: In clinical study duloxetine treated patients (80 and 120 mg/day) showed significantly greater improvement in the HAMD(17) total score at week 8 compared with placebo. Paroxetine was not significantly different from placebo on mean change on the HAMD(17). Duloxetine 120 mg/day also showed significant improvement on most secondary efficacy measures (six of nine) compared with placebo while duloxetine 80 mg/day (three of nine) and paroxetine (three of nine) were significantly superior to placebo on fewer secondary measures. Both duloxetine doses met statistical criteria for non-inferiority to paroxetine 6.
• Side effects: Nausea occurs more frequently with duloxetine. The incidence of sexual dysfunction is significantly higher with paroxetine 5.

• Efficacy:
  Major depressive disorder: Both bupropion SR and paroxetine were safe and effective for the treatment of depression in the elderly. 15
• Side effects: Because of its favorable side effect profile, bupropion SR may provide a safe and effective nonserotonergic treatment alternative that is well suited as an antidepressant for the elderly. Headache, insomnia, dry mouth, agitation, dizziness, and nausea occurred in > 10% of patients in both groups; somnolence, diarrhea, constipation, and anorexia occurred in > 10% of patients in the paroxetine group. No statistically significant differences between groups in vital signs or weight were found. 15

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

• Efficacy:
  Major depressive disorder: Mirtazapine has faster onset of overall therapeutic efficacy. Mirtazapine and paroxetine are equally effective after 6 weeks of therapy 1.
  In compative 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.
• Side effects: Nausea, vomiting, tremor, and sweating are more common with paroxetine. The incidence of weight increase and influenza-like symptoms are higher with mirtazapine 1. Mirtazapine appeart to have better tolerability. Patients on paroxetine are more likely to discontinue therapy because of adverse events.

• Efficacy:
  Major depressive disorder: Trazodone and paroxetine are equally effective at reducing symptoms of depression and promoting remission. Onset of efficacy is slightly faster with paroxetine treatment. Trazodone may be of advantage in depressed patients with sleep difficulties 25.
• Side effects: Adverse drug reactions with trazodone are mainly of the nervous system, and with paroxetine mainly gastrointestinal 25.

• Paroxetine (Paxil) Medical Facts

• 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; Mirtazapine vs. Paroxetine Study Group. Double-blind, randomized comparison of mirtazapine and paroxetine in elderly depressed patients. Am J Geriatr Psychiatry. 2002 Sep-Oct;10(5):541-50. PubMed
• 3. Vieta E, Martinez-Ara'n A, Goikolea JM, Torrent C, Colom F, Benabarre A, Reinares M. A randomized trial comparing paroxetine and venlafaxine in the treatment of bipolar depressed patients taking mood stabilizers. J Clin Psychiatry. 2002 Jun;63(6):508-12. PubMed
• 4. Vieta E, Martinez-Ara'n A, Goikolea JM, Torrent C, Colom F, Benabarre A, Reinares M. A randomized trial comparing paroxetine and venlafaxine in the treatment of bipolar depressed patients taking mood stabilizers. J Clin Psychiatry. 2002 Jun;63(6):508-12. PubMed
• 5. Delgado PL, Brannan SK, Mallinckrodt CH, Tran PV, McNamara RK, Wang F, Watkin JG, Detke MJ. Sexual functioning assessed in 4 double-blind placebo- and paroxetine-controlled trials of duloxetine for major depressive disorder. J Clin Psychiatry. 2005 Jun;66(6):686-92. PubMed
• 6. Perahia DG, Wang F, Mallinckrodt CH, Walker DJ, Detke MJ. Duloxetine in the treatment of major depressive disorder: a placebo- and paroxetine-controlled trial. Eur Psychiatry. 2006 Sep;21(6):367-78. Epub 2006 May 11. PubMed
• 7. Pollack M, Mangano R, Entsuah R, Tzanis E, Simon NM. A randomized controlled trial of venlafaxine ER and paroxetine in the treatment of outpatients with panic disorder. Psychopharmacology (Berl). 2007 Jun 23. PubMed
• 8. Denys D, van Megen HJ, van der Wee N, Westenberg HG. A double-blind switch study of paroxetine and venlafaxine in obsessive-compulsive disorder. J Clin Psychiatry. 2004 Jan;65(1):37-43. PubMed
• 9. Liebowitz MR, Gelenberg AJ, Munjack D. Venlafaxine extended release vs placebo and paroxetine in social anxiety disorder. Arch Gen Psychiatry. 2005 Feb;62(2):190-8. PubMed
• 10. Poirier MF, Boyer P. Venlafaxine and paroxetine in treatment-resistant depression. Double-blind, randomised comparison. Br J Psychiatry. 1999 Jul;175:12-6. PubMed
• 11. Ballu's C, Quiros G, De Flores T, de la Torre J, Palao D, Rojo L, Gutie'rrez M, Casais L, Riesgo Y. The efficacy and tolerability of venlafaxine and paroxetine in outpatients with depressive disorder or dysthymia. Int Clin Psychopharmacol. 2000 Jan;15(1):43-8. PubMed
• 12. Stuppaeck CH, Geretsegger C, Whitworth AB, Schubert H, Platz T, Ko"nig P, Hinterhuber H, Fleischhacker WW. A multicenter double-blind trial of paroxetine versus amitriptyline in depressed inpatients. J Clin Psychopharmacol. 1994 Aug;14(4):241-6. PubMed
• 13. Bignamini A, Rapisarda V. A double-blind multicentre study of paroxetine and amitriptyline in depressed outpatients. Italian Paroxetine Study Group. 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
• 15. Weihs KL, Settle EC Jr, Batey SR, Houser TL, Donahue RM, Ascher JA. Bupropion sustained release versus paroxetine for the treatment of depression in the elderly. J Clin Psychiatry 2000 Mar; 61(3):196-202 PubMed
• 16. Perna G, Bertani A, Caldirola D, Smeraldi E, Bellodi L. A comparison of citalopram and paroxetine in the treatment of panic disorder: a randomized, single-blind study. Pharmacopsychiatry. 2001 May;34(3):85-90. PubMed
• 17. Bielski RJ, Bose A, Chang CC. A double-blind comparison of escitalopram and paroxetine in the long-term treatment of generalized anxiety disorder. Ann Clin Psychiatry. 2005 Apr-Jun;17(2):65-9. PubMed
• 18. Baldwin DS, Huusom AK, Maehlum E. Escitalopram and paroxetine in the treatment of generalised anxiety disorder: randomised, placebo-controlled, double-blind study. Br J Psychiatry. 2006 Sep;189:264-72. PubMed
• 19. Baldwin DS, Cooper JA, Huusom AK, Hindmarch I. A double-blind, randomized, parallel-group, flexible-dose study to evaluate the tolerability, efficacy and effects of treatment discontinuation with escitalopram and paroxetine in patients with major depressive disorder. Int Clin Psychopharmacol. 2006 May;21(3):159-69. PubMed
• 20. Boulenger JP, Huusom AK, Florea I, Baekdal T, Sarchiapone M. A comparative study of the efficacy of long-term treatment with escitalopram and paroxetine in severely depressed patients. Curr Med Res Opin. 2006 Jul;22(7):1331-41. PubMed
• 21. Judge R, Parry MG, Quail D, Jacobson JG. Discontinuation symptoms: comparison of brief interruption in fluoxetine and paroxetine treatment. Int Clin Psychopharmacol. 2002 Sep;17(5):217-25. PubMed
• 22. Geretsegger C, Bo"hmer F, Ludwig M. Paroxetine in the elderly depressed patient: randomized comparison with fluoxetine of efficacy, cognitive and behavioural effects. Int Clin Psychopharmacol. 1994 Spring;9(1):25-9. PubMed
• 23. Chouinard G, Saxena B, Be'langer MC, Ravindran A, Bakish D, Beauclair L, Morris P, Vasavan Nair NP, Manchanda R, Reesal R, Remick R, O'Neill MC. A Canadian multicenter, double-blind study of paroxetine and fluoxetine in major depressive disorder. J Affect Disord. 1999 Jul;54(1-2):39-48. PubMed
• 24. Bandelow B, Behnke K, Lenoir S, Hendriks GJ, Alkin T, Goebel C, Clary CM. Sertraline versus paroxetine in the treatment of panic disorder: an acute, double-blind noninferiority comparison. J Clin Psychiatry. 2004 Mar;65(3):405-13 PubMed
• 25. Kasper S, Olivieri L, Di Loreto G, Dionisio P. A comparative, randomised, double-blind study of trazodone prolonged-release and paroxetine in the treatment of patients with major depressive disorder. Curr Med Res Opin. 2005 Aug;21(8):1139-46. PubMed

Published: March 31, 2008
Last updated: January 09, 2010