Psychotropic malignant syndrome Psychotropic malignant syndrome (Gurrera et al. 2011) is characterized by increased tone, myotonia, temperature instability (>100.4 F or 38°C at least twice), autonomic instability such as tachycardia, tachycardia >25% above baseline, shortness of breath >50% above baseline, elevated blood pressure (>25% above baseline) and fluctuations within 24 hours (>20 mmHg (diastolic or >25 mmHg (systolic)), delirium, myoglobinuria and creatine kinase elevation (at least >4 parameters). >25%) and fluctuations within 24 hours (>20 mmHg (diastolic) or >25 mmHg (systolic), delirium, myoglobinuria and creatine kinase elevations (at least 4 times the parameters) (Gurrera et al. 2011), elevated granulocytes and liver enzymes (lactate dehydrogenase and aspartate aminotransferase), and decreased serum iron levels. However, none of the laboratory parameters are specific for the diagnosis of NMS. eeg can suggest symptoms of metabolic encephalopathy, such as a general slowing of the electroencephalogram (Caroff and Mann 1988; Strawn et al. 2007). In those patients taking both antipsychotics and 5-hydroxytryptamine blockers, biological indicators may help in the differential diagnosis, given the similarity between NMS and 5-hydroxytryptamine syndrome. In principle, the use of either antipsychotic medication may lead to NMS, and if NMS occurs, the antipsychotic medication needs to be discontinued immediately. In addition to general treatment measures, special pharmacological or somatic treatment may be considered. Patients with malignant syndrome need to be transferred to the ICU for close monitoring, stabilization of the vital body, and treatment of symptoms such as hyperthermia. Other medications that may contribute to this syndrome (e.g., lithium salts, antidepressants) need to be discontinued. There is a lack of effective specific treatment. The myorelaxant nifurtimox (2.5/10 mg/kg body weight per day, IV) may be effective in treating this syndrome (Sakkas et al. 1991). However, a META analysis that included 271 case reports from 1980 to 2006 showed that the combination of nifafoxacin and other drugs may increase the time to clinical recovery and that nifafoxacin alone increases overall mortality (Reulbach et al. 2007). At one time the authors concluded that there is no evidence-based treatment strategy that is currently included (Reulbach et al. 2007). These reports are contradictory and therefore lack convincing evidence for the routine application of nifedipine for the treatment of psychiatric drug malignant syndrome (evidence classification F). However, there are some cases in which nifedipine can be considered, such as extremely elevated body temperature, myotonia and hypermetabolism (Strawn et al. 2007) (evidence classification C). The administration of 6-10 doses of ECT may be useful, but randomized controlled studies are lacking (Trollor and Sachdev 1999; Supprian 2004) (Evidence Classification C, Recommendation Level 4). There is a lack of sufficient clinical trial evidence on the treatment strategy to be used after the occurrence of malignant syndrome. An important conflict is the increased risk (more than 30%) of recurrence of malignant syndrome in patients given the same antipsychotic after the onset of malignant syndrome (Caroff and Mann 1988; Pope et al. 1991; Strawn et al. 2007), yet the vast majority of individuals require long-term antipsychotic treatment. One report summarized some routine approaches to prevent recurrence of the malignant syndrome (Strawn et al. 2007): 1. minor episodes should be reported in detail 2. detailed documentation of antipsychotic prescriptions is needed 3. consideration of medication changes 4. risk factors should be reduced (e.g., rapid dosing, ultra-high doses of antipsychotics) 5. discontinuation of medication for at least 2 weeks after the occurrence of the malignant syndrome before re 6. low doses of low potency traditional antipsychotics or atypical antipsychotics need to be slowly dosed after a trial 7. patients should be carefully monitored for early signs of malignant syndrome 8. written consent of patients and their families is required, taking into account the benefits of reintroducing antipsychotics and the risk of recurrence of malignant syndrome. A review has reported (literature includes 1972-2011) that clozapine can be given with caution after patients presenting with malignant syndrome, neutropenia rather than granulocytic leukocyte deficiency and myocarditis (Manu et al. 2011). However, this review on malignant syndrome was based on only five cases, and the mean time to reintroduction of clozapine after the onset of malignant syndrome was 8.5 weeks (Manu et al. 2011). Case reports (Mendhekar et al. 2002; Norgard and Stark 2006) of reintroduction of antipsychotics after malignant syndrome are available, but evidence from controlled trials is lacking. Based on this very limited evidence, it is possible to administer antipsychotics after the onset of malignant syndrome (Strawn et al. 2007; Wells et al. 1988) (evidence category C3, recommendation level 4).