What are the side effects of olanzapine?

Side Effects of Olanzapine

Olanzapine's most clinically significant side effects are metabolic complications—particularly weight gain (occurring in approximately 40% of patients), diabetes mellitus, and dyslipidemia—which require systematic monitoring and often outweigh concerns about neurological side effects. 1, 2

Most Common Side Effects (≥5% incidence)

In Adults with Schizophrenia

• Postural hypotension, constipation, weight gain, dizziness, personality disorder, and akathisia are the most frequently reported adverse reactions 1
• Somnolence, agitation, insomnia, and headache occur commonly 3
• Dry mouth and anticholinergic effects (constipation) are dose-dependent 3

In Adolescents with Schizophrenia

• Sedation, weight increase, headache, increased appetite, dizziness, abdominal pain, pain in extremity, fatigue, and dry mouth are most common 1

In Bipolar I Disorder (Adults)

• Asthenia, dry mouth, constipation, increased appetite, somnolence, dizziness, and tremor predominate 1

In Bipolar I Disorder (Adolescents)

• Sedation, weight increase, increased appetite, headache, fatigue, dizziness, dry mouth, abdominal pain, and pain in extremity are most frequent 1

Critical Metabolic Side Effects Requiring Monitoring

Weight Gain

• Approximately 40% of patients experience weight gain, particularly with high starting doses and in underweight patients at baseline 2, 4
• Weight gain is significantly more frequent with olanzapine compared to haloperidol and risperidone 5
• Regular weight monitoring is mandatory throughout treatment 1

Hyperglycemia and Diabetes Mellitus

• Extreme hyperglycemia associated with ketoacidosis, hyperosmolar coma, or death has been reported 1
• Fasting blood glucose testing is required at baseline and periodically during treatment 1
• The risk of diabetes development necessitates ongoing symptom monitoring 1, 2

Dyslipidemia

• Undesirable alterations in lipids occur with olanzapine treatment 1
• Fasting lipid profile testing is required at baseline and periodically during treatment 1, 2

Neurological Side Effects

Extrapyramidal Symptoms (EPS)

• Olanzapine is associated with significantly fewer extrapyramidal symptoms than haloperidol and risperidone 5
• At high doses (>40 mg daily), EPS frequency increases to 27% 6
• Akathisia can occur at therapeutic doses 1
• The drug has a favorable profile regarding EPS at recommended doses 1

Tardive Dyskinesia

• Risk exists but is lower than with typical antipsychotics 1
• Discontinuation should be considered if clinically appropriate when tardive dyskinesia develops 1

Sedation

• Somnolence is one of the most frequent adverse effects, occurring in 25% of patients at high doses 3, 6
• Sedation may be more pronounced in elderly patients 7
• The drug has potential to impair judgment, thinking, and motor skills 1

Seizures

• Use cautiously in patients with seizure history or conditions that lower seizure threshold 1

Cardiovascular Side Effects

Orthostatic Hypotension

• Orthostatic hypotension with dizziness, tachycardia, bradycardia, and syncope may occur, especially during initial dose titration 1
• Frequency is 2% at high doses 6
• Particular caution is needed in patients with cardiovascular disease, cerebrovascular disease, or conditions affecting hemodynamic responses 1
• May be potentiated by concurrent diazepam or alcohol use 1

QTc Prolongation

• Olanzapine is associated with lower risk of QT interval prolongation compared to typical antipsychotics like haloperidol 7
• QTc prolongation occurred in only 1% of high-dose patients 6
• Baseline ECG monitoring is not routinely required 7
• Risk increases when combined with other QTc-prolonging medications 8

Endocrine Side Effects

Hyperprolactinemia

• Olanzapine is relatively prolactin-sparing compared to other antipsychotics 2, 5
• 30% of adults develop elevated prolactin concentrations on olanzapine versus 10.5% on placebo 8
• Untreated asymptomatic hyperprolactinemia carries risks including reduced bone mineral density and increased breast cancer risk in women 8

Hematologic Side Effects

Leukopenia, Neutropenia, and Agranulocytosis

• Unlike clozapine, olanzapine does not cause agranulocytosis 5, 3
• However, leukopenia and neutropenia have been reported with antipsychotics including olanzapine 1
• Patients with history of clinically significant low WBC or drug-induced leukopenia/neutropenia require frequent CBC monitoring during initial months 1

Hepatic Side Effects

• Transient asymptomatic liver enzyme elevations occur 5, 3
• Patients with hepatic impairment may require reduced starting doses of 2.5 mg 7

Anticholinergic Effects

• Constipation and dry mouth are common and dose-dependent 5, 3
• Use caution in patients with urinary retention, prostatic hypertrophy, constipation, paralytic ileus, or related conditions 1
• Risk of additive anticholinergic effects when combined with other anticholinergic drugs 1

Serious and Life-Threatening Side Effects

Neuroleptic Malignant Syndrome (NMS)

• Immediate discontinuation and close monitoring are required if NMS develops 1
• NMS occurred in 2% of patients receiving high-dose olanzapine 6

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)

• Discontinue olanzapine immediately if DRESS is suspected 1

Mortality in Elderly Patients with Dementia

• FDA black box warning: increased mortality in elderly patients with dementia-related psychosis 7

Fatal Interactions

• Fatalities have been reported with concurrent use of benzodiazepines and high-dose olanzapine due to oversedation and respiratory depression 7, 9
• Use lowest effective doses of both agents if combination is necessary 7

Special Population Considerations

Elderly Patients

• Sedation, falls, and orthostatic hypotension risks are heightened 7
• Start at 2.5 mg once daily with maximum dose not exceeding 10 mg/day 7
• Monitor for excessive sedation, falls, and orthostatic hypotension daily 7

Pregnant Patients

• May cause extrapyramidal and/or withdrawal symptoms in neonates with third trimester exposure 1

Common Pitfalls to Avoid

• Failing to monitor metabolic parameters (weight, glucose, lipids) systematically—these are the most important long-term risks 7, 1
• Delaying intervention decisions until substantial weight gain has occurred; switch-or-stay decisions need early assessment 2
• Combining with multiple antipsychotics, which increases risk of excessive dopamine blockade and cardiac adverse effects 8
• Using standard adult doses in elderly patients without dose reduction 7
• Inadequate monitoring for orthostatic hypotension during dose titration 1