What medications can cause a false positive phenobarbital or barbiturate result on a urine drug screen (UDS)?

Medications That Can Cause False Positive Barbiturate or Phenobarbital Results on Urine Drug Screens

Several commonly prescribed medications can cause false positive results for barbiturates or phenobarbital on urine drug screens, including certain antidepressants, antihistamines, NSAIDs, and antipsychotics. These false positives typically occur with immunoassay screening methods and should be confirmed with more specific testing methods.

Common Medications Causing False Positive Barbiturate Results

Antidepressants

• Sertraline (Zoloft)
• Bupropion (Wellbutrin)
• Trazodone and its metabolite meta-chlorophenylpiperazine (m-CPP) 1
• Venlafaxine (Effexor)
• Clomipramine

Antihistamines

• Diphenhydramine (Benadryl)
• Brompheniramine
• Doxylamine (found in some OTC sleep aids)
• Promethazine (Phenergan)

NSAIDs

• Ibuprofen (Advil, Motrin)
• Naproxen (Aleve)

Antipsychotics

• Quetiapine (Seroquel)
• Chlorpromazine
• Thioridazine

Other Medications

• Ranitidine (Zantac)
• Verapamil (calcium channel blocker)
• Certain quinolone antibiotics (ofloxacin, gatifloxacin) 2

Understanding Drug Testing Mechanisms

Immunoassay Limitations

• Most routine urine drug screens use immunoassay technology which has lower specificity
• These tests detect structural similarities between compounds rather than identifying the exact substance
• Cross-reactivity with medications that share structural features with barbiturates can lead to false positives 2

Confirmation Testing

• Gas chromatography-mass spectrometry (GC-MS) or liquid chromatography-mass spectrometry (LC-MS/MS) are considered gold standard confirmation tests 3
• These methods can distinguish between true barbiturate presence and false positives
• Always confirm positive immunoassay results with these more specific methods before making clinical decisions 2

Clinical Implications

Interpreting Test Results

• Document all medications the patient is currently taking before interpreting drug screen results 3
• Consider the possibility of false positives when unexpected barbiturate results appear in patients taking medications from the above list
• Unexpected positive results should prompt a conversation with the patient rather than immediate punitive action 3

Patient Management

• Never dismiss patients from care based solely on urine drug test results, as this could constitute patient abandonment 3
• If a positive barbiturate result is unexpected, consider:
  1. Reviewing all current medications
  2. Ordering confirmation testing with GC-MS or LC-MS/MS
  3. Discussing results with the patient in a non-accusatory manner

Detection Windows and Testing Considerations

• Phenobarbital has a long half-life (80-120 hours) and can be detected in urine for several days to weeks after use 4
• Short-acting barbiturates like secobarbital have shorter detection windows (typically 2-4 days) 4
• Baseline urine drug testing should be performed before initiating therapy with controlled substances to establish a patient's substance use profile 3

Common Pitfalls to Avoid

1. Assuming all positive results indicate substance abuse - Remember that many common medications can cause false positives
2. Failing to confirm positive results - Always verify positive immunoassay results with more specific testing methods
3. Making clinical decisions based solely on screening tests - Screening tests are designed to be sensitive but may lack specificity
4. Not considering patient's medication list - Always review current medications when interpreting unexpected results
5. Taking punitive action without confirmation - False accusations of substance abuse can damage the patient-provider relationship

By understanding which medications can trigger false positive barbiturate results and following appropriate confirmation protocols, clinicians can avoid misinterpretation of drug screening results and ensure appropriate patient care.