Olanzapine is an atypical antipsychotic drug of the thienobenzodiazepine group, which became a prominent part of psychiatric clinical practice in the last two decades. Still, adverse reactions to this drug and its potential side effects can be very costly and cause suffering for the patient, resulting in potential disability or sometimes even death.

The introduction of olanzapine and other second-generation antipsychotics is generally considered a breakthrough in the treatment of people with schizophrenia due to the lower incidence of so-called “typical” extrapyramidal side effects such as parkinsonism, dyskinesia, dystonia and akathisia, when compared to high-potency first-generation antipsychotics.

Common side effects

Albeit structurally and functionally related to clozapine (which is a drug that became famous as the first “atypical” antipsychotic), olanzapine possesses a more favorable side effect profile. The most common adverse effects are mild to moderate sedation, dizziness, constipation, akathisia (restlesness) and increased levels of liver transaminases (namely ALT).

Most notable metabolic side effects are weight gain, type II diabetes mellitus, dyslipidemia, hyperglycemia, insulin resistance, hyperprolactinemia, hypertension and cardiovascular disease. Furthermore, the prevalence of diabetes in schizophrenic patients is approximately 1.5 to 2 times greater than the prevalence reported in the general population.

Olanzapine can impair hypothalamic thermoregulatory mechanisms, resulting in hyperthermia. In addition, the use of anticholinergic medications and dehydration can raise body temperature even more. Arthralgia, joint disorders, neck rigidity, back pain, increased creatine kinase and tardive dyskinesia represent neuromuscular side effects of this drug.

Hypersensitive reaction with fever and hepatitis are most common dermatological side effects linked to olanzapine usage. Other dermatological adverse reactions are various hyperpigmentations of the skin, vesiculobullous rash eruptive xanthomas and purpura associated with thrombocytopenia.

In comparison with first generation antiphsychotics, olanzapine has not been associated with significant increase in prolactin levels. Different research groups have proven that elevation of prolactin during olanzapine treatment was not greater in comparison to placebo and significantly less compared to haloperidol.

Contraindications and precautions

Postural hypotension with subsequent reflex tachycardia, dizziness and sometimes even syncope can be observed during the initial dose titration period. These reactions stem from α-1 adrenergic blocking effects; hence olanzapine should be used cautiously in patients with cardiovascular or cerebrovascular disease, in dehydrated patients, in patients taking antihypertensive medications, as well as in the elderly.

Patients with a history of a clinically significant low white blood cell count or drug induced neutropenia should frequently monitor complete blood count during the first few months of taking olanzapine, as leukopenia, neutropenia and agranulocytosis have all been reported as likely side effects of the drug.

There may also be occurrence of a withdrawal syndrome, with symptoms such as myoclonic jerking, headache, nightmares, restlessness, piloerection, depression and blurred vision. The possibility of a suicide attempt is inherent in schizophrenia and bipolar disorders, thus close supervision of high-risk patients should always accompany therapy with olanzapine.