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.