clozapine_flashcards
What is Clozapine?
Clozapine is one of the first atypical agents developed and carries a significant risk of agranulocytosis, requiring full blood count monitoring during treatment.
Why is full blood count monitoring essential during Clozapine treatment?
Clozapine carries a significant risk of agranulocytosis, which is why full blood count monitoring is essential during treatment.
When should Clozapine be used according to the BNF?
Clozapine should be introduced if schizophrenia is not controlled despite the sequential use of two or more antipsychotic drugs (one of which should be a second-generation antipsychotic drug), each for at least 6-8 weeks.
What are the adverse effects of Clozapine?
The adverse effects of Clozapine include agranulocytosis, neutropaenia, reduced seizure threshold, constipation, myocarditis, and hypersalivation.
What are the specifics of agranulocytosis and neutropaenia related to Clozapine?
Agranulocytosis occurs in 1% of patients and neutropaenia in 3% of patients treated with Clozapine.
How can Clozapine affect seizure thresholds?
Clozapine can induce seizures in up to 3% of patients by reducing the seizure threshold.
What cardiovascular condition should be monitored before starting Clozapine?
A baseline ECG should be taken before starting treatment with Clozapine to monitor for myocarditis.
What gastrointestinal side effect is common with Clozapine?
Constipation is a common gastrointestinal side effect of Clozapine.
What adjustment might be necessary if smoking is started or stopped during Clozapine treatment?
Dose adjustment of Clozapine might be necessary if smoking is started or stopped during treatment.
summarise
Clozapine
Clozapine, one of the first atypical agents to be developed, carries a significant risk of agranulocytosis and full blood count monitoring is therefore essential during treatment. For this reason, clozapine should only be used in patients resistant to other antipsychotic medication. The BNF states:
Clozapine should be introduced if schizophrenia is not controlled despite the sequential use of two or more antipsychotic drugs (one of which should be a second-generation antipsychotic drug), each for at least 6-8 weeks.
Adverse effects of clozapine
agranulocytosis (1%), neutropaenia (3%)
reduced seizure threshold - can induce seizures in up to 3% of patients
constipation
myocarditis: a baseline ECG should be taken before starting treatment
hypersalivation
Dose adjustment of clozapine might be necessary if smoking is started or stopped during treatment.
A 35-year-old man with schizophrenia has been on clozapine for five years and has been well controlled and stable for that time. However, at his most recent check-up, the clozapine levels were found to be above the recommended range and his dose is therefore reduced.
Which of the following is most likely to cause a rise in clozapine blood levels?
Alcohol abstinence
Omitting doses
Smoking cessation
Stress
Weight gain
Smoking cessation
Smoking cessation can cause a rise in clozapine blood levels
Smoking cessation can cause a significant rise in clozapine levels, and so it should be discussed with a psychiatrist before stopping smoking. Starting smoking, or smoking more, can reduce clozapine levels. Stopping drinking can also reduce levels, as alcohol binges can increase the level. Omitting doses will cause a reduction in clozapine levels, and stress and weight gain won’t have significant effects on the level.
A 53-year-old gentleman presents to the GP surgery with constipation which has been ongoing for many years. He reports not having opened his bowels for ten days. He has a past medical history of atrial fibrillation, type II diabetes mellitus, gastro-oesophageal reflux disease and paranoid schizophrenia. His medication includes apixaban, clozapine, digoxin, metformin and lansoprazole. On examination, he has a firm, non-tender abdomen, and is fecally impacted on PR examination. Which of the above medication is likely to be contributing to his chronic constipation?
Apixaban
Clozapine
Digoxin
Metformin
Lansoprazole
Clozapine
One of the most common side effects of clozapine is constipation/intestinal obstruction
One of the most common side effects of clozapine is constipation. This can lead to potentially serious side effects. Indeed studies show that there is a higher mortality from GI side effects (such as bowel obstruction and perforation) than from agranulocytosis. Regarding the other medication - digoxin, metformin and lansoprazole can all cause diarrhoea. Apixaban is not known to cause constipation.
A 37-year-old male has presented to the emergency department following a witnessed seizure. The witness reports them having a tonic-clonic seizure that lasted approximately 10 minutes. They were drowsy for 15 minutes following this, but is now alert and talking to you on admission. They have a past medical history of schizophrenia and have reported multiple seizures since starting a new medication 3 weeks ago.
Which of the following medications is most likely to have precipitated this event?
Aripiprazole
Clozapine
Olanzapine
Quetiapine
Risperidone
Clozapine
Clozapine reduces seizure threshold, making seizures more likely
All of the above medications are atypical antipsychotic drugs that are used for an array of indications. Of these, the only notable drug that reduces seizure threshold is clozapine. Clozapine is an effective medication but carries a number of serious side effects which you must be aware of: agranulocytosis, neutropenia, reduced seizure threshold, and myocarditis.
All atypical antipsychotics can cause weight gain and hyperprolactinemia. However, generally speaking, aripiprazole has a good side effect profile and is less likely to increase prolactin levels or cause other side effects.
Olanzapine is notorious for its associations with dyslipidemia and weight gain, and is also associated with diabetes and sedation. It is for this reason that some patients are purposefully given olanzapine if they are underweight and cannot sleep.
Quetiapine is also associated with weight gain and dyslipidemia. However, one of the most notable side effects of this drug is postural hypotension.
Risperidone can increase the likelihood of developing extrapyramidal side effects, as well as cause postural hypotension and sexual dysfunction.
A 36-year-old with a long standing history of schizophrenia presents to the emergency department in status epilepticus. Once he is treated, he tells the doctor he has been having a lot of seizures recently.
Which of the following medications is most likely to be causing the seizures?
Clozapine
Diazepam
Fluoxetine
Haloperidol
Olanzapine
Clozapine
Clozapine reduces seizure threshold, making seizures more likely
Clozapine is an atypical antipsychotic used for treatment resistant schizophrenia. It has many side-effects, one of which is that it reduces the seizure threshold, which is most likely to be causing the seizures described in the question. Olanzapine is another atypical antipsychotic, and haloperidol is a typical antipsychotic, but neither are associated with reduced seizure threshold. Fluoxetine is an SSRI, and diazepam is a benzodiazepine, and is actually used to treat seizures.
