Serotonin syndrome induced by the combined use of metaxalone, phentermine, and duloxetine: A case report

Abstract

Serotonin syndrome is a potentially life-threatening condition caused by increased serotonergic activity. Although this condition is commonly associated with certain antidepressants, this report describes a case of serotonin syndrome induced by the combined use of metaxalone and phentermine with duloxetine and bupropion. Our patient developed serotonin syndrome following the administration of metaxalone for severe back spasms. Symptoms resolved following the discontinuation of these medications, provision of supportive care, and administration of lorazepam and cyproheptadine. This case report adds to the existing literature, as studies on metaxalone-induced serotonin syndrome are currently limited. This case report also highlights the importance of monitoring polypharmacy, especially when prescribing less common medications such as metaxalone as well as weight-loss medications such as phentermine.

Keywords

Serotonin syndrome / Serotonin toxicity / Metaxalone / Phentermine / Selective serotonin reuptake inhibitors / Polypharmacy

Funding

None.

Conflict of interest

The authors declare that they have no competing interests.

References

[1] Scotton WJ, Hill LJ, Williams AC, Barnes NM. Serotonin syndrome: Pathophysiology, clinical features, management, and potential future directions. Int J Tryptophan Res. 2019;12:117864691987392. doi: 10.1177/1178646919873925

[2] Talton CW.Serotonin syndrome/serotonin toxicity. Fed Pract. 2020; 37(10):452-459. doi: 10.12788/fp.0042

[3] Dunkley EJC, Isbister GK, Sibbritt D, Dawson AH, Whyte IM. The hunter serotonin toxicity criteria: Simple and accurate diagnostic decision rules for serotonin toxicity. QJM. 2003; 96(9):635-642. doi: 10.1093/qjmed/hcg109

[4] Huecker MR, Smiley A, Saadabadi A. Bupropion. In: StatPearls. Available from: https://www.ncbi.nlm.nih.gov/pubmed/9554319 [Last accessed on 2024 Jul 22].

[5] Bosak AR, Skolnik AB. Serotonin syndrome associated with metaxalone overdose. J Med Toxicol. 2014; 10(4):402-405. doi: 10.1007/s13181-014-0404-5

[6] Martini DI, Nacca N, Haswell D, Cobb T, Hodgman M. Serotonin syndrome following metaxalone overdose and therapeutic use of a selective serotonin reuptake inhibitor. Clin Toxicol. 2015; 53(3):185-187. doi: 10.3109/15563650.2015.1009993

[7] Surmaitis RM, Nappe TM, Cook MD. Serotonin syndrome associated with therapeutic metaxalone in a patient with cirrhosis. Am J Emerg Med. 2016; 34(2):346.e5-e6. doi: 10.1016/j.ajem.2015.06.043

[8] Suissa K, Schneeweiss S, Kim DW, Patorno E. Prescribing trends and clinical characteristics of patients starting antiobesity drugs in the United States. Diabetes Obes Metab. 2021; 23(7):1542-1551. doi: 10.1111/dom.14367

[9] Ulus IH, Maher TJ, Wurtman RJ. Characterization of phentermine and related compounds as monoamine oxidase (MAO) inhibitors. Biochem Pharmacol. 2000; 59(12):1611-1621. doi: 10.1016/s0006-2952(00)00306-3

[10] Westanmo AD, Gayken J, Haight R. Duloxetine: A balanced and selective norepinephrine- and serotonin-reuptake inhibitor. Am J Health Syst Pharm. 2005; 62(23):2481-2490. doi: 10.2146/ajhp050006

[11] Foley KF, DeSanty KP, Kast RE.Bupropion: Pharmacology and therapeutic applications. Expert Rev Neurother. 2006; 6(9):1249-1265. doi: 10.1586/14737175.6.9.1249

[12] Perez CI, Kalyanasundar B, Moreno MG, Gutierrez R. The triple combination phentermine plus 5-HTP/carbidopa leads to greater weight loss, with fewer psychomotor side effects than each drug alone. Front Pharmacol. 2019;10:1327. doi: 10.3389/fphar.2019.01327

[13] Gillman PK. New data on metaxalone (Skelaxin) and serotonin toxicity (serotonin syndrome): Warning of potential for fatalities if combined with serotonin re-uptake inhibitors. Psycho Trop Commentaries. 2018;6:22-32.

[14] King Pharmaceuticals, Inc. Inc. Skelaxin (Metaxalone) Tablets: Prescribing Information (Rev. March 2018). U.S. Food and Drug Administration; 2018. Available from: https://www.fda.gov/drugsatfda [Last accessed on 2024 Jul 21].

[15] Knadler MP, Lobo E, Chappell J, Bergstrom R. Duloxetine: Clinical pharmacokinetics and drug interactions. Clin Pharmacokinet. 2011; 50(5):281-294. doi: 10.2165/11539240-000000000-00000

[16] Kotlyar M, Brauer LH, Tracy TS, et al. Inhibition of CYP2D6 activity by bupropion. J Clin Psychopharmacol. 25(3): 226-229. doi: 10.1097/01.jcp.0000162805.46453.e3

[17] Lobo ED, Bergstrom RF, Reddy S, et al. In vitro and in vivo evaluations of cytochrome P 450 1A2 interactions with duloxetine. Clin Pharmacokinet. 2008; 47(3):191-202. doi: 10.2165/00003088-200847030-00005

[18] Li L, Mi Q. Serotonin syndrome from duloxetine monotherapy: A case report. Cureus. 2023; 15(6):e40933. doi: 10.7759/cureus.40933

[19] Thorpe EL, Pizon AF, Lynch MJ, Boyer J. Bupropion induced serotonin syndrome: A case report. J Med Toxicol. 2010; 6(2):168-171. doi: 10.1007/s13181-010-0021-x

[20] Naranjo CA, Busto U, Sellers EM, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther. 1981; 30(2):239-245. doi: 10.1038/clpt.1981.154

[21] Möller HJ, Seemüller F, Schennach-Wolff R, Stübner S, Rüther E, Grohmann R. History, background, concepts and current use of comedication and polypharmacy in psychiatry. Int J Neuropsychopharmacol. 2014; 17(7): 983-996. doi: 10.1017/S1461145713000837