Can vilazodone (Selective Serotonin Reuptake Inhibitor (SSRI)) show up as positive on a drug screen?

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Last updated: December 12, 2025View editorial policy

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Vilazodone and Drug Screening

Vilazodone does not typically cause false-positive results on standard urine drug screens. The medication is not structurally similar to substances commonly tested in drug panels and lacks the chemical properties that would trigger cross-reactivity with standard immunoassays.

Understanding Drug Screen Methodology

Standard urine drug screens use immunoassay technology that detects specific drug classes through antibody recognition of target molecules or their metabolites. These screening tests have fair specificity (70% to 85%) and can produce false-positive results when substances cross-react with the antibodies used in the assay 1.

Why Vilazodone Is Unlikely to Cause False Positives

Vilazodone is a selective serotonin reuptake inhibitor (SSRI) with 5-HT1A receptor partial agonist activity, making it pharmacologically distinct from substances typically screened in drug testing panels 2, 3.

  • Standard drug panels test for substances such as amphetamines, opiates, benzodiazepines, cannabinoids, cocaine metabolites, and phencyclidine 1.
  • SSRIs as a class, including vilazodone, do not share structural similarities with these commonly screened substances and therefore do not trigger positive immunoassay results 1.
  • Vilazodone is primarily metabolized by the hepatic CYP450 3A4 enzyme system into metabolites that are pharmacologically distinct from illicit substances 4.

Important Clinical Caveats

When interpreting any drug screen result, clinicians must know the patient's complete medication history, including all prescribed medications, as some legitimate medications can cause false-positive results 1.

  • For example, fluoroquinolone antibiotics can cross-react with opiate immunoassays, but this is unrelated to vilazodone 1.
  • Drug testing cannot distinguish between appropriate use and misuse of prescribed medications 1.
  • If a positive result occurs in a patient taking vilazodone, it likely represents either use of another substance or a false-positive from a different medication or food substance 1.

Practical Recommendations

If an unexpected positive drug screen occurs in a patient taking vilazodone, request confirmatory testing using gas chromatography-mass spectrometry (GC-MS) or liquid chromatography-mass spectrometry (LC-MS), which are highly specific and will not falsely identify vilazodone as an illicit substance 1.

  • Confirmatory tests are highly unlikely to yield false-positive results and can definitively identify the specific substance present 1.
  • Contact the testing laboratory directly when results do not correlate with clinical findings to discuss potential cross-reactivity and the specific substances included in the test panel 1.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Other Antidepressants.

Handbook of experimental pharmacology, 2019

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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