Metabolic and endocrine disorders
Olanzapine has the highest risk of obesity and metabolic disorders compared to other antipsychotics. In patients taking olanzapine 15 mg per day, after a year of therapy, body weight increases by an average of 11.8 kg. An increase in weight during treatment with this drug is noted up to 12% of the initial weight of patients. Weight gain can be up to 20-45 kg.
The consequences of obesity and metabolic disorders caused by antipsychotics seem to be no different from the consequences of obesity caused by any other causes, that is, they include an increased risk of coronary heart disease, arterial hypertension, cancer, diabetes mellitus, osteoarthritis, sleep apnea , cholelithiasis, myocardial infarction and stroke. The use of olanzapine statistically significantly increases the risk of developing diabetes by 6 times.
The metabolic disturbances mentioned above are caused by olanzapine not only in patients with mental disorders, but also in mentally healthy individuals. Studies have also shown that olanzapine reduces insulin sensitivity in healthy men after eight or ten days of use.
Diabetic ketoacidosis, a relatively rare and extremely dangerous complication of diabetes, can also be caused by olanzapine. Cases have been repeatedly noted when diabetic ketoacidosis developed suddenly, in the absence of previously diagnosed diabetes. The possibility of diabetic ketoacidosis must always be kept in mind: its mental manifestations are easily confused with the symptoms of schizophrenia.
At the beginning of treatment, especially when choosing a dosage, observation is necessary:
- extrapyramidal side effects,
- orthostatic hypotension and reflex tachycardia,
- drowsiness,
- weight gain,
- hyperglycemia and hyperlipoproteinemia are possible.
The risk of orthostatic hypotension is increased when olanzapine is taken concomitantly with benzodiazepines. Drowsiness at the beginning of treatment develops often, so the drug is best taken at night.
Due to the possibility of developing agranulocytosis, it is desirable to conduct weekly blood monitoring during the first 18 weeks of therapy in patients taking olanzapine, and then monthly.
When initially prescribing olanzapine, it is necessary to assess the likelihood of a patient gaining weight, taking into account his body mass index, history, general clinical feeling of a tendency to be overweight. When observing a patient taking olanzapine, it is important to consider the basic principle of weight gain control: a seven percent increase in body weight from the initial body weight is an absolute contraindication to further use of the drug.
To prevent the development of life-threatening conditions associated with diabetes (acidosis and coma), early recognition and treatment of developing diabetes is necessary. Psychiatrists in therapy with olanzapine should be alert to symptoms of diabetes such as weight loss, drowsiness, thirst, polyuria, and, if necessary, provide their patient with an endocrinologist's consultation.
Olanzapine can also cause the development of neuroleptic malignant syndrome, a potentially fatal symptom complex, the clinical manifestations of which include:
- a significant increase in body temperature,
- muscle rigidity,
- changes in mental status and autonomic disorders (unstable pulse or blood pressure, tachycardia, cardiac arrhythmia, increased sweating).
Additional signs may include an increase in CPK levels, myoglobinuria (rhabdomyolysis), and acute renal failure. Clinical manifestations of neuroleptic malignant syndrome or a significant increase in body temperature without other symptoms of this syndrome require the abolition of all antipsychotics, including olanzapine.
In comparative studies lasting more than 6 weeks, treatment with olanzapine was sometimes accompanied by the development of tardive dyskinesia (an irreversible neurological side effect). With the development of signs of tardive dyskinesia, it is recommended to reduce the dose or stop olanzapine. Symptoms of tardive dyskinesia may increase or begin after discontinuation of the drug.
With extreme caution, the drug should be used with an increase in the activity of AST and ALT in patients with insufficiency of liver function, a limited functional reserve of the liver, or in patients receiving treatment with potentially hepatotoxic drugs. In the event of an increase in AST and / or ALT activity during treatment with olanzapine, careful monitoring of the patient and, if necessary, dose reduction is required.
Olanzapine should be used with caution in patients with a history of seizures or those exposed to factors that lower the seizure threshold. Seizures have rarely been observed in these patients treated with olanzapine.
Under in vitro conditions, olanzapine exhibits dopamine antagonism and, like other antipsychotics, inhibits the action of levodopa and dopamine agonists.
Withdrawal of olanzapine may result in cholinergic withdrawal effects, including flu-like symptoms, insomnia, agitation, confusion, restlessness, anxiety, and extrapyramidal disorders. To prevent the cholinergic effects of withdrawal, a gradual decrease in the dose of the drug is recommended (and, if it is planned to switch to another antipsychotic, a gradual increase in the doses of this antipsychotic), with the development of withdrawal symptoms, a “step back” to the previous dose of the drug being withdrawn, and its slower withdrawal, in if necessary, the appointment of correctors and benzodiazepines.
