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.¹ 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).

One controlled study showed that taking clozapine can decrease blood levels of selenium, a mineral with antioxidant activity.² 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.

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.³ Controlled studies are necessary to determine whether supplementing N-acetyl-cysteine and vitamin C might prevent harmful side effects in people taking clozapine.

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.⁴ Controlled studies are necessary to determine whether supplementing N-acetyl-cysteine and vitamin C might prevent harmful side effects in people taking clozapine.

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.⁶ 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.

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.⁷ 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.⁸ 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.