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Tolerability of Serotonin Norepinephrine Reuptake Inhibitor Antidepressants

Published online by Cambridge University Press:  07 November 2014

Abstract

All three serotonin norepinephrine reuptake inhibitors (SNRIs) inhibit the reuptake of both serotonin and norepinephrine but they do so with differing affinity ratios. Venlafaxine has a 30-fold higher affinity for serotonin than for norepinephrine while duloxetine has a 10-fold selectivity for serotonin. Milnacipran has a balanced (1:1) ratio of potency for inhibition of reuptake of the two neurotransmitters. The most frequent adverse event with SNRIs is nausea. Not unexpectedly, adverse effects related to a noradrenergic stimulation, such as dry mouth, sweating, and constipation, are found more frequently with SNRIs than with selective serotonin reuptake inhibitors. At true SNRI doses, venlafaxine is associated with dose-dependent cardiovascular phenomena (principally increased blood pressure), an effect which is less frequent with duloxetine and rare with milnacipran. Serious and potentially fatal hepatotoxity has been reported with duloxetine. This problem appears to be unique to duloxetine and not a characteristic of the SNRI class. There are differences in overdose toxicity between venlafaxine and the other SNRIs, possibly related to its increased cardiotoxicity.

Type
Research Article
Copyright
Copyright © Cambridge University Press 2008

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References

1. Stahl, SM, Grady, MM, Moret, C, Briley, M. SNRIs: their pharmacology, clinical efficacy, and tolerability in comparison with other classes of antidepressants. CNS Spectr. 2005;10:732747.Google Scholar
2. Puech, A, Montgomery, SA, Prost, JF, et al. Milnacipran, a new serotonin and noradrenaline reuptake inhibitor: an overview of its antidepressant activity and clinical tolerability. Int Clin Psychopharmacol. 1997;12:99108.CrossRefGoogle ScholarPubMed
3. Wellington, K, Perry, CM. Venlafaxine extended-release: a review of its use in the management of major depression. CNS Drugs. 2001;15:643669.CrossRefGoogle ScholarPubMed
4. Raskin, J, Goldstein, DJ, Mallinckrodt, CH, et al. Duloxetine in the long-term treatment of major depressive disorder. J Clin Psychiatry. 2003;64:12371244.CrossRefGoogle ScholarPubMed
5. Vis, PM, van Baardewijk, M, Einarson, TR. Duloxetine and venlafaxine-XR in the treatment of major depressive disorder: a meta-analysis of randomized clinical trials. Ann Pharmacother. 2005;39:17981807.CrossRefGoogle ScholarPubMed
6. Eckert, L, Lançon, C. Duloxetine compared with fluoxetine and venlafaxine: use of meta-regression analysis for indirect comparisons. BMC Psychiatry. 2006;24:630.Google Scholar
7. Lopez-Ibor, J, Guelfi, JD, Pletan, Y, Tournoux, A, Prost, JF. Milnacipran and selective serotonin reuptake inhibitors in major depression. Int Clin Psychopharmacol. 1996;11(Suppl 4):4146.Google Scholar
8. Stahl, SM, Entsuah, R, Rudolph, RL. Comparative efficacy between venlafaxine and SSRIs: a pooled analysis of patients with depression. Biol Psychiatry. 2002;52:11661174.Google Scholar
9. Goldstein, DJ, Lu, Y, Detke, MJ, et al. Duloxetine in the treatment of depression: a double-blind placebo-controlled comparison with paroxetine. J Clin Psychopharmacol. 2004;24:389399.Google Scholar
10. Hartford, J, Kornstein, S, Liebowitz, M, et al. Duloxetine as an SNRI treatment for generalized anxiety disorder: results from a placebo and active-controlled trial. Int Clin Psychopharmacol. 2007;22:167174.Google Scholar
11. Perahia, DG, Pritchett, YL, Kajdasz, DK, et al. A randomized, double-blind comparison of duloxetine and venlafaxine in the treatment of patients with major depressive disorder. J Psychiatr Res. 2008;42:2234.CrossRefGoogle ScholarPubMed
12. Feighner, JP. Cardiovascular safety in depressed patients: focus on venlafaxine. J Clin Psychiatry. 1995;56:574579.Google Scholar
13. Thase, ME. Effects of venlafaxine on blood pressure: a meta-analysis of original data from 3744 depressed patients. J Clin Psychiatry. 1998;59:502508.Google Scholar
14. Khalifa, M, Daleau, P, Turgeon, J. Mechanism of sodium channel block by venlafaxine in guinea pig ventricular myocytes. J Pharmacol Exp Ther. 1999;291:280284.Google Scholar
15. Combes, A, Peytavin, G, Theron, D. Conduction disturbances associated with venlafaxine. Ann Intern Med. 2001;134:166167.Google Scholar
16. 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;13:121128.Google Scholar
17. 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;16:145151.CrossRefGoogle Scholar
18. Montgomery, SA, Prost, JF, Solles, A, et al. Efficacy and tolerability of milnacipran: an overview. Int Clin Psychopharmacol. 1996;11(Suppl 4):4751.CrossRefGoogle ScholarPubMed
19. 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):3037.Google Scholar
20. hase, ME, Tran, PV, Wiltse, C, et al. Cardiovascular profile of duloxetine, a dual reuptake inhibitor of serotonin and norepinephrine. J Clin Psychopharmacol. 2005;25:132140.Google Scholar
21. FDA Medication Guide: CYMBALTA (duloxetine hydrochloride) delayedrelease capsules. Available at: http://www.fda.gov/cder/foi/label/2007/021427s009s011s013lbl.pdf. Accessed June 13, 2008.Google Scholar
22. Hanje, AJ, Pell, LJ, Votolato, NA, Frankel, WL, Kirkpatrick, RB. Case report: fulminant hepatic failure involving duloxetine hydrochloride. Clin Gastroenterol Hepatol. 2006;4:912917.Google Scholar
23. Phillips, BB, Digmann, RR, Beck, MG. Hepatitis associated with lowdose venlafaxine for postmenopausal vasomotor symptoms. Ann Pharmacother. 2006;40:323327.CrossRefGoogle ScholarPubMed
24. FDA Medication Guide: EFFEXOR XR (venlafaxine hydrochloride) extended-release capsules. Available at: http://www.fda.gov/cder/foi/label/2008/020151s052,020699s083lbl.pdf. Accessed June 13, 2008.Google Scholar
25. Rosen, RC, Lane, RM, Menza, M. Effects of SSRIs on sexual function: a critical review. J Clin Psychopharmacol. 1999;19:6785.Google Scholar
26. Keltner, NL, McAfee, KM, Taylor, CL. Mechanisms and treatments of SSRIinduced sexual dysfunction. Perspect Psychiatr Care. 2002;38:111116.CrossRefGoogle ScholarPubMed
27. Clayton, AH, Pradko, JF, Croft, HA, et al. Prevalence of sexual dysfunction among newer antidepressants. J Clin Psychiatry. 2002;63:357366.Google Scholar
28. Montejo, AL, Llorca, G, Izquierdo, JA, Rico-Villademoros, F. Incidence of sexual dysfunction associated with antidepressant agents: a prospective multicenter study of 1022 outpatients. Spanish Working Group for the Study of Psychotropic-Related Sexual Dysfunction. J Clin Psychiatry. 2001;62(Suppl 3):1021.Google Scholar
29. Baldwin, D, Moreno, R, Briley, M. Resolution of sexual dysfunction during acute treatment of major depression with milnacipran. Hum Psychopharmacology. In press.Google Scholar
30. 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;51:819.Google Scholar
31. 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;14:457470.CrossRefGoogle ScholarPubMed
32. Black, K, Shea, C, Dursun, S, et al. Selective serotonin reuptake inhibitor discontinuation syndrome: proposed diagnostic criteria. J Psychiatry Neurosci. 2000;25:255261.Google ScholarPubMed
33. Markowitz, JS, DeVane, CL, Liston, HL, Montgomery, SA. An assessment of selective serotonin reuptake inhibitor discontinuation symptoms with citalopram. Int Clin Psychopharmacol. 2000;15:329333.Google Scholar
34. Michelson, D, Fava, M, Amsterdam, J, et al. Interruption of selective serotonin reuptake inhibitor treatment. Double-blind, placebo-controlled trial. Br J Psychiatry. 2000;176:363368.CrossRefGoogle ScholarPubMed
35. Pinzani, V, Ginies, E, Robert, L, et al. Venlafaxine withdrawal syndrome: report of six cases and review of the literature. Rev Med Interne. 2000;21:282284.Google Scholar
36. 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;11:281283.Google Scholar
37. Perahia, DG, Kajdasz, DK, Desaiah, D, Haddad, PM. Symptoms following abrupt discontinuation of duloxetine treatment in patients with major depressive disorder. J Affect Disord. 2005;89:207212.Google Scholar
38. Vandel, P, Sechter, D, Weiller, et al. Post-treatment emergent adverse events in depressed patients following treatment with milnacipran and paroxetine. Hum Psychopharmacol Clin Exp. 2004;19:585586.Google Scholar
39. Preskorn, SH, Shah, R, Neff, M, Golbeck, AL, Choi, J. The potential for clinically significant drug-drug interactions involving the CYP 2D6 system: effects with fluoxetine and paroxetine versus sertraline. J Psychiatr Pract. 2007;13:512.Google Scholar
40. Otton, SV, Ball, SE, Cheung, SW, et al. Venlafaxine oxidation in vitro is catalysed by CYP2D6. Br J Clin Pharmacol. 1996;41:149156.Google Scholar
41. Puozzo, C, Leonard, BE. Pharmacokinetics of milnacipran in comparison with other antidepressants. Int Clin Psychopharmacol. 1996;11(Suppl 4):1527.CrossRefGoogle ScholarPubMed
42. Sawada, Y, Ohtani, H. Pharmacokinetics and drug interactions of antidepressive agents. Nippon Rinsho. 2001;59:15391545.Google Scholar
43. Jick, SS, Dean, AD, Jick, H. Antidepressants and suicide. Br Med J. 1995;310:215218.Google Scholar
44. Barbey, JT, Roose, SP. SSRI safety in overdose. J Clin Psychiatry. 1998;59(Suppl 15):4248.Google Scholar
45. Settle, EC Jr. Antidepressant drugs: disturbing and potentially dangerous adverse effects. J Clin Psychiatry. 1998;59(Suppl 16):2530.Google Scholar
46. Mazur, JE, Doty, JD, Krygiel, AS. Fatality Related to a 30-g venlafaxine overdose. Pharmacotherapy. 2003;23:16681672.Google Scholar
47. 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;55:104108.Google Scholar
48. Ereshefsky, L. Drug-drug interactions involving antidepressants: focus on venlafaxine. J Clin Psychopharmacol. 1996;16(Suppl 2):3753.Google Scholar
49. Kelly, CA, Dhaun, N, Laing, WJ, et al. Comparative toxicity of citalopram and the newer antidepressants after overdose. J Toxicol Clin Toxicol. 2004;42:6771.Google Scholar
50. Buckley, NA, McManus, PR. Fatal toxicity of serotoninergic and other antidepressant drugs: analysis of United Kingdom mortality data. Br Med J. 2002;325:13321333.Google Scholar
51. Cheeta, S, Schifano, F, Oyefeso, A, et al. Antidepressant-related deaths and antidepressant prescriptions in England and Wales, 1998-2000. Br J Psychiatry. 2004;184:4147.CrossRefGoogle ScholarPubMed
52. Montgomery, SA, Baldwin, DS, Blier, P, et al. Which antidepressants have demonstrated superior efficacy? A review of the evidence. Int Clin Psychopharmacol. 2007;22:323329.Google Scholar