Drug-drug interactions
Another major concern is that the medical disease state may affect the metabolism and elimination of psychotropic medications. This concern is most evident for patients with liver and renal disease, but may also be substantial for patients with GI disorders that affect absorption and for patients with cardiopulmonary disease. While a review of this topic is well beyond the scope of this article, exhaustive reviews exist and the medical literature and medication product information help guide medication choice and dosing in various disease conditions.4 Psychotropic medication dosing strategies can be found for most medical conditions.
The issue that often creates the greatest degree of trepidation in prescribing psychotropic agents for patients with medical comorbidity is the potential for drug-drug interactions. In many ways, psychiatrists are well prepared for this issue because there are multiple examples of interactions between psychotropic medications themselves. Drug-drug interactions can result in increased serum levels of one or both coadministered drugs, with a consequent increase in drug toxicity.
Drug-drug interactions can also cause a decrease in the serum level of 1 or more of the coadministered drugs and can lead to lack or loss of efficacy, for either the psychiatric or medical condition. Some interactions result from the pharmacodynamic effects (or receptor affinities) of drugs that lead to additive or antagonistic effects. Others are a result of pharmacokinetic alterations (either inhibition or induction) produced by a drug on the metabolic pathway of another, or alterations in protein binding.
Drug metabolism is most often accomplished via the cytochrome P-450 system in conjunction with the UDP-glucuronosyltransferases. These systems can be extensively affected by psychotropic drugs. Inhibition of other systems, such as P-glycoprotein efflux transporters and the organic anion transporting polypeptides, may be significant, but they are less studied.
The combinations and permutations of potential drug interactions are staggering, and no individual could possibly commit them to memory. Furthermore, when considering drug-drug interactions, clinicians must take into account not only prescribed medications but also over-the-counter medications, supplements, and complementary/alternative agents that the patient is taking. Fortunately, multiple tools exist to assist the clinician in anticipating and identifying potential interactions; thus, it is necessary to only understand the potential mechanisms for the interactions, to check before prescribing, and to observe closely while patients are receiving treatment.5,6 Therapeutic drug monitor-ing can be useful in this regard; however, it is available for a limited number of medications.
Prescribing psychotropic medications for patients with medical illness is an important part of PM practice, but it is not limited to PM practice and increasingly will be encountered by the general psychiatrist. Our evidence base for psychotropic safety and efficacy is mounting, and awareness of a few key principles ensures that practitioners feel more comfortable prescribing and patients receive the treatment that they need.
