What are the common side effects of antipsychotic medications?

Common Side Effects of Antipsychotic Medications

Antipsychotic medications produce a wide array of side effects that can be serious, long-lasting, and are a major cause of medication non-adherence—clinicians must systematically monitor for extrapyramidal symptoms, metabolic complications, sedation, and cardiovascular effects using validated rating scales at regular intervals. 1

Neurological Side Effects

Extrapyramidal Symptoms (EPS)

These are among the most common and distressing side effects, particularly with first-generation antipsychotics:

Acute EPS (occur early in treatment):

• Dystonia: Sudden spastic muscle contractions affecting neck, eyes (oculogyric crisis), or torso. Risk factors include young age, male gender, and high-potency agents. Can be life-threatening with laryngospasm. Responds to anticholinergic or antihistaminic medications 1
• Parkinsonism: Bradykinesia, tremors, and rigidity mimicking Parkinson's disease. Treated with anticholinergic agents or amantadine 1
• Akathisia: Severe restlessness with pacing and agitation, often misinterpreted as psychotic agitation. Difficult to treat; may respond to dose reduction, β-blockers, or benzodiazepines. Managed with dose reduction, or switching to quetiapine/olanzapine, or adjunctive propranolol 1, 2

Important caveat: Children and adolescents may be at higher risk for EPS than adults 1

Tardive Dyskinesia (TD): Involuntary movements that may persist even after medication discontinuation. Some patients experience withdrawal dyskinesias that typically resolve over time. Requires monitoring with the Abnormal Involuntary Movement Scale every 3-6 months. If TD occurs, consider dose reduction or switching to an atypical antipsychotic 1

Tardive Dystonia: Slow movements culminating in spasms, often disabling and associated with TD 1

Neuroleptic Malignant Syndrome (NMS)

A rare but potentially fatal reaction characterized by fever, muscle rigidity, altered mental status, and autonomic instability. Treated with bromocriptine and anticholinergic agents in youth 1

Seizures

Clozapine carries approximately 3% risk of seizures in adults, with risk increasing at higher doses and rapid titration. Youth may have higher rates 1

Cognitive Effects

• Sedation, cognitive blunting, apathy, and memory deficits, especially with low-potency agents having greater anticholinergic activity 1
• However, atypical antipsychotics show benefits in fine motor function, memory, and executive function compared to traditional neuroleptics 1
• Anticholinergic burden should be minimized, particularly with clozapine, olanzapine, and quetiapine 2

Metabolic and Endocrine Side Effects

Weight Gain: The most common significant problem with atypical antipsychotics, can be extreme 1

Cardiometabolic Complications:

• Diabetes mellitus risk
• Dyslipidemia
• Metabolic syndrome
• Management: Adjunctive metformin should be offered when starting olanzapine or clozapine (start 500mg daily, increase to 1g twice daily) 2

Hyperprolactinemia: Leads to sexual dysfunction, amenorrhea, and is particularly distressing. Risperidone, paliperidone, and amisulpride carry higher risk 1, 3

Cardiovascular Side Effects

• Orthostatic hypotension and tachycardia 1
• QTc prolongation: Can lead to torsades de pointes. Risk increases with coadministration of other QT-prolonging medications. Requires baseline and periodic ECG monitoring 4, 1
• Sinus tachycardia and other dysrhythmias 4

Hematological Side Effects

Agranulocytosis:

• Approximately 1% risk with clozapine, potentially fatal but usually reversible if detected early
• Youth may have higher rates than adults
• Requires weekly WBC monitoring for 6 months, then biweekly 1
• Can occur with any antipsychotic agent, though primarily associated with clozapine 1

Other Common Side Effects

• Sedation and daytime drowsiness (75% of patients) 1, 5
• Dry mouth (58.2%) 5
• Sexual dysfunction (highly distressing, 26-35% report) 1, 5
• Lowered seizure threshold 1
• Hepatic effects: Elevated liver enzymes, cholestatic jaundice with phenothiazines 1
• Hypersalivation (particularly with clozapine) 1

Monitoring Requirements

Before initiating treatment, obtain: 2

• BMI, waist circumference, blood pressure
• HbA1c, fasting glucose, lipids
• Prolactin, liver function tests, renal function
• Full blood count, ECG

During treatment:

• Weekly BMI, waist circumference, blood pressure for 6 weeks
• Fasting glucose at 4 weeks
• Repeat all measures at 3 months, then annually
• EPS assessment every 3-6 months using validated scales 1

Critical Clinical Pearls

Most distressing side effects (leading to non-adherence): erectile dysfunction, sexual dysfunction, and amenorrhea—not necessarily the most common ones 5

Common pitfall: 71.5% of patients do not spontaneously report side effects to clinicians, making systematic assessment with validated rating scales essential 5

Atypical vs. Typical agents: While atypical antipsychotics theoretically have lower EPS risk, some (particularly risperidone) still produce significant extrapyramidal symptoms. The distinction between "typical" and "atypical" is neither valid nor useful clinically 1, 6

Age considerations: Children and adolescents may have higher rates of side effects and greater difficulty communicating concerns due to developmental issues 1