Grapefruit Juice and Metabolism

Certain types of food in the stomach can alter the rate of drug absorption, and other foods can alter the rate of drug metabolism. The most well-known is grapefruit juice. Grapefruit juice suppresses cytochrome P450 enzymes in the liver, and these liver enzymes normally break down a large variety of drugs (including some psychotropic drugs). If the enzymes are suppressed, drug levels can build up to potentially toxic levels. In this case, the effects can persist long after consuming grapefruit juice. As of 2013, at least 85 drugs have been shown to interact adversely with grapefruit juice (Bailey et al., 2013). Some psychotropic drugs that likely interact with grapefruit juice include carbamazepine (Tegretol), prescribed for bipolar disorder; diazepam (Valium), used to treat anxiety, alcohol withdrawal, and muscle spasms; and fluvoxamine (Luvox), used to treat obsessive-compulsive disorder and depression. A link at the end of this chapter gives the latest list of drugs reported to have this unusual interaction.

Individualized Therapy, Metabolic Differences, and Potential Prescribing Approaches for the Future

Mental illnesses contribute to more disability in Western countries than all other illnesses, including cancer and heart disease. Globally, depression and anxiety disorders are among the highest causes of health burden, and the mental health system in most countries is under-resourced (Santomauro et al., 2021). The numbers of people affected by mental health issues are astonishing, with estimates that 25% of adults experience a mental health issue in any given year, and this affects not only the individual but also their friends and family. One in 17 adults experience a serious mental illness (Kessler et al., 2005). Newer antidepressants are probably the most frequently prescribed drugs for treating mental health issues, although there is no “magic bullet” for treating depression or other conditions. Pharmacotherapy with psychological therapy may be the most beneficial treatment approach for many psychiatric conditions, but many questions remain unanswered. For example, why does one antidepressant help one individual yet has no effect on another? Antidepressants can take 4 to 6 weeks to start improving depressive symptoms, and we don’t understand why. Many individuals do not respond to the first prescribed antidepressant and may need to try various medications before finding an effective treatment. Some individuals show no improvement with any antidepressants (Ioannidis, 2008). As our understanding of individual differences improves, we can more quickly and effectively assist those in distress.

Recent interest has focused on personalized treatment approaches. Genetic variations in cytochrome P450 enzymes affect drug-metabolism rates. The general population falls into the following 4 categories: 1) ultra-extensive metabolizers break down certain drugs (like some antidepressants) very, very quickly, 2) extensive metabolizers are also able to break down drugs fairly quickly, 3) intermediate metabolizers break down drugs more slowly than the two above groups, and finally 4) poor metabolizers break down drugs much more slowly than the other groups. Now consider someone receiving a prescription for an antidepressant—what would be the consequences if they were an ultra-extensive metabolizer or a poor metabolizer? The ultra-extensive metabolizer would be told it will probably take 4 to 6 weeks for the antidepressants to begin working (this is true), but they metabolize the medication so quickly that it will never be effective for them. In contrast, the poor metabolizer given the same dose of that antidepressant may build up such high levels in their blood (because they are not breaking down the drug), that they will have a wide range of side effects–also not a positive outcome. What if instead, prior to prescribing an antidepressant, the doctor could take a blood sample and determine which type of metabolizer a patient actually was? They could make an informed decision about the best dose to prescribe. New genetic tests are available to individualize treatment. A blood sample can determine (at least for some drugs) which category an individual fits into, but we need data to determine if this actually is effective for treating depression or other mental illnesses (Zhou, 2009). While currently costly and often not covered by insurance, such genetic testing may become crucial in psychopharmacology’s future. This research, along with studies on cell membranes, neuronal DNA, and receptor-site alterations, aims to explain the delayed onset of antidepressant effects.