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Fluoxetine (Prozac) appears to be the weakest of the SSRIs. Due to it's very long half-life and relatively weak potency as a serotonin inhibitor it has less prominent discotinuation symptoms than many other antidepressants.

Fluoxetine uniqe features led to that Prozac is the only SSRI approved by the FDA for use in children 8 years of age and older.

• Efficacy:
• Major depressive disorder: Citalopram is as effective as fluoxetine in the treatment of unipolar major depression. In the study citalopram showed an earlier onset of recovery than fluoxetine 12.
• Bulimia nervosa: In the study patients treated with fluoxetine displayed a greater reduction in introjected anger, whereas those treated with citalopram displayed a greater reduction in depressive feelings. Citalopram may be useful in depressed patients with bulimia, whereas fluoxetine is more specific for those with introjected anger and bulimia 13.

• 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 1.

• Efficacy:
• Major depression. Sertraline and fluoxetine have comparable antidepressant efficacy in the treatment of Major depression. However, sertraline has advantages over fluoxetine in those patients with severe depression and low anxiety in the melancholia 17, 18.
• Obsessive-compulsive disorder. Both medications have significant efficacy in the treatment of moderate to severe OCD. However, patients treated with sertraline have a greater likelihood of remission as well as an earlier improvement 20.
• Tolerability: Sertraline is considered to be better tolerated than fluoxetine 19.
• Side effects: Sertraline has advantages over fluoxetine on parameters such as sleep and weight disturbance in severely depressed patients, and sleep disturbance, weight, cognitive disturbance and retardation in melancholic patients 18.
  Fluoxetine treatment is associated with a higher incidence of agitation, anxiety and insomnia than sertraline 19.
• Withdrawal syndrome: Fluoxetine has fewer discontinuation-emergent events than sertraline 21.

• Efficacy:
  Major depressive disorder: Venlafaxine appears to be superior to fluoxetine and prodeces higher rate of remission in the treatment for depression 24. Venlafaxine's superior remission rates in the more severely anxious patients and its ability to improve psychic anxiety compared with fluoxetine suggest that venlafaxine's early efficacy on anxiety symptoms may be the basis for its superior efficacy in depression 25.
• Drug interactions: Fluoxetine has a higher potential for drug interactions with drugs metabolized by CYP2D6 (e.g. amphetamines, selected beta-blockers, dextromethorphan, lidocaine, mirtazapine, nefazodone, paroxetine, risperidone, ritonavir, thioridazine, tricyclic antidepressants) 26.

• Efficacy:
• Depression: Bupropion SR and fluoxetine are similarly effective and well tolerated in the treatment of depression. There were no statistically significant differences between both medications on any of the efficacy variables 15, 16.
• Premenstrual dysphoric disorder: Fluoxetine is significantly superior to bupropion in the treatment of premenstrual dysphoric disorder 14.
• Side effects: Fluoxetine is more frequently associated with sexual dysfunction compared with bupropion SR. Bupropion SR may be an appropriate initial choice for the treatment of depression in patients concerned about sexual functioning 15.

• Efficacy:
• Major depressive disorder: Both drugs are effective in relieving the symptoms of depression 5. Recent memory can be improved significantly with the fluoxetine treatment 6.
• Anxious depression: Fluoxetine and amitriptyline have comparable efficacy in the treatment of major depression with associated anxiety 3.
• Fibromyalgia: Fluoxetine and amitriptyline are similarly effective treatments for FM, and they work better in combination than either medication alone 2.
• Musculo-skeletal pain: In the study moderate or good pain relief was reported by 82% patients with amitriptyline, and by 77% patients with fluoxetine. Fluoxetine relieved low back pain and whiplash associated cervical pain with efficacy similar to that of amitriptyline 4.
• Migraine headache: Amitriptyline appears to be more effective than fluoxetine for migraine headache prophylaxis 9.
• Side effects: Adverse effects are more frequent and more severe with the amitriptyline 3. The most frequent side effects with fluoxetine are nausea, nervousness, sleep disturbances, and headaches; and dry mouth, dizziness, and drowsiness with amitriptyline 5, 6, 8. Weight gain is associated more with amitriptyline 7.

• Efficacy:
  Major depressive disorder: Mirtazapine is significantly more effective than fluoxetine after 3 and 4 weeks of therapy in the treatment of moderate to severe major depressive disorder 10, 11.
• Side effects: Both drugs are generally well tolerated. Tolerability profiles are comparable except for changes in body weight. Mirtazapine is associated with significantly more pronounced body weight gain compared to the fluoxetine. In the study mirtazapine treatment was associared with a mean weight gain of 0.8 +/- 2.7 kg, whereas fluoxetine was associated with a mean decrease in weight of 0.4 +/- 2.1 kg 10, 11.

• Fluoxetine (Prozac) Medical Facts

• 1. 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
• 2. Goldenberg D, Mayskiy M, Mossey C, Ruthazer R, Schmid C. A randomized, double-blind crossover trial of fluoxetine and amitriptyline in the treatment of fibromyalgia. Arthritis Rheum. 1996 Nov;39(11):1852-9. PubMed
• 3. Versiani M, Ontiveros A, Mazzotti G, Ospina J, Da'vila J, Mata S, Pacheco A, Plewes J, Tamura R, Palacios M. Fluoxetine versus amitriptyline in the treatment of major depression with associated anxiety (anxious depression): a double-blind comparison. Int Clin Psychopharmacol. 1999 Nov;14(6):321-7. PubMed
• 4. Schreiber S, Vinokur S, Shavelzon V, Pick CG, Zahavi E, Shir Y. A randomized trial of fluoxetine versus amitriptyline in musculo-skeletal pain. Isr J Psychiatry Relat Sci. 2001;38(2):88-94. PubMed
• 5. Feighner JP. A comparative trial of fluoxetine and amitriptyline in patients with major depressive disorder. J Clin Psychiatry. 1985 Sep;46(9):369-72. PubMed
• 6. Keegan D, Bowen RC, Blackshaw S, Saleh S, Dayal N, Remillard F, Shrikhande S, Cebrian Perez S, Boulton A. A comparison of fluoxetine and amitriptyline in the treatment of major depression. Int Clin Psychopharmacol. 1991 Summer;6(2):117-24. PubMed
• 7. Altamura AC, De Novellis F, Guercetti G, Invernizzi G, Percudani M, Montgomery SA. Fluoxetine compared with amitriptyline in elderly depression: a controlled clinical trial. Int J Clin Pharmacol Res. 1989;9(6):391-6. PubMed
• 8. Young JP, Coleman A, Lader MH. A controlled comparison of fluoxetine and amitriptyline in depressed out-patients. Br J Psychiatry. 1987 Sep;151:337-40. PubMed
• 9. Amelin AV, Skoromets AA, Korenko LA, Tumelevich BCh, Gonchar MA. A comparative efficiency of amitriptyline, fluoxetine and maprotiline in prevention of migraine in attack-free period. Zh Nevrol Psikhiatr Im S S Korsakova. 2000;100(8):20-3. PubMed
• 10. Versiani M, Moreno R, Ramakers-van Moorsel CJ, Schutte AJ; Comparative Efficacy Antidepressants Study Group Comparison of the effects of mirtazapine and fluoxetine in severely depressed patients. CNS Drugs. 2005;19(2):137-46. PubMed
• 11. Wheatley DP, van Moffaert M, Timmerman L, Kremer CM. Mirtazapine: efficacy and tolerability in comparison with fluoxetine in patients with moderate to severe major depressive disorder. Mirtazapine-Fluoxetine Study Group. J Clin Psychiatry. 1998 Jun;59(6):306-12. PubMed
• 12. Patris M, Bouchard JM, Bougerol T, Charbonnier JF, Chevalier JF, Clerc G, Cyran C, Van Amerongen P, Lemming O, Hopfner Petersen HE. Citalopram versus fluoxetine: a double-blind, controlled, multicentre, phase III trial in patients with unipolar major depression treated in general practice. Int Clin Psychopharmacol. 1996 Jun;11(2):129-36. PubMed
• 13. Leombruni P, Amianto F, Delsedime N, Gramaglia C, Abbate-Daga G, Fassino S. Citalopram versus fluoxetine for the treatment of patients with bulimia nervosa: a single-blind randomized controlled trial. Adv Ther. 2006 May-Jun;23(3):481-94. PubMed
• 14. Pearlstein TB, Stone AB, Lund SA, Scheft H, Zlotnick C, Brown WA. Comparison of fluoxetine, bupropion, and placebo in the treatment of premenstrual dysphoric disorder. J Clin Psychopharmacol. 1997 Aug;17(4):261-6. PubMed
• 15. Coleman CC, King BR, Bolden-Watson C, Book MJ, Segraves RT, Richard N, Ascher J, Batey S, Jamerson B, Metz A. A placebo-controlled comparison of the effects on sexual functioning of bupropion sustained release and fluoxetine. Clin Ther. 2001 Jul;23(7):1040-58. PubMed
• 16. Feighner JP, Gardner EA, Johnston JA, Batey SR, Khayrallah MA, Ascher JA, Lineberry CG. Double-blind comparison of bupropion and fluoxetine in depressed outpatients. J Clin Psychiatry. 1991 Aug;52(8):329-35. PubMed
• 17. Feiger AD, Flament MF, Boyer P, Gillespie JA Sertraline versus fluoxetine in the treatment of major depression: a combined analysis of five double-blind comparator studies. Int Clin Psychopharmacol. 2003 Jul;18(4):203-10. PubMed
• 18. Flament MF, Lane RM, Zhu R, Ying Z. Predictors of an acute antidepressant response to fluoxetine and sertraline. PubMed
• 19. Aguglia E, Casacchia M, Cassano GB, Faravelli C, Ferrari G, Giordano P, Pancheri P, Ravizza L, Trabucchi M, Bolino F, et al. Double-blind study of the efficacy and safety of sertraline versus fluoxetine in major depression. Int Clin Psychopharmacol. 1993 Fall;8(3):197-202. PubMed
• 20. Bergeron R, Ravindran AV, Chaput Y, Goldner E, Swinson R, van Ameringen MA, Austin C, Hadrava V. Sertraline and fluoxetine treatment of obsessive-compulsive disorder: results of a double-blind, 6-month treatment study. J Clin Psychopharmacol. 2002 Apr;22(2):148-54. PubMed
• 21. Rosenbaum JF, Fava M, Hoog SL, Ascroft RC, Krebs WB. Selective serotonin reuptake inhibitor discontinuation syndrome: a randomized clinical trial. Biol Psychiatry. 1998 Jul 15;44(2):77-87. 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. Silverstone PH, Ravindran A. Once-daily venlafaxine extended release (XR) compared with fluoxetine in outpatients with depression and anxiety. Venlafaxine XR 360 Study Group. J Clin Psychiatry. 1999 Jan;60(1):22-8. PubMed
• 25. Rudolph RL, Feiger AD. A double-blind, randomized, placebo-controlled trial of once-daily venlafaxine extended release (XR) and fluoxetine for the treatment of depression. J Affect Disord. 1999 Dec;56(2-3):171-81. PubMed
• 26. Amchin J, Ereshefsky L, Zarycranski W, Taylor K, Albano D, Klockowski PM. Effect of venlafaxine versus fluoxetine on metabolism of dextromethorphan, a CYP2D6 probe. J Clin Pharmacol. 2001 Apr;41(4):443-51. PubMed