Using drug abuse screenings or tests to support medication adherence for patients taking controlled substances

With tens of thousands of drug overdose deaths reported every year,¹ clinicians struggle to ensure medication adherence and mitigate misuse in at-risk patients. This challenge is exacerbated by the use of synthetic drugs that are not detected using standard drug tests.

Implementing a responsible drug testing protocol for patients who have been prescribed controlled substances for mental health conditions, chronic pain, or to support substance abuse recovery can help prevent harmful drug-to-drug interactions while allowing for early identification, intervention, and treatment.

In this article:

Clinical challenge | Why it matters | Ordering recommendations | Interpreting test results | Next steps | Supporting resources

Clinical challenge: Monitoring medication adherence during mental health, chronic pain, and medication-assisted treatments

Healthcare providers most commonly prescribe controlled substances to 3 unique patient populations, each with unique risks and concerns:

• Those with a mental health condition and who may be at higher risk for medication misuse, accidental overdose, and addiction
• Those with chronic pain who may take controlled substances long-term and have co-occurring mental health conditions
• Those in substance abuse recovery through medication-assisted treatment who may also have physical comorbidities from past drug abuse

Even when controlled substances are appropriately prescribed, the risk of misuse is high and the consequences are significant.

A continuing drug misuse crisis

Though drug overdose deaths have dropped from a 10-year high in 2024, they still exceeded 67,000 in 2025, with more likely going unreported.¹ In the United States, fentanyl was most frequently involved in overdose deaths and the most common concomitant drug found with other drugs, including xylazine- and oxycodone-involved drug overdose deaths.²

For clinicians prescribing controlled substances, including medication-assisted treatment, the challenge isn’t just how to monitor for medication compliance. They must also identify and address patients at risk of drug misuse and weigh the risks of potential drug-to-drug interactions. This becomes increasingly difficult as more variations of novel psychoactive substances (NPS) are discovered and put some individuals at an even higher risk of misuse.³

Use of novel psychoactive substances is rising

NPS mimic the effects of controlled substances and/or illicit drugs. Also known as synthetic or designer drugs, they’ve been able to circumvent national and international drug scheduling laws.⁴

NPS usage can cause significant physiological and neurological effects, including psychosis, seizures, anxiety, acute coronary syndrome, respiratory depression, and vomiting. Deaths linked to the use of NPS have been recorded.⁵

Since 2018, there’s been a dramatic increase of NPS detections in the US.⁶ But despite the potential dangers of NPS, they often aren’t detected through traditional drug testing.

Why it matters: Monitoring patients for medication adherence can support drug abuse prevention

Clinical drug testing provides you with an objective tool to determine which substances your patients are taking. Using drug abuse screening tests to monitor medication adherence can help to

• Identify prescription drug use or nonuse (medication adherence)
• Complement prescription drug monitoring programs (PDMPs) to provide a more complete picture of patient status
• Identify substance use disorder early to help improve treatment success
• Identify potential drug-drug interactions and harmful polysubstance use
• Detect use of NPS and other illicit substances
• Meet expectations of medical boards and regulatory agencies
• Maintain patient access to prescription therapies
• Identify drug diversion
• Mitigate risk and keep patients and communities safe while protecting clinician practices

Early detection of drug misuse can support more effective prevention, intervention, and treatment options.

Drug abuse screenings and tests are supported by guidelines

In the 2022 Clinical Practice Guideline for Prescribing Opioids for Pain, the Centers for Disease Control and Prevention (CDC) recommends reviewing a patient’s history of controlled substance prescriptions using a state prescription drug monitoring program, as well as considering drug testing for prescribed medications and other controlled substances.⁸ Likewise, the Association for Diagnostics & Laboratory Medicine (ADLM) (formerly the American Association for Clinical Chemistry (AACC) Academy) recommends the use of drug testing for relevant over-the-counter medications, prescribed and nonprescribed drugs, and illicit substances for chronic pain patients being treated with opioids.⁹

The American Society of Addiction Medicine (ASAM) also supports the use of drug testing in clinical addiction medicine as a therapeutic tool supporting patient treatment and recovery.¹⁰

Ordering recommendations: Screening for medication adherence

When screening for drug compliance, clinicians will choose between 2 methods: presumptive drug testing and definitive drug testing.

Presumptive drug testing

Presumptive drug testing is often used as an initial drug screen. It typically uses an immunoassay, in which an antibody binds to a substance which signals a positive result. A presumptive drug test provides qualitative results (positive or negative) rather than quantitative (a quantitation of drugs).

Definitive drug testing

Definitive drug testing, on the other hand, identifies specific molecules in a sample. It uses gas or liquid chromatography to separate analytes, followed by mass spectrometry to identify them based on their unique mass. A definitive drug test provides both qualitative and quantitative results. NPS can only be detected with targeted definitive drug tests.

Medical best practices include beginning with presumptive drug testing and, when needed, confirming positive results with definitive drug testing. This strategy helps minimize over-testing while providing clinicians with the information they need to make informed decisions.

Recommended tests: Presumptive drug testing panel with reflex

Drug Monitoring, Panel 9, with Confirmation, with D/L Isomers, Urine

• Test code: 13021
• CPT® code: 80307*

Components include Alcohol Metabolites/EtG [39366], Amphetamines with Reflex d/l Isomers [39368], Barbiturates [39369], Benzodiazepines [39371], Buprenorphine with Naloxone [39373], Cocaine Metabolite [39374], Fentanyl [39375], Heroin Metabolite [39376], Marijuana Metabolite [39377], Methadone Metabolite [39379], MDMA/MDA [39378], Opiates [39380], Oxycodone [39381], Phencyclidine [39382], Specimen Validity Test [39343]

Note: Each of the component tests may also be ordered individually.

Recommended tests: Definitive drug testing urine panels

Drug Monitoring, Novel Psychoactive Substances (NPS), Qualitative, Urine

• Test code: 13086
• CPT codes: 80364, 80347, 80352, 80371, 80376, 80354 (HCPCS: G0480)* 

Components include Designer Benzodiazepines [13793], Designer Fentanyl Analogs [13794], Designer Opioids [13795], Designer Stimulants [13796], Synthetic Cannabinoids [13797], Other Illicit Additives [13798]

Drug Monitoring Assess Panel, Comprehensive, Qualitative, Urine

• Test code: 11878
• CPT codes: 80325, 80359, 80340, 80337, 80333, 80338, 80344, 80345, 80346, 80353, 80355, 80357, 80349, 80360, 80370, 80361, 80365, 80366, 80354, 80356, 80358, 80323, 80373, 80372, 80348, 80363, 80330, 80376, 83992, 80368 (HCPCS: G0483)*

Recommended tests: Definitive drug testing oral fluid panels

Drug Toxicology Monitoring Base Panel, with Confirmation, Oral Fluid

• Test code: 36862
• CPT code: 80307* 

Components include Amphetamines [93977], Benzodiazepines [93979], Cocaine [93980], Marijuana [93981], Methadone [93984], Opioids [93987]

Note: Each of the component tests may also be ordered individually.

* CPT code is subject to a Medicare Limited Coverage Policy and may require a signed ABN when ordering.

Interpreting test results: Detecting the presence of a drug

Results will return with 1 of the following options:

• Positive result: indicates a drug or its metabolite has been definitively detected at or above its cutoff value
• Negative result: indicates a drug or its metabolite was not detected at levels at or above its cutoff value
• Interference: indicates that the presence or absence of the drug or its metabolite cannot be determined because of interfering substances, which typically are artifacts of the patient matrix collected for analysis

Note that although testing detects the presence of a drug, it does not reveal the dosage of the drug or determine clinical impairment. Safest prescribing habits should include a combination of tools and laboratory test results to correctly detect drug-use patterns.

For patients who receive a positive or inconclusive result, clinicians may consider ordering definitive drug testing to get a clearer picture of patient drug use.

Next steps: Implementing a responsible testing protocol

Consider establishing a drug monitoring protocol for patients on controlled medication for mental health conditions, chronic pain, or substance abuse recovery, and for those at risk for drug misuse disorders. Key elements of a drug monitoring protocol when prescribing controlled medications include

• Establish which individuals to monitor
• Evaluate patient risk factors
• Review the state prescription drug monitoring program
• Create written treatment agreements
• Discuss the risks and benefits of therapy with the patient
• Review patient responsibilities
• Conduct baseline testing
• Conduct periodic, risk-based drug monitoring

When paired with other treatment and recovery supports, drug abuse screenings and tests can be a powerful tool to support drug abuse prevention efforts.

Supporting resources