Clozapine is an atypical neuroleptic used to control symptoms of schizophrenia when other treatments are
Interactions with Vitamins, Herbs, and Foods
In some cases, an herb or supplement may appear in more than one category, which may seem
contradictory. For clarification, read the full article for details about the summarized
May Be Beneficial:Depletion or
interference—The medication may deplete or interfere with the absorption or
function of the nutrient. Taking these nutrients may help replenish them.
May Be Beneficial:Side effect
reduction/prevention—Taking these supplements may help reduce the likelihood and/or
severity of a potential side effect caused by the medication.
Avoid:Reduced drug absorption/bioavailability—Avoid these supplements
when taking this medication since the supplement may decrease the absorption and/or activity
of the medication 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
Interactions with Dietary Supplements
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
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.
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
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
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 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.
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.
References (To view, roll mouse over the "References" heading; to hide, click on the heading)
1. Potkin SG, Jin Y, Bunney BG, et al. Effect of clozapine and adjunctive
high-dose glycine in treatment-resistant schizophrenia. Am J Psychiatry
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
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
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
The information presented in Aisle7 is for informational purposes only.
It is based on scientific studies (human, animal, or in vitro), clinical experience,
or traditional usage as cited in each article. The results reported may not necessarily occur
in all individuals. For many of the conditions discussed, treatment with prescription or over
the counter medication is also available. Consult your doctor, practitioner, and/or pharmacist
for any health problem and before using any supplements or before making any changes in