When pressed for time, most clinicians rely on online drug interaction checkers. Here are the most commonly used options:

Most interactions in psychiatry will not result in a serious outcome. Many, however, may result in decreased efficacy or increased adverse effects — and these can be easily avoided. To understand drug-drug interactions, it helps to revisit some core concepts.

Drugs are substrates of specific enzymes, meaning they rely on specific enzymatic pathways for metabolism. An inhibitor binds more tightly to an enzyme than the usual substrate and prevents the enzyme from doing its job. As a result, the substrate cannot be metabolized as quickly as it otherwise would, and its serum levels become higher than expected. An inducer, by contrast, stimulates the production of extra enzymes. With more enzymes available, the substrate is broken down more rapidly, leading to lower serum drug levels.

Timing is also an important consideration. Inhibition happens quickly — it can occur with the first dose of a medication and can subside within five half-lives of the inhibitor once it is discontinued. Induction, on the other hand, requires the body to synthesize more CYP450 enzymes, a process that can take up to four weeks. This accounts for the delayed auto-induction seen with carbamazepine. For induction to subside, these extra enzymes must also be broken down — a process that could likewise take several weeks.

As a general rule of thumb, any drug prescribed with its inhibitor should be started at half the usual dose and titrated more slowly. A drug prescribed with its inducer may need to be dosed higher after the few weeks it takes for induction to occur. One important exception: when the substrate is a prodrug. Tamoxifen, hydrocodone, and tramadol rely on CYP2D6 to be converted into active metabolites. In the presence of a potent inhibitor such as fluoxetine or paroxetine, patients may experience a drop in therapeutic effect rather than increased effects.

Practical Tips for Quickly Identifying Significant Drug Interactions

• Identify the 10 drugs you most commonly prescribe and memorize their major drug interactions.
• Antidepressants, antipsychotics, antibiotics, antiretrovirals, and older anticonvulsants have a high likelihood of significant interactions — be particularly vigilant if your patient is taking any of these.
• Recognize drugs with a narrow therapeutic window — those for which the toxic dose is not much higher than the therapeutic dose. Commonly used examples include lithium, carbamazepine, warfarin, digoxin, phenytoin, and phenobarbital.
• Be alert to drugs that cause serious outcomes if blood levels are significantly increased or decreased — including oral contraceptives, lamotrigine, clozapine, tricyclic antidepressants, and warfarin.
• Drugs with long half-lives — such as diazepam or aripiprazole — can be particularly problematic when involved in drug interactions, since metabolic inhibitors or hepatic dysfunction can make them ultra-long lasting. Use extra caution with new or rarely prescribed drugs, where unreported interactions may not yet have surfaced.
• The risk of drug interactions can increase exponentially as the number of drugs increases. Setting a threshold to check for interactions is helpful (eg, any patient on three or more drugs).

Most Common Clinically Significant Drug Interactions in Psychiatry