Fatal intoxication with milnacipran

Fanton, Laurent; Bévalot, Fabien; Grait, Habdelhamid; Meur, C. Le; Gaillard, Yvan; Malicier, D.

doi:10.1016/j.jflm.2007.12.006

Cited by 10 publications

(5 citation statements)

References 12 publications

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“…Fanton et al have described a fatality in a 42-year-old female who was found dead in the back of a car. While numerous agents were suspected as part of her ingestion, only milnacipran concentrations were significantly elevated [11].…”

Section: Discussionmentioning

confidence: 95%

Cardiotoxicity and Serotonin Syndrome Complicating a Milnacipran Overdose

2011

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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.

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Section: Discussionmentioning

confidence: 95%

Cardiotoxicity and Serotonin Syndrome Complicating a Milnacipran Overdose

2011

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“…Considering that the required dose for the epidural route is about 1/10-1/30 of the dose for oral administration [29], the 3 mg of epidural milnacipran in rat may be equivalent to an oral administration of about 1,960-5,880 mg for a human adult. In addition, considering the fact that the maximal recommended dose per os for milnacipran is 200 mg in human adults [4], the maximal epidural dose calculated is 6.7-20 mg. A study by Mochizucki administered maximal 120 mg/kg of milnacipran per os with the neuropathic rat model; this 120 mg/kg of oral milnacipran is equivalent to 4-12 mg/kg epidural dose [6]. We believed this 3 mg of epidural milnacipran was sufficient for the evaluation of neurotoxicity in the rat because it was approximately 9.8-25.2 fold greater than clinically used doses in human adult and 1,700 times greater than previously reported maximal intrathecal dose of 1.0 µg/kg [8], and the Dura mater of small animals has greater diffusibility than that of the human [29,30].…”

Section: Discussionmentioning

confidence: 99%

“…Milnacipran is known as a balanced SNRI with minimal side effects and broad safety margin [3,4]. Intrathecally-administered milnacipran shows an antiallodynic effect in animal models [3,5-8].…”

Section: Introductionmentioning

confidence: 99%

“…However, there is no animal study on the neurotoxicity of neuraxial milnacipran. Although oral milnacipran has been used safely in clinical settings [4], its safety should be substantiated by preliminary animal studies for the intrathecal or epidural administration in clinical settings [10,11]. The aim of this study was to evaluate the neurotoxicity of epidural milnacipran in rats.…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of the Neurological Safety of Epidural Milnacipran in Rats

et al. 2012

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BackgroundMilnacipran is a balanced serotonin norepinephrine reuptake inhibitor with minimal side effects and broad safety margin. It acts primarily on the descending inhibitory pain pathway in brain and spinal cord. In many animal studies, intrathecal administration of milnacipran is effective in neuropathic pain management. However, there is no study for the neurological safety of milnacipran when it is administered neuraxially. This study examined the neurotoxicity of epidural milnacipran by observing behavioral and sensory-motor changes with histopathological examinations of spinal cords in rats.MethodsSixty rats were divided into 3 groups, with each group receiving epidural administration of either 0.3 ml (3 mg) of milnacipran (group M, n = 20), 0.3 ml of 40% alcohol (group A, n = 20), or 0.3 ml of normal saline (group S, n = 20).ResultsThere were no abnormal changes in the behavioral, sensory-motor, or histopathological findings in all rats of groups M and S over a 3-week observation period, whereas all rats in group A had abnormal changes.ConclusionsBased on these findings, the direct epidural administration of milnacipran in rats did not present any evidence of neurotoxicity in behavioral, sensory-motor and histopathological evaluations.

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“…Milnacipran has been shown to be safe in overdose, with doses as high as 2.8 g causing no serious effects and no mortality 32. No deaths have been reported following milnacipran overdose, with the exception of a case of multiple drug overdose where high blood levels of milnacipran, fluoxetine, norfluoxetine, sertraline, cyamemazine, nordiazepam, and oxazepam were found 33. In contrast, lethal consequences of venlafaxine overdose have been reported, with a frequency of over 34 per 1000 person-years.…”

Section: Milnacipran and Venlafaxine Ir Flexibly Titrated To 200 Mg/daymentioning

confidence: 99%

Antidepressant therapy with milnacipran and venlafaxine

Mansuy¹

2010

NDT

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Specific serotonin norepinephrine reuptake inhibitors (SNRIs) have been described as “better tolerated tricyclic antidepressants” or as “boosted” selective serotonin reuptake inhibitors (SSRIs). Venlafaxine has become a therapeutic reference treatment for major depression. Although less widely studied, indirect comparisons with another SNRI, milnacipran, suggest an equivalent efficacy. This paper discusses these indirect comparisons and the recently published first double-blind, head-to-head comparison. Venlafaxine has potency at serotonin transporters which is about 30-fold greater than that at norepinephrine transporters while milnacipran has a similar potency at each transporter. Thus, at low doses, venlafaxine acts essentially as a SSRI, with significant noradrenergic activity only occurring at higher doses. To overcome the problem of the differing profile of venlafaxine at increasing doses, the first head-to-head study compared the therapeutic effects and tolerability of the two antidepressants when flexibly titrated to the high dose of 200 mg/day. The study showed that the two SNRIs have similar efficacy and safety profiles. Both drugs produced about 42% remissions at the end of the 20-week study. The most frequent adverse events in both groups were nausea, dizziness, headache, and sweating. Certain specific differences in tolerability are discussed.

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Fatal intoxication with milnacipran

Cited by 10 publications

References 12 publications

Cardiotoxicity and Serotonin Syndrome Complicating a Milnacipran Overdose

Cardiotoxicity and Serotonin Syndrome Complicating a Milnacipran Overdose

Evaluation of the Neurological Safety of Epidural Milnacipran in Rats

Antidepressant therapy with milnacipran and venlafaxine

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