2. INTRODUCTION
A severe disorder associated with
1. Increase in dose of dopamine
receptor antagonists. (mostly
antipsychotics)
OR
2.Rapid withdrawal of dopaminergic
agents.
Unpredictable
Potentially life-threatening.
3. 1956 - First case reported.
1960 – Current name was introduced in a
French study.
Rare.
• 1960-1997: Incidence 0.2-3.2%
• Current incidence : 0.01 – 0.02%
Mortality rate – 10%.
7. DEVELOPMENT AND COURSE
Heterogeneous in onset, presentation,
progression and outcome.
Onset – from hours to days.
16% : within 24hrs.
66% : within 1 week.
Virtually all cases : within 30 days.
Alteration in mental status and other
neurological signs typically precede systemic
signs. (>80%)
8. DEVELOPMENT AND COURSE
CONT..
Self-limited in most cases.
Mean recovery time : 7-10 days.
63% : within 1 week.
Nearly all : within 30 days.
Mortality results from :
respiratory failure
cardiovascular collapse
myoglobinuric renal failure
arrhythmias
DIC
9. RISK FACTORS
Concurrent medical and neuropsychiatric
issues
1.Dehydration
2.Psychomotor agitation
3.Encephalitis and traumatic brain injury
4.Mood disorders
5.Preexisting catatonia
6.History of NMS- in 15%-20% of cases.
7.Low serum iron
Younger age
Male gender
10. ANTIPSYCHOTIC-RELATED RISK
FACTORS
High potency conventional antipsychotics –
higher risk
Atypical antipsychotics: Less incidence.
Parental routes
Higher titration rates
Higher total doses
11. PATHOPHYSIOLOGY
Precise mechanisms are unproven.
Drug induced dopamine blockade, followed
by abrupt discontinuation of the drug
Sudden dopaminergic dysregulation
12. PATHOPHYSIOLOGY
Supportive evidence for this hypothesis:
1) All drugs associated are dopamine receptor
blockers.
2) Risk of NMS appears to be correlated with the
dopamine receptor binding affinity of drugs.
3) Dopaminergic drugs are used in the treatment of
NMS.
4) Patients with central dopamine tract lesions
develop similar syndromes.
5) Low levels of homovanillic acid (dopamine
metabolite) detected in patients with acute NMS.
13. PATHOPHYSIOLOGY CONT..
Also family clusters of NMS have found that A1
allele of dopamine D2 receptor gene may be over
expressed in these patients, this allele reduces
the density and function of the dopamine
receptor
18. MANAGEMENT
Immediate withdrawal of the offending agent.
Supportive care – mainstay of management
Aggressive fluid resuscitation
Monitoring and correction of electrolyte
imbalances.
Cooling measures (cooling blankets, ice packs, ice
water enema)
Monitoring for complications – cardiorespiratory
failure, renal failure, aspiration pneumonia,
coagulopathies.
Dialysis – renal failure
Ventilator support – respiratory failure
19. MANAGEMENT CONT..
Pharmacological management
No general consensus on use of pharmacological
therapies in uncomplicated cases.
Numerous anecdotal reports and meta-analyses
support the use of several empiric
pharmacological therapies in more severe cases.
May shorten the course and reduce mortality.
20. MANAGEMENT CONT..
Dopaminergic agents
Bromocriptine
Starting dose - 2.5mg bd/tds by mouth
Increase dose by 2.5mg every 24hrs.
Max. dose – 45mg/day
At least for 10 days (oral antipsychotics)
or 2-3 weeks (depot antipsychotics)
May worsen psychosis,hypotension and
induce emesis
22. MANAGEMENT CONT..
Dantrolene
Started with 1-2.5mg/kg initial IV bolus
Then 1mg/kg every 6hrly up to a max. dose of
10mg/kg/day for 8days
Switching to oral form after first few days for
another 7days
Discontinued once symptoms begins to resolve.
(Risk of hepatotoxicity)
23. MANAGEMENT CONT..
Benzodiazepines
May hasten the recovery in milder cases.
May control agitation.
Lorazepam
Starting test dose 1-2mg IM/IV, if effective
switch to mouth
Carbamazepine
Reported to have some effect.
Clonidine
24. MANAGEMENT CONT..
ECT - good outcome with both unilateral and
bilateral treatments
can be effective when,
1. Poor response to supportive care and
pharmacological management.
2. When idiopathic malignant catatonia
cannot be excluded.
3. Persistent residual catatonia and
parkinsonism after the resolution of
acute symptoms.
25. ANTIPSYCHOTIC USE AFTER NMS
Estimated risk of 30% of developing NMS again
with re-introduction of antipsychotics.
Precautions:
At least 2 weeks should be allowed from recovery
before rechallenge.
Low potency conventional antipsychotics/ atypical
antipsychotics.
Considering alternative therapies like ECT
Start with a low dose and titrate gradually
Careful monitoring for early signs of NMS.
26. RECOMMENDATIONS
Conservative use of antipsychotics.
Cautious use of antipsychotics in patients with
increased risk
Early diagnosis.
Prompt discontinuation of offending agents.
Early supportive care and medical management.