Emergent Treatment of Neuroleptic Malignant Syndrome Induced by Antipsychotic Monotherapy Using Dantrolene

Ngo, Vivian; Guerrero, A Izquierdo; Lanum, David; Burgett-Moreno, Michelle; Fenati, Gregory; Barr, Steven; Neeki, Michael

doi:10.5811/cpcem.2018.11.39667

Cited by 10 publications

(7 citation statements)

References 21 publications

(30 reference statements)

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“…Oral dantrolene is approved by the FDA for the treatment of chronic muscle spasticity. 15 Dantrolene has also been used off license for treating muscle spasms and hyperthermia unresponsive to conventional therapies in neuroleptic malignant syndrome, 16 MDMA intoxication, 17 and heat stroke, 9,18 and for treating muscle symptoms or recurrent rhabdomyolysis in MHS patients carrying pathogenic RYR1 variants. [19][20][21] However, a black box warning of liver failure was included in the package insert after 2% of patients (19/1044) who received dantrolene developed liver injury and 3 patients died.…”

Section: Discussionmentioning

confidence: 99%

Oral Dantrolene for Myopathic Symptoms in Malignant Hyperthermia–Susceptible Patients: A 25-Year Retrospective Cohort Study of Adverse Effects and Tolerability

Moreno

Kraeva

Zvaritch

et al. 2022

Anesthesia &Amp; Analgesia

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BACKGROUND: Patients susceptible to malignant hyperthermia (MH) may experience disabling manifestations of an unspecified myopathy outside the context of anesthesia, including myalgia, fatigue, or episodic rhabdomyolysis. Clinical observations suggest that oral dantrolene may relief myopathic symptoms in MH-susceptible (MHS) patients. However, high-dose oral dantrolene has been associated with severe hepatotoxicity. METHODS: In a retrospective database review (1994–2018), we investigated a cohort of patients who were diagnosed as MHS by a positive caffeine-halothane contracture test (CHCT), had myopathic manifestations, and received oral dantrolene. Our aim was to investigate the occurrence of serious adverse effects and the adherence to oral dantrolene therapy. We also explored factors associated with self-reported clinical improvement, considering as nonresponders patients with intolerable adverse effects or who reported no improvement 8 weeks after starting treatment. RESULTS: Among 476 MHS patients with positive CHCT, 193 had muscle symptoms, 164 started oral dantrolene, 27 refused treatment, and 2 were excluded due to abnormal liver function before starting therapy. There were no serious adverse effects reported. Forty-six of 164 patients (28%; 95% confidence interval [CI], 22%–35%) experienced mild to moderate adverse effects. Twenty-two patients (22/164, 13%; 95% CI, 9%–19%) discontinued treatment, among which 16 due to adverse effects and 6 due to lack of improvement. One hundred forty-two patients (87%; 95% CI, 80%–90%) adhered to therapy and reported improvement of myalgia (n = 78), fatigue (n = 32), or rhabdomyolysis/hiperCKemia (n = 32). The proportion of responders was larger among patients with MH history than among those referred due to a clinical myopathy with nonpertinent anesthetic history (97% vs 79%, respectively; 95% CI of the difference, 8.5–28; P < .001). Patients with a sarcoplasmic reticulum Ca2+ release channel ryanodine receptor gene (RYR1) variant had higher odds of responding to dantrolene treatment (OR, 6.4; 95% CI, 1.3–30.9; P = .013). Dantrolene median dose was 50 (25–400) and 200 (25–400) mg·day–1 in responders and nonresponders, respectively. CONCLUSIONS: We found that oral dantrolene produced no serious adverse effects within the reported dose range, and was well tolerated by most MH-susceptible patients presenting myopathic symptoms. Our study provides dosing and adverse effect data as a basis for further randomized controlled clinical trials to determine the efficacy of oral dantrolene for symptomatic relief in MHS-related myopathies.

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Section: Discussionmentioning

confidence: 99%

Oral Dantrolene for Myopathic Symptoms in Malignant Hyperthermia–Susceptible Patients: A 25-Year Retrospective Cohort Study of Adverse Effects and Tolerability

Moreno

Kraeva

Zvaritch

et al. 2022

Anesthesia &Amp; Analgesia

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“…On the other hand, dantrolene is a central and peripheral muscle relaxant widely used for patients with MS. Nevertheless, similarly to cyproheptadine, studies have failed to show its efficacy [17]. For these reasons, after discontinuing duloxetine and re-starting all her antiparkinson medication, we treated our patient only with supportive measures.…”

Section: Featuresmentioning

confidence: 99%

A Case Report on Serotonin Syndrome in a Patient With Parkinson’s Disease: Diagnostic and Management Challenges

Nemet¹,

Andrijević²,

Nedeljkov³

et al. 2023

Cureus

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Patients with Parkinson's disease are often at risk of polypharmacy, which can lead to serious medication side effects and interactions. Serotonin syndrome (SS) can develop in this patient population due to a possible drug-drug interaction between antidepressants and antiparkinson drugs with serotoninergic activity. On the other hand, these patients are also at risk of malignant syndrome (MS) secondary to dopaminergic medication withdrawal. In this case report, we present a 71-year-old female with Parkinson's disease who developed symptoms suggestive of SS. The patient was admitted to the medical intensive care unit at the Institute for Pulmonary Diseases of Vojvodina in the Republic of Serbia due to impaired consciousness and a previously witnessed cardiorespiratory arrest. Her chronic antiparkinson medication regimen consisted of levodopa, benserazide, entacapone, ropinirole, and rasagiline. Furthermore, she had been prescribed duloxetine for a remote history of depression, which she had only been taking intermittently. Several days before admission, however, the patient started taking duloxetine again due to low mood. Upon admission, laboratory tests revealed leukocytosis with neutrophilia, elevated C-reactive protein, procalcitonin, lactate, urea, and creatinine. Serum creatine kinase (CK) levels were also elevated at 1250 U/L. Six hours after admission to the ICU, the patient developed hyperthermia, hyperreflexia, spontaneous myoclonus, and tremors. Her CK levels continued to rise, reaching 6900 U/L, and her renal function worsened. Due to the possibility of either SS or MS, external cooling measures with frozen gel packs were administered, resulting in the patient's stabilization over a few hours. Further, serotoninergic medication (rasagiline and duloxetine) was discontinued. On the fifth day of hospitalization, a head CT showed signs of cytotoxic edema. On the 11th day, the patient became hemodynamically unstable and passed away despite all adequate resuscitative measures.The purpose of this case report is to raise awareness of possible SS in patients taking monoamine oxidase-B (MAO-B) inhibitors such as rasagiline. Clinicians should have a high index of suspicion for this complication, especially in patients who are treated for comorbid depression with serotoninergic drugs. Furthermore, we emphasize the importance of correctly differentiating SS from MS, which are both risks for patients with Parkinson's disease. A correct approach to these patients is of utmost importance for adequate management and optimal outcomes.

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“…This mechanism has mainly been studied in skeletal muscle; however, studies in cultured neurons have shown that dantrolene can block up to 70% of the Ca 2+ rise coming from the endoplasmic reticulum because of NMDAr activation, as well as reducing neuronal apoptosis [115]. The dose required for the treatment of malignant hyperthermia and neuroleptic malignant syndrome is similar, oscillating between 1 and 2.5 mg/kg for neuroleptic malignant syndrome and 2.5 mg/kg for malignant hyperthermia [144]. As for the dosage used to achieve the desired effect in TBI, studies have shown how an interval from 10-100 µM of dantrolene administered during the appropriate therapeutic window will target and reduce excitotoxicity.…”

Section: Dantrolenementioning

confidence: 99%

Revisiting Excitotoxicity in Traumatic Brain Injury: From Bench to Bedside

et al. 2022

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Traumatic brain injury (TBI) is one of the leading causes of morbidity and mortality. Consequences vary from mild cognitive impairment to death and, no matter the severity of subsequent sequelae, it represents a high burden for affected patients and for the health care system. Brain trauma can cause neuronal death through mechanical forces that disrupt cell architecture, and other secondary consequences through mechanisms such as inflammation, oxidative stress, programmed cell death, and, most importantly, excitotoxicity. This review aims to provide a comprehensive understanding of the many classical and novel pathways implicated in tissue damage following TBI. We summarize the preclinical evidence of potential therapeutic interventions and describe the available clinical evaluation of novel drug targets such as vitamin B12 and ifenprodil, among others.

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Emergent Treatment of Neuroleptic Malignant Syndrome Induced by Antipsychotic Monotherapy Using Dantrolene

Cited by 10 publications

References 21 publications

Oral Dantrolene for Myopathic Symptoms in Malignant Hyperthermia–Susceptible Patients: A 25-Year Retrospective Cohort Study of Adverse Effects and Tolerability

Oral Dantrolene for Myopathic Symptoms in Malignant Hyperthermia–Susceptible Patients: A 25-Year Retrospective Cohort Study of Adverse Effects and Tolerability

A Case Report on Serotonin Syndrome in a Patient With Parkinson’s Disease: Diagnostic and Management Challenges

Revisiting Excitotoxicity in Traumatic Brain Injury: From Bench to Bedside

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