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References

Schizophrenia and related psychoses CHAPTER 1 Risk factors for developing NMS include being male, dehydration, exhaustion and confusion/agitation.4,37 Although NMS has commonly been reported to occur at standard doses of antipsychotics, there is some evidence that higher dosage or combined antipsychotic medications may also be risk factors.2 Young adult males seem to be particularly at risk, while the condition is more likely to be lethal in older people.4,16,38,39 Other predictors of mortality with NMS are the presence of respiratory difficulties, the severity of hyperthermia, and failing to stop antipsychotic medication.39 The incidence and mortality rate of NMS are difficult to establish and probably vary as medication regimens change and recognition of NMS waxes and wanes. The incidence of NMS has been estimated at 0.02–0.03%, with a mortality rate of 5.6%.25 However, data from a drug safety programme from 1993 to 2015 yielded an overall incidence of 0.16%,10 while a similar study, covering the period 2004 to 2017, reported an incidence of 0.11%.40 High-­potency FGAs seem to be associated with the greatest incidence, while SGAs and low-­potency FGAs seem to have a lower incidence.3,10,17 Most available antipsychotic medications have been reported to be associated with NMS,41–45 including more recently introduced SGAs such as lurasidone,46 ziprasidone,47,48 iloperidone,49 aripiprazole,6,50,52 paliperidone53 (including paliperidone palmitate),54 asenapine55 and risperidone injection.56 Mortality is probably lower with SGAs than with FGAs,3,57–59 although the clinical picture is essentially similar58 except that rigidity and fever may be less common.3,58 In 2020, NMS had yet to be associated with pimavanserin, cariprazine, brexpiprazole or lumateperone,60 and we could find no reports of NMS being linked to these drugs in mid-­2024. NMS is also sometimes seen with other medications, such as antidepressants,61–64 valproate,65,66 phenytoin31 and lithium.67,68 The co-­prescription of SSRIs69 or cholinesterase inhibitors70,71 with antipsychotic medication may increase the risk of NMS. NMS-­ type syndromes induced by combinations of SGA and SSRI medications may share their symptoms and pathogenesis with the serotonin syndrome.72,73 Benzodiazepines are a recommended treatment for NMS,26 but an association between their use and NMS has been reported, possibly confounded by diagnosis or explained by the occurrence of NMS-­like symptoms during benzodiazepine withdrawal.17,18,74 NMS is also occasionally seen in people given non-­psychotropic dopamine antagonists such as metoclopramide75 and prochlorperazine.76,77 References

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