Alternative Routes of Administration of Clozapine

Clozapine is the only antipsychotic with proven effectiveness in treatment-resistant schizophrenia. It is usually administered using commercially available oral tablets, but not all patients are willing or able to take medicines in this way. Orodispersible clozapine tablets are available from several manufacturers and may be useful where swallowing solid dosage forms is difficult, or as an aid to observe compliance. Liquid formulations of clozapine can be prepared extemporaneously or purchased commercially, but most preparations are suspensions (clozapine is poorly soluble) and patients may find them unpalatable. The administration of clozapine (suspension or crushed tablets) via enteral feeding tubes (predominantly nasogastric) has been reported both in medically unwell patients and in patients refusing clozapine. Enteral administration is likely to be superseded by intramuscular clozapine, which has recently been re-introduced and is being widely used in some countries. Successful use of this formulation in enforced treatment strategies has been described by several authors with good long-term outcomes when switched to oral treatment. Intramuscular clozapine has also been used in physically ill patients who are unable to take any form of enteral medication. Other methods of delivery (transdermal, nasal) are not yet commercially available, but offer promise of further treatment options for this group of seriously ill patients.