Food Interactions Seen With Many Psychotropics

There is an extensive literature detailing drug-drug interactions involving psychotropic medications, but less attention has been devoted to interactions between psychotropics and foods. In fact, however, food-drug interactions have been identified for many psychotropics. Most of the listed food-psychotropic interactions are pharmacokinetic, involving drug absorption, metabolism, and/or excretion. The list is not exhaustive, nor is the discussion that follows. (A table showing interactions between psychotropics and foods and references that provide additional information can be accessed here.)

Pharmacokinetic Interactions

Absorption

The presence of food in the stomach or small bowel affects the rate and/or extent of absorption for many drugs. This may be a significant factor for drugs such as buspirone, lurasidone, sertraline, vilazodone, and ziprasidone, all of which have potentially increased absorption in the presence of food. For other drugs, including certain hypnotics and anticonvulsants, the rate of absorption is slowed in the presence of food, so the speed of drug onset is slower. This can be used to advantage for drugs such as immediate-release trazodone, as slowed absorption can reduce the risk of orthostatic hypotension.

Since 1989, when the first interaction between drugs and grapefruit juice (GFJ) was serendipitously discovered, interactions with GFJ have been extensively studied, mostly by in vitro methods. Various compounds present in GFJ influence the activity of several enzymes and transporters, including CYP3A and p-glycoprotein; in vivo evidence exists for clinically relevant inhibition of CYP3A, but only in the GI tract with normal GFJ consumption. Drugs that should be avoided when GFJ is ingested include buspirone, mifepristone, pimozide, and ziprasidone. Drugs for which caution is advised with GFJ include carbamazepine and benzodiazepines.

In vivo evidence also supports altered activity of organic anion transporter proteins in the presence of GFJ, but the significance for psychotropics is not known. Even for CYP3A, clinically relevant interactions are limited to oral drugs significantly metabolized by 3A that undergo extensive first-pass metabolism at the gut wall. When these interactions do occur, CYP3A inhibition is irreversible, such that it would take as long as three days for 3A activity in the intestine to return after GFJ consumption.

Metabolism

In vitro and animal studies have demonstrated that kale and other leafy green vegetables competitively inhibit the activities of many CYP enzymes, including CYP1A2, 2D6, 2C19, and 3A4, among others. Although the amount of kale that would have to be ingested to cause this inhibition is at least an order of magnitude more than would be usual, the potential for additive inhibition should be considered. For example, kale and fluvoxamine could significantly inhibit 1A2, and kale and fluoxetine (or other psychotropics) could significantly inhibit 2D6; kale and fluoxetine, vilazodone, or fluvoxamine could significantly inhibit 2C19. For CYP3A4, psychotropic inducers such as carbamazepine, phenobarbital, or St. John’s wort could mitigate inhibitory effects of kale. Similarly, soy milk and miso have been reported to induce the activity of p-glycoprotein and CYP3A4, but the clinical significance of this is not known.

Excretion

It is well known that lithium has a very significant interaction with dietary sodium; the higher the sodium intake, the lower the lithium level. Initiation of a low-salt diet can result in lithium toxicity. In addition, good hydration is important for all patients, but particularly for those on lithium, to avoid renal injury.

Relatively less is known about the human multidrug and toxic compounds extrusion transporter 1 (hMATE1), which is a cation exporter that functions in the liver and kidneys to facilitate the excretion of xenobiotics and toxic drug metabolites; hMATE1 activity is inhibited by compounds present in food such as quercetin (present in red wine, dark-red or purple fruits, and green leafy vegetables) and isorhamnetin (present in almonds, pears, onions, and fennel). The significance of this inhibition for the metabolism of various psychotropics is not known.

Pharmacodynamic Interactions

One of the most infamous of the pharmacodynamic food-drug interactions is the tyramine reaction. This occurs when foods with high tyramine content are ingested in the presence of a nonselective MAOI. Restricted foods include tap beer, red wine, sherry, liqueurs, aged cheeses, cured meats, fermented cabbage, soy sauce, yeast extracts, and broad-bean pods. Improperly stored or spoiled foods also are problematic. The mechanism of this interaction involves the release of excessive noradrenaline into the synaptic cleft and sympathetic overstimulation. ■