From the Guidelines
Sodium valproate and amisulpride can potentially contribute to Neuroleptic Malignant Syndrome (NMS), with amisulpride carrying a higher risk due to its antipsychotic properties that block dopamine receptors. The risk of NMS is associated with the disruption of dopaminergic pathways in the brain, and both medications, especially when used in combination, can increase this risk [ 1 ]. According to the evidence, the incidence of NMS has been difficult to determine, with estimates ranging from 0.02% to 3%, and mortality from NMS has decreased from 76% in the 1960s to <10% to 15% more recently [ 1 ].
Key Points to Consider
- Amisulpride, as an antipsychotic medication, is more likely to contribute to NMS than sodium valproate due to its mechanism of action involving dopamine receptor blockade [ 1 ].
- Sodium valproate, although less commonly implicated, can also contribute to NMS, particularly when combined with antipsychotics, through disruption of dopaminergic pathways [ 1 ].
- Clinicians should monitor patients on these medications for early signs of NMS, including high fever, muscle rigidity, altered mental status, autonomic instability, and elevated creatine kinase levels [ 1 ].
- Prompt recognition and immediate discontinuation of the suspected medications, along with supportive care, are crucial in managing NMS [ 1 ].
Management and Treatment
The management of NMS involves primarily supportive care and removal of the initiating agent. If NMS is triggered by the abrupt withdrawal of an anti-Parkinsonism drug, reintroduction of the drug may be considered. Cardiorespiratory compromise may be managed with standard, supportive measures. Dehydration or elevated creatine kinase and rhabdomyolysis may be treated with IV fluids. For agitation, experts suggest benzodiazepines as the first-line agent [ 1 ]. Fever can be treated with external cooling measures, such as cooling blankets [ 1 ].
From the Research
Sodium Valproate and NMS
- Sodium valproate has been associated with Neuroleptic Malignant Syndrome (NMS) in several case reports 2, 3.
- Valproate can precipitate NMS, especially when used with antipsychotic drugs concurrently 2.
- A case report described a 17-year-old male patient who developed NMS after taking only valproate for two months 2.
- Another case report described a 60-year-old woman who developed NMS after valproate was added to her treatment with olanzapine 3.
Amisulpride and NMS
- Amisulpride, an antipsychotic drug, has been associated with NMS in a case report 4.
- A 42-year-old female patient developed NMS two weeks after amisulpride was started, with symptoms including muscular pain, stiffness, weakness, and fever 4.
- The patient required surgical intervention due to extensive rhabdomyolysis and compartment syndrome 4.
General Information on NMS
- NMS is a life-threatening idiosyncratic reaction that usually occurs after the administration of antipsychotic drugs 2, 5.
- The risk of NMS seems to be lower for second-generation antipsychotics (SGA), but it can still occur 4, 5.
- The treatment of NMS should be individualized and based empirically on the character, duration, and severity of the clinical signs and symptoms noted 5.