From the Guidelines
Olanzapine is associated with significant adverse effects, including metabolic disturbances, sedation, anticholinergic effects, and extrapyramidal symptoms, which can impact morbidity, mortality, and quality of life. According to the study published in the Annals of Oncology in 2018 1, olanzapine may cause drowsiness, orthostatic hypotension, and metabolic effects with long-term use. The suggested starting dose of olanzapine is 2.5-5 mg p.o. or s.c. stat, with a reduced dose recommended for older patients and those with hepatic impairment.
Some of the key adverse effects of olanzapine include:
- Metabolic disturbances, such as weight gain, hyperglycemia, insulin resistance, and dyslipidemia, which can lead to diabetes and cardiovascular complications with long-term use
- Sedation and somnolence, especially at treatment initiation, affecting up to 40% of patients
- Anticholinergic effects, including dry mouth, constipation, urinary retention, and blurred vision
- Extrapyramidal symptoms (EPS) like parkinsonism, akathisia, and dystonia, though these occur less frequently than with typical antipsychotics
- Hyperprolactinemia, which may lead to sexual dysfunction, menstrual irregularities, and gynecomastia
- Rare but serious adverse effects, including QT prolongation, neuroleptic malignant syndrome, and agranulocytosis
- Increased risk of cerebrovascular events and mortality in elderly patients with dementia
Regular monitoring of weight, blood glucose, lipid profiles, and complete blood counts is essential, particularly during the first few months of treatment, to minimize the risk of these adverse effects and optimize patient outcomes. The study highlights the importance of careful dose titration and monitoring in vulnerable populations, such as older adults and those with hepatic impairment 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 various adverse effects, including weight gain, metabolic abnormalities, and changes in lipid and glucose profiles 3, 4, 5, 6, 7
- Studies have shown that olanzapine can cause significant weight gain, with some patients experiencing early weight gain (EWG) of ≥5% during the first month of treatment 3
- The risk of metabolic abnormalities, including weight gain, is higher in patients receiving higher doses of olanzapine (>10 mg/day) 3
- Treatment duration and co-prescription of other medications, such as antipsychotics, antidepressants, benzodiazepines, and antihypertensive agents, can also contribute to weight gain in olanzapine-treated patients 3
- Olanzapine has been shown to increase fasting glucose and lipid levels, particularly in non-geriatric adult patients, and these changes are not always correlated with weight gain 4, 5, 6
- The mechanism of olanzapine-induced weight gain and metabolic effects is thought to involve increased food intake, as well as direct effects on lipid and glucose metabolism independent of food intake and weight gain 6
Comparison with Other Antipsychotics
- Olanzapine has been compared to other second-generation antipsychotics, such as risperidone, iloperidone, and ziprasidone, in terms of its metabolic effects 4, 6, 7
- Studies have shown that olanzapine is associated with a higher risk of weight gain and metabolic dysregulation compared to some other antipsychotics, such as amisulpride and ziprasidone 7
- However, the metabolic effects of olanzapine can vary depending on the individual patient and the specific treatment regimen 3, 5