Severe serotonin syndrome due to high-dose venlafaxine: A rare case successfully managed with chlorpromazine

Year 2025, Volume: 3 Issue: 3, 134 - 138, 29.10.2025

Mehmet Batuhan Duman Husnu Serdar Kiziltunc

https://doi.org/10.61845/agrimedical.1716160

Abstract

Serotonin syndrome is a potentially life-threatening clinical condition caused by excessive serotonergic activity within the central nervous system. In this report, we present the case of a 40-year-old woman with a diagnosis of major depressive disorder who developed serotonin syndrome following a suicidal ingestion of 3000 mg extended-release venlafaxine. The patient manifested agitation, clonus, generalized tonic–clonic seizures, and altered mental status. Despite intensive supportive care and administration of oral cyproheptadine, no clinical improvement was achieved. However, following intramuscular administration of 25 mg chlorpromazine, the patient demonstrated rapid neurological and hemodynamic recovery. This case highlights that severe serotonin syndrome may occur after ingestion of a single serotonergic agent at high doses, and that chlorpromazine may provide therapeutic benefit in cases where conventional treatments fail.

Keywords

Serotonin syndrome , Venlafaxine hydrochloride , Chlorpromazine

Ethical Statement

An informed consent form was obtained from the patient and/or the patient’s legal representative for the collection and publication of the patient’s clinical information

Yüksek doz venlafaksine bağlı şiddetli serotonin sendromu: Klorpromazin ile başarıyla yönetilen nadir bir olgu

Abstract

Serotonin sendromu, merkezi sinir sistemindeki aşırı serotonerjik aktiviteye bağlı olarak gelişen, potansiyel olarak yaşamı tehdit edebilen klinik bir tablodur. Bu yazıda, majör depresif bozukluk tanısıyla takip edilen ve suisidal amaçlı 3000 mg uzatılmış salınımlı venlafaksin alan 40 yaş kadın hastada gelişen serotonin sendromu olgusu sunulmaktadır. Hastada ajitasyon, klonus, jeneralize tonik-klonik nöbet ve bilinç değişikliği gelişmiştir. Yoğun destek tedavisi ve oral siproheptadin uygulanmasına rağmen klinik düzelme sağlanamamıştır. Ancak intramüsküler yoldan 25 mg klorpromazin uygulanmasının ardından hastada hızlı nörolojik ve hemodinamik iyileşme gözlenmiştir. Bu olgu, tek bir serotonerjik ajanın yüksek doz alımı sonrasında ciddi serotonin sendromu gelişebileceğini ve konvansiyonel tedavilerin yetersiz kaldığı durumlarda klorpromazinin terapötik fayda sağlayabileceğini desteklemektedir.

Keywords

Serotonin sendromu , Venlafaksin hidroklorür , Klorpromazin

Ethical Statement

An informed consent form was obtained from the patient and/or the patient’s legal representative for the collection and publication of the patient’s clinical information

References

• Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352(11):1112-20.
• Birmes P, Coppin D, Schmitt L, Lauque D. Serotonin syndrome: a brief review. CMAJ. 2003;168(11):1439-42.
• Mason PJ, Morris VA, Balcezak TJ. Serotonin syndrome. Presentation of 2 cases and review of the literature. Medicine (Baltimore). 2000;79(4):201-9.
• Bodner RA, Lynch T, Lewis L, Kahn D. Serotonin syndrome. Neurology. 1995;45(2):219-23.
• Sternbach H. The serotonin syndrome. Am J Psychiatry. 1991;148(6):705-13.
• Prakash S, Rathore C, Rana K, Prakash A. Fatal serotonin syndrome: a systematic review of 56 cases in the literature. Clin Toxicol (Phila). 2021;59(2):89-100
• Shouan A, Kumar R, Lal V, Grover S. Linezolid-induced serotonin syndrome. Ind Psychiatry J. 2020;29(2):345-348.
• Daniels RJ. Serotonin syndrome due to venlafaxine overdose. J Accid Emerg Med. 1998;15(5):333-4.
• Hanekamp BB, Zijlstra JG, Tulleken JE, Ligtenberg JJ, van der Werf TS, Hofstra LS. Serotonin syndrome and rhabdomyolysis in venlafaxine poisoning: a case report. Neth J Med. 2005;63(8):316-8.
• Sidlak AM, Koivisto KO, Marino RT, Abesamis MG. Serotonin toxicity from isolated bupropion overdoses. Clin Toxicol (Phila). 2020;58(12):1347-49.
• Isbister GK. Electrocardiogram changes and arrhythmias in venlafaxine overdose. Br J Clin Pharmacol. 2009;67(5):572-6.
• Khan IA. Long QT syndrome: diagnosis and management. Am Heart J. 2002;143(1):7-14
• Krishnamoorthy T, Knighton J, Merton L. The role of electroencephalography in the diagnosis of serotonin syndrome. J Intensive Care Soc. 2016;17(3):258-261.
• Mikkelsen N, Damkier P, Pedersen SA. Serotonin syndrome-A focused review. Basic Clin Pharmacol Toxicol. 2023;133(2):124-129.
• Graudins A, Stearman A, Chan B. Treatment of the serotonin syndrome with cyproheptadine. J Emerg Med. 1998;16(4):615-9.
• Chiew AL, Isbister GK. Management of serotonin syndrome (toxicity). Br J Clin Pharmacol. 2025;91(3):654-661.
• Graham PM. Successful treatment of the toxic serotonin syndrome with chlorpromazine. Med J Aust. 1997;166(3):166-7.
• Gillman PK. Serotonin syndrome treated with chlorpromazine. J Clin Psychopharmacol. 1997;17(2):128-9.