Severe Serotonin Syndrome Induced by Mirtazapine Monotherapy

Hernández, José L.; Ramos, Francisco Javier; Infante, Jon; Rebollo, Mariano; González‐Macías, Jesús

doi:10.1345/aph.1a302

Cited by 44 publications

(20 citation statements)

References 16 publications

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“…6,7 Based on animal studies, serotonin syndrome is thought to be the result of increased activation or modification of mainly 5-HT1 (especially 5-HT1A) and 5-HT2 receptors in the lower brain stem and spinal cord neurons. [8][9][10][11][12] A literature search utilizing the search terms serotonin syndrome and mutism yielded only one previous case report. While SSRIs such as sertraline in combination with opiate analgesics such as methadone have a high potential for causing the serotonin syndrome, mutism is a known albeit rarely reported manifestation of this syndrome.…”

Section: Discussionmentioning

confidence: 99%

A Case of Serotonin Syndrome and Mutism associated with Methadone

Bush

Miller

Friedman

2006

Journal of Palliative Medicine

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A patient was seen on the palliative care service at our institution who developed serotonin syndrome and mutism associated with methadone use. Serotonin syndrome is often described as a clinical triad of mental status changes, autonomic hyperactivity, and neuromuscular abnormalities, but not all of these findings are consistently present in all patients with the disorder. The incidence of the serotonin syndrome is thought to mirror the increasing number of proserotonergic agents being used in clinical practice. In 2002, the Toxic Exposure Surveillance System, which receives case descriptions from office-based practices, inpatient settings, and emergency departments, reported 26,733 incidences of exposure to selective serotonin-reuptake inhibitors (SSRIs) that caused significant toxic effects in 7349 persons and resulted in 93 deaths. Serotonin syndrome is not an idiopathic drug reaction; it is a predictable consequence of excess serotonergic agonism of central nervous system (CNS) receptors and peripheral serotonergic receptors. The myriad of symptoms with which serotonin syndrome may present is compounded by the fact that more than 85% of physicians are unaware of serotonin syndrome as a clinical diagnosis. Other SSRIs such as fluoxetine and fluvoxamine have been shown to increase methadone plasma concentrations in dependent patients. Although the exact mechanism is unknown, there are several pathways via which a significant interaction could occur. This would include the effects methadone has on N-methyl-D-aspartate (NMDA) in addition to the impact of methadone on the cytochrome P450 enzyme system. The mainstay of treatment of serotonin syndrome is withdrawal of the offending agent and supportive care. These actions resulted in resolution of our patient's symptoms. Serotonin syndrome is becoming more common, and with the utilization of polypharmacy on many palliative care services should be considered as unifying differential diagnosis in the appropriate setting.

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Section: Discussionmentioning

confidence: 99%

A Case of Serotonin Syndrome and Mutism associated with Methadone

Bush

Miller

Friedman

2006

Journal of Palliative Medicine

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“…Serotonin syndrome has been reported with the use of mirtazapine in a small number of elderly individuals. 22,23 This is characterized by diaphoresis, lowgrade fever, hypertension, tachycardia, cogwheel rigidity, hyperreflexia, tremor, and myoclonus. Although it rarely occurs, it should be considered when treating elderly patients.…”

Section: Discussionmentioning

confidence: 99%

Mirtazapine for reducing nocturnal itch in patients with chronic pruritus: a pilot study

Hundley

Yosipovitch

2004

Journal of the American Academy of Dermatology

171

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“…There were some drug combinations that have been associated with an ADR (such as serotonin toxicity) and were not listed on Micromedex®, such as pethidine with tramadol [16], or mirtazapine with sertraline [17,18]. Despite controversy regarding the serotonergic potential of mirtazapine [19], it is listed in Micromedex® as a major drug interaction when combined with fluoxetine and venlafaxine due to the increased risk of serotonin toxicity.…”

Section: Cohort Selectionmentioning

confidence: 99%

“…Identified drugs were subsequently confirmed using quantitative gas chromatography-mass spectrometry with List compiled using drug interaction and severity data from Drugdex® Evaluations in the Micromedex® Internet database [8]. Drugs with an asterisk (e.g., pethidine*) are combinations where an adverse drug reaction has been reported involving this combination; however, it did not feature on the Micromedex® list [16][17][18][57][58][59][60][61]. The mechanisms of interactions are explained within the Micromedex® database *Not from Micromedex a Only includes combinations observed in this study lower limits of quantitation at the low end of their respective blood concentrations when used therapeutically.…”

Section: Toxicological Analysismentioning

confidence: 99%

Deaths involving contraindicated and inappropriate combinations of serotonergic drugs

2010

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In the Australian state of Victoria, all fatalities that were recorded from 2002 through to 2008 involving the use of certain serotonin active drugs (tramadol, venlafaxine, fluoxetine, sertraline, citalopram and paroxetine), were reviewed to assess the incidence of contraindicated or ill advised drug combinations. More than 1,000 were identified of which 326 cases formed the basis of this study. These cases involved contraindicated or inappropriate drug combinations that can lead to adverse drug reactions (ADRs) and subsequent fatal toxicity. Of these, 46% were drug-related, 35% were a result of natural disease and 13% were classified as external injury cases. The remaining cases were those where the cause of death (COD) was unascertained. Tramadol was the most common drug, usually detected alongside a serotonergic antidepressant (in 20% of cases). Twenty-five (8%) cases involved contraindicated drug combinations while the remainder (301 cases, 92%) involved drug combinations that are associated with adverse interactions ranging from minor to major severity. Of these 326 cases, the Coroner determined 166 cases (51%) to be acts of intentional self-harm or drug misuse, with the remainder unascertained or attributed to natural disease. Very few post-mortem reports and Coroners' findings made mention of possible ADRs when such combinations were actually present. The majority of cases comprising contraindicated drug combinations involved the combined use of five drugs (24%) at the time of death. A combination of three to five drugs was most common in cases involving inadvisable drug combinations. Combined drug toxicity was the most common COD, with heart disease the most common co-morbidity.

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Severe Serotonin Syndrome Induced by Mirtazapine Monotherapy

Cited by 44 publications

References 16 publications

A Case of Serotonin Syndrome and Mutism associated with Methadone

A Case of Serotonin Syndrome and Mutism associated with Methadone

Mirtazapine for reducing nocturnal itch in patients with chronic pruritus: a pilot study

Deaths involving contraindicated and inappropriate combinations of serotonergic drugs

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