RARE DISEASE
Neuroleptic malignant syndrome
Neuroleptic malignant syndrome
Neuroleptic malignant syndrome
Drug discovery
1
drug
With orphan designation
Overview
Neuroleptic Malignant Syndrome (NMS) is a rare, life-threatening idiosyncratic reaction to antipsychotics or dopamine D2 receptor antagonists, characterized by hyperthermia (>38°C), severe muscle rigidity, autonomic instability, altered mental status, and elevated creatine kinase. Diagnosis requires exclusion of infections, malignant hyperthermia, and serotonin syndrome. Mortality rates range from 5–11.6%, driven by complications like rhabdomyolysis, renal failure, and respiratory collapse [1][4][6][12].
Therapies
Immediate discontinuation of the offending agent [1][6][13].
Supportive care: Aggressive hydration, cooling, and ICU monitoring for complications (e.g., renal failure, aspiration) [1][8][11].
Pharmacotherapy: Benzodiazepines (first-line for agitation), dantrolene (muscle rigidity), bromocriptine/amantadine (dopaminergic agents). Electroconvulsive therapy (ECT) for refractory cases [3][6][13].
Categories: rare neurological diseases
Research Papers
589 drug discovery papers about Neuroleptic malignant syndrome, with 1 next-in-class emerging drug candidate forecasted to outperform the average preclinical success rate. Recent publications:
589 drug discovery papers about Neuroleptic malignant syndrome, with 1 next-in-class emerging drug candidate forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-09-18 | Case Report: Paralytic ileus as an early manifestation of evolving neuroleptic malignant syndrome in a patient receiving anti-psychotics.
Neuroleptic malignant syndrome (NMS) is an uncommon, but potentially life- threatening complication of antipsychotic therapy, primarily resulting from central dopaminergic blockade. NMS is a clinical diagnosis and occurs rarely in patients receiving atypical antipsychotics agents. Gastrointestinal manifestations, including severe hypomotility and paralytic ileus, are recognized adverse effects of antipsychotic medications. However, paralytic ileus preceding the characteristic neuromuscular and autonomic features of NMS is exceptionally rare and underrecognized as an early manifestation of the syndrome. We report the case of a 49-year-old man who presented with progressive abdominal distension secondary to intestinal pseudo-obstruction as an early manifestation of NMS. This atypical and underreported presentation highlights the importance of maintaining a high index of suspicion for NMS in patients receiving antipsychotic therapy who develop unexplained gastrointestinal dysmotility. Prompt recognition, immediate discontinuation of the offending antipsychotic agent, and early initiation of treatment with dantrolene and bromocriptine resulted in a favorable clinical outcome.
2026-07-30 | Cervical cutthroat injury with complete hypopharyngeal transection: a case report
Penetrating neck trauma involving the aerodigestive tract is a life-threatening emergency. We report a case of an 18-year-old male patient with a zone II cervical wound that caused complete hypopharyngeal transection and a thyroid cartilage fracture. Initial airway control was achieved by direct translaryngeal intubation through the wound, followed by bilateral chest tube placement for pneumothoraces that developed after positive pressure ventilation. Surgical management included tracheostomy, primary hypopharyngeal and laryngeal reconstruction, and vascular control. The postoperative course was complicated by aspiration pneumonia, a strap muscle abscess requiring drainage, opioid withdrawal, and neuroleptic malignant syndrome. Despite these complications, the patient survived and was discharged after approximately 1 month with a gastrostomy tube because of persistent severe dysphagia. This case illustrates the need for flexible airway management, definitive surgical repair, and close postoperative surveillance for complex systemic complications in severe penetrating neck trauma.
2026-06-03 | Atypical neuroleptic malignant syndrome in a geriatric palliative care patient: a case report and review of the literature.
Neuroleptic malignant syndrome (NMS) is a rare but potentially life-threatening adverse reaction to antipsychotic medications that carries significant diagnostic complexity in its atypical forms, particularly among elderly patients with polypharmacy and multiple comorbidities in whom the classic diagnostic criteria are frequently unmet. Timely recognition of atypical NMS is critical, as diagnostic delays are associated with increased morbidity and mortality even in clinically mild presentation. We present a 71-year-old Caucasian male patient with schizophrenia on chronic risperidone and quetiapine therapy who developed atypical NMS following administration of haloperidol 64 drops for insomnia during hospitalization for urinary tract infection in a palliative care unit. The patient presented with low-grade fever (37.9 °C) and mildly elevated creatine kinase (600 U/L) without classic rigidity or autonomic instability. Due to unavailability of dantrolene and bromocriptine at the facility, the patient was successfully managed with intravenous diazepam and aggressive hydration therapy. Complete resolution of fever and normalization of creatine kinase levels were achieved with conservative management. This case highlights the importance of recognizing atypical NMS presentations in elderly patients and demonstrates that successful outcomes can be achieved with supportive care when first-line agents are unavailable.
2026-06-01 | Clozapine rebound catatonia or malignant neuroleptic syndrome? Case report
Introduction Abrupt discontinuation of clozapine is not recommended except in cases of serious, life threatening side effects. Catatonia and malignant neuroleptic syndrome (MNS) are severe neuropsychiatric conditions that can present with overlapping clinical features, including stupor, mutism, rigidity, and altered consciousness. However, their etiologies and therapeutic implications differ substantially. While MNS is typically triggered by potent dopamine D2 receptor antagonism and requires discontinuation of neuroleptic therapy, catatonia may arise in the context of primary psychiatric disorders or as a rebound phenomenon following abrupt clozapine withdrawal. Distinguishing between these syndromes is critical to guide treatment. Objectives The aim is to present the case of a patient with schizophrenia who developed overlapping symptoms of catatonia and neuroleptic malignant syndrome. Case presentation We describe a male patient, 45 years of age, with chronic schizophrenia who had been maintained on clozapine therapy up to 450 mg/day for over 18 years. After psycho-social stress and certain worsening of his mental condition clozapine was abruptly discontinued and fluphenazine 7.5 mg/day was introduced into the therapy. He became less alert and nonresponsive. A worsening of negative symptoms of schizophrenia was suspected and he was hospitalized in the psychiatric ward of a general hospital. On the third day of hospitalization, he begins to have difficulty breathing. CT angiography indicated a pulmonary embolism. The patient is out of contact, sweating, febrile up, and impaired in consciousness. He was then referred to the university clinic for neurology. Due to difficulty breathing, he was immidiately transferred to the ICU. Psychiatrist was consulted. Mental state examination: The patient is mechanically restrained. Not responsive. He actively resists when we try to open his eyes. He is febrile at 38.2 o C. After the restraints are removed, the following was noted: a marked rigor of a plastic type (flexibilitas cerea) exists in all muscles.The “psychological pillow” phenomenon is present. Treatment: After the administration of diazepam i.v. 2x 10 mg, muscle rigidity partially subsided. It was decided to reintroduce clozapine, and the dose was gradually increased. The patient’s condition improved daily, and was transferred to the university psychiatric clinic for additional stabilization. He was discharged in good general condition. Conclusions This case highlights the diagnostic challenge of differentiating clozapine-sensitive catatonia from MNS. Short-lived fever, partial benzodiazepine responsiveness, and clinical recovery following clozapine reintroduction favored a diagnosis of rebound catatonia rather than MNS. Awareness of this phenomenon is essential to avoid misdiagnosis and inappropriate treatment. Disclosure of Interest None Declared
2026-05-18 | Rhabdomyolysis caused by neuroleptic malignant syndrome requiring long-term hemodialysis: A case report and literature review.
Neuroleptic malignant syndrome (NMS) can be complicated by rhabdomyolysis, a known cause of acute kidney injury (AKI) that typically resolves within a short period. However, some cases of NMS-associated rhabdomyolysis require hemodialysis. We report a woman in her fifties who developed AKI secondary to NMS-associated rhabdomyolysis and required prolonged renal replacement therapy (RRT). She experienced sepsis and contrast exposure, and dialysis independence was achieved only after 2 months, the longest reported duration. This case highlights that NMS-associated rhabdomyolysis-induced AKI may lead to prolonged dialysis, particularly in the presence of additional risk factors for renal injury.
cell therapies
2025-06-04 | Case Report: Neuroleptic malignant syndrome in a 15-year-old female following of psychotropic drugs.
Neuroleptic Malignant Syndrome (NMS) is a rare but life-threatening neurological emergency associated with dopamine receptor blockade. It is characterized by hyperthermia, autonomic instability, muscle rigidity, and altered mental status. Early recognition and intervention are crucial to prevent severe complications. We report a case of a 15-year-old female diagnosed with major depressive disorder (MDD), with a body mass index (BMI) of 13.7, who developed severe NMS with rapid-onset rhabdomyolysis and vocal cord dysfunction following an overdose of quetiapine, sertraline, and lorazepam. The clinical presentation posed a diagnostic challenge due to overlapping features with serotonin syndrome. Despite aggressive supportive care, she developed acute kidney injury secondary to rhabdomyolysis, necessitating plasmapheresis and hemoperfusion. Additionally, post-extubation vocal cord dysfunction led to aspiration pneumonia, requiring prolonged airway management. This case highlights the complexity of diagnosing NMS in the context of polypharmacy, the potential for rapid rhabdomyolysis, and the rarity of vocal cord involvement. The successful use of plasmapheresis as an adjunct therapy suggests a possible role in severe NMS with organ dysfunction. Early recognition and individualized management remain key to optimizing outcomes.
small molecules
2026-09-18 | Case Report: Paralytic ileus as an early manifestation of evolving neuroleptic malignant syndrome in a patient receiving anti-psychotics.
Neuroleptic malignant syndrome (NMS) is an uncommon, but potentially life- threatening complication of antipsychotic therapy, primarily resulting from central dopaminergic blockade. NMS is a clinical diagnosis and occurs rarely in patients receiving atypical antipsychotics agents. Gastrointestinal manifestations, including severe hypomotility and paralytic ileus, are recognized adverse effects of antipsychotic medications. However, paralytic ileus preceding the characteristic neuromuscular and autonomic features of NMS is exceptionally rare and underrecognized as an early manifestation of the syndrome. We report the case of a 49-year-old man who presented with progressive abdominal distension secondary to intestinal pseudo-obstruction as an early manifestation of NMS. This atypical and underreported presentation highlights the importance of maintaining a high index of suspicion for NMS in patients receiving antipsychotic therapy who develop unexplained gastrointestinal dysmotility. Prompt recognition, immediate discontinuation of the offending antipsychotic agent, and early initiation of treatment with dantrolene and bromocriptine resulted in a favorable clinical outcome.
2026-07-30 | Cervical cutthroat injury with complete hypopharyngeal transection: a case report
Penetrating neck trauma involving the aerodigestive tract is a life-threatening emergency. We report a case of an 18-year-old male patient with a zone II cervical wound that caused complete hypopharyngeal transection and a thyroid cartilage fracture. Initial airway control was achieved by direct translaryngeal intubation through the wound, followed by bilateral chest tube placement for pneumothoraces that developed after positive pressure ventilation. Surgical management included tracheostomy, primary hypopharyngeal and laryngeal reconstruction, and vascular control. The postoperative course was complicated by aspiration pneumonia, a strap muscle abscess requiring drainage, opioid withdrawal, and neuroleptic malignant syndrome. Despite these complications, the patient survived and was discharged after approximately 1 month with a gastrostomy tube because of persistent severe dysphagia. This case illustrates the need for flexible airway management, definitive surgical repair, and close postoperative surveillance for complex systemic complications in severe penetrating neck trauma.
2026-06-03 | Atypical neuroleptic malignant syndrome in a geriatric palliative care patient: a case report and review of the literature.
Neuroleptic malignant syndrome (NMS) is a rare but potentially life-threatening adverse reaction to antipsychotic medications that carries significant diagnostic complexity in its atypical forms, particularly among elderly patients with polypharmacy and multiple comorbidities in whom the classic diagnostic criteria are frequently unmet. Timely recognition of atypical NMS is critical, as diagnostic delays are associated with increased morbidity and mortality even in clinically mild presentation. We present a 71-year-old Caucasian male patient with schizophrenia on chronic risperidone and quetiapine therapy who developed atypical NMS following administration of haloperidol 64 drops for insomnia during hospitalization for urinary tract infection in a palliative care unit. The patient presented with low-grade fever (37.9 °C) and mildly elevated creatine kinase (600 U/L) without classic rigidity or autonomic instability. Due to unavailability of dantrolene and bromocriptine at the facility, the patient was successfully managed with intravenous diazepam and aggressive hydration therapy. Complete resolution of fever and normalization of creatine kinase levels were achieved with conservative management. This case highlights the importance of recognizing atypical NMS presentations in elderly patients and demonstrates that successful outcomes can be achieved with supportive care when first-line agents are unavailable.
2026-06-01 | Clozapine rebound catatonia or malignant neuroleptic syndrome? Case report
Introduction Abrupt discontinuation of clozapine is not recommended except in cases of serious, life threatening side effects. Catatonia and malignant neuroleptic syndrome (MNS) are severe neuropsychiatric conditions that can present with overlapping clinical features, including stupor, mutism, rigidity, and altered consciousness. However, their etiologies and therapeutic implications differ substantially. While MNS is typically triggered by potent dopamine D2 receptor antagonism and requires discontinuation of neuroleptic therapy, catatonia may arise in the context of primary psychiatric disorders or as a rebound phenomenon following abrupt clozapine withdrawal. Distinguishing between these syndromes is critical to guide treatment. Objectives The aim is to present the case of a patient with schizophrenia who developed overlapping symptoms of catatonia and neuroleptic malignant syndrome. Case presentation We describe a male patient, 45 years of age, with chronic schizophrenia who had been maintained on clozapine therapy up to 450 mg/day for over 18 years. After psycho-social stress and certain worsening of his mental condition clozapine was abruptly discontinued and fluphenazine 7.5 mg/day was introduced into the therapy. He became less alert and nonresponsive. A worsening of negative symptoms of schizophrenia was suspected and he was hospitalized in the psychiatric ward of a general hospital. On the third day of hospitalization, he begins to have difficulty breathing. CT angiography indicated a pulmonary embolism. The patient is out of contact, sweating, febrile up, and impaired in consciousness. He was then referred to the university clinic for neurology. Due to difficulty breathing, he was immidiately transferred to the ICU. Psychiatrist was consulted. Mental state examination: The patient is mechanically restrained. Not responsive. He actively resists when we try to open his eyes. He is febrile at 38.2 o C. After the restraints are removed, the following was noted: a marked rigor of a plastic type (flexibilitas cerea) exists in all muscles.The “psychological pillow” phenomenon is present. Treatment: After the administration of diazepam i.v. 2x 10 mg, muscle rigidity partially subsided. It was decided to reintroduce clozapine, and the dose was gradually increased. The patient’s condition improved daily, and was transferred to the university psychiatric clinic for additional stabilization. He was discharged in good general condition. Conclusions This case highlights the diagnostic challenge of differentiating clozapine-sensitive catatonia from MNS. Short-lived fever, partial benzodiazepine responsiveness, and clinical recovery following clozapine reintroduction favored a diagnosis of rebound catatonia rather than MNS. Awareness of this phenomenon is essential to avoid misdiagnosis and inappropriate treatment. Disclosure of Interest None Declared
2026-05-18 | Rhabdomyolysis caused by neuroleptic malignant syndrome requiring long-term hemodialysis: A case report and literature review.
Neuroleptic malignant syndrome (NMS) can be complicated by rhabdomyolysis, a known cause of acute kidney injury (AKI) that typically resolves within a short period. However, some cases of NMS-associated rhabdomyolysis require hemodialysis. We report a woman in her fifties who developed AKI secondary to NMS-associated rhabdomyolysis and required prolonged renal replacement therapy (RRT). She experienced sepsis and contrast exposure, and dialysis independence was achieved only after 2 months, the longest reported duration. This case highlights that NMS-associated rhabdomyolysis-induced AKI may lead to prolonged dialysis, particularly in the presence of additional risk factors for renal injury.
cell therapies
2025-06-04 | Case Report: Neuroleptic malignant syndrome in a 15-year-old female following of psychotropic drugs.
Neuroleptic Malignant Syndrome (NMS) is a rare but life-threatening neurological emergency associated with dopamine receptor blockade. It is characterized by hyperthermia, autonomic instability, muscle rigidity, and altered mental status. Early recognition and intervention are crucial to prevent severe complications. We report a case of a 15-year-old female diagnosed with major depressive disorder (MDD), with a body mass index (BMI) of 13.7, who developed severe NMS with rapid-onset rhabdomyolysis and vocal cord dysfunction following an overdose of quetiapine, sertraline, and lorazepam. The clinical presentation posed a diagnostic challenge due to overlapping features with serotonin syndrome. Despite aggressive supportive care, she developed acute kidney injury secondary to rhabdomyolysis, necessitating plasmapheresis and hemoperfusion. Additionally, post-extubation vocal cord dysfunction led to aspiration pneumonia, requiring prolonged airway management. This case highlights the complexity of diagnosing NMS in the context of polypharmacy, the potential for rapid rhabdomyolysis, and the rarity of vocal cord involvement. The successful use of plasmapheresis as an adjunct therapy suggests a possible role in severe NMS with organ dysfunction. Early recognition and individualized management remain key to optimizing outcomes.
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Drug Discovery Landscape
1 orphan drug designation for Neuroleptic malignant syndrome.
1 orphan drug designation for Neuroleptic malignant syndrome.
Drug | Therapy type | Orphan designation | Clinical trial status | Sponsor |
|---|---|---|---|---|
Dantrolene sodium | small molecules | FDA | — | Norwich Eaton Pharmaceuticals |
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