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Clozapine

Also indexed as: Clozaril®

Clozapine is an atypical neuroleptic used to control symptoms of schizophrenia when other treatments are ineffective.

Interactions with Dietary Supplements

Glycine
The use of glycine may interfere with the efficacy of clozapine as an antipsychotic drug. In a double-blind trial, people with chronic, treatment-resistant schizophrenia were given clozapine (400–1,200 mg per day) and either glycine (30 g per day) or placebo for 12 weeks.1 The combination of clozapine and glycine was not effective at decreasing symptoms. In contrast, participants who took clozapine without glycine had a 35% reduction in some symptoms. Therefore, the combination should be avoided until more is known.

N-acetyl cysteine and Vitamin C
Clozapine can inhibit the formation of immune cells that protect the body from invading organisms. Test tube studies show that N-acetyl-cysteine and vitamin C block the formation of immune cell–damaging compounds produced when clozapine is broken down.2 Controlled studies are necessary to determine whether supplementing N-acetyl-cysteine and vitamin C might prevent harmful side effects in people taking clozapine.

Selenium
One controlled study showed that taking clozapine can decrease blood levels of selenium, a mineral with antioxidant activity.3 While more research is needed to determine whether people taking clozapine might require selenium supplementation, until more information is available, some health practitioners recommend supplementation.

L-tryptophan
Some people who take clozapine become mentally depressed after taking the drug for a few weeks. Studies have shown that clozapine can reduce blood levels of the amino acid L-tryptophan, which is often deficient in people with depression.4 More controlled research is needed to determine whether the interaction is significant and whether individuals taking clozapine might benefit from supplemental L-tryptophan or 5-hydroxytryptophan (5-HTP).

Interactions with Foods and Other Compounds

Alcohol
Drinking alcoholic beverages together with clozapine can cause side effects, such as drowsiness and dizziness.5 Consequently, people taking clozapine should avoid alcohol, especially when it is necessary to stay alert.

Caffeine
Caffeine is a compound found in coffee, colas, and tea, as well as in some over-the-counter products. One 31-year-old woman taking clozapine who consumed nearly 1,000 mg of caffeine daily experienced side effects from the drug.6 A subsequent study involving individuals with schizophrenia who were stabilized on clozapine, showed that caffeine avoidance resulted in significantly lower blood levels of the drug.7 Controlled research is needed to determine whether problems might occur when individuals taking clozapine change the amount of caffeine they consume each day. Until more information is available, individuals taking clozapine should talk with their healthcare practitioner before making changes in their caffeine intake.

Smoking
Controlled studies show that smoking cigarettes can significantly reduce blood levels of clozapine,8 which can become a problem if an individual either starts or stops smoking while taking the drug. Those who start smoking may experience more symptoms of schizophrenia, while those who quit smoking might experience unwanted side effects of the drug. Consequently, people taking clozapine should talk with their healthcare practitioner before making changes in their smoking habit.

Summary of Interactions for Clozapine

Depletion or interference L-tryptophan
Selenium
Adverse interaction None known
Side effect reduction/prevention N-acetyl cysteine*
Vitamin C
Supportive interaction None known
Reduced drug absorption/bioavailability Glycine

For the convenience of the reader, the information in the summary is categorized as follows: “Depletion or interference” indicates the drug may deplete or interfere with the absorption or function of the supplement or herb. “Adverse interaction” indicates that the supplement or herb used together with the drug may result in undesirable effects. “Side effect reduction/prevention” indicates the supplement or herb may reduce the likelihood and/or severity of a potential side effect caused by the drug. “Supportive interaction” indicates the supplement or herb may support or aid the function of the drug. “Reduced drug absorption/bioavailability” indicates that the supplement or herb may decrease the absorption and/or activity of the drug in the body. An asterisk (*) next to an item in the summary indicates that the interaction is supported only by weak, fragmentary, and/or contradictory scientific evidence.

References:

1. Potkin SG, Jin Y, Bunney BG, et al. Effect of clozapine and adjunctive high-dose glycine in treatment-resistant schizophrenia. Am J Psychiatry 1999;156:145–7.

2. Linday LA, Pippenger CE, Howard A, Lieberman JA. Free radical scavenging enzyme activity and related trace metals in clozapine-induced agranulocytosis: a pilot study. J Clin Psychopharmacol 1995;15:353–60.

3. Williams DP, Pirmohamed M, Naisbitt DJ, et al. Neutrophil cytotoxicity of the chemically reactive metabolite(s) of clozapine: possible role in agranulocytosis. J Pharmacol Exp Ther 1997;283:1375–82.

4. Meltzer HY. Clinical studies on the mechanism of action of clozapine: the dopamine-serotonin hypothesis of schizophrenia. Psychopharmacology 1989;99 Suppl:S18–27 (Berlin).

5. Sifton DW, ed. Physicians Desk Reference. Montvale, NJ: Medical Economics Company, Inc., 2000, 2008–12.

6. Wetzel H, Anghelescu I, Szegedi A, et al. Pharmacokinetic interactions of clozapine with selective serotonin reuptake: differential effects of fluvoxamine and paroxetine in a prospective study. J Clin Psychopharmacol 1998;18:2–9.

7. Odom-White A, deLeon J. Clozapine levels and caffeine. J Clin Psychiatry 1996;57:175–6.

8. Carrillo JA, Herraiz AG, Ramos SI, Benitez J. Effect of caffeine withdrawal from the diet on the metabolism of clozapine in schizophrenic patients. J Clin Psychopharmacol 1998;18:311–6.