Neuroleptic malignant syndrome
(NMS) [8][9][10]
Description: life-threatening neurological disorder usually associated with
antipsychotics; autonomic instability
Etiology
o Reaction to antipsychotic drugs (more common with high-potency
FGAs than with SGAs)
o Agents that affect the CNS (e.g., carbamazepine, lithium, venlafaxine)
o Certain antiemetics (e.g., metoclopramide, promethazine)
o Genetic predisposition
Pathophysiology: The underlying mechanism is not well understood;
disruption of numerous neurotransmitter pathways is suspected.
o Central D receptor blockade in the nigrostriatal pathway
2
Clinical features: Onset usually occurs within 2 weeks of the first dose.
o Muscle rigidity (lead-pipe rigidity), akinesia, tremor
o Autonomic instability
Hyperthermia
Tachycardia, dysrhythmias, labile blood pressure
Tachypnea
Diaphoresis
o Mental status change (encephalopathy)
Confusion
Delirium
Reduced vigilance
Stupor
Diagnostics
o ↑↑ Creatine kinase
o Leukocytosis
o ↑ Transaminases
o Metabolic acidosis
o Myoglobinuria
Differential diagnosis
o See “Differential diagnosis of drug-induced hyperthermia.”
Treatment
o Discontinuation of the antipsychotic drug
o Pharmacotherapy
Dantrolene
Alternatives: bromocriptine, apomorphine, or amantadine
To remember the different symptoms of neuroleptic malignant
syndrome, think FALTER: Fever, Autonomic
instability, Leukocytosis, Tremor, Elevated enzymes (creatine
kinase, transaminases), Rigor
Serotonin syndrome [11]
Description: a life-threatening condition caused by serotonergic overactivity
Cause: ingestion of any drug that increases serotonin levels
o MAOIs, SSRIs, SNRIs, TCAs, vortioxetine, vilazodone, trazodone , buspir
one
o tramadol, ondansetron, MDMA, dextromethorphan, meperidine, St.
John's wort, triptans, linezolid
o Increased risk with
Concurrent use of two or more serotonergic drugs
Switching from one serotonergic drug to another without
tapering
Clinical features [11]
o Classic triad: neuromuscular excitability, autonomic dysfunction,
altered mental status
o diaphoresis, hyperthermia
o Cardiovascular: hypertension, tachycardia
o nausea; diarrhea
o delirium, psychomotor agitation
o hypertonia (especially in the lower
extremities), hyperreflexia, myoclonus, tremor; ataxia; mydriasis; seizure
Treatment [11]
o Immediate discontinuation of serotonergic drugs
o Supportive care
Antihypertensives, fluid replacement
Benzodiazepines for sedation
Cyproheptadine
5-HT receptor antagonists
2A
Used for cases of serotonin syndrome that do not respond
to supportive care
Serotonin syndrome causes HARM: Hyperthermia, Autonomic instability, Rise in
blood pressure, and Myoclonus.
Delirium tremens
Definition: persistent alteration of
consciousness and sympathetic hyperactivity due to alcohol withdrawal
Onset
o Most commonly occurs 48–96 hours after last consumption of alcohol
o Symptoms commonly manifest during hospitalization, when the patient
is no longer able to drink alcohol.
Clinical features
o Symptoms of altered mental status
Impaired consciousness and disorientation
Visual and tactile hallucinations (usually small moving objects,
e.g., mice, crawling insects)
o Symptoms of autonomic instability
Tachycardia
Hypertension
Anxiety
Nausea
o Symptoms of neurological impairment
Psychomotor agitation (e.g., fidgeting, restlessness, tearfulness)
Generalized tonic-clonic seizures
Insomnia
Rest and intention tremor (first high-frequency, then low-
frequency)
In contrast to patients with alcoholic hallucinosis, patients with delirium tremens have
impaired consciousness and abnormal vital signs.
Treatment
IV fluid therapy and electrolyte disbalance correction
Thiamine: for Wernicke encephalopathy prophylaxis or treatment
Dextrose
Folate and multivitamins
IV benzodiazepines for control of psychomotor agitation and seizures
o Long-acting; diazepam, chlordiazepoxide
o Short-acting (e.g., lorazepam, oxazepam): especially for patients
with liver disease
Antipsychotics (e.g., haloperidol, risperidone)
o psychotic symptoms (never as independent medication)
Lorazepam, Oxazepam, and Temazepam are preferred in those who drink a
LOT because they are not metabolized by the liver and therefore safe in alcoholic
liver disease.
In the case of alcohol withdrawal seizures, benzodiazepines are preferred over
other anticonvulsants to prevent further seizures.
In contrast to patients with alcoholic hallucinosis, patients with delirium tremens have
impaired consciousness and abnormal vital signs.
Lithium toxicity [4]
Causes
Increase in dosage (lithium has a narrow therapeutic window)
Renal impairment
Low effective circulating volume (e.g., due to dehydration, loop
diuretic use, cirrhosis, congestive heart failure)
Medications that can precipitate lithium toxicity by increasing renal absorption of
lithium:
o Thiazide diuretics
o NSAIDs (except aspirin)
o ACE inhibitors
Clinical features
Gastrointestinal
o Nausea, vomiting, and diarrhea
Neuromuscular
o Altered mental status, confusion
o Somnolence
o Delirium, encephalopathy
o Coarse tremors, seizures, fasciculations, myoclonic jerks
o Ataxia, slurred speech
o Hyperreflexia
Acute renal failure
LITHIUM: “Lithium can cause Irregular Thyroxine levels
(hypothyroidism or hyperthyroidism), Heart (Ebstein
anomaly), nephrogenic diabetes Insipidus, and Uncontrolled Muscle movements (tremor).”
Treatment of adverse effects [5][6]
General measures
o Reassurance, avoidance of exacerbating factors (e.g., caffeine, stress),
and follow-up
Tremor: beta blockers (e.g., propranolol) if persistent or severe tremor
Nephrogenic diabetes insipidus: amiloride
Lithium toxicity
o Discontinuation of lithium
o Hydration with isotonic fluid (0.9% NaCl solution) and electrolyte correction
o Hemodialysis: first-line treatment for severe lithium toxicity
Indications
Altered mental status, seizures, and/or life-
threatening arrhythmias
Hemodialysis
o Ventilatory support if required
Monitoring serum levels of lithium is important because of its narrow therapeutic window.
