Drug-nutrient interactions in mental health disorders

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By Kellie Blake, RDN, LD, IFNCP

Mental health disorders are often difficult to treat and many patients end up with long lists of medication. Psychiatric polypharmacy is common with up to one-third of psychiatric out-patients receiving three or more psychotropic drugs concomitantly. Drug-drug interactions are a concern, but drug-nutrient interactions, while more difficult to quantify, are likely common. I suspect many patients and providers are unaware of these important interactions.

As integrative practitioners, we understand the importance of nutrients in mental health disorders. The emerging field of nutritional psychiatry is dedicated to identifying nutrient deficiencies that underlie mental health symptoms and working with patients to correct these deficiencies to improve symptoms and quality of life and to reduce prescription medication use. But medications are often necessary and can be life-saving for many, so it’s important for providers to understand the many possible drug-nutrient interactions.

Drug-nutrient interactions are complex and can exert their effects in a variety of ways. Since oral medications are absorbed through the lining of the stomach or small intestine, food in the digestive tract and gastric acid secretion may affect drug bioavailability and effectiveness. In addition, high protein diets and diets that alter the gut microbiome can affect the metabolism of many drugs. While drugs can affect appetite, food absorption, and vitamin and mineral status, nutritional deficiencies can impact drug absorption and metabolism.

Overlooked drug-nutrient interactions can have serious consequences, but can also reduce medication effectiveness and alter nutrient status impacting mental health symptoms. Patients with mental health disorders are often treated with antidepressant, anticonvulsant, antipsychotic, and antimanic medications. Each class of drug comes with its own potential drug-nutrient interactions.

Antidepressant drugs

A variety of antidepressants are available including selective serotonin reuptake inhibitors and serotonin norepinephrine reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs), and tricyclic antidepressants (TCAs). SSRIs provide antidepressant effects by increasing the levels of serotonin in the brain. Fluoxetine has been associated with hypoglycemia related to increased insulin levels and long-term use of sertraline and paroxetine are associated with higher LDL cholesterol levels potentially increasing cardiovascular disease risk. In addition, as reported in one review, citalopram use is associated with a 14 percent reduction in copper levels.

An additional consideration with serotonergic antidepressants is the use of supplements containing L-tryptophan and 5-hydroxytryptophan (5-HTP). While both may increase the efficacy of antidepressant drugs, toxicity risk is also increased. Both L-tryptophan and 5-HTP should be avoided in those taking MAOIs and should be used in low doses and monitored closely in those taking other types of antidepressants.

MAOIs provide their antidepressant effect by blocking the enzyme, monoamine oxidase, which breaks down excess tyramine in the body. Tyramine is an amino acid important in blood pressure control.  MAOIs combined with foods high in tyramine can lead to a potentially fatal hypertensive crisis. As reported in the Journal of Clinical Psychiatry, high tyramine foods to avoid include aged cheeses, aged or cured meats, potentially spoiled meat, fish, and poultry, fava beans, Marmite concentrated yeast extract, sauerkraut, soy bean condiments, and tap beer. An additional consideration with MAOIs is the potential to prevent the conversion of vitamin B6 into its active form.

TCAs provide antidepressant effects by blocking serotonin and norepinephrine transporters. Amytriptylline absorption may be decreased by a high fiber diet, but use of this medication may also increase appetite and influence blood sugar regulation.

Anticonvulsant drugs

Anticonvulsants are used to control seizures and minimize brain damage caused from seizure activity by decreasing the triggering of abnormal neurons or limiting abnormal activity in the brain. A variety of anticonvulsants may cause vitamin D deficiency by increasing vitamin D metabolism in the liver, which compromises calcium status. So, long-term use of anticonvulsants may cause bone disorders. In addition, this class of drug competes with biotin for absorption in the small intestine. Anticonvulsants can cause an increase in homocysteine levels thus affecting levels of folic acid, vitamin B6 and B12 increasing the risk of cardiovascular disease. Further, anticonvulsants alter the metabolism of alcohol and alcohol can alter the metabolism of this class of drug.

Antipsychotic drugs

Antipsychotic drugs block receptors for neurotransmitters such as dopamine and serotonin to reduce the symptoms of schizophrenia, but can also decrease agitation and aggression and stabilize mood. Antipsychotic drugs may influence micronutrient status. Chlorpromazine may cause riboflavin and vitamin B12 deficiencies, which both can mimic psychiatric symptoms. Furthermore, antipsychotic drugs can reduce magnesium levels which is associated with symptoms of depression, irritability, hallucinations, and agitation. The co-administration of vitamin C with fluphenazine may decrease medication effectiveness. In addition, abruptly reducing caffeine intake can decrease serum concentrations of clozapine, so medication dosing may need to be altered in these patients. Antipsychotic drugs can also increase appetite leading to weight gain.

Antimanic drugs

Antimanic drugs influence neuroprotective pathways including the upregulation of brain-derived neurotrophic factor (BDNF). Lithium can cause sodium depletion, so patients on lithium can experience decreased lithium elimination leading to toxicity when consuming a low-sodium diet. On the other hand, high sodium diets may increase lithium excretion decreasing its effectiveness. A moderate sodium diet is recommended along with adequate water intake. In addition, psyllium husk supplementation can decrease blood lithium levels and abrupt changes in caffeine consumption can increase blood lithium levels. Many antimanic drugs are also anticonvulsants, so careful review of vitamin D and homocysteine status is important.

Understanding drug-nutrient interactions is vital for maximizing medication effectiveness, improving patient outcomes, and preventing adverse side effects. Providers should be aware of potential drug-nutrient interactions and understand how to adjust medication dosage and timing for optimal benefit. In addition, a personalized nutrition protocol appropriate for the prevention and mitigation of drug-nutrient interactions is necessary.

References

Bushra, R., Aslam, N., & Khan, A. Y. (2011) Food-drug interactions. Oman medical journal. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3191675/

Gaby, Alan. (2017) Nutritional Medicine, 2^nd Edition. Retrieved from: https://bookshelf.vitalsource.com/books/9781532322009

Gardner, D. M. (1996) The making of a user friendly MAOI diet. The Journal of clinical psychiatry. Retrieved from: https://pubmed.ncbi.nlm.nih.gov/8617704/

Gezmen-Karadağ, M. (2018) Role of food‑drug interactions in neurological and psychological diseases. Acta neurobiologiae experimentalis. Retrieved from: https://pubmed.ncbi.nlm.nih.gov/30295676/

Kaiser Permanente. Lithium Drug Information. Retrieved from: https://wa.kaiserpermanente.org/kbase/topic.jhtml?docId=hn-1422002.

Kukreja, S. (2013). Polypharmacy in psychiatry: a review. Mens sana monographs. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3653237/

Merck Manual Professional Version. Nutrient-Drug Interactions. Retrieved from: https://www.merckmanuals.com/