Nms vs ss

neuroleptic malignant syndrome vs serotonin syndrome

1. Serotonin Syndrome vs Neuroleptic Malignant Syndrome Presented by D r. Rakesh Mehta 1

2. NEUROLEPTIC MALIGNANT SYNDROME NMS is a life-threatening complica­tion that can occur anytime during the course of antipsychotic treatment. The syndrome consist of altered mental status, generalized rigidity, hyperthermia, and autonomic instability.

3. Pathophysiology Decreased levels of dopamine activity :

4. Causes Usually caused by antipsychotic drug use Typical>Atypical Withdrawl of dopaminergic drugs Levodopa Other anti-dopaminergic drugs Metoclopramide Amantadine Others (Berman 2011) Lithium Promethazine Phenelzine Dosulepin

5. Epidemiology About 0.01 to 0.02 percent of patients treated with antipsychot­ics develop neuroleptic malignant syndrome. Men > Female Young> Old 6

6. Course and Prognosis Evolve over 24-72 hours If untreated symptoms may last for 10-14 days The diagnosis is often missed : agitation may be mistakenly as exacerbation of the psychosis Mortality : 10-20% (more if depot injection)

7. Risk Factors Heredity Organic brain disease, particularly basal ganglia disorders Low serum iron Rapid dose escalation Dehydration History of NMS More than one antipsychotic 8

8. NMS - Clinical Characteristics Develops quickly over hours to days Early signs Change in mental status Catatonia like features Extrapyramidal symptoms unresponsive to antiparkinsonian agents Autonomic dysfunction 9

9. Clinical Characteristics Hyperthermia Muscle rigidity - “lead pipe rigidity ” Agitated Delirium and/or catatonia Autonomic dysfunction Tachycardia Profuse diaphoresis Labile blood pressure 10

10. Laboratory findings Rhabdomyolysis (↑ CPK) Leukocytosis (↑WBC) Myoglobinuria ( may cause AKI) Low serum iron Metabolic acidosis 11

11. Differential Diagnosis of NMS Infections Serotonin Syndrome Catatonia Agitated delirium Malignant hyperthermia Seizures 12

12. Treatment of NMS Cessation of neuroleptics Re-introduction of dopamine agonists if removed Hydration Temperature reduction Intensive monitoring Supportive care 13

13. Treatment of NMS Dantrolene Dantrolene can be administered intravenously starting with an initial bolus dose of 1 to 2.5 mg/kg followed by 1 mg/kg every 6 hours up to a maximum dose of 10mg/kg/d ( Bhanushali 2004) Bromocriptine Administered orally (or via NG tube), starting with 2.5 mg 2 or 3 times daily and increasing doses by 2.5 mg every 24 hours until a response or until reaching a maximum dose of 45 mg/d for at least 10 days (Strawn 2007) Amantadine 200-400 mg/day Levodopa 14

14. Treatment of NMS Benzodiazepines Benzodiazepines reduce rigidity Intravenous lorazepam is preferred Rapid onset of action Longer effective length of action High doses (18-24mg daily) often required and tolerated ECT Definitive treatment ECT considered if… Unresponsive to pharmacologic treatment in first 24-48 hours Prominent features of catatonia or severe rigidity 15

15. Serotonin Syndrome (SS) Serotonin syndrome can be a serious complication of treatment with SSRIs, TCAs, MAOIs and other serotonergic medications It usually occurs when 2 or more serotonin-modifying agents are used in combination or in overdose settings 16

16. Pathophysiology Occurs due to excessive serotonergic activity in the CNS and PNS, usually in the context of initiation or dose increase of a serotonergic agent. 17

17. Increase 5-HT synthesis - Tryptophan 2. MAO inhibitors (non-selective) - Isocarboxazid -phenelzine 3. Increased 5-HT release - Amphetamine - MDMA, cocaine 4. 5- HT 1A receptor agonist - Mirtazipne , Rizatriptan, ergotamine, 5. 5- HT 2A receptor antagonist - 2 nd gen Antipsychotics(quetiapine, olanzapine) 6. 5-HT reuptake inhibitors - SSRI, SNRI, TCA, Opioids,

18. Clinical Characteristics Clinical triad Cognitive/behavioral alterations Delirium Catatonia Agitation Lethargy  Coma Autonomic instability Hyperthermia Tachycardia Diaphoresis Dilated pupils Neuromuscular abnormalities Myoclonus Hyperreflexia Rigidity seizures 19

19. SS - Clinical Characteristics There are no specific tests available for the diagnosis of serotonin syndrome Blood levels of serotonin do not correlate with clinical findings Nonspecific laboratory findings may include… Elevated total white blood cell count, CPK levels, and transaminases, Decreased serum bicarbonate level Severe cases can evolve to include… Disseminated intravascular coagulation, rhabdomyolysis, and metabolic acidosis Renal failure and myoglobinuria Adult respiratory distress syndrome 20

20. SS – Risk Factors Administration of 2 or more serotonergic medications Overdose Use of lithium Classically MAOI and SSRI or other serotonergic agent Now much more commonly 3-6 serotonergic agents E.g. SSRI + trazodone + tramadol Overdose on SSRI, SNRI, atypical antipsychotic or combination 21

21. SS – Differential Diagnosis NMS Antidepressant withdrawal syndrome Alcohol and substance withdrawal states Extrapyramidal side-effects 22

22. SS – Clinical Course and Outcomes Clinical course and outcome Rapid onset Usually self-limited, with an uneventful resolution, once the offending agent has been discontinued Clues to Serotonin Syndrome Look for it in every case of overdose Look for it in any patient on >4 psychiatric medications Consider it in all catatonic patients Keep an eye out for the twitchy patient 23

23. Treatment of SS Management starts with early recognition of the syndrome, and supportive care Discontinuation of the causative drugs Supportive therapy Hydration Cooling 24

24. Treatment of SS Benzodiazepines Help with catatonic features Act as muscle relaxants Help with agitation Cyproheptadine First-generation antihistamine with serotonin antagonist properties May consider an initial dose of 12mg followed by 2mg every 2 hours if symptoms continue Maintenance dosage is 8mg every 6 hours Chlorpromazine Fairly potent 5-HT2 and 5-HT1A receptor antagonist 25

25. NMS vs. SS Neuroleptic Malignant Syndrome Serotonin Syndrome Precipitated by Dopamine antagonists Serotoninergic agents Onset Variable (1-3 days) Variable (<1d) Vital Signs Hypertension, tachycardia, tachypnea Hypertension, tachycardia, tachypnea Temperature Hyperthermia Hyperthermia Mucosa Sialorrhea Sialorrhea Skin Diaphoresis Diaphoresis Mental Status Delirium Delirium Muscles “Lead pipe” rigidity Increased tone Reflexes Hyporeflexia Hyperreflexia, clonus Pupils Normal Dilated 26 Adapted from Birmes et al, CMAJ 2003

26. References Berman BD. Neuroleptic malignant syndrome: a review for neurohospitalists . The Neurohospitalist . 2011 Jan;1(1):41-7. Bhanushali MJ, Tuite PJ. The evaluation and management of patients with neuroleptic malignant syndrome. Neurologic Clin. 2004;22(2):389-411 Strawn JR, Keck PE, Caroff SN. Neuroleptic malignant syndrome. Am J Psychiatry. 2007;164(5):870-876. Birmes P, Coppin D, Schmitt L, Lauque D. Serotonin syndrome: a brief review. Cmaj . 2003 May 27;168(11):1439-42.