Hostname: page-component-55f67697df-zh294 Total loading time: 0 Render date: 2025-05-10T09:59:43.744Z Has data issue: false hasContentIssue false
  • English
  • Français

SNRIs: The Pharmacology, Clinical Efficacy, and Tolerability in Comparison with Other Classes of Antidepressants

Published online by Cambridge University Press:  07 November 2014

Stephen M. Stahl ,
Meghan M. Grady ,
Chantal Moret  and
Mike Briley
Get access Rights & Permissions [Opens in a new window]

Abstract

The class of serotonin and norepinephrine reuptake inhibitors (SNRIs) now comprises three medications: venlafaxine, milnacipran, and duloxetine. These drugs block the reuptake of both serotonin (5-HT) and norepinephrine with differing selectivity. Whereas milnacipran blocks 5-HT and norepinephrine reuptake with equal affinity, duloxetine has a 10-fold selectivity for 5-HT and venlafaxine a 30-fold selectivity for 5-HT. All three SNRIs are efficacious in treating a variety of anxiety disorders. There is no evidence for major differences between SNRIs and SSRIs in their efficacy in treating anxiety disorders. In contrast to SSRIs, which are generally ineffective in treating chronic pain, all three SNRIs seem to be helpful in relieving chronic pain associated with and independent of depression. Tolerability of an SNRI at therapeutic doses varies within the class. Although no direct comparative data are available, venlafaxine seems to be the least well-tolerated, combining serotonergic adverse effects (nausea, sexual dysfunction, withdrawal problems) with a dose-dependent cardiovascular phenomenon, principally hypertension. Duloxetine and milnacipran appear better tolerated and essentially devoid of cardiovascular toxicity.

Type
Review Articles
Information
CNS Spectrums , Volume 10 , Issue 9 , September 2005 , pp. 732 - 747
Copyright
Copyright © Cambridge University Press 2005

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Article purchase

Temporarily unavailable

References

REFERENCES

1.Wong, DT, Bymaster, FP, Engleman, EA. Prozac (fluoxetine, Lilly 110140), the first selective serotonin uptake inhibitor and an antidepressant drug: twenty years since its first publication. Life Sci. 1995;57:411–441.Google Scholar
2.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.CrossRefGoogle ScholarPubMed
3.Cookson, J. Side-effects of antidepressants. Br J Psychiatry Suppl. 1993;(20):20–24.Google Scholar
4.Burrows, GD, Maguire, KP, Norman, TR. Antidepressant efficacy and tolerability of the selective norepinephrine reuptake inhibitor reboxetine: a review. J Clin Psychiatry. 1998;59(Suppl 14):4–7.Google Scholar
5.Nelson, JC. A review of the efficacy of serotonergic and noradrenergic reuptake inhibitors for treatment of major depression. Biol Psychiatry. 1999;46:1301–1308.Google Scholar
6.Poston, WS, Foreyt, JP. Sibutramine and the management of obesity. Expert Opin Pharmacother. 2004;5:633–642.CrossRefGoogle ScholarPubMed
7.Millan, MJ, Lejeune, F, Gobert, A. Reciprocal autoreceptor and heteroreceptor control of serotonergic, dopaminergic and noradrenergic transmission in the frontal cortex: relevance to the actions of antidepressant agents. J Psychopharmacol. 2000;14:114–138.CrossRefGoogle Scholar
8.Owens, MJ. Selectivity of antidepressants: from the monoamine hypothesis of depression to the SSRI revolution and beyond. J Clin Psychiatry. 2004;65(Suppl 4):5–10.Google Scholar
9.Benveniste, H, Huttemeier, PC. Microdialysis—theory and application. Prog Neurobiol. 1990;35:195–215.Google Scholar
10.Bymaster, FP, Katner, JS, Nelson, DL, et al.Atomoxetine increases extracellular levels of norepinephrine and dopamine in prefrontal cortex of rat: a potential mechanism for efficacy in attention deficit/hyperactivity disorder. Neuropsychopharmacology. 2002;27:699–711.CrossRefGoogle Scholar
11.Bymaster, FP, Zhang, W, Carter, PA, et al.Fluoxetine, but not other selective serotonin uptake inhibitors, increases norepinephrine and dopamine extracellular levels in prefrontal cortex. Psychopharmacology (Berl). 2002;160:353–361.Google Scholar
12.Wong, DT, Bymaster, FP. Dual serotonin and noradrenaline uptake inhibitor class of antidepressants potential for greater efficacy or just hype? Prog Drag Res. 2002;58:169–222.CrossRefGoogle ScholarPubMed
13.Invemizzi, RW, Garattini, S. Role of presynaptic alpha2-adrenoceptors in antidepressant action: recent findings from microdialysis studies. Prog Neuropsychopharmacol Biol Psychiatry. 2004;28:819–827.Google Scholar
14.Wikell, C, Bergqvist, PB, Hjorth, S, Apelqvist, G, Bjork, H, Bengtsson, F. Brain monoamine output alterations after a single venlafaxine challenge in experimental hepatic encephalopathy. Clin Neuropharmacol. 1998;21:296–306.Google Scholar
15.Dawson, LA, Nguyen, HQ, Geiger, A. Effects of venlafaxine on extracellular concentrations of 5-HT and noradrenaline in the rat frontal cortex: augmentation via 5-HT1A receptor antagonism. Neuropharmacology. 1999;38:1153–1163.CrossRefGoogle ScholarPubMed
16.Koch, S, Hemrick-Luecke, SK, Thompson, LK, et al.Comparison of effects of dual transporter inhibitors on monoamine transporters and extracellular levels in rats. Neuropharmacology. 2003;45:935–944.Google Scholar
17.Vaishnavi, SN, Nemeroff, CB, Plott, SJ, et al.Milnacipran: a comparative analysis of human monoamine uptake and transporter binding affinity. Biol Psychiatry. 2004;55:320–322.Google Scholar
18.Millan, MJ, Gobert, A, Lejeune, F, et al.S33005, a novel ligand at both serotonin and norepinephrine transporters: I. Receptor binding, electrophysiological, and neurochemical profile in comparison with venlafaxine, reboxetine, citalopram, and clomipramine. J Pharmacol Exp Ther. 2001;298:565–580.Google Scholar
19.Weikop, P, Kehr, J, Scheel-Kruger, J. The role of alphal- and alpha2-adrenoreceptors on venlafaxine-induced elevation of extracellular serotonin, noradrenaline and dopamine levels in the rat prefrontal cortex and hippocampus. J Psychopharmacol. 2004;18:395–403.Google Scholar
20.Piacentini, MF, Clinckers, R, Meeusen, R, Sarre, S, Ebinger, G, Michotte, Y. Effects of venlafaxine on extracellular 5-HT, dopamine and noradrenaline in the hippocampus and on peripheral hormone concentrations in the rat in vivo. Life Sci. 2003;73:2433–2442.Google Scholar
21.Moret, C, Marien, M. Effects of venlafaxine on extracellular levels of 5-HT and noradrenaline in guinea pig hypothalamus. Society for Neuroscience Abstracts. 1997;23:1225. Abstract 485.5.Google Scholar
22.David, DJ, Bourin, M, Jego, G, Przybylski, C, Jolliet, P, Gardier, AM. Effects of acute treatment with paroxetine, citalopram and venlafaxine in vivo on noradrenaline and serotonin outflow: a microdialysis study in Swiss mice. Br J Pharmacol. 2003;140:1128–1136.Google Scholar
23.Mochizuki, D, Tsujita, R, Yamada, S, et al.Neurochemical and behavioural characterization of milnacipran, a serotonin and noradrenaline reuptake inhibitor in rats. Psychopharmacology (Berl). 2002;162:323–332.Google Scholar
24.Moret, C, Briley, M. Effects of milnacipran and pindolol on extracellular noradrenaline and serotonin levels in guinea pig hypothalamus. J Neurochem. 1997;69:815–822.Google Scholar
25.Kihara, T, Ikeda, M. Effects of duloxetine, a new serotonin and norepinephrine uptake inhibitor, on extracellular monoamine levels in rat frontal cortex. J Pharmacol Exp Ther. 1995;272:177–183.Google ScholarPubMed
26.Gobert, A, Rivet, JM, Cistarelli, JM, Millan, MJ. Buspirone enhances duloxetine- and fluoxetine-induced increases in dialysate levels of dopamine and noradrenaline, but not serotonin, in the frontal cortex of freely moving rats. J Neurochem. 1997;68:1326–1329.Google Scholar
27.Engleman, EA, Perry, KW, Mayle, DA, Wong, DT. Simultaneous increases of extracellular monoamines in microdialysates from hypothalamus of conscious rats by duloxetine, a dual serotonin and norepinephrine uptake inhibitor. Neuropsychopharmacology. 1995;12:287–295.CrossRefGoogle ScholarPubMed
28.Gur, E, Dremencov, E, Lerer, B, Newman, ME. Venlafaxine: acute and chronic effects on 5-hydroxytryptamine levels in rat brain in vivo. Eur J Pharmacol. 1999;372:17–24.CrossRefGoogle ScholarPubMed
29.Bel, N, Artigas, F. Modulation of the extracellular 5-hydroxytryptamine brain concentrations by the serotonin and noradrenaline reuptake inhibitor, milnacipran. Microdialysis studies in rats. Neuropsychopharmacology. 1999;21:745–754.CrossRefGoogle ScholarPubMed
30.Felton, TM, Kang, TB, Hjorth, S, Auerbach, SB. Effects of selective serotonin and serotonin/noradrenaline reuptake inhibitors on extracellular serotonin in rat diencephalon and frontal cortex. Naunyn Schmiedebergs Arch Pharmacol. 2003;367:297–305.CrossRefGoogle Scholar
31.Harvey, AT, Rudolph, RL, Preskorn, SH. Evidence of the dual mechanisms of action of venlafaxine. Arch Gen Psychiatry. 2000;57:503–509.Google Scholar
32.Chalon, SA, Granier, LA, Vandenhende, FR, et al.Duloxetine increases serotonin and norepinephrine availability in healthy subjects: a double-blind, controlled study. Neuropsychopharmacology. 2003;28:1685–1693.Google Scholar
33.Palmier, C, Puozzo, C, Lenehan, T, et al.Monoamine uptake inhibition by plasma from healthy volunteers after single oral doses of the antidepressant, milnacipran. Eur J Clin Pharmacol. 1998;37:235–238.CrossRefGoogle Scholar
34.Turcotte, JE, Debonnel, G, de Montigny, C, Hebert, C, Blier, P. Assessment of the serotonin and norepinephrine reuptake blocking properties of duloxetine in healthy subjects. Neuropsychopharmacology. 2001;24:511–521.CrossRefGoogle ScholarPubMed
35.Vincent, S, Bieck, PR, Garland, EM, et al.Clinical assessment of norepinephrine transporter blockade through biochemical and pharmacological profiles. Circulation. 2004;109:3202–3207.CrossRefGoogle ScholarPubMed
36.Abdelmawla, AH, Langley, RW, Szabadi, E, et al.Comparison of the effects of venlafaxine, desipramine, and paroxetine on noradrenaline- and methoxamine-evoked constriction of the dorsal hand vein. Br J Clin Pharmacol. 1999;48:345–354.Google Scholar
37.Puozzo, C, Leonard, BE. Pharmacokinetics of milnacipran in comparison with other antidepressants. Int Clin Psychopharmacol. 1996;11(Suppl 4):15–27.Google Scholar
38.Troy, SM, Parker, VP, Hicks, DR, Pollack, GM, Chiang, ST. Pharmacokinetics and effect of food on the bioavailability of orally administered venlafaxine. J Clin Pharmacol. 1997;37:954–961.Google Scholar
39.Lantz, RJ, Gillespie, TA, Rash, TJ, et al.Metabolism, excretion, and pharmacokinetics of duloxetine in healthy human subjects. Drug Metab Dispos. 2003;31:1142–1150.Google Scholar
40.Otton, SV, Ball, SE, Cheung, SW, Inaba, T, Rudolph, RL, Sellers, EM. Venlafaxine oxidation in vitro is catalysed by CYP2D6. Br J Clin Pharmacol. 1996;41:149–156.CrossRefGoogle ScholarPubMed
41.Sawada, Y, Ohtani, H. Pharmacokinetics and drug interactions of antidepressive agents [Japanese]. Nippon Rinsho. 2001;59:1539–1545.Google Scholar
42.Perahia, D, Pritchett, YL, Lee, TC, Tran, PF. Comparing duloxetine and venlafaxine in the treatment of major depressive disorder using a global benefit-risk approach. Available at: http://www.nimh.nih.gov/ncdeu/2005abstracts.pdf. Abstracts of NCDEU 2005; Poster 1-14.Google Scholar
43.Lopez-Ibor, J, Guelfi, JD, Pletan, Y, Toumoux, A, Prost, JF. Milnacipran and selective serotonin reuptake inhibitors in major depression. Int Clin Psychopharmacol. 1996;11(Suppl 4):41–46.CrossRefGoogle ScholarPubMed
44.Puech, A, Montgomery, SA, Prost, JF, Solles, A, Briley, M. Milnacipran, a new serotonin and noradrenaline reuptake inhibitor: an overview of its antidepressant activity and clinical tolerability. Int Clin Psychopharmacol. 1997;12:99–108.Google Scholar
45.Thase, ME, Entsuah, AR, Rudolph, RL. Remission rates during treatment with venlafaxine or selective serotonin reuptake inhibitors. Br J Psychiatry. 2001;178:234–241.Google Scholar
46.Stahl, SM, Entsuah, R, Rudolph, RL. Comparative efficacy between venlafaxine and SSRIs: a pooled analysis of patients with depression. Biol Psychiatry. 2002;52:1166–1174.Google Scholar
47.Goldstein, DJ, Lu, Y, Detke, MJ, Wiltse, C, Mallinckrodt, C, Demitrack, MA. Duloxetine in the treatment of depression: a double-blind placebo-controlled comparison with paroxetine. J Clin Psychopharmacol. 2004;24:389–399.CrossRefGoogle ScholarPubMed
48.Anderson, IM. Meta-analytical studies on new antidepressants. Br Med Bull. 2001;57:161–178.Google Scholar
49.Citalopram: clinical effect profile in comparison with clomipramine. A controlled multicenter study. Danish University Antidepressant Group. Psychopharmacology (Berl). 1986;90:131–138.Google Scholar
50.Paroxetine: a selective serotonin reuptake inhibitor showing better tolerance, but weaker antidepressant effect than clomipramine in a controlled multicenter study. Danish University Antidepressant Group. J Affect Disord. 1990;18:289–299.CrossRefGoogle Scholar
51.Anderson, IM, Tomenson, BM. The efficacy of selective serotonin reuptake inhibitors in depression: a meta-analysis of studies against tricyclic antidepressants. J Psychopharmacol. 1994;8:238–249.CrossRefGoogle ScholarPubMed
52.Nelson, JC, Mazure, CM, Jatlow, PI, Bowers, MB Jr, Price, LH. Combining norepinephrine and serotonin reuptake inhibition mechanisms for treatment of depression: a doubleblind, randomized study. Biol Psychiatry. 2004;55:296–300.CrossRefGoogle ScholarPubMed
53.Smith, D, Dempster, C, Glanville, J, Freemantle, N, Anderson, I. Efficacy and tolerability of venlafaxine compared with selective serotonin reuptake inhibitors and other antidepressants: a meta-analysis. Br J Psychiatry. 2002;180:396–404.CrossRefGoogle ScholarPubMed
54.Holliday, SM, Benfield, P. Venlafaxine. A review of its pharmacology and therapeutic potential in depression. Drugs. 1995;49:280–294.Google Scholar
55.Preskom, SH. Antidepressant drug selection: criteria and options. J Clin Psychiatry. 1994;55(Suppl A):6–22.Google Scholar
56.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;9:139–143.Google Scholar
57.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.Google Scholar
58.Entsuah, AR, Huang, H, Thase, ME. Response and remission rates in different subpopulations with major depressive disorder administered venlafaxine, selective serotonin reuptake inhibitors, or placebo. J Clin Psychiatry. 2001;62:869–877.Google Scholar
59.Nemeroff, CB, Entsuah, R, Willard, LB, et al. Comprehensive pooled analysis of remission data: venlafaxine vs. SSRIs (COMPARE). Poster presented at: Annual Meeting of the American Psychiatric Association. May 17-22, 2003; San Francisco, Calif.Google Scholar
60.SirD'Souza, R, George, T, et al. Comparative efficacy of sertraline and venlafaxine XR in major depression. Poster presented at: Annual Meeting of the American Psychiatric Association; May 1-6, 2004; New York, NY.Google Scholar
61.Owens, MJ, Knight, DL, Nemeroff, CB. Second-generation SSRIs: human monoamine transporter binding profile of escitalopram and R-fluoxetine. Biol Psychiatry. 2001;50:345–350.Google Scholar
62.Bielski, RJ, Ventura, D, Chang, CC. A double-blind comparison of escitalopram and venlafaxine extended release in the treatment of major depressive disorder. J Clin Psychiatry. 2004;65:1190–1196.CrossRefGoogle ScholarPubMed
63.Montgomery, SA, Huusom, AK, Bothmer, J. A randomised study comparing escitalopram with venlafaxine XR in primary care patients with major depressive disorder. Neuropsychobiology. 2004;50:57–64.Google Scholar
65.Clerc, G, Milnacipran/Fluvoxamine Study Group. Antidepressant efficacy and tolerability of milnacipran, a dual serotonin and noradrenaline reuptake inhibitor: a comparison with fluvoxamine. Int Clin Psychopharmacol. 2001;16:145–151.Google Scholar
64.Sechter, D, Vandel, P, Weiller, E, et al.A comparative study of milnacipran and paroxetine in outpatients with major depression. J Affect Disord. 2004;83:233–236.Google Scholar
66.Montes, JM, Ferrando, L, Saiz-Ruiz, J. Remission in major depression with two antidepressant mechanisms: results from a naturalistic study. J Affect Disord. 2004;79:229–234.Google Scholar
67.Detke, MJ, Wiltse, CG, Mallinckrodt, CH, et al.Duloxetine in the acute and long-term treatment of major depressive disorder: a placebo- and paroxetine-controlled trial. Eur Neuropsychopharmacol. 2004;14:457–470.Google Scholar
68.Thase, ME, Lu, Y, Joliat, MJ, et al. Remission in placebo-controlled trials of duloxetine with an SSRI comparator. Poster presented at: Annual Meeting of the American Psychiatric Association; May 17-22, 2003; San Francisco, Calif.Google Scholar
69.Duloxetine product information. Cymbalta Web site. Available at: http://www.cymbalta.com/index.jsp. Accessed on June 1, 2005.Google Scholar
70.Kessler, RC, McGonagle, KA, Zhao, S, et al.Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States. Results from the National Comorbidity Survey. Arch Gen Psychiatry. 1994;51:8–19.Google Scholar
71.Silverstone, PH. Qualitative review of SNRIs in anxiety. J Clin Psychiatry. 2004;65(Suppl 17):19–28.Google Scholar
72.Tanaka, M, Yoshida, M, Emoto, H, Ishii, H. Noradrenaline systems in the hypothalamus, amygdala and locus coeruleus are involved in the provocation of anxiety: basic studies. Eur J Pharmacol. 2000;405:397–406.Google Scholar
73.Ressler, KJ, Nemeroff, CB. Role of serotonergic and noradrenergic systems in the pathophysiology of depression and anxiety disorders. Depress Anxiety. 2000;12(Suppl 1):2–19.Google Scholar
74.Iny, LJ, Pecknold, J, Suranyi-Cadotte, BE, et al.Studies of a neurochemical link between depression, anxiety, and stress from [3H]imipramine and [3H]paroxetine binding on human platelets. Biol Psychiatry. 1994;36:281–291.Google Scholar
75.Gorman, JM. Treatment of generalized anxiety disorder. J Clin Psychiatry. 2002;63(Suppl 8):17–23.Google Scholar
76.Pollack, MH, Zaninelli, R, Goddard, A, et al.Paroxetine in the treatment of generalized anxiety disorder: results of a placebo-controlled, flexible-dosage trial. J Clin Psychiatry. 2001;62:350–357Google Scholar
77.Rocca, P, Fonzo, V, Scotta, M, Zanalda, E, Ravizza, L. Paroxetine efficacy in the treatment of generalized anxiety disorder. Acta Psychiatr Scand. 1997;95:444–450.CrossRefGoogle ScholarPubMed
78.Feldman, S, Weidenfeld, J. The excitatory effects of the amygdala on hypothalamo-pituitary-adrenocortical responses are mediated by hypothalamic norepinephrine, serotonin, and CRF-41. Brain Res Bull. 1998;45:389–393.Google Scholar
79.Sevy, S, Papadimitriou, GN, Surmont, DW, Goldman, S, Mendlewicz, J. Noradrenergic function in generalized anxiety disorder, major depressive disorder, and healthy subjects. Biol Psychiatry. 1989;25:141–152.Google Scholar
80.Rickels, K, Pollack, MH, Sheehan, DV, Haskins, JT. Efficacy of extended-release venlafaxine in non-depressed outpatients with generalized anxiety disorder. Am J Psychiatry. 2000;157:968–974.Google Scholar
81.Gelenberg, AJ, Lydiard, RB, Rudolph, RL, Aguiar, L, Haskins, JT, Salinas, E. Efficacy of venlafaxine extended-release capsules in nondepressed outpatients with generalized anxiety disorder: A 6-month randomized controlled trial. JAMA. 2000;283:3082–3088.Google Scholar
82.Davidson, JR, DuPont, RL, Hedges, D, et al.Efficacy, safety, and tolerability of venlafaxine extended release and buspirone in outpatients with generalized anxiety disorder. J Clin Psychiatry. 1999;60:528–535.Google Scholar
83.Hackett, D, Haudiquet, V, Salinas, E. A method for controlling for a high placebo response rate in a comparison of venlafaxine XR and diazepam in the short-term treatment of patients with generalised anxiety disorder. Eur Psychiatry. 2003;18:182–187.Google Scholar
84.Allgulander, C, Hackett, D, Salinas, E. Venlafaxine extended release (ER) in the treatment of generalised anxiety disorder: twenty-four-week placebo-controlled dose-ranging study. Br J Psychiatry. 2001;179:15–22.CrossRefGoogle Scholar
85.Allgulander, C, Mangano, R, Zhang, J, et al.Efficacy of Venlafaxine ER in patients with social anxiety disorder: a double-blind, placebo-controlled, parallel-group comparison with paroxetine. Hum Psychopharmacol. 2004;19:387–396.Google Scholar
86.Rickels, K, Mangano, R, Khan, A. A double-blind, placebo-controlled study of a flexible dose of venlafaxine ER in adult outpatients with generalized social anxiety disorder. J Clin Psychopharmacol. 2004;24:488–496.Google Scholar
87.Liebowitz, MR, Mangano, RM, Bradwejn, J, Asnis, G; SAD Study Group. A randomized controlled trial of venlafaxine extended release in generalized social anxiety disorder. J Clin Psychiatry. 2005;66:238–247.Google Scholar
88.Liebowitz, MR, Gelenberg, AJ, Munjack, D. Venlafaxine extended release vs placebo and paroxetine in social anxiety disorder. Arch Gen Psychiatry. 2005;62:190–198.Google Scholar
89.Whitaker, T, Bradwejn, J, Emilien, G, et al. Treatment of panic disorder with venlafaxine XR. Poster presented at: Annual Meeting of the American College of Neuropsychopharmacology; December 7-11, 2003; San Juan, PR.Google Scholar
90.Pollack, MH, Emilien, G, Tzanis, E, et al. Venlafaxine XR and paroxetine in the short-term treatment of panic disorder. Poster presented at: Annual Meeting of the World Federation for the Society of Biological Psychiatry; February 6-13, 2004; Sydney, Australia.Google Scholar
91.Liebowitz, MR, Asnis, G, Tzanis, E, et al. A placebo-controlled trial of venlafaxine XR in the short-term treatment of panic disorder. Poster presented at: Annual Meeting of the Collegium Internationale Neuropsychopharmacologicum; June 20-24, 2004; Paris, France.Google Scholar
92.Davidson, J, Lipschitz, A, Musgnung, J. A double-blind comparison of venlafaxine XR, sertraline, and placebo in the treatment of PTSD. Poster presented at: Annual meeting of the New Clinical Drug Evaluation Unit; June 1-4, 2004; Phoenix, Ariz.Google Scholar
93.Denys, D, van der Wee, N, van Megen, HJ, Westenberg, HG. A double blind comparison of venlafaxine and paroxetine in obsessive-compulsive disorder. J Clin Psychopharmacol. 2003;23:568–575.Google Scholar
94.Davidson, JR, Meoni, P, Haudiquet, V, Cantillon, M, Hackett, D. Achieving remission with venlafaxine and fluoxetine in major depression: its relationship to anxiety symptoms. Depress Anxiety. 2002;16:4–13.CrossRefGoogle ScholarPubMed
95.Tsukamoto, T, Kondoh, R, Ichikawa, K. Efficacy and safety of milnacipran in the treatment of generalized anxiety disorder: an open study. Int J Psychiatry Clin Pract. 2004;8:255–258Google Scholar
96.Dunner, DL, Goldstein, DJ, Mallinckrodt, C, Lu, Y, Detke, MJ. Duloxetine in treatment of anxiety symptoms associated with depression. Depress Anxiety. 2003;18:53–61.Google Scholar
97.Stahl, SM. Does depression hurt? J Clin Psychiatry. 2002;63:273–274.Google Scholar
98.Briley, M. New hope in the treatment of painful symptoms in depression. Curr Opin Investig Drugs. 2003;4:42–45.Google Scholar
99.Briley, M. Clinical experience with dual action antidepressants in different chronic pain syndromes. Hum Psychopharmacol. 2004(19 Suppl 1):S21–S25.Google Scholar
100.Delgado, PL. Common pathways of depression and pain. J Clin Psychiatry. 2004;65 (Suppl 12):16–19.Google Scholar
101.Fishbain, DA, Cutler, R, Rosomoff, HL, Rosomoff, RS. Evidence-based data from animal and human experimental studies on pain relief with antidepressants: a structured review. Pain Med. 2000;1:310–316.Google Scholar
102.Entsuah, AR. Venlafaxine vs SSRIs: comparison of somatic symptom resolution. World J Biol Psychiatry. 2004;5(Suppl 1):92–97.Google Scholar
103.Max, MB, Lynch, SA, Muir, J, Shoaf, SE, Smoller, B, Dubner, R. Effects of desipramine, amitriptyline, and fluoxetine on pain in diabetic neuropathy. N Engl J Med. 1992;326:1250–1256.Google Scholar
104.Max, MB. Treatment of post-herpetic neuralgia: antidepressants. Ann Neurol. 1994;35(Suppl):S50–S53.Google Scholar
105.Staiger, TO, Gaster, B, Sullivan, MD, Deyo, RA. Systematic review of antidepressants in the treatment of chronic low back pain. Spine. 2003;28:2540–2545.106.Google Scholar
Sayar, K, Aksu, G, Ak, I, Tosun, M. Venlafaxine treatment of fibromyalgia. Ann Pharmacother. 2003;7:1561–1565.Google Scholar
107.Sumpton, JE, Moulin, DE. Treatment of neuropathic pain with venlafaxine. Ann Pharmacother. 2001;35:557–559.CrossRefGoogle ScholarPubMed
108.Sindrup, SH, Bach, FW, Madsen, C, Gram, LF, Jensen, TS. Venlafaxine versus imipramine in painful polyneuropathy: a randomized, controlled trial. Neurology. 2003;60:1284–1289.Google Scholar
109.Tasmuth, T, Hartel, B, Kalso, E. Venlafaxine in neuropathic pain following treatment of breast cancer. Eur J Pain. 2002;6:17–24.Google Scholar
110.Vitton, O, Gendreau, M, Gendreau, J. A double-blind placebo-controlled trial of milnacipran in the treatment of fibromyalgia. Hum Psychopharmacol. 2004;19(Suppl 1):S27–S35.Google Scholar
111.Detke, MJ, Lu, Y, Goldstein, DJ, Hayes, JR, Demitrack, MA. Duloxetine, 60 mg once daily, for major depressive disorder: a randomized double-blind placebo-controlled trial. J Clin Psychiatry. 2002;63:308–315.Google Scholar
112.Brannan, SK, Mallinckrodt, CH, Detke, MJ, Watkin, JG, Tollefson, GD. Onset of action for duloxetine 60 mg once daily: double-blind, placebo-controlled studies. J Psychiatr Res. 2005;39:161–172.Google Scholar
113.Arnold, LM, Lu, Y, Crofford, LJ, et al.A double-blind, multicenter trial comparing duloxetine with placebo in the treatment of fibromyalgia patients with or without major depressive disorder. Arthritis Rheum. 2004;50:2974–2984.Google Scholar
114.Norregaard, J, Volkmann, H, Danneskiold-Samsoe, B. A randomized controlled trial of citalopram in the treatment of fibromyalgia. Pain. 1995;61:445–449.Google Scholar
115.Anderberg, UM, Marteinsdottir, I, von Knorring, L. Citalopram in patients with fibromyalgia—a randomized, double-blind, placebo-controlled study. Eur J Pain. 2000;4:27–35.Google Scholar
116.Arnold, LM, Hess, EV, Hudson, JI, Welge, JA, Berno, SE, Keck, PE Jr.A randomized, placebo-controlled, double-blind, flexible-dose study of fluoxetine in the treatment of women with fibromyalgia. Am J Med. 2002;112:191–197.Google Scholar
117.O'Malley, PG, Jackson, JL, Santoro, J, Tomkins, G, Balden, E, Kroenke, K. Antidepressant therapy for unexplained symptoms and symptom syndromes. J Fam Pract. 1999;48:980–990.Google Scholar
118.O'Malley, PG, Balden, E, Tomkins, G, Santoro, J, Kroenke, K, Jackson, JL. Treatment of fibromyalgia with antidepressants: a meta-analysis. J Gen Intern Med. 2000;15:659–666.Google Scholar
119.Aragona, M, Bancheri, L, Perinelli, D, et al.Randomized double-blind comparison of serotonergic (Citalopram) versus noradrenergic (Reboxetine) reuptake inhibitors in outpatients with somatoform, DSM-IV-TR pain disorder. Eur J Pain. 2005;9:33–38.Google Scholar
120.Wellington, K, Perry, CM. Venlafaxine extended-release: a review of its use in the management of major depression. CNS Drugs. 2001;15:643–669.Google Scholar
121.Raskin, J, Goldstein, DJ, Mallinckrodt, CH, Ferguson, MB. Duloxetine in the long-term treatment of major depressive disorder. J Clin Psychiatry. 2003;64:1237–1244.Google Scholar
122.Rosen, RC, Lane, RM, Menza, M. Effects of SSRIs on sexual function: a critical review. J Clin Psychopharmacol. 1999;19:67–85.Google Scholar
123.Keltner, NL, McAfee, KM, Taylor, CL. Mechanisms and treatments of SSRI-induced sexual dysfunction. Perspect Psychiatr Care. 2002;38:111–116.Google Scholar
124.Clayton, AH, Pradko, JF, Croft, HA, et al.Prevalence of sexual dysfunction among newer antidepressants. J Clin Psychiatry. 2002;63:357–366.Google Scholar
125.Deakin, B, Dursun, S. Optimizing antidepressant treatment: efficacy and tolerability. Int Clin Psychopharmacol. 2002;17(Suppl 1):S13–S24.Google Scholar
126.McGahuey, CA, Gelenberg, AJ, Laukes, CA, et al.The Arizona Sexual Experience Scale (ASEX): reliability and validity. J Sex Marital Ther. 2000;26:25–40.Google Scholar
127.Black, K, Shea, C, Dursun, S, Kutcher, S. Selective serotonin reuptake inhibitor discontinuation syndrome: proposed diagnostic criteria. J Psychiatry Neurosci. 2000;25:255–261.Google Scholar
128.Judge, R, Parry, MG, Quail, D, Jacobson, JG. Discontinuation symptoms: comparison of brief interruption in fluoxetine and paroxetine treatment. Int Clin Psychopharmacol. 2002;17:217–225.Google Scholar
129.Michelson, D, Fava, M, Amsterdam, J, et al.Interruption of selective serotonin reuptake inhibitor treatment. Double-blind, placebo-controlled trial. Br J Psychiatry. 2000;176:363–368.Google Scholar
130.Pinzani, V, Ginies, E, Robert, L, Peyriere, H, Abbar, M, Blayac, JP. Venlafaxine withdrawal syndrome: report of six cases and review of the literature [French]. Rev Med Interne. 2000;21:282–284.Google Scholar
131.Trenque, T, Piednoir, D, Frances, C, et al.Reports of withdrawal syndrome with the use of SSRIs: a case/non-case study in the French Pharmacovigilance database. Pharmacoepidemiol Drug Saf. 2002;11:281–283.CrossRefGoogle ScholarPubMed
132.Vandel, P, Sechter, D, Weiller, , et al.Post-treatment emergent adverse events in depressed patients following treatment with milnacipran and paroxetine. Hum Psychopharmacol. 2004;19:585–586.Google Scholar
133.Feighner, JP. Cardiovascular safety in depressed patients: focus on venlafaxine. J Clin Psychiatry. 1995;56:574–579.Google Scholar
134.Thase, ME. Effects of venlafaxine on blood pressure: a meta-analysis of original data from 3744 depressed patients. J Clin Psychiatry. 1998;59:502–508.Google Scholar
135.Khalifa, M, Daleau, P, Turgeon, J. Mechanism of sodium channel block by venlafaxine in guinea pig ventricular myocytes. J Pharmacol Exp Ther. 1999;291:280–284.Google Scholar
136.Combes, A, Peytavin, G, Theron, D. Conduction disturbances associated with venlafaxine. Ann Intern Med. 2001;134:166–167.Google Scholar
137.Committee for the Safety of Medicines page. Medicine and Healthcare Products Regulatory Agency Web site. Available at: http://www.mca.gov.uk/aboutagency/regframework/csm/csmhome.htm. Accessed on December 13, 2004.Google Scholar
138.Guelfi, JD, Ansseau, M, Corruble, E, et al.A double-blind comparison of the efficacy and safety of milnacipran and fluoxetine in depressed inpatients. Int Clin Psychopharmacol. 1998;13:121–128.Google Scholar
139.Montgomery, SA, Prost, JF, Solles, A, Briley, M. Efficacy and tolerability of milnacipran: an overview. Int Clin Psychopharmacol 1996;11(Suppl 4):47–51.Google Scholar
140.Schatzberg, AF. Efficacy and tolerability of duloxetine, a novel dual reuptake inhibitor, in the treatment of major depressive disorder. J Clin Psychiatry. 2003;64(Suppl 13):30–37.Google Scholar
141.Thase, ME, Tran, PV, Wiltse, C, Pangallo, BA, Mallinckrodt, C, Detke, MJ. Cardiovascular profile of duloxetine, a dual reuptake inhibitor of serotonin and norepinephrine. J Clin Psychopharmacol. 2005;25:132–140.Google Scholar
142.Jick, SS, Dean, AD, Jick, H. Antidepressants and suicide. BMJ. 1995;310:215–218.Google Scholar
143.Barbey, JT, Roose, SP. SSRI safety in overdose. J Clin Psychiatry. 1998;59(Suppl 15):42–48.Google Scholar
144.Isbister, GK, Bowe, SJ, Dawson, A, et al.Relative toxicity of selective serotonin reuptake inhibitors (SSRIs) in overdose. J Toxicol Clin Toxicol. 2004;42:277–285.Google Scholar
145.Dams, R, Benijts, TH, Lambert, WE, et al.A fatal case of serotonin syndrome after combined moclobemide-citalopram intoxication. J Anal Toxicol. 2001;25:147–151.Google Scholar
146.Schweizer, E, Feighner, J, Mandos, LA, et al.Comparison of venlafaxine and imipramine in the acute treatment of major depression in outpatients. J Clin Psychiatry. 1994;55:104–108.Google Scholar
147.Ereshefsky, L. Drug-drug interactions involving antidepressants: focus on venlafaxine. J Clin Psychopharmacol. 1996;16(Suppl 2):37S–53S.Google Scholar
148.Settle, EC Jr.Antidepressant drugs: disturbing and potentially dangerous adverse effects. J Clin Psychiatry. 1998;59(Suppl 16):25–30.Google Scholar
149.Mazur, JE, Doty, JD, Krygiel, AS. Fatality related to a 30-g venlafaxine overdose. Pharmacotherapy. 2003;23:1668–1672.Google Scholar
150.Kelly, CA, Dhaun, N, Laing, WJ, et al.Comparative toxicity of citalopram and the newer antidepressants after overdose. J Toxicol Clin Toxicol. 2004;42:67–71.Google Scholar
151.Buckley, NA, McManus, PR. Fatal toxicity of serotoninergic and other antidepressant drugs: analysis of United Kingdom mortality data. BMJ. 2002;325:1332–1333.Google Scholar
152.Cheeta, S, Schifano, F, Oyefeso, A, et al.Antidepressant-related deaths and antidepressant prescriptions in England and Wales, 1998-2000. Br J Psychiatry. 2004;184:41–47.Google Scholar
153.Medicine and Healthcare Products Regulatory Agency Web site. Available at: http://www.mhra.gov.uk. Accessed on December 13, 2004.Google Scholar
154.Thompson, C. Mirtazapine versus selective serotonin reuptake inhibitors. J Clin Psychiatry. 1999;60(Suppl 17):18–22Google Scholar
155.Nierenberg, AA, DeCecco, LM. Definitions of antidepressant treatment response, remission, nonresponse, partial response, and other relevant outcomes: a focus on treatment-resistant depression. J Clin Psychiatry 2001;62(Suppl 16):5–9.Google Scholar
156.Paykel, ES, Ramana, R, Cooper, Z, et al.Residual symptoms after partial remission: an important outcome in depression. Psychol Med. 1995;25:1171–1180.Google Scholar