What are the side effects of haloperidol (antipsychotic medication)?

Side Effects of Haloperidol

Haloperidol causes extrapyramidal symptoms (EPS), QTc prolongation, and tardive dyskinesia as its most clinically significant side effects, with EPS being the most common and QTc prolongation carrying the highest mortality risk. 1, 2

Extrapyramidal Symptoms (Most Common)

Acute Dystonia

• Sudden spastic muscle contractions affecting neck, eyes (oculogyric crisis), or torso, typically occurring within the first few days of treatment 1, 3
• Young males are at highest risk for acute dystonic reactions 1, 3
• Immediate treatment with benztropine 1-2 mg IM/IV or diphenhydramine provides rapid relief, sometimes within minutes 1, 3

Drug-Induced Parkinsonism

• Bradykinesia, tremors, and muscle rigidity resulting from dopamine D2 receptor blockade 1, 3
• Can be difficult to distinguish from negative symptoms of psychosis 1
• Higher incidence at higher haloperidol doses and in younger patients 4
• Anticholinergic agents (benztropine) or mild dopaminergic agents (amantadine) are effective treatments 1, 3

Akathisia

• Subjective restlessness and physical agitation, often manifesting as pacing 1, 3
• Frequently misinterpreted as anxiety or worsening psychosis, leading to inappropriate dose escalation 3
• Incidence rate of 31.7% with haloperidol treatment 5
• Benzodiazepines (lorazepam) are more effective than anticholinergics for akathisia management 4

Tardive Dyskinesia (Potentially Irreversible)

• Involuntary, rhythmical movements of tongue, face, mouth, or jaw (tongue protrusion, cheek puffing, chewing movements) that may become permanent 2, 6
• Risk increases with long-term therapy, particularly in elderly patients on high doses, especially females 2
• Fine vermicular tongue movements may be an early warning sign; stopping medication at this stage may prevent full syndrome development 2
• No known effective treatment exists once established; antiparkinson agents do not alleviate symptoms 2
• Risk is approximately 5% per year in young patients 3

Tardive Dystonia

• Delayed onset choreic or dystonic movements that are often persistent and potentially irreversible 2
• Distinct from tardive dyskinesia syndrome 2

Cardiovascular Effects (Highest Mortality Risk)

QTc Prolongation and Arrhythmias

• Mean QTc prolongation of 7 ms with oral/IM haloperidol, with significantly higher risk via IV administration 7
• 46% increased risk of ventricular arrhythmia and/or sudden cardiac death (adjusted OR 1.46,95% CI 1.17-1.83) 7
• Torsades de pointes is the most feared complication, particularly when QTc exceeds 500 ms 1, 7

High-Risk Factors Requiring Heightened Monitoring

• Female gender and age >65 years 7
• Baseline QTc >500 ms 7
• Hypokalemia or hypomagnesemia 1, 7
• Concomitant use of other QTc-prolonging medications (see Table 5 in pediatric guidelines for comprehensive list including ondansetron, azithromycin, ciprofloxacin, diphenhydramine) 1
• IV administration route 1, 7

Monitoring Requirements

• Baseline ECG before initiating therapy 7
• Close clinical observation, cardiorespiratory monitoring, pulse oximetry when tolerated 1
• Consider medication adjustment if QTc exceeds 500 ms or increases >60 ms from baseline 7
• Monitor and correct electrolytes, particularly potassium (maintain >4.5 mEq/L) and magnesium 7

Other Cardiovascular Effects

• Orthostatic hypotension and sinus tachycardia 1

Neuroleptic Malignant Syndrome (Medical Emergency)

• Characterized by hyperpyrexia, muscle rigidity, altered mental status, and autonomic instability 2
• Requires immediate haloperidol discontinuation 2
• Heat stroke and hyperpyrexia can occur independently of full NMS 2

Central Nervous System Effects

• Insomnia, restlessness, anxiety, agitation, drowsiness, depression, lethargy 2
• Headache, confusion, vertigo 2
• Grand mal seizures 2
• Exacerbation of psychotic symptoms including hallucinations 2
• Catatonic-like behavioral states responsive to drug withdrawal and/or anticholinergic treatment 2
• Delirium (haloperidol is recommended for treatment but can also be a causative agent when drug-induced delirium is considered) 1

Falls Risk

• Somnolence, postural hypotension, and motor/sensory instability increase fall risk, leading to fractures or injuries 2
• Complete fall risk assessments required at initiation and recurrently during long-term therapy 2

Hematologic Effects

• Mild, usually transient leukopenia and leukocytosis 2
• Minimal decreases in red blood cell counts, anemia 2
• Agranulocytosis (rare, typically only with concomitant medications) 2

Hepatic Effects

• Impaired liver function and/or jaundice 2

Endocrine and Metabolic Effects

• Lactation, breast engorgement, mastalgia 2
• Menstrual irregularities, gynecomastia, impotence, altered libido 2
• Hyperglycemia, hypoglycemia, hyponatremia 2

Dermatologic Reactions

• Maculopapular and acneiform skin reactions 2
• Photosensitivity (isolated cases) 2
• Hair loss 2

Gastrointestinal Effects

• Anorexia, constipation, diarrhea 2
• Hypersalivation, dyspepsia, nausea, vomiting 2

Autonomic Effects

• Dry mouth, blurred vision, urinary retention 2
• Diaphoresis, priapism 2
• Worsening of anticholinergic delirium in patients intoxicated with anticholinergic substances 1

Respiratory Effects

• Laryngospasm, bronchospasm 2
• Increased depth of respiration 2
• Risk of bronchopneumonia (some fatal), potentially related to lethargy and decreased thirst sensation leading to dehydration and reduced pulmonary ventilation 2

Ophthalmologic Effects

• Cataracts, retinopathy, visual disturbances 2

Withdrawal Effects

• Transient dyskinetic signs may occur after abrupt discontinuation in patients on maintenance therapy 2
• Gradual withdrawal is recommended to reduce occurrence of withdrawal emergent neurological signs 2

Pregnancy and Neonatal Effects

• Neonates exposed during third trimester are at risk for extrapyramidal and/or withdrawal symptoms: agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, feeding disorders 2
• Complications range from self-limited to requiring intensive care and prolonged hospitalization 2
• Reports of limb malformations with first-trimester use (causal relationship not established) 2

Critical Pitfalls to Avoid

• Do not use prophylactic anticholinergics routinely; reserve for high-risk patients (young males, history of dystonic reactions, compliance concerns) 3
• IV haloperidol carries substantially higher cardiac risk than oral or IM routes 1, 7
• Akathisia is often mistaken for worsening psychosis, leading to inappropriate dose increases rather than treatment with benzodiazepines 3
• Anticholinergics can paradoxically worsen agitation in patients with anticholinergic or sympathomimetic drug ingestions 3
• Adding anticholinergics to antipsychotics with high intrinsic anticholinergic properties potentiates adverse effects 8