You’ve taken sertraline for two years, and it’s working. Now a new employer wants a urine drug screen before your start date, and a question comes up somewhere between the offer letter and the collection site: could your medication show up as something it isn’t?
Occasionally, yes. A handful of common psychiatric medications are known to trip the first stage of a drug screen. Drug testing was designed with this exact problem in mind, though, and a flagged screen is where the checking begins.
Why a Screen Can Flag a Medication You Take
Most drug tests start with an immunoassay, a fast and inexpensive screen that uses antibodies built to latch onto a specific drug or drug class. Antibodies recognize molecules by shape. If a medication, or something your body breaks it down into, looks similar enough to the target, the antibody can bind to it anyway.
This is called cross-reactivity, and it’s the reason a screening result is treated as preliminary. A 2014 review in the Journal of Analytical Toxicology gathered reports of false positives across nearly every major drug class. Its authors concluded that an immunoassay positive should be considered presumptive until a second, independent method confirms it.
On paperwork, a flagged sample may be described as “non-negative” or “presumptive positive.” If the wording on a lab report leaves you guessing, this plain-English glossary of drug testing terms explains each one and links to the official source behind it.
Psychiatric Medications With Documented Cross-Reactions
Three widely prescribed medications come up repeatedly in the research:
| Medication | Can screen positive for | What the evidence shows |
| Sertraline (Zoloft) | Benzodiazepines | Its FDA prescribing information lists false-positive benzodiazepine screens as a known effect |
| Bupropion (Wellbutrin) | Amphetamines | In a review of more than 10,000 urine screens at one hospital’s emergency department, 41% of false-positive amphetamine results came from patients taking bupropion |
| Quetiapine (Seroquel) | Tricyclic antidepressants, methadone | Documented in published case reports, including a case series of psychiatric inpatients |
Cross-reactivity varies from one brand of test kit to another, so plenty of people take these medications for years without a flagged result. Which drugs the test looks for matters too.
Benzodiazepines, methadone, and tricyclic antidepressants aren’t part of the standard federal workplace panel. The sertraline and quetiapine interactions mostly come up with expanded panels, which are common in hospitals, treatment programs, court-ordered monitoring, and some private employers’ testing. Bupropion is a different story, since amphetamines are on standard workplace panels, including the federal one.
What Happens After a Positive Screen
A flagged screen should go on to confirmation testing. Labs use gas chromatography-mass spectrometry (GC/MS) or liquid chromatography-tandem mass spectrometry (LC-MS/MS), which identify the exact molecule in the sample. Sertraline’s own prescribing information names GC/MS as the way to tell it apart from a benzodiazepine.
In federally regulated testing, and in many employer programs built on the same model, the result then goes to a Medical Review Officer. The MRO is a physician who contacts you before your employer hears anything and gives you the chance to explain a legitimate medical reason. Your employer learns the outcome, and your medical details stay with the MRO.
Prescribed stimulants and benzodiazepines are a separate case. If you take Adderall for ADHD or a benzodiazepine for anxiety, a positive for that class is accurate, because the medication is there. The MRO handles this as well, and in regulated programs, a verified prescription means the result is reported as negative.
Outside regulated programs, confirmation isn’t always automatic. A clinic or treatment program may act on an in-office screen, so it’s fair to ask whether a positive was confirmed before any decision is made about your care. For a closer look at what happens between a screen and a final result, this drug testing information hub walks through each stage and the federal rules behind it.
What You Can Do Before and After a Test
- Keep a current list of everything you take, including over-the-counter medications and supplements, along with your prescriber’s contact details.
- Tell the person reviewing your result about your prescriptions. In regulated testing, that’s the MRO, who will reach out to you directly.
- Ask whether a positive screen was confirmed.
- Don’t stop or skip a psychiatric medication to get through a test. Stopping some medications abruptly can bring on discontinuation symptoms or a return of the symptoms they treat. It may not help anyway, since sertraline’s prescribing information notes that false-positive results can continue for several days after the last dose.
If a test is coming up, mention it to your prescriber or therapist. It’s a routine question, and they can tell you whether anything on your medication list is worth flagging ahead of time.
Keeping a Flagged Screen in Perspective
A positive screen while you’re taking an antidepressant or antipsychotic is a question that still needs an answer. The screening stage is designed to cast a wide net, and confirmation testing exists because the people who built these programs expected some lookalike molecules to get caught in it.
Knowing which of your medications can cross-react, and knowing how (and who) to ask whether a result was confirmed, puts you in a good position before you ever reach the collection site.
Treatment that’s working is worth protecting. A drug screen doesn’t have to change it.
Sources
- Saitman A, Park HD, Fitzgerald RL. False-positive interferences of common urine drug screen immunoassays: a review. Journal of Analytical Toxicology. 2014;38(7):387-396.
- Viatris Specialty LLC. Zoloft (sertraline hydrochloride) prescribing information, revised 2023. Section 2.6: Discontinuation of treatment, and section 7.3: False-positive screening tests for benzodiazepines.
- Nasky KM, Cowan GL, Knittel DR. False-positive urine screening for benzodiazepines: an association with sertraline? A two-year retrospective chart analysis. Psychiatry (Edgmont). 2009;6(7):36-39.
- Casey ER, Scott MG, Tang S, Mullins ME. Frequency of false positive amphetamine screens due to bupropion using the Syva EMIT II immunoassay. Journal of Medical Toxicology. 2011;7(2):105-108.
- Sloan KL, Haver VM, Saxon AJ. Quetiapine and false-positive urine drug testing for tricyclic antidepressants. American Journal of Psychiatry. 2000;157(1):148-149.
- Fischer M, Reif A, Polak T, Pfuhlmann B, Fallgatter AJ. False-positive methadone drug screens during quetiapine treatment. Journal of Clinical Psychiatry. 2010;71(12):1696.
- U.S. Department of Transportation. Procedures for Transportation Workplace Drug and Alcohol Testing Programs, 49 CFR Part 40.
