Antipsychotics
Antipsychotics are used for the treatment of acute episodes and relapse prevention. They remain the primary treatment for psychosis and schizophrenia and are available as oral, intramuscular (IM) or medium or long-acting IM preparations/depots.
Antipsychotics have different potency and affinity at receptors, hence their very different side effect profiles. Irrespective of the different pharmacodynamics, there is no convincing evidence that any antipsychotic, except clozapine, is more effective than another.
Clozapine is licensed for use in people with ‘treatment-resistant’ schizophrenia, which is defined as a “lack of satisfactory clinical improvement despite the use of adequate doses of at least two different antipsychotic agents, including an atypical antipsychotic agent, prescribed for adequate duration”.
Routine monitoring is a prerequisite of clozapine use and dispensing must not occur without a valid blood test. Prescribers and pharmacists must be registered with the companies that manufacture Clozaril, Denzapine or Zaponex to be able to dispense clozapine. Due to a high occurrence of side effects, clozapine is slowly titrated to a treatment dose. A break in treatment of greater than 48 hours requires re-titration due to the increased risk of seizures, cardiac issues and enhanced sedation.
Clozapine levels are affected by the hydrocarbons in cigarette smoke so stopping smoking can significantly increase plasma levels and should be monitored. Nicotine replacement therapy (NRT) will have the same effect so the same caution should be taken when recommending NRT.
Clozapine has been associated with varying degrees of impairment of intestinal peristalsis – from constipation, which is very common, to very rare intestinal obstruction, faecal impaction, and paralytic ileus (impaired bowel motor activity without physical obstruction). Identification and treatment of any symptoms of constipation should be addressed promptly.
Specific antibiotics can interact with clozapine by either increasing or decreasing the levels of clozapine or by increasing the risk of neutropenia (a decrease in the number of neutrophils in the blood).