Chapter 5: Psychopharmacology

5.3: Recent Issues Related to Psychotropic Drugs and Metabolism

Grapefruit Juice and Metabolism

Image of slices of grapefruit
Figure 3. Grapefruit can interfere with enzymes in the liver that help the body to process certain drugs.

Certain types of food in the stomach can alter the rate of drug absorption, and other foods can also 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 of the psychotropic drugs). If the enzymes are suppressed, drug levels can build up to potentially toxic levels. In this case, the effects can persist for extended periods of time after the consumption of 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 are likely to 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 experiences 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 have no effect on another? Antidepressants can take 4 to 6 weeks to start improving depressive symptoms, and we don’t really understand why. Many people do not respond to the first antidepressant prescribed and may have to try different drugs before finding something that works for them. Other people just do not improve with antidepressants (Ioannidis, 2008). As we better understand why individuals differ, the easier and more rapidly we will be able to help people in distress.

One area that has received interest recently has to do with an individualized treatment approach. We now know that there are genetic differences in some of the cytochrome P450 enzymes and their ability to break down drugs. The general population falls into the following 4 categories: 1) ultra-extensive metabolizers break down certain drugs (like some of the current 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 either of the two above groups and finally 4) poor metabolizers break down drugs much more slowly than all of the other groups. Now consider someone receiving a prescription for an antidepressant—what would the consequences be if they were either an ultra-extensive metabolizer or a poor metabolizer? The ultra-extensive metabolizer would be given antidepressants and told it will probably take 4 to 6 weeks 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 daily dose of the same antidepressant may build up such high levels in their blood (because they are not breaking the drug down), that they will have a wide range of side effects and feel really badly – 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 then make a more informed decision about the best dose to prescribe. New genetic tests are now available to better individualize treatment in this way. 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). Currently, this genetic test is expensive and not many health-insurance plans cover this screen, but this may be an important component in the future of psychopharmacology. Again, this is just one area of research to explain the length of time that it takes for antidepressants to kick in. Other research is investigating additional processes such as changes in the cell membrane and neuron DNA as well as changes at receptor sites.

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