Clozapine Printable Version

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Introduction to Clozapine

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Clozapine (Clozaril, Versacloz) is an atypical antipsychotic (the first atypical) that is used in treatment resistant schizophrenia or schizoaffective disorder. It is also indicated for suicidal behavior in schizophrenia or schizoaffective disorder. It's reserved for the treatment resistant because approximately 0.4% of patients will develop a reduction in white blood cells that has been fatal in the past. Because of these risks clozapine is under a REMS (risk evaluation and mitigation strategies) system in the United States. The prescribing doctor, patient, and dispensing pharmacy must all register with the government. Patients must get their bloodwork done weekly for the first six months of treatment and monthly thereafter. Due to these restrictions clozapine is under-utilized in the US compared to other countries.

Using Clozapine


Clozapine dosage:
12.5 mg PO once daily or every 12 hours initially; increase in increments of 25 to 50 mg per day if well tolerated, to achieve target dosage of 300 to 450 mg per day by end of two weeks. Subsequently may increase dose once or twice weekly in increments of up to 100 mg; not to exceed 900 mg per day. [1]

Clozapine and recreational drugs:
The hydrocarbons in smoke (tobacco or marijuana) inhibit clozapine's metabolism into norclozapine, which can lead to lesser efficacy. [2] Caffeine can be helpful in combating some clozapine side effects such as increased appetite, sedation, and constipation, but increases clozapine blood levels, therefore caffeine consumption should be kept at a constant amount for the duration of clozapine therapy. [3] Clozapine is a poor trip-ender because of the amount and severity of side effects compared to other antipsychotics that might be a better choice. When combining drugs that can be psychotomimetic, including cannabis, with an antipsychotic, reactions can be unpredictable.

Dangers of Clozapine


Clozapine side effects:
Clozapine in particular is prone to causing metabolic syndrome (weight gain, insulin resistance, and high tryglycerides). Clozapine is purported to be the only antipsychotic medication that does not cause movement side effects (psuedoparkinsonism or tardive dyskinesia) although these do appear rarely, and it can cause the blood effects mentioned above. Other side effects include hypersalivation, sedation, and dizziness.

Pharmacology of Clozapine

"Demonstrates weak D2-receptor and D1- receptor blocking activity, but noradrenolytic, anticholinergic, andtihistaminic, and arousal reaction inhibiting effects are significant; also possesses antiserotoninergic (5-HT1C, 5-HT2, 5-HT3) properties.
Affinity for mesolimbic dopamine D4 receptor accounts for striking effects in control of behavioral and psychiatric symptoms with low incidence of EPS; histamine receptor blockade accounts for increased incidence of sleep disturbances." [4]

Clozapine metabolism

Bioavailability: 50-60%
Onset: 15 minutes
Duration: 4-12 hours
Metabolism: CYP1A2, into norclozapine
Half-life: 12 hours
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References

  1. ^medscape app, "clozapine pharmacology" accessed 8/20/20
  2. ^medscape app, "clozapine dosage" accessed 8/22/20
  3. ^Laitman, Robert, et. al. Meaningful Recovery from Schizophrenia and Serious Mental Illness: Hope & Help. 4th ed. CreateSpace independent publishing platform, 2017.
  4. ^O'Connell, M; Vandenberg, A 2020 "CYP450 interactions between illicit substances and prescription medications" Current Psychiatry, 19(8):40-42,51 (https://drugs-forum.com/studies/cyp...substances-and-prescription-medications.9561/)