Side-Effect Profile of Fluoxetine in Comparison with Other SSRIs, Tricyclic and Newer Antidepressants: A Meta-Analysis of Clinical Trial Data

Background: In the last ten years, SSRIs have increasingly replaced TCAs as comparators of newer antidepressants (ADs), because of their better tolerability profile. In particular, fluoxetine has become a reference drug for the treatment of depression, but the occurrence of individual side effects in depressed subjects treated with fluoxetine and each comparator AD have not been systematically investigated. Methods: This meta-analysis investigated the frequency of side effects induced by fluoxetine or alternative ADs and compared the occurrence of individual side effects in depressed subjects. All randomised clinical trials (RCTs) comparing fluoxetine with any other AD drug in patients with major depression were located by searching the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register and the Cochrane Controlled Trials Register. Two reviewers independently extracted information. Results: Significantly less percentage of patients treated with fluoxetine experienced any side effects in comparison with TCAs (50.9 % vs 60.3 %, 29 RCTs; RR = 0.84, p = 0.003), but not in comparison with other SSRIs (59.4 % vs 59.3 %, 15 RCTs; RR = 1.00, p = 0.902). In addition, fluoxetine was better tolerated in comparison with TCAs and related ADs (RR 0.61, 95 % CI 0.52, 0.71), but not in comparison with other SSRIs. Regard to individual side effects, activating (insomnia, agitation, tremor and anxiety) and gastrointestinal adverse events (nausea, vomiting, diarrhoea, weight loss and anorexia) were significantly more frequent in fluoxetine-treated patients, whereas cholinergic side effects were significantly less frequent. Conclusions: Fluoxetine compared to other ADs had more activating and gastrointestinal adverse effects, which often require additional pharmacotherapy or other managements strategies, leading to discontinuation and non-compliance and increasing the costs. This information is relevant to base on evidence the prescription of ADs in everyday clinical practice.

References

• 1 Trindade E, Menon D, Topfer L A, Coloma C. Adverse effects associated with selective serotonin reuptake inhibitors and tricyclic antidepressants: a meta-analysis.  Cmaj. 1998;  159 1245-52
• 2 Degner D, Grohmann R, Kropp S, Ruther E, Bender S, Engel R R. et al . Severe adverse drug reactions of antidepressants: results of the German multicenter drug surveillance program AMSP.  Pharmacopsychiatry. 2004;  37 Suppl 1 S39-45
• 3 Anderson I M, Tomenson B M. Treatment discontinuation with selective serotonin reuptake inhibitors compared with tricyclic antidepressants: a meta-analysis.  Bmj. 1995;  310 1433-8
• 4 Anderson I M. SSRIS versus tricyclic antidepressants in depressed inpatients: a meta-analysis of efficacy and tolerability.  Depress Anxiety. 1998;  7 Suppl 1 11-7
• 5 Anderson I M. Selective serotonin reuptake inhibitors versus tricyclic antidepressants: a meta-analysis of efficacy and tolerability.  J Affect Disord. 2000;  58 19-36
• 6 Anderson I M. Meta-analytical studies on new antidepressants.  Br Med Bull. 2001;  57 161-78
• 7 Barbui C, Hotopf M. Amitriptyline v. the rest: still the leading antidepressant after 40 years of randomised controlled trials.  Br J Psychiatry. 2001;  178 129-44
• 8 MacGillivray S, Arroll B, Hatcher S, Ogston S, Reid I, Sullivan F. et al . Efficacy and tolerability of selective serotonin reuptake inhibitors compared with tricyclic antidepressants in depression treated in primary care: systematic review and meta-analysis.  BMJ. 2003;  326 1-6
• 9 Barbui C, Guaiana G, Hotopf M. Amitriptyline for inpatients and SSRIs for outpatients with depression? Systematic review and meta-regression analysis.  Pharmacopsychiatry. 2004;  37 93-7
• 10 Beasley C M Jr., Koke S C, Nilsson M E, Gonzales J S. Adverse events and treatment discontinuations in clinical trials of fluoxetine in major depressive disorder: an updated meta-analysis.  Clin Ther. 2000;  22 1319-30
• 11 Laupacis A, Sackett D L, Roberts R S. An assessment of clinically useful measures of the consequences of treatment.  N Engl J Med. 1988;  318 1728-33
• 12 Altman D G. Confidence intervals for the number needed to treat.  BMJ. 1998;  317 1309-1312
• 13 Edwards J G, Anderson I. Systematic review and guide to selection of selective serotonin reuptake inhibitors.  Drugs. 1999;  57 507-33
• 14 Davidson R A. Source of funding and outcome of clinical trials.  J Gen Intern Med. 1986;  1 155-8
• 15 Egger M, Smith G D, Sterne J A. Uses and abuses of meta-analysis.  Clin Med. 2001;  1 478-84
• 16 Beasley C M Jr., Dornseif B E, Bosomworth J C, Sayler M E, Rampey A H Jr., Heiligenstein J H. et al . Fluoxetine and suicide: a meta-analysis of controlled trials of treatment for depression.  Bmj. 1991;  303 685-92
• 17 Healy D. Lines of evidence on the risks of suicide with selective serotonin reuptake inhibitors.  Psychother Psychosom. 2003;  72 71-9
• 18 Khan A, Khan S, Kolts R, Brown W A. Suicide Rates in Clinical Trials of SSRIs, Other Antidepressants, and Placebo: Analysis of FDA Reports.  Am J Psychiatry. 2003;  160 790-2
• 19 Whittington C J, Kendall T, Fonagy P, Cottrell D, Cotgrove A, Boddington E. Selective serotonin reuptake inhibitors in childhood depression: systematic review of published versus unpublished data.  Lancet. 2004;  363 1341-5
• 20 Meyboom R H, Egberts A C, Edwards I R, Hekster Y A, de Koning F H, Gribnau F W. Principles of signal detection in pharmacovigilance.  Drug Saf. 1997;  16 355-365
• 21 Murray C Y, Lopez A D. Global mortality, disability, and the contribution of risk factors: Global Burden of Disease Study.  Lancet. 1997;  349 1436-1442
• 22 Storosum J G, Elferink A J, van Zwieten B J, van den Brink W, Huyser J. Natural course and placebo response in short-term, placebo-controlled studies in major depression: a meta-analysis of published and non-published studies.  Pharmacopsychiatry. 2004;  37 32-6
• 23 Haberfellner E M, Rittmannsberger H. Spontaneous remission of SSRI-induced orgasm delay.  Pharmacopsychiatry. 2004;  37 127-30

Appendix: References of studies included in the systematic review

Aguglia E, Casacchia M, Cassano GB, Faravelli C, Ferrari G, Giordano P, et al. Double-blind study of the efficacy and safety of sertraline versus fluoxetine in major depression. Int Clin Psychopharmacol 1993; 8: 197 - 202

Alby JM, Ferreri M, Cabane J, De Bodinat C, Dagens V. Efficacy of tianeptine for the treatment of major depression and dysthymia with somatic complaints. A comparative study versus fluoxetine. Annales De Psychiatrie 1993; 8: 136 - 144

Altamura AC, Percudani M, Guercetti G, Invernizzi G. Efficacy and tolerability of fluoxetine in the elderly: a double-blind study versus amitryptiline. Int Clin Psychopharmacol 1989; 4 Suppl 1: 103 - 6

Alves C, Cachola I, Brandao J. Efficacy and tolerability of venlafaxine and fluoxetine in outpatients with major depression. Primary Care Psychiatry 1999; 5: 57 - 63

Andreoli V, Caillard V, Deo RS, Rybakowski JK, Versiani M. Reboxetine, a new noradrenaline selective antidepressant, is at least as effective as fluoxetine in the treatment of depression. J Clin Psychopharmacol 2002; 22: 393 - 9

Ansseau M, Papart P, Troisfontaines B, Bartholome F, Bataille M, Charles G, et al. Controlled comparison of milnacipran and fluoxetine in major depression. Psychopharmacology (Berl) 1994; 114: 131 - 7

Beasley CM, Jr., Holman SL, Potvin JH. Fluoxetine compared with imipramine in the treatment of inpatient depression. A multicenter trial. Ann Clin Psychiatry 1993; 5: 199 - 207

Bennie EH, Mullin JM, Martindale JJ. A double-blind multicenter trial comparing sertraline and fluoxetine in outpatients with major depression. J Clin Psychiatry 1995; 56: 229 - 37

Berlanga C, Arechavaleta B, Heinze G, et a. A double-blind comparison of nefazodone and fluoxetine in the treatment of depressed outpatients. Salud Mental 1997; 20: 1 - 8

Besancon G, Cousin R, Guitton B, Lavergne F. [Double-blind study of mianserin and fluoxetine in ambulatory therapy of depressed patients]. Encephale 1993; 19: 341 - 5

Bhenke K, Jensen GS, Graubaum H-J, Gruenwald J. Hypericum perforatum versus fluoxetine in the treatment of mild to moderate depression. Advances in Therapy 2002; 19: 43 - 52

Bougerol T, Scotto J-C, Patris M, et a. Citalopram and fluoxetine in major depression: Comparison of two clinical trials in a psychiatrist setting and in general practice. Clin drug Invest 1997; 14: 77 - 89

Bowden CL, Schatzberg AF, Rosenbaum A, Contreras SA, Samson JA, Dessain E, et al. Fluoxetine and desipramine in major depressive disorder. J Clin Psychopharmacol 1993; 13: 305 - 11

Boyer P, Danion JM, Bisserbe JC, Hotton JM, Troy S. Clinical and economic comparison of sertraline and fluoxetine in the treatment of depression. A 6-month double-blind study in a primary-care setting in France. Pharmacoeconomics 1998; 13: 157 - 69

Brasseur R. A multicentre open trial of fluoxetine in depressed out-patients in Belgium. Int Clin Psychopharmacol 1989; 4 Suppl 1: 107 - 11

Bremner JD. Fluoxetine in depressed patients: a comparison with imipramine. J Clin Psychiatry 1984; 45: 414 - 9

Bressa GM, Brugnoli R, Pancheri P. A double-blind study of fluoxetine and imipramine in major depression. Int Clin Psychopharmacol 1989; 4 Suppl 1: 69 - 73

Byerley WF, Reimherr FW, Wood DR, Grosser BI. Fluoxetine, a selective serotonin uptake inhibitor, for the treatment of outpatients with major depression. J Clin Psychopharmacol 1988; 8: 112 - 5

Cassano GB, Puca F, Scapicchio PL, Trabucchi M. Paroxetine and fluoxetine effects on mood and cognitive functions in depressed nondemented elderly patients. J Clin Psychiatry 2002; 63: 396 - 402

Chouinard G. A double-blind controlled clinical trial of fluoxetine and amitriptyline in the treatment of outpatients with major depressive disorder. J Clin Psychiatry 1985; 46: 32 - 7

Chouinard G, Saxena B, Belanger MC, Ravindran A, Bakish D, Beauclair L, et al. A Canadian multicenter, double-blind study of paroxetine and fluoxetine in major depressive disorder. J Affect Disord 1999; 54: 39 - 48

Clerc GE, Ruimy P, Verdeau-Palles J. A double-blind comparison of venlafaxine and fluoxetine in patients hospitalized for major depression and melancholia. The Venlafaxine French Inpatient Study Group. Int Clin Psychopharmacol 1994; 9: 139 - 43

Cohn JB, Collins G, Ashbrook E, Wernicke JF. A comparison of fluoxetine imipramine and placebo in patients with bipolar depressive disorder. Int Clin Psychopharmacol 1989; 4: 313 - 22

Cohn JB, Wilcox C. A comparison of fluoxetine, imipramine, and placebo in patients with major depressive disorder. J Clin Psychiatry 1985; 46: 26 - 31

Corne SJ, Hall JR. A double-blind comparative study of fluoxetine and dothiepin in the treatment of depression in general practice. Int Clin Psychopharmacol 1989; 4: 245 - 54

Corrigan MH, Denahan AQ, Wright CE, Ragual RJ, Evans DL. Comparison of pramipexole, fluoxetine, and placebo in patients with major depression. Depress Anxiety 2000; 11: 58 - 65

Costa e Silva J. Randomized, double-blind comparison of venlafaxine and fluoxetine in outpatients with major depression. J Clin Psychiatry 1998; 59: 352 - 7

Dalery J, Rochat C, Peyron E, Bernard G. The efficacy and acceptability of amineptine versus fluoxetine in major depression. Int Clin Psychopharmacol 1997; 12 Suppl 3: S35 - 8

de Jonghe F, Ravelli DP, Tuynman-Qua H. A randomized, double-blind study of fluoxetine and maprotiline in the treatment of major depression. Pharmacopsychiatry 1991; 24: 62 - 7

De Nayer A, Geerts S, Ruelens L, Schittecatte M, De Bleeker E, Van Eeckhoutte I, et al. Venlafaxine compared with fluoxetine in outpatients with depression and concomitant anxiety. Int J Neuropsychopharmacol 2002; 5: 115 - 20

De Ronchi D, Rucci P, Lodi M, et a. Fluoxetine and amitriptyline in elderly depressed patients: a 10-week, double-blind study on course of neurocognitive adverse events and depressive symptoms. Arch Geront Geriatrics 1998; 6S: 125 - 140

De Wilde J, Spiers R, Mertens C, Bartholome F, Schotte G, Leyman S. A double-blind, comparative, multicentre study comparing paroxetine with fluoxetine in depressed patients. Acta Psychiatr Scand 1993; 87: 141 - 5

Debus JR, Rush AJ, Himmel C, Tyler D, Polatin P, Weissenburger J. Fluoxetine versus trazodone in the treatment of outpatients with major depression. J Clin Psychiatry 1988; 49: 422 - 6

Demyttenaere K, Van Ganse E, Gregoire J, Gaens E, Mesters P. Compliance in depressed patients treated with fluoxetine or amitriptyline. Belgian Compliance Study Group. Int Clin Psychopharmacol 1998; 13: 11 - 7

Diaz-Martinez A, Benassinni O, Ontiveros A, Gonzalez S, Salin R, Basquedano G, et al. A randomized, open-label comparison of venlafaxine and fluoxetine in depressed outpatients. Clin Ther 1998; 20: 467 - 76

Dierick M, Ravizza L, Realini R, Martin A. A double-blind comparison of venlafaxine and fluoxetine for treatment of major depression in outpatients. Prog Neuropsychopharmacol Biol Psychiatry 1996; 20: 57 - 71

Dowling B, Webb MGT, Halpin CM, Sangiwa MGH. Fluoxetine: a comparative study with dothiepin. Irish J Psychiatry 1990; 11: 3 - 7

Duarte A, Mikkelsen H, Delini-Stula A. Moclobemide versus fluoxetine for double depression: a randomized double-blind study. J Psychiatr Res 1996; 30: 453 - 8

Fabre LF, Scharf MB, Itil TM. Comparative efficacy and safety of nortriptyline and fluoxetine in the treatment of major depression: a clinical study. J Clin Psychiatry 1991; 52 Suppl: 62 - 7

Fairweather DB, Stanley N, Yoon JS, Hindmarch I. The effects of fluoxetine and dothiepin on cognitive function in depressed patients in general practice. Hum Psychopharmacol 1999; 14: 325 - 332

Falk WE, Rosenbaum JF, Otto MW, Zusky PM, Weilburg JB, Nixon RA. Fluoxetine versus trazodone in depressed geriatric patients. J Geriatr Psychiatry Neurol 1989; 2: 208 - 14

Fava M, Amsterdam JD, Deltito JA, Salzman C, Schwaller M, Dunner DL. A double-blind study of paroxetine, fluoxetine, and placebo in outpatients with major depression. Ann Clin Psychiatry 1998; 10: 145 - 50

Fava M, Hoog SL, Judge RA, Kopp JB, Nilsson ME, Gonzales JS. Acute efficacy of fluoxetine versus sertraline and paroxetine in major depressive disorder including effects of baseline insomnia. J Clin Psychopharmacol 2002; 22: 137 - 47

Fava M, Judge R, Hoog SL, Nilsson ME, Koke SC. Fluoxetine versus sertraline and paroxetine in major depressive disorder: changes in weight with long-term treatment. J Clin Psychiatry 2000; 61: 863 - 7

Fawcett J, Zajecka JM, Kravitz HM, et a. Fluoxetine versus amitriptyline in adult outpatients with major depression. Curr Ther Res 1989; 45: 821 - 832

Feighner JP. A comparative trial of fluoxetine and amitriptyline in patients with major depressive disorder. J Clin Psychiatry 1985; 46: 369 - 72

Feighner JP, Boyer WF, Merideth CH, Hendrickson GG. A double-blind comparison of fluoxetine, imipramine and placebo in outpatients with major depression. Int Clin Psychopharmacol 1989; 4: 127 - 34

Feighner JP, Cohn JB. Double-blind comparative trials of fluoxetine and doxepin in geriatric patients with major depressive disorder. J Clin Psychiatry 1985; 46: 20 - 5

Feighner JP, Gardner EA, Johnston JA, Batey SR, Khayrallah MA, Ascher JA, et al. Double-blind comparison of bupropion and fluoxetine in depressed outpatients. J Clin Psychiatry 1991; 52: 329 - 35

Ferreri M. Fluoxetine versus amineptine in the treatment of outpatients with major depressive disorders. Int Clin Psychopharmacol 1989; 4 Suppl 1: 97 - 101

Finkel SI, Richter EM, Clary CM, Batzar E. Comparative efficacy of sertraline vs. fluoxetine in patients age 70 or over with major depression. Am J Geriatr Psychiatry 1999; 7: 221 - 7

Flament MF, Lane R. Acute antidepressant response to fluoxetine and sertraline in psychiatric outpatients with psychomotor agitation. Int J Psychiatry Clin Practice 2001; 5: 103 - 109

Friede M, Henneicke von Zepelin HH, Freudenstein J. Differential therapy of mild to moderate depressive episodes (ICD-10 F 32.0; F 32.1) with St. John’s wort. Pharmacopsychiatry 2001; 34 Suppl 1: S38 - 41

Gagiano CA. A double blind comparison of paroxetine and fluoxetine in patients with major depression. Br J Clin Res 1993; 4: 145 - 152

Gattaz WF, Vogel P, Kick H, Kohnen R. Moclobemide versus fluoxetine in the treatment of inpatients with major depression. J Clin Psychopharmacol 1995; 15: 35S-40S

Geerts S, Bruynooghe F, De Cuyper H, Demeulemeester F, Haazen L. Moclobemide versus fluoxetine for major depressive episodes. Clin Neuropharmacol 1994; 17 Suppl 1: S50 - 7

Gillin JC, Rapaport M, Erman MK, Winokur A, Albala BJ. A comparison of nefazodone and fluoxetine on mood and on objective, subjective, and clinician-rated measures of sleep in depressed patients: a double-blind, 8-week clinical trial. J Clin Psychiatry 1997; 58: 185 - 92

Ginestet D. Fluoxetine in endogenous depression and melancholia versus clomipramine. Int Clin Psychopharmacol 1989; 4 Suppl 1: 37 - 40

Goldstein DJ, Mallinckrodt C, Lu Y, Demitrack MA. Duloxetine in the treatment of major depressive disorder: a double-blind clinical trial. J Clin Psychiatry 2002; 63: 225 - 31

Guelfi JD, Ansseau M, Corruble E, Samuelian JC, Tonelli I, Tournoux A, et al. A double-blind comparison of the efficacy and safety of milnacipran and fluoxetine in depressed inpatients. Int Clin Psychopharmacol 1998; 13: 121 - 8

Guelfi JD, Bouhassira M, Bonett-Perrin E, Lancrenon S. [The study of the efficacy of fluoxetine versus tianeptine in the treatment of elderly depressed patients followed in general practice]. Encephale 1999; 25: 265 - 70

Harrer G, Schmidt U, Kuhn U, Biller A. Comparison of equivalence between the St. John’s wort extract LoHyp-57 and fluoxetine. Arzneimittelforschung 1999; 49: 289 - 96

Jakovljevic M, Vujic D, Henigsberg N, Aleksandrovsky Y, Faltus F, Szerenberger W. Central-East European Study of Fluoxetine (Portal, Lek) and Maprotiline (Ladiomil, Pliva) in Major Depressive Episode. Psychiatria Danubina 1996; 8: 1 - 5

Joyce PR, Mulder RT, Luty SE, Sullivan PF, McKenzie JM, Abbott RM, et al. Patterns and predictors of remission, response and recovery in major depression treated with fluoxetine or nortriptyline. Aust N Z J Psychiatry 2002; 36: 384 - 91

Judd FK, Moore K, Norman TR, Burrows GD, Gupta RK, Parker G. A multicentre double blind trial of fluoxetine versus amitriptyline in the treatment of depressive illness. Aust N Z J Psychiatry 1993; 27: 49 - 55

Kaufeler R, Meier B, Brattstrom A. Efficacy and tolerability of Ze 117 St. John’s wort extract in comparison with placebo, imipramine and fluoxetine for the treatment of mild to moderate depression according to ICD-10. An overview. Pharmacopsychiatry 2001; 34 Suppl 1: S49 - 50

Keegan D, Bowen RC, Blackshaw S, Saleh S, Dayal N, Remillard F, et al. A comparison of fluoxetine and amitriptyline in the treatment of major depression. Int Clin Psychopharmacol 1991; 6: 117 - 24

Kerkhofs M, Rielaert C, de Maertelaer V, Linkowski P, Czarka M, Mendlewicz J. Fluoxetine in major depression: efficacy, safety and effects on sleep polygraphic variables. Int Clin Psychopharmacol 1990; 5: 253 - 60

Kuha S, Mehtonen O-P, Henttonen A, Naarala M. The efficacy of fluoxetine versus maprotiline in depressed patients and by dose. Nordisk Psykiatrisk Tidsskrift 1991; 45: 109 - 117

La Pia S, Giorgio D, Ciriello R, et a. Double blind controlled study to evaluate the effectiveness and tolerability of fluoxetine versus mianserin in the treatment of depressive disorders among the elderly and their effects on cognitive-behavioral parameters. New Trends Exp Clin Psychiatry 1992; 8: 139 - 146

Laakmann G, Blaschke D, Engel R, Schwarz A. Fluoxetine vs amitriptyline in the treatment of depressed out-patients. Br J Psychiatry Suppl 1988: 64 - 8

Lapierre YD, Joffe R, McKenna K, Bland R, Kennedy S, Ingram P, et al. Moclobemide versus fluoxetine in the treatment of major depressive disorder in adults. J Psychiatry Neurosci 1997; 22: 118 - 26

Levine S, Deo R, Mahadevan K. A comparative trial of a new antidepressant, fluoxetine. Int Clin Psychopharmacol 1989; 4 Suppl 1: 41 - 5

Levkovitz Y, Caftori R, Avital A, Richter-Levin G. The SSRIs drug Fluoxetine, but not the noradrenergic tricyclic drug Desipramine, improves memory performance during acute major depression. Brain Res Bull 2002; 58: 345 - 50

Loeb C, Albano C, Gandolfo C. Fluoxetine versus imipramine. Int Clin Psychopharmacol 1989; 4 Suppl 1: 75 - 9

Lonnqvist J, Sintonen H, Syvalahti E, Appelberg B, Koskinen T, Mannikko T, et al. Antidepressant efficacy and quality of life in depression: a double-blind study with moclobemide and fluoxetine. Acta Psychiatr Scand 1994; 89: 363 - 9

Loo H, Saiz-Ruiz J, Costa e Silva J, Ansseau M, Herrington R, Vaz-Serra A, et al. Efficacy and safety of tianeptine in the treatment of depressive disorders in comparison with fluoxetine. J Affect Disord 1999; 56: 109 - 18

Manna V, Martucci N, Agnoli A. Double-blind controlled study on the clinical efficacy and safety of fluoxetine vs clomipramine in the treatment of major depressive disorders. Int Clin Psychopharmacol 1989; 4 Suppl 1: 81 - 8

Marchesi C, Ceccherininelli A, Rossi A, Maggini C. Is anxious-agitated major depression responsive to fluoxetine? A double-blind comparison with amitriptyline. Pharmacopsychiatry 1998; 31: 216 - 21

Martenyi F, Dossenbach M, Mraz K, Metcalfe S. Gender differences in the efficacy of fluoxetine and maprotiline in depressed patients: a double-blind trial of antidepressants with serotonergic or norepinephrinergic reuptake inhibition profile. Eur Neuropsychopharmacol 2001; 11: 227 - 32

Masco HL, Sheetz MS. Double-blind comparison of fluoxetine and amitryptyline in the treatment of major depressive illness. Advances in Therapy 1985; 2: 275 - 284

Massana J, Moller HJ, Burrows GD, Montenegro RM. Reboxetine: a double-blind comparison with fluoxetine in major depressive disorder. Int Clin Psychopharmacol 1999; 14: 73 - 80

McGrath PJ, Stewart JW, Janal MN, Petkova E, Quitkin FM, Klein DF. A placebo-controlled study of fluoxetine versus imipramine in the acute treatment of atypical depression. Am J Psychiatry 2000; 157: 344 - 50

Muijen M, Roy D, Silverstone T, Mehmet A, Christie M. A comparative clinical trial of fluoxetine, mianserin and placebo in depressed outpatients. Acta Psychiatr Scand 1988; 78: 384 - 90

Newhouse PA, Krishnan KR, Doraiswamy PM, Richter EM, Batzar ED, Clary CM. A double-blind comparison of sertraline and fluoxetine in depressed elderly outpatients. J Clin Psychiatry 2000; 61: 559 - 68

Nielsen BM, Behnke K, Arup P, Christiansen PE, Geisler A, Ipsen E, et al. A comparison of fluoxetine and imipramine in the treatment of outpatients with major depressive disorder. Acta Psychiatr Scand 1993; 87: 269 - 72

Noguera R, Altuna R, Alvarez E, Ayuso JL, Casais L, Udina C. Fluoxetine vs. clomipramine in depressed patients: a controlled multicentre trial. J Affect Disord 1991; 22: 119 - 24

Novotny V, Faltus F. Tianeptine and fluoxetine in major depression: a 6-week randomised double-blind study. Hum Psychopharmacol 2002; 17: 299 - 303

Ontiveros A, Garcia-Barriga C. A double-blind, comparative study of paroxetine and fluoxetine in out-patients with depression. Br J Clin Res 1997; 8: 23 - 32

Ontiveros JA, Brandi F, Brunner E. Estudio doble-ciego sobre fluoxetina vs amitriptilina en los sintomas depresivos y de ansiedad, y calidad de vida de los adultos con depresion mayor. Salud Mental 1998; 21: 58 - 63

Pakesch G, Dossenbach M. [Efficacy and safety of fluoxetine versus clomipramine in ambulatory patients with a depressive syndrome in a clinical trial with private practitioners]. Wien Klin Wochenschr 1991; 103: 176 - 82

Pande AC, Birkett M, Fechner-Bates S, Haskett RF, Greden JF. Fluoxetine versus phenelzine in atypical depression. Biol Psychiatry 1996; 40: 1017 - 20

Perry PJ, Garvey MJ, Kelly MW, Cook BL, Dunner FJ, Winokur G. A comparative trial of fluoxetine versus trazodone in outpatients with major depression. J Clin Psychiatry 1989; 50: 290 - 4

Peters UH, Lenhard P, Metz M. Therapy of depression in the psychiatrist’s office - A double-blind multicenter study. Nervenheilkunde 1990; 9: 28 - 31

Poelinger W, Haber H. Fluoxetine 40 mg vs maprotiline 75 mg in the treatment of out-patients with depressive disorders. Int Clin Psychopharmacol 1989; 4 Suppl 1: 47 - 50

Preskorn SH, Silkey B, Beber J, Dorey C. Antidepressant response and plasma concentrations of fluoxetine. Ann Clin Psychiatry 1991; 3: 147 - 151

Rapaport M, Coccaro E, Sheline Y, Perse T, Holland P, Fabre L, et al. A comparison of fluvoxamine and fluoxetine in the treatment of major depression. J Clin Psychopharmacol 1996; 16: 373 - 8

Remick RA, Claman J, Reesal R, et a. Comparison of fluoxetine and desipramine in depressed outpatients. Curr Ther Res 1993; 53: 457 - 465

Remick RA, Keller FD, Gibson RE, Carter D. A comparison between fluoxetine and doxepin in depressed patients. Curr Ther Res 1989; 46: 842 - 848

Reynaert C, Parent M, Mirel J, Janne P, Haazen L. Moclobemide versus fluoxetine for a major depressive episode. Psychopharmacology (Berl) 1995; 118: 183 - 7

Robertson MM, Abou Saleh MT, Harrison DA, Nairac BL. A double-blind controlled comparison of fluoxetine and lofepramine in major depressive illness. J Psychopharmacol 1994; 8: 98 - 103

Ropert R. Fluoxetine versus clomipramine in major depressive disorders. Int Clin Psychopharmacol 1989; 4 Suppl 1: 89 - 95

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; 56: 171 - 81

Rush AJ, Armitage R, Gillin JC, Yonkers KA, Winokur A, Moldofsky H, et al. Comparative effects of nefazodone and fluoxetine on sleep in outpatients with major depressive disorder. Biol Psychiatry 1998; 44: 3 - 14

Sandor P, Baker B, Irvine J, Dorian P, McKessok D, Mendlowitz S. Effectiveness of fluoxetine and doxepin in treatment of melancholia in depressed patients. Depress Anxiety 1998; 7: 69 - 72

Schone W, Ludwig M. A double-blind study of paroxetine compared with fluoxetine in geriatric patients with major depression. J Clin Psychopharmacol 1993; 13: 34S-39S

Sechter D, Troy S, Paternetti S, Boyer P. A double-blind comparison of sertraline and fluoxetine in the treatment of major depressive episode in outpatients. Eur Psychiatry 1999; 14: 41 - 8

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; 60: 22 - 8

Smeraldi E. Amisulpride versus fluoxetine in patients with dysthymia or major depression in partial remission: a double-blind, comparative study. J Affect Disord 1998; 48: 47 - 56

South Wales Antidepressant Drug Trial Group. A double-blind multi-centre trial of fluoxetine and dothiepin in major depressive illness. Int Clin Psychopharmacol 1988; 3: 75 - 81

Sramek JJ, Kashkin K, Jasinsky O, et a. Placebo-controlled study of ABT-200 versus fluoxetine in the treatment of major depressive disorder. Depression 1995; 3: 199 - 203 1995; 3: 199 - 203

Stark P, Hardison CD. A review of multicenter controlled studies of fluoxetine vs. imipramine and placebo in outpatients with major depressive disorder. J Clin Psychiatry 1985; 46: 53 - 8

Stephenson DA, Harris B, Davies RH, Mullin JM, Richardson E, Boardman H, et al. The impact of antidepressants on sleep and anxiety: a comparative study of fluoxetine and dothiepin using the Leeds Sleep Evaluation Questionnaire. Hum Psychopharmacol 2000; 15: 529 - 534

Stratta P, Bolino F, Cupillari M, Casacchia M. A double-blind parallel study comparing fluoxetine with imipramine in the treatment of atypical depression. Int Clin Psychopharmacol 1991; 6: 193 - 6

Suleman MI, Sebit MB, Acuda SW, Siziya S. Fluoxetine and moclobemide versus amitriptyline in major depression: A single blind randomized clinical trial in Zimbabwe. Central African J Med 1997; 43: 38 - 40

Suri RA, Altshuler LL, Rasgon NL, Calcagno JL, Frye MA, Gitlin MJ, et al. Efficacy and response time to sertraline versus fluoxetine in the treatment of unipolar major depressive disorder. J Clin Psychiatry 2000; 61: 942 - 6

Tamminen TT, Lehtinen VV. A double-blind parallel study to compare fluoxetine with doxepin in the treatment of major depressive disorders. Int Clin Psychopharmacol 1989; 4 Suppl 1: 51 - 6

Taneri Z, Kohler R. Fluoxetine versus nomifensine in outpatients with neurotic or reactive depressive disorder. Int Clin Psychopharmacol 1989; 4 Suppl 1: 57 - 61

Thompson C, Peveler RC, Stephenson D, McKendrick J. Compliance with antidepressant medication in the treatment of major depressive disorder in primary care: a randomized comparison of fluoxetine and a tricyclic antidepressant. Am J Psychiatry 2000; 157: 338 - 43

Tignol J. A double-blind, randomized, fluoxetine-controlled, multicenter study of paroxetine in the treatment of depression. J Clin Psychopharmacol 1993; 13: 18S-22S

Tollefson GD, Greist JH, Jefferson JW, Heiligenstein JH, Sayler ME, Tollefson SL, et al. Is baseline agitation a relative contraindication for a selective serotonin reuptake inhibitor: a comparative trial of fluoxetine versus imipramine. J Clin Psychopharmacol 1994; 14: 385 - 91

Tylee A, Beaumont G, Bowden MW, Reynolds A. A double-blind, randomized, 12-week comparison study of the safety and efficacy of venlafaxine and fluoxetine in moderate to severe major depression in general-practice. Tylee A, BeaumontG, Bowden MW, Reynolds A. A double-blind, randomized, 12-week comparison study of the safety and efficacy of venlafaxine and fluoxetine in moderate to severe major depression in general-practice. Primary Care Psychiatry 1997; 3: 51 - 8. 1997; 3: 51 - 58

Tzanakaki M, Guazzelli M, Nimatoudis I, Zissis NP, Smeraldi E, Rizzo F. Increased remission rates with venlafaxine compared with fluoxetine in hospitalized patients with major depression and melancholia. Int Clin Psychopharmacol 2000; 15: 29 - 34

Upward JW, Edwards JG, Goldie A, Waller DG. Comparative effects of fluoxetine and amitriptyline on cardiac function. Br J Clin Pharmacol 1988; 26: 399 - 402

Van Moffaert M, Bartholome F, Cosyns P, De Nayer AR, Mertens C. A controlled comparison of sertraline and fluoxetine in acute and continuation treatment of major depression. Hum Psychopharmacol 1995; 10: 393 - 405

Venditti LN, Arcelus A, Birnbaum H, Greenberg P, Barr CE, Rowland C, et al. The impact of antidepressant use on social functioning: reboxetine versus fluoxetine. Int Clin Psychopharmacol 2000; 15: 279 - 89

Versiani M, Ontiveros A, Mazzotti G, Ospina J, Davila J, Mata S, et al. Fluoxetine versus amitriptyline in the treatment of major depression with associated anxiety (anxious depression): a double-blind comparison. Int Clin Psychopharmacol 1999; 14: 321 - 7

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; 59: 306 - 12

Williams R, Edwards RA, Newburn GM, Mullen R, Menkes DB, Segkar C. A double-blind comparison of moclobemide and fluoxetine in the treatment of depressive disorders. Int Clin Psychopharmacol 1993; 7: 155 - 8

Wolf R, Dykierek P, Gattaz WF, Maras A, Kohnen R, Dittmann RW, et al. Differential effects of trimipramine and fluoxetine on sleep in geriatric depression. Pharmacopsychiatry 2001; 34: 60 - 5

Young JP, Coleman A, Lader MH. A controlled comparison of fluoxetine and amitriptyline in depressed out-patients. Br J Psychiatry 1987; 151: 337 - 40