Neuroleptic malignant syndrome: Difference between revisions

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*Life threatening neurologic emergency associated with the use of neuroleptic agents<ref>Su YP, Chang CK, Hayes RD, Harrison S, Lee W, Broadbent M, et al. Retrospective chart review on exposure to psychotropic medications associated with neuroleptic malignant syndrome. Acta Psychiatr Scand. Nov 15 2013</ref><ref>Trollor JN, Chen X, Sachdev PS. Neuroleptic malignant syndrome associated with atypical antipsychotic drugs. CNS Drugs. 2009;23(6):477-92</ref>
*Life threatening neurologic emergency associated with the use of neuroleptic agents<ref>Su YP, Chang CK, Hayes RD, Harrison S, Lee W, Broadbent M, et al. Retrospective chart review on exposure to psychotropic medications associated with neuroleptic malignant syndrome. Acta Psychiatr Scand. Nov 15 2013</ref><ref>Trollor JN, Chen X, Sachdev PS. Neuroleptic malignant syndrome associated with atypical antipsychotic drugs. CNS Drugs. 2009;23(6):477-92</ref>
**Can occur with single dose, increasing dose, or same dose as usual <ref>Dunkley, E. J. C., Isbister, G. K., Sibbritt, D., Dawson, A. H. and Whyte, I. M. (2003) ‘The Hunter Serotonin Toxicity Criteria: simple and accurate diagnostic decision rules for serotonin toxicity’, QJM, 96(9), pp. 635–642. doi: 10.1093/qjmed/hcg109</ref>
**Can occur with single dose, increasing dose, or same dose as usual <ref>Dunkley, E. J. C., Isbister, G. K., Sibbritt, D., Dawson, A. H. and Whyte, I. M. (2003) ‘The Hunter Serotonin Toxicity Criteria: simple and accurate diagnostic decision rules for serotonin toxicity’, QJM, 96(9), pp. 635–642. doi: 10.1093/qjmed/hcg109</ref>
**May also occur with withdrawal of anti-Parkinson medication or use of antiemetics
**Most often seen with "typical" high potency antipsychotics ([[haloperidol]])
***also occurs with newer "atypicals" ([[risperidone]], [[olanzapine]])
***antiemetics ([[metoclopramide]], [[promethazine]])
***withdrawal of anti-Parkinson medication
*Develops over 1-3 days
*Develops over 1-3 days
*Majority of deaths occur from complications of muscle rigidity
*Majority of deaths occur from complications of muscle rigidity
*Mortality rates up to 5 to 20% <ref>Shalev A. Mortality from neuroleptic malignant syndrome. J Clin Psychiatry. 1989;50(1):18-25.</ref>


==Clinical Features==
==Clinical Features==
*Develops over 1-3 days
*Tetrad of:<ref>Gurrera RJ, Velamoor V, Cernovsky ZZ. A Validation Study of the International Consensus Diagnostic Criteria for Neuroleptic Malignant Syndrome. J Clin Psychopharmacol. Aug 22 2013</ref>
*Tetrad of:<ref>Gurrera RJ, Velamoor V, Cernovsky ZZ. A Validation Study of the International Consensus Diagnostic Criteria for Neuroleptic Malignant Syndrome. J Clin Psychopharmacol. Aug 22 2013</ref>
*[[Altered mental status]]
**[[Altered mental status]] - [[agitated delirium]] progressing to stupor/[[coma]]
**Agitated delirium progressing to stupor/coma
**Muscle rigidity - generalized, "lead pipe" rigidity
*Muscular Rigidity
**[[Hyperthermia]] >38C (87%); >40C (40%)
**Generalized, "lead pipe" rigidity
**Autonomic instability - [[tachycardia]], [[hypertension]], diaphoresis
*[[Hyperthermia]]
 
**>38C (87%)
===Complications===
**>40C (40%)
*[[Dehydration]]
*Autonomic Instability
*[[Electrolyte imbalance]]
**Tachycardia
*[[Acute renal failure]] ([[rhabdomyolysis]])
**Hypertension
*[[Dysrhythmias ]]
**Diaphoresis
*[[ACS]]
*[[Respiratory failure]]
**Chest wall rigidity, aspiration [[pneumonia]], [[PE]]
*[[DIC]]
*[[Seizure]] ([[hyperthermia]], [[electrolyte derangements]])
*[[Hepatic failure]]
*[[Sepsis]]


==Differential Diagnosis==
==Differential Diagnosis==
*[[Serotonin Syndrome]]
*[[Serotonin Syndrome]]
**More likely to have hyperreflexia, myoclonus, ataxis, N/V, diarrhea
**Serotonin syndrome more likely to have hyperreflexia, myoclonus, ataxia, nausea and vomiting, diarrhea
**Rigidity and hyperthermia, if present, is less severe than in NMS
**Rigidity and hyperthermia, if present, is less severe than in NMS; more commonly presents with clonus and hyperreflexia
*[[Malignant Hyperthermia]]
*[[Malignant Hyperthermia]]
**Distinguish by clinical setting (use of inhalational anesthetics or sux)
**Distinguish by clinical setting (use of inhalational anesthetics or sux)
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*[[Sympathomimetics]]
*[[Sympathomimetics]]
**Rigidity is not seen
**Rigidity is not seen
*[[Meningitis]]/[[encephalitis]]
*[[Alcohol_Withdrawal*Delirium_Tremens|Delirium Tremens]]
*[[Heat Stroke]]


{{Movement disorder DDX}}
{{AMS and fever DDX}}
{{AMS and fever DDX}}


==Diagnosis==
==Evaluation==
===Workup===
*Total CK
*Total CK
**Typically >1000
**Typically >1000
**Correlates with degree of rigidity
**Correlates with degree of rigidity
*CBC
*CBC
**WBC >10K is typical
**[[leukocytosis|WBC >10K]] is typical
*Chemistry
*Chemistry
**May show hypocalcemia, hypomagnesemia, hyperkalemia, metabolic acidosis
**May show [[hypocalcemia]], [[hypomagnesemia]], [[hyperkalemia]], [[metabolic acidosis]]
*UA
*[[Urinalysis]]
**Myoglobinuria (from rhabdo)
**Myoglobinuria (from rhabdo)
*LFT
*[[LFTs]]
**Transaminitis
**Transaminitis
*CT/[[LP]]
*[[head CT|CT]]/[[LP]]
**CSF may have mildly elevated protein
**CSF may have mildly elevated protein


{{Serotonin syndrome vs neuroleptic malignant syndrome}}
{{Serotonin syndrome vs neuroleptic malignant syndrome}}


==Treatment==
==Management==
*The causative agent should be stopped
*The causative agent should be stopped
*Discontinue all dopamine blocking agents
*If precipitant is a dopaminergic therapy (L-dopa or Carbidopa) it can be restarted later at lower doses as an outpatient
*If precipitant is a dopaminergic therapy (L-dopa or Carbidopa) it can be restarted later at lower doses as an outpatient
===Supportive Care===
===Supportive Care===
*Agitation should be controlled with [[Benzodiazepines]]  
*Agitation should be controlled with [[Benzodiazepines]]  
**Lorazepam 2 mg IV q5 min until agitation and muscle rigidity resolves
*[[Fluid resuscitation]]
*[[Fluid resuscitation]]
*Cooling measures
*Cooling measures
*Intubation and paralysis for severe cases, chest wall rigidity or respiratory failure
**Use NON-DEPOLARIZING paralytic agent


===Directed Medical therapy<ref>Addonizio G, Susman VL, Roth SD. Neuroleptic malignant syndrome: review and analysis of 115 cases. Biol Psychiatry. Aug 1987;22(8):1004-20 </ref>===
===Directed Medical Therapy<ref>Addonizio G, Susman VL, Roth SD. Neuroleptic malignant syndrome: review and analysis of 115 cases. Biol Psychiatry. Aug 1987;22(8):1004-20 </ref>===
*Controversial with unclear and disputed efficacy  
''Controversial with unclear and disputed efficacy''
*Dantrolene
*[[Dantrolene]] (skeletal muscle relaxant) - Consider only in patients with severe rigidity
**Skeletal muscle relaxant; may cause hepatotoxicity in pts w/ liver disease
**May cause hepatotoxicity in patients with liver disease
**Consider only in pts with severe rigidity
**0.25-2mg/kg IV q6-12hr, max dose 10mg/kg/day
**Give 0.25-2mg/kg IV q6-12hr
*[[Bromocriptine]] (dopamine agonist)
*Bromocriptine
**2.5mg PO q6-8hr, max dose 40mg/day
**Dopamine agonist
*[[Amantadine]] (alternative to bromocriptine)
**Give 2.5mg NG q6-8hr
**100mg PO initially; titrate up as needed to max dose 200mg q12hr
*Amantadine
 
**Alternative to bromocriptine
===Electroconvulsive Therapy===
**Give 100mg PO/NG initially; titrate up as needed to max dose 200mg q12hr
*Limited case series suggest that ECT can be effective in NMS refractory to pharmacotherapy<ref>Morcos N et al., Electroconvulsive therapy for neuroleptic malignant syndrome: a case series. J ECT. 2019.</ref>
 
==Disposition==
*Admit, usually to ICU
 
 
==See Also==


==Complications==
*Dehydration
*[[Electrolyte imbalance]]
*[[Acute renal failure]] ([[rhabdo]])
*[[Dysrhythmias ]]
*[[ACS]]
*[[Respiratory failure]]
**Chest wall rigidity, aspiration [[PNA]], [[PE]]
*[[DIC]]
*[[Seizure]] ([[hyperthermia]], [[electrolyte derangements]])
*[[Hepatic failure]]
*[[Sepsis]]


==References==
==References==
<references/>
<references/>


[[Category:Psych]]
[[Category:Psychiatry]]
[[Category:Tox]]
[[Category:Toxicology]]

Revision as of 05:41, 1 January 2021

Background

  • Life threatening neurologic emergency associated with the use of neuroleptic agents[1][2]
  • Develops over 1-3 days
  • Majority of deaths occur from complications of muscle rigidity
  • Mortality rates up to 5 to 20% [4]

Clinical Features

Complications

Differential Diagnosis

  • Serotonin Syndrome
    • Serotonin syndrome more likely to have hyperreflexia, myoclonus, ataxia, nausea and vomiting, diarrhea
    • Rigidity and hyperthermia, if present, is less severe than in NMS; more commonly presents with clonus and hyperreflexia
  • Malignant Hyperthermia
    • Distinguish by clinical setting (use of inhalational anesthetics or sux)
    • Hyperthermia, muscle rigidity, and dysautonomia is similar to NMS though more fulminant
  • Anticholinergic Toxicity
    • Diaphoresis, rigidity, elevated CK are absent
    • Flushing, mydriasis, bladder distension are common
  • Sympathomimetics
    • Rigidity is not seen

Movement Disorders and Other Abnormal Contractions

Altered mental status and fever

Evaluation

Serotonin syndrome vs Neuroleptic malignant syndrome

  • History of a new serotonergic drug or a dose increase of a serotonergic drug are helpful
  • Serotonin syndrome is usually much more acute in onset than NMS which may develop over days or weeks
  • Presence of ‘lead pipe’ rigidity is typical of NMS, while serotonin syndrome typically manifests with tremor and hyperreflexia
  • Elevations in CK, LFTs, and WBC, coupled with a low iron level, distinguishes NMS from serotonin syndrome among patients taking both neuroleptic and serotonin agonist medications simultaneously

Management

  • The causative agent should be stopped
  • Discontinue all dopamine blocking agents
  • If precipitant is a dopaminergic therapy (L-dopa or Carbidopa) it can be restarted later at lower doses as an outpatient

Supportive Care

  • Agitation should be controlled with Benzodiazepines
    • Lorazepam 2 mg IV q5 min until agitation and muscle rigidity resolves
  • Fluid resuscitation
  • Cooling measures
  • Intubation and paralysis for severe cases, chest wall rigidity or respiratory failure
    • Use NON-DEPOLARIZING paralytic agent

Directed Medical Therapy[6]

Controversial with unclear and disputed efficacy

  • Dantrolene (skeletal muscle relaxant) - Consider only in patients with severe rigidity
    • May cause hepatotoxicity in patients with liver disease
    • 0.25-2mg/kg IV q6-12hr, max dose 10mg/kg/day
  • Bromocriptine (dopamine agonist)
    • 2.5mg PO q6-8hr, max dose 40mg/day
  • Amantadine (alternative to bromocriptine)
    • 100mg PO initially; titrate up as needed to max dose 200mg q12hr

Electroconvulsive Therapy

  • Limited case series suggest that ECT can be effective in NMS refractory to pharmacotherapy[7]

Disposition

  • Admit, usually to ICU


See Also

References

  1. Su YP, Chang CK, Hayes RD, Harrison S, Lee W, Broadbent M, et al. Retrospective chart review on exposure to psychotropic medications associated with neuroleptic malignant syndrome. Acta Psychiatr Scand. Nov 15 2013
  2. Trollor JN, Chen X, Sachdev PS. Neuroleptic malignant syndrome associated with atypical antipsychotic drugs. CNS Drugs. 2009;23(6):477-92
  3. Dunkley, E. J. C., Isbister, G. K., Sibbritt, D., Dawson, A. H. and Whyte, I. M. (2003) ‘The Hunter Serotonin Toxicity Criteria: simple and accurate diagnostic decision rules for serotonin toxicity’, QJM, 96(9), pp. 635–642. doi: 10.1093/qjmed/hcg109
  4. Shalev A. Mortality from neuroleptic malignant syndrome. J Clin Psychiatry. 1989;50(1):18-25.
  5. Gurrera RJ, Velamoor V, Cernovsky ZZ. A Validation Study of the International Consensus Diagnostic Criteria for Neuroleptic Malignant Syndrome. J Clin Psychopharmacol. Aug 22 2013
  6. Addonizio G, Susman VL, Roth SD. Neuroleptic malignant syndrome: review and analysis of 115 cases. Biol Psychiatry. Aug 1987;22(8):1004-20
  7. Morcos N et al., Electroconvulsive therapy for neuroleptic malignant syndrome: a case series. J ECT. 2019.