Antidepressants: Clinically Relevant Drug Interactions to Be Considered

Abstract

Drug interactions in clinical practice are common and have developed into an increasing challenge for the medical profession. Specifically antidepressant drugs (ADs), which are among the 5 most frequently prescribed drugs, are predestined for adverse drug interactions because of their multiple mechanisms of action and/or their influence on drug-metabolizing cytochrome P450 (CYP) enzymes. Although selective serotonin reuptake inhibitors (SSRIs) and other new-generation ADs have an overall improved safety profile, their potential for drug interactions is to be considered. A review of the current literature has been performed, and selected examples of clinically relevant interactions with ADs have been chosen. With regard to pharmacodynamic interactions, the serotonin syndrome, the risk of bleeding under SSRI therapy, and the corrected Q–T interval prolongation are discussed in this review. The inhibitory effects of new-generation ADs on CYP enzymes show great variability and might be relevant for prescription recommendations in elderly patients and in patients with polypharmacy. The CYP-enzyme-inducing effect of St. John’s wort, a popular over-the-counter herbal drug, may lead to decreased plasma levels of CYP substrates. When comparing prescription data and observed adverse drug events, there is fortunately a safety gap between the number of potential drug-drug interactions and the number of clinically observed side effects due to drug-drug interactions.

Risk of bleeding associated with combined use of selective serotonin reuptake inhibitors and antiplatelet therapy following acute myocardial infarction

“…25 In contrast, we found similar risks of bleeding for SSRIs of high and intermediate affinity, which suggests that affinity to serotonin did not play an important role in the drug interactions of SSRIs and antiplatelet agents. Inhibition of cytochrome P450 by certain SSRIs has also been associated with increased risk of drug interactions causing bleeding; 21 however, this hypothesis could not be verified in our study because of the limited number of patients using combinations involving these SSRIs.…”

“…19,20 Inhibition of cyto chrome P450 by certain SSRIs has also been associated with increased risk of drug interaction causing bleeding; 21 however, data on this issue are scarce. We examined the risk of bleeding associated with the use of SSRIs when combined with single and dual antiplatelet therapy among patients following acute myocardial infarction.…”

Managing depression in primary care

“…(30,31) SSRIs such as fluoxetine, fluvoxamine and paroxetine have strong potential to inhibit CYP, which can lead to clinically significant interactions with other drugs. In contrast, escitalopram, sertraline and mirtazapine have little inhibitory effect on CYP, (31,32) and therefore can be considered in a patient who is on multiple other drugs. SSRIs are also associated with gastrointestinal bleeding.…”

Herbal drugs and drug interactions

“…It is used in the treatment of mild to moderate depression, however, it should be rememebered that it may interact with other antidepressant drugs used by the patient. SJW acts by inhibiting the reuptake of monoamines including serotonin, noradrenalin and dopamine, and the amino acid neurotransmitters gamma-aminobutyric acid and glutamate (1,21,73). Thus, there may be an interaction of SJW with other serotonin reuptake inhibitors such as paroxetin, sertaline, venlafaxine, and nefozodone, resulting in symptoms of central serotonin syndrome.…”