Cardiotoxicity and Serotonin Syndrome Complicating a Milnacipran Overdose

Abstract

Milnacipran is a selective serotonin and norepinephrine reuptake inhibitor, recently approved for use in the USA for treatment of fibromyalgia. This case report describes a 59-year-old woman who ingested 3,000 mg of milnacipran in a suicide attempt. Following the ingestion, she became obtunded and developed autonomic instability. She required mechanical ventilation, treatment for hypertension, and then ultimately vasopressor support for refractory hypotension. In addition, she developed a transient, acute cardiac dysfunction with global hypokinesis and an ejection fraction of 30%. Resolution of the cardiac dysfunction was documented on repeat echocardiogram 2 days after the initial study. This was confirmed by cardiac catheterization performed 4 days after the acute ingestion in which coronary arteriogram was normal and left ventricular ejection fraction was 70%. Acute overdose was confirmed by quantification of plasma milnacipran concentration of 8,400 ng/mL obtained 5 h post-ingestion. To our knowledge, this represents the first case of cardiac toxicity complicating a milnacipran overdose in the medical literature.

What About Cardiotoxicity? An Evaluation of Cardiac Markers in Children with Suicidal Attempt by Drug Overdose

“…12 How-ever, cardiotoxicity due to suicide attempt by drug overdose has been reported in a few previous case reports and these reports included only one specific drug's effect and none of these cases were in pediatric age. 6,8,13 Hypothesized mechanisms for cardiac involvement were; drug's direct toxic effect to myocardium or indirect effect that could be explained by ischemic and metabolic changes due to drug overdose. 6,7 Another rare explanation is that suicide attempt might have important risk factors in development of stress cardiomyopathy named Takatsubo cardiomyopathy.…”

Norepinephrine transporter function and human cardiovascular disease

“…Stress-induced cardiomyopathy has been reported after overdosing with the unspecific NET inhibitor nortriptyline (27), the combined selective NET and serotonin transporter (SERT) inhibitors venlafaxine (22,91,130), and milnacipran (74), as well as with amphetamines that also exert NET inhibition (3). Among other pharmacological actions, cocaine inhibits NET function (37).…”

“…However, findings from cases of drug overdosing suggest that both NET inhibition with or without additional SERT inhibition can be cardiotoxic with tachycardia and increases of blood pressure being the most frequent findings (54,77). In case reports, overdosing and, rarely, normal doses (107, 115) of NET/SERT inhibitors have been linked with frank cardiomyopathy (22,27,74,91,130).…”

Safety and Efficacy of an On-Site Intensive Treatment Protocol for Mild and Moderate Sympathomimetic Toxicity at Australian Music Festivals

“…4,6 Drug effects that contribute to severe hyperthermia, leading to morbidity and death, include delaying the onset of exhaustion beyond usual temperature set-points; profound vasoconstriction that leads to a reduction in peripheral heat loss; activation of brown fat triggering non-shivering thermogenesis; inhibition of gammabutyric acid receptors that increases neuronal hyper-excitability causing seizures, clonus, and coma; and in extreme cases, the development of mitochondrial "uncoupling" that results in profound heat production. [7][8][9] Problems that are seen as a consequence of extreme temperature elevation include progressive rhabdomyolysis, the development of coagulopathy, 10 and the development of heart failure with reduced ejection fraction 11,12 and vasodilation. 13 Early identification and treatment of SST reduces morbidity.…”