Thorazine (Chlorpromazine) Side Effects
Chlorpromazine causes a wide range of adverse effects that can be serious and long-lasting, with the most clinically significant being extrapyramidal symptoms, cardiovascular effects including orthostatic hypotension, sedation, and anticholinergic effects. 1, 2
Major Categories of Side Effects
Extrapyramidal Symptoms (EPS)
Low-potency agents like chlorpromazine have more anticholinergic side effects compared to high-potency agents, though EPS can still occur 1:
- Acute dystonia: Sudden spastic muscle contractions affecting neck, eyes (oculogyric crisis), or torso; can be life-threatening with laryngospasm; responds to anticholinergic or antihistaminic medications 1
- Parkinsonism: Mask-like facies, drooling, tremors, pill-rolling motion, cogwheel rigidity, shuffling gait; typically controlled with antiparkinsonian agents 2
- Akathisia: Severe restlessness with pacing and physical agitation; often misinterpreted as psychotic agitation; difficult to treat 1
- Tardive dyskinesia: Rhythmical involuntary movements of tongue, face, mouth, or jaw; may be irreversible; appears with long-term therapy; no effective treatment exists 2
Cardiovascular Effects
- Orthostatic hypotension: Common and clinically significant 3, 4, 1
- QTc prolongation: Can lead to torsades de pointes and dysrhythmias 5, 2
- Sinus tachycardia and other dysrhythmias 5
Anticholinergic Effects
Chlorpromazine has significant anticholinergic properties 1:
- Sedation and cognitive blunting
- Memory deficits
- Dry mouth
- Constipation and adynamic ileus
- Urinary retention
- Nasal congestion
- Mydriasis or miosis 2
Neuroleptic Malignant Syndrome (NMS)
A potentially fatal complication characterized by 2:
- Hyperpyrexia
- Muscle rigidity
- Altered mental status
- Autonomic instability (irregular pulse/blood pressure, tachycardia, diaphoresis, cardiac dysrhythmias)
- Requires immediate discontinuation of the drug
Metabolic and Endocrine Effects
- Considerable weight gain 1, 2
- Hyperprolactinemia leading to 6, 2:
- Lactation and breast engorgement
- Amenorrhea
- Gynecomastia
- Sexual dysfunction and impotence
- Reduced bone mineral density
- Increased breast cancer risk in women
- Hyperglycemia, hypoglycemia, and glycosuria 2
Ocular Changes (Long-term Use)
With prolonged therapy (typically ≥2 years at ≥300 mg/day) 2, 7:
- Fine particulate deposits in lens and cornea
- Star-shaped opacities in anterior lens
- Epithelial keratopathy
- Pigmentary retinopathy
- May cause visual impairment; lesions may regress after discontinuation
Dermatologic Effects
- Photosensitivity 1
- Skin pigmentation (slate-gray color) with prolonged high-dose use 2
- Mild urticarial reactions
- Rare: exfoliative dermatitis, toxic epidermal necrolysis 2
- Contact dermatitis in healthcare workers (use gloves when handling) 2
Hematologic Effects
- Elevated liver enzymes
- Cholestatic jaundice (phenothiazine class effect) 1
Neurologic Effects
Other Notable Effects
- Falls risk due to somnolence, postural hypotension, and motor/sensory instability 2
- Priapism 2
- Hyperpyrexia or mild fever after large IM doses 2
- Peripheral edema 2
- Rare: sudden death (cardiac arrest or asphyxia from cough reflex failure) 2
Critical Monitoring Requirements
Before initiating treatment 6:
- BMI, waist circumference, blood pressure
- HbA1c, glucose, lipids
- Prolactin, liver function tests
- Urea, electrolytes, full blood count
- Electrocardiogram
- Abnormal Involuntary Movement Scale every 3-6 months for tardive dyskinesia screening
- Periodic ocular examinations for long-term patients on moderate-to-high doses
- Regular assessment for falls risk
Special Populations
Pregnancy: Use only if benefits clearly outweigh risks; neonates exposed in third trimester are at risk for extrapyramidal and withdrawal symptoms 2
Nursing mothers: Excreted in breast milk; discontinue nursing or drug 2
Children/adolescents: May have higher risk of EPS than adults and greater difficulty communicating concerns 1