How to use clozapine: A guide for prescribers

‘Treatment-resistant schizophrenia’ is probably a neurochemically-distinct disease state whose underlying causes may well be entirely different from ‘ordinary’ schizophrenia.
If true, this means that additional trials of non-clozapine antipsychotic medications will probably fail.
In such cases, clozapine has the strongest evidence for efficacy.

If a patient has not enjoyed a therapeutic response to two therapeutic trials of non-clozapine antipsychotic medication, it is quite possible that the patient’s symptoms are being mediated through neurochemical pathways not affected by the failed medications.
Since most non-clozapine antipsychotics medications are D2 receptor blockers, lack of response may mean that the symptoms aren’t caused by excessive signaling at the D2 receptor. If this is the case, the physician should offer medications with alternate mechanisms of action.

Biochemical studies reveal that patients who respond to non-clozapine antipsychotic medications (i.e., D2 receptor blockers) have evidence of exaggerated dopamine signaling; whereas treatment-nonresponders have normal dopamine signaling. Biochemical studies confirm what medication non-response has been telling us: patients without dopamine psychosis don’t benefit from dopamine-blocking drugs.

Clozapine is specifically approved by the FDA for treatment-resistant schizophrenia. It is also uniquely FDA-approved to reduce suicidal behavior in patients with schizophrenia or schizoaffective disorder. Notably, clozapine is not a significant blocker of the D2 receptor.

On 28 February 2017, Drs. Erik Messamore and Sara Dugan discussed clozapine with the First Episode Schizophrenia Treatment Group. The talk addressed:

  • evidence that ‘treatment-resistant schizophrenia’ is a neurochemically different type of illness, distinctly different from treatment-responsive schizophrenia;
  • how to initiate therapy with clozapine
  • what to do in cases of therapy interruption
  • possible side effects from clozapine and how to address them; and
  • drug-drug interactions relevant to clozapine.

Because this is extremely specific to the prescribing audience, the PowerPoint slides are only available by email.
Send us a request if you’d like a copy of the PowerPoint deck.