From the Guidelines
Olanzapine can cause significant adverse effects, including weight gain, metabolic changes, sedation, and anticholinergic effects, and its use should be carefully monitored, especially in elderly patients or those with a history of diabetes or cardiovascular disease, as recommended by the most recent study 1.
Common Adverse Effects
- Weight gain and metabolic changes, such as elevated blood glucose, cholesterol, and triglycerides, which may lead to diabetes and cardiovascular issues 1
- Sedation and drowsiness, especially when starting treatment 1
- Anticholinergic effects, including dry mouth, constipation, blurred vision, and urinary retention 1
- Extrapyramidal symptoms, such as tremor, rigidity, and akathisia, although these occur less frequently than with typical antipsychotics 1
Serious Adverse Effects
- Neuroleptic malignant syndrome, characterized by fever, muscle rigidity, and autonomic instability 1
- Tardive dyskinesia, involuntary movements that may become permanent 1
- Agranulocytosis, a rare but potentially life-threatening decrease in white blood cell count 1
- Increased prolactin levels, potentially causing sexual dysfunction, menstrual irregularities, or gynecomastia 1
Special Considerations
- Elderly patients should be used with caution, as they may be more susceptible to the adverse effects of olanzapine, such as sedation, orthostatic hypotension, and metabolic changes 1
- Patients with a history of diabetes or cardiovascular disease should be closely monitored, as olanzapine may exacerbate these conditions 1
- Olanzapine should not be used in combination with other medications that may increase the risk of adverse effects, such as metoclopramide, phenothiazines, or haloperidol 1
From the FDA Drug Label
ADVERSE REACTIONS Most common adverse reactions (≥5% and at least twice that for placebo) associated with: Oral Olanzapine Monotherapy: Schizophrenia (Adults) – postural hypotension, constipation, weight gain, dizziness, personality disorder, akathisia. (6. 1) Schizophrenia (Adolescents) – sedation, weight increased, headache, increased appetite, dizziness, abdominal pain, pain in extremity, fatigue, dry mouth. (6.1) Manic or Mixed Episodes, Bipolar I Disorder (Adults) – asthenia, dry mouth, constipation, increased appetite, somnolence, dizziness, tremor. (6. 1) Manic or Mixed Episodes, Bipolar I Disorder (Adolescents) – sedation, weight increased, increased appetite, headache, fatigue, dizziness, dry mouth, abdominal pain, pain in extremity. (6. 1)
The most common adverse effects of olanzapine include:
- Postural hypotension
- Constipation
- Weight gain
- Dizziness
- Personality disorder
- Akathisia
- Sedation
- Headache
- Increased appetite
- Abdominal pain
- Pain in extremity
- Fatigue
- Dry mouth 2 2 2
From the Research
Olanzapine Adverse Effects
- Olanzapine treatment has been associated with metabolic abnormalities, including weight gain, dyslipidemia, hypertension, and type 2 diabetes 3, 4, 5.
- A study found that olanzapine-treated patients were at risk of weight gain regardless of the dose, with higher doses associated with increased glucose levels and lower doses associated with increased total and HDL cholesterol and systolic and diastolic blood pressure 3.
- Another study found that olanzapine promoted substantial weight gain and increased visceral fat, while the metabolic profile did not show the same magnitude of change, suggesting a dissociation between weight gain and blood parameters 5.
- Metformin has been studied as a potential treatment for olanzapine-induced weight gain, with meta-analysis showing that metformin was associated with a significant reduction in body weight, waist circumference, and body-mass index (BMI) compared to placebo 6.
- A study in healthy volunteers found that olanzapine treatment led to increased food intake and body weight, with associated trends towards lipid abnormalities and insulin resistance, suggesting that olanzapine produces its weight and metabolic effects primarily by increasing food intake 7.
Factors Influencing Olanzapine Adverse Effects
- Treatment duration and co-prescription of other medications, such as antipsychotics, antidepressants, benzodiazepines, and/or antihypertensive agents, were associated with larger weight gain in olanzapine-treated patients 3.
- The risk of early weight gain (EWG) was higher in patients receiving higher doses of olanzapine (>10 mg/day) 3.
- Genetic risk of mental illness, attendant lifestyle, and concomitant medications may also confound the relationships between olanzapine and metabolic effects 7.