Clinical Update

Spotlight on Potential Interactions Involving Behavioral Health & Substance Use Disorder Medications

Drug-drug and drug-food interactions (DDIs) contribute to adverse drug events (ADEs) which can range in severity from mild effects to life-threatening. DDIs may be more likely to occur or more problematic in some individuals, depending on the number of medications they take, recent events in their medical care, and the complexity of their medical history. DDIs can easily go undiagnosed which contributes to the estimated $30.1 billion cost to the collective healthcare system.1-4 Other research has noted that the risk of an ADE or DDI increases with polypharmacy, and the number of patients taking five or more prescription drugs (which is the definition of polypharmacy) has more than doubled between 1988 and 2018.5-6 Patients with multiple diagnoses or receiving care from multiple healthcare providers may be at increased risk of DDIs and related ADEs.

While multiple tools exist for identifying DDIs, each can have limitations. Individuals may fail to report all prescription drugs, over the counter (OTC) medications, and herbal supplements. Pharmacy-based drug utilization review may be incomplete if the patient uses multiple pharmacies, and OTC medications may not be included in the pharmacy software for evaluation. Prescription Drug Monitoring Programs (PDMPs) are informative regarding controlled substances only and automated DDI identification software is only able to analyze the data that has been entered; omissions can result in an incomplete DDI analysis.

The task of understanding and mitigating DDIs can be quite complex and is best supported by the right tools to help clinicians have clarity regarding recently ingested substances and the risk for interactions between those substances. Aegis Sciences Corporation offers a laboratory-developed and validated test on urine and saliva samples which utilizes a liquid chromatography-tandem mass spectrometry-based (LC/MS/MS) confirmatory method to detect many commonly-prescribed substances capable of impacting prescription medication pharmacokinetics (such as drug absorption or metabolism) or pharmacodynamics.

Aegis DDI testing (for substances outlined in Table 1) can be added with medication adherence monitoring to provide a broad evaluation of potential DDI and adverse event risk. (For more information about InterACT Rx testing, go to

A data analysis was performed on the reported DDIs from samples collected 1/1/2021 thru 3/16/2023. This data is not inclusive of all samples reported during the time frame as DDI testing is only performed based on clinician order and is not ordered on every sample.  DDIs were examined for the frequency of interactions by drug class involved. Interacting pairs of substances have been selected for special focus for this discussion due to their relevancy to the behavioral health and substance use disorder (SUD) space.

The data analysis included 501,478 potential DDIs reported from 169,357 samples. A total of 2,136 unique pairs of interacting substances were identified (with some drugs interacting with multiple other substances). Buprenorphine was the most frequently involved drug in a reported DDI with 105,555 (21%) of the interactions involving buprenorphine. Other drugs frequently involved in potential DDIs include Amphetamine (33,832), Citalopram/Escitalopram (31,285), Quetiapine (31,037), Bupropion (27,770), Duloxetine (20,995), Fluoxetine (20,242), and Methadone (10,439).  The 30 most-frequently involved drugs in DDIs reported are shown in Figure 1.

Antidepressants & Antipsychotics were involved in 238,403 (48%) of the DDIs reported.  Benzodiazepines contributed to 66,782 (13%). Figure 2 shows the top 10 classes of drugs involved in DDIs.