Assessment of N-acetylcysteine as an Alternative for the Treatment of the Premenstrual Dysphoric Disorder: A Randomized Clinical Trial
Introduction: Premenstrual dysphoric disorder (PMDD) is a common condition affecting females' quality of life in a significant negative manner. Verities of medical treatments have been investigated for whether the prevention or treatment of this condition with uncertain outcomes. The current stud has aimed to assess the efficacy of N-acetylcysteine (NAC) versus fluoxetine for the treatment of PMDD.
Methods: The current randomized clinical trial has been conducted on 119 childbearing females, randomly divided into three groups of either treatment with 10 mg of fluoxetine twice daily or 450 mg of NAC twice daily or placebo in 2016-18. The participants used the agents for two weeks following menstruation. These treatment approaches performed for two menstrual cycles. The questionnaires of Hamilton and daily record of severity of problems (DRSP) were filled before and following the interventions for both groups, and the results were compared.
Results: The baseline DRSP and Hamilton scores were not statistically different among the three groups(P-value>0.05) while by the end of the study all of the groups presented significantly improved scores(P-value<0.001). Comparison of three groups revealed remarkable inferiority of placebo to the other two groups(P-value<0.05) while no statistical difference was found between N-acetylcysteine with fluoxetine in terms of neither Hamilton(P-value=0.120) nor DRSP scores(P-value=0.749).
Conclusion: The current study showed significant improvement in the PMDD symptoms following use of whether placebo or fluoxetine or NAC. Comparison of the agents revealed remarkable superiority of both fluoxetine and NAC to the placebo while NAC and fluoxetine had similar efficacy on the PMDD symptoms relief.
2. Cohen LS, Miner C, Brown E, Freeman EW, Halbreich U, Sundell K, et al. Premenstrual daily fluoxetine for premenstrual dysphoric disorder: a placebo-controlled, clinical trial using computerized diaries. Obstetrics & Gynecology. 2002;100(3):435-44.
3. Bäckström T, Bäckström F. Drugs for the Management of Premenstrual Syndrome and Related Syndromes. Gynecological Drug Therapy. 2016:47.
4. Rapkin AJ, Lewis EI. Treatment of premenstrual dysphoric disorder. Women’s Health. 2013;9(6):537-56.
5. Ozcan H, Oral E, Gulec M, Turkez H, Gulec TC, Ustundag MF, et al. Total oxidant–antioxidant and paraoxonase-1 levels in premenstrual dysphoric disorder: a follow-up study. Psychiatry and Clinical Psychopharmacology. 2017;27(2):116-24.
6. Hantsoo L, Epperson CN. Premenstrual dysphoric disorder: epidemiology and treatment. Current psychiatry reports. 2015;17(11):87.
7. Rojansky N, Halbreich U, Zander K, Barkai A, Goldstein S. Imipramine receptor binding and serotonin uptake in platelets of women with premenstrual changes. Gynecologic and obstetric investigation. 1991;31(3):146-52.
8. Pearlstein TB, Bachmann GA, Zacur HA, Yonkers KA. Treatment of premenstrual dysphoric disorder with a new drospirenone-containing oral contraceptive formulation. Contraception. 2005;72(6):414-21.
9. Marjoribanks J, Brown J, O'Brien PMS, Wyatt K. Selective serotonin reuptake inhibitors for premenstrual syndrome. Cochrane Database of Systematic Reviews. 2013(6).
10. Shah NR, Jones J, Aperi J, Shemtov R, Karne A, Borenstein J. Selective serotonin reuptake inhibitors for premenstrual syndrome and premenstrual dysphoric disorder: a meta-analysis. Obstetrics and gynecology. 2008;111(5):1175.
11. Dimmock PW, Wyatt KM, Jones PW, O'brien PS. Efficacy of selective serotonin-reuptake inhibitors in premenstrual syndrome: a systematic review. The Lancet. 2000;356(9236):1131-6.
12. Steiner M, Hirschberg AL, Bergeron R, Holland F, Gee MD, Van Erp E. Luteal phase dosing with paroxetine controlled release (CR) in the treatment of premenstrual dysphoric disorder. American journal of obstetrics and gynecology. 2005;193(2):352-60.
13. Freeman EW, Sondheimer SJ. Premenstrual dysphoric disorder: recognition and treatment. Primary care companion to the Journal of clinical psychiatry. 2003;5(1):30.
14. Steinberg EM, Cardoso GM, Martinez PE, Rubinow DR, Schmidt PJ. Rapid response to fluoxetine in women with premenstrual dysphoric disorder. Depression and anxiety. 2012;29(6):531-40.
15. Tuladhar ET, Rao A. Plasma protein oxidation and total antioxidant power in premenstrual syndrome. Asian Pacific Journal of Tropical Medicine. 2010;3(3):237-40.
16. Sadowska AM. N-Acetylcysteine mucolysis in the management of chronic obstructive pulmonary disease. Therapeutic advances in respiratory disease. 2012;6(3):127-35.
17. Millea PJ. N-acetylcysteine: multiple clinical applications. American family physician. 2009;80(3).
18. Sadowska A, Manuel-Y-Keenoy B, De Backer W. Antioxidant and anti-inflammatory efficacy of NAC in the treatment of COPD: discordant in vitro and in vivo dose-effects: a review. Pulmonary pharmacology & therapeutics. 2007;20(1):9-22.
19. Lasram MM, Lamine AJ, Dhouib IB, Bouzid K, Annabi A, Belhadjhmida N, et al. Antioxidant and anti-inflammatory effects of N-acetylcysteine against malathion-induced liver damages and immunotoxicity in rats. Life sciences. 2014;107(1-2):50-8.
20. Hamilton M. A rating scale for depression J Neurol Neurosurg Psychiatry 23: 56–62. View Article. 1960.
21. Association AP. Diagnostic and statistical manual of mental disorders (DSM-5®): American Psychiatric Pub; 2013.
22. Endicott J, Nee J, Harrison W. Daily Record of Severity of Problems (DRSP): reliability and validity. Archives of women's mental health. 2006;9(1):41-9.
23. Kialashaki A, Shokouhi F, Tofighi M, Zafari M, Zarenegad N. Effect of lavandula essence on premenstrual syndrome. Journal of Mazandaran University of Medical Sciences. 2012;22(93):48-56.
24. Halbreich U, Borenstein J, Pearlstein T, Kahn LS. The prevalence, impairment, impact, and burden of premenstrual dysphoric disorder (PMS/PMDD). Psychoneuroendocrinology. 2003;28:1-23.
25. Kugaya A, Epperson CN, Zoghbi S, van Dyck CH, Hou Y, Fujita M, et al. Increase in prefrontal cortex serotonin2A receptors following estrogen treatment in postmenopausal women. American journal of psychiatry. 2003;160(8):1522-4.
26. Kleinstäuber M, Witthöft M, Hiller W. Cognitive-behavioral and pharmacological interventions for premenstrual syndrome or premenstrual dysphoric disorder: a meta-analysis. Journal of clinical psychology in medical settings. 2012;19(3):308-19.
27. Landén M, Thase ME. A model to explain the therapeutic effects of serotonin reuptake inhibitors: the role of 5-HT2 receptors. Psychopharmacology bulletin. 2006;39(1):147.
28. Trauger JW, Jiang A, Stearns BA, LoGrasso PV. Kinetics of allopregnanolone formation catalyzed by human 3α-hydroxysteroid dehydrogenase type III (AKR1C2). Biochemistry. 2002;41(45):13451-9.
29. Landén M, Nissbrandt H, Allgulander C, Sörvik K, Ysander C, Eriksson E. Placebo-controlled trial comparing intermittent and continuous paroxetine in premenstrual dysphoric disorder. Neuropsychopharmacology. 2007;32(1):153.
30. Northoff H, Symons S, Zieker D, Schaible EV, Schäfer K, Thoma S, et al. Gender-and menstrual phase dependent regulation of inflammatory gene expression in response to aerobic exercise. Exerc Immunol Rev. 2008;14(86):103.
31. Gaskins AJ, Wilchesky M, Mumford SL, Whitcomb BW, Browne RW, Wactawski-Wende J, et al. Endogenous reproductive hormones and C-reactive protein across the menstrual cycle: the BioCycle Study. American journal of epidemiology. 2012;175(5):423-31.
32. O’Brien SM, Fitzgerald P, Scully P, Landers A, Scott LV, Dinan TG. Impact of gender and menstrual cycle phase on plasma cytokine concentrations. Neuroimmunomodulation. 2007;14(2):84-90.
33. Berk M, Dean O, Cotton SM, Gama CS, Kapczinski F, Fernandes BS, et al. The efficacy of N-acetylcysteine as an adjunctive treatment in bipolar depression: an open label trial. Journal of affective disorders. 2011;135(1-3):389-94.
34. Magalhães PV, Dean OM, Bush AI, Copolov DL, Malhi GS, Kohlmann K, et al. N-acetylcysteine for major depressive episodes in bipolar disorder. Brazilian Journal of Psychiatry. 2011;33(4):374-8.
35. Berk M, Dean OM, Cotton SM, Jeavons S, Tanious M, Kohlmann K, et al. The efficacy of adjunctive N-acetylcysteine in major depressive disorder: a double-blind, randomized, placebo-controlled trial. The Journal of clinical psychiatry. 2014;75(6):628-36.
Copyright (c) 2020 Journal of Pharmaceutical Care
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.