Can an adult or adolescent patient with anxiety, substance dependence, and Attention Deficit Hyperactivity Disorder (ADHD) take Librium (chlordiazepoxide), naltrexone, and Strattera (atomoxetine) together?

Can Librium, Naltrexone, and Strattera Be Taken Together?

Yes, this combination can be used together with appropriate monitoring, as there are no absolute contraindications to combining chlordiazepoxide (Librium), naltrexone, and atomoxetine (Strattera) for treating comorbid anxiety, substance dependence, and ADHD. However, specific precautions and monitoring protocols must be followed.

Key Considerations Before Initiating This Combination

Critical Contraindication to Address First

• Naltrexone cannot be used concomitantly with opiate medications and requires complete opioid detoxification before initiation 1
• If the patient has opioid use disorder, they must be opioid-free for 7-10 days before starting naltrexone to avoid precipitated withdrawal 1
• Naltrexone is specifically indicated for alcohol and opioid dependence, not benzodiazepine dependence 1

Benzodiazepine Use Considerations

• Librium (chlordiazepoxide) is a Schedule IV controlled substance with concerns for abuse and dependence 1
• In patients with substance use disorders, benzodiazepines should generally be avoided or used with extreme caution due to high abuse potential 1
• Consider whether the anxiety disorder can be managed with non-benzodiazepine alternatives (SSRIs, SNRIs, or buspirone) given the substance dependence history 1

Atomoxetine as Preferred ADHD Treatment in Substance Use Disorders

• Atomoxetine is particularly useful for patients at risk of substance abuse, as it has negligible risk of abuse or misuse and is not a controlled substance 2, 3
• Pharmacologic treatment of ADHD appears to reduce the risk of substance abuse in individuals with ADHD 4
• When treating adults with ADHD and substance abuse, clinicians should begin pharmacotherapy with medications that have little likelihood of diversion or low liability, such as atomoxetine 4

Pharmacological Interactions and Safety Profile

No Direct Drug-Drug Interactions

• There are no clinically significant pharmacological interactions between these three medications based on their metabolic pathways 5
• Atomoxetine undergoes extensive biotransformation via CYP2D6, while naltrexone and chlordiazepoxide have different metabolic pathways 2

Cardiovascular Monitoring Required

• Blood pressure and heart rate should be monitored periodically, especially in the first 12 weeks of treatment with naltrexone 1
• Atomoxetine is associated with statistically significant increases in both heart rate and blood pressure, though typically not clinically significant 2
• Assess cardiovascular history before initiating atomoxetine 5

Common Adverse Effects to Monitor

• Atomoxetine: headache, abdominal pain, decreased appetite, nausea, somnolence 2
• Naltrexone: nausea, gastrointestinal symptoms 1
• Chlordiazepoxide: sedation, cognitive impairment, paradoxical disinhibition (especially in younger patients) 1

Recommended Monitoring Protocol

Initial Assessment

• Confirm complete opioid detoxification if opioid use disorder is present 1
• Obtain baseline blood pressure, heart rate, and weight 5
• Assess for absolute contraindications: active psychosis, seizure disorders, or untreated cardiovascular disease 1
• Evaluate hepatic function, as atomoxetine exposure increases with hepatic insufficiency 2

Ongoing Monitoring

• Monthly consultations initially for dose adjustment and response evaluation 5
• Monitor blood pressure, heart rate, and weight at each visit 5
• Assess for suicidal ideation, particularly with atomoxetine (black-box warning for suicidal ideation in pediatric/adolescent populations) 2
• Monitor for signs of benzodiazepine misuse or escalating doses 1
• Use standardized assessment scales for ADHD and anxiety symptoms 5

Dosing Considerations

Start Low and Titrate Slowly

• Atomoxetine: Start with lower doses and titrate based on response and tolerability 2
• Consider that poor CYP2D6 metabolizers have greater exposure to atomoxetine; CYP2D6 inhibitors can produce similar effects 2
• Naltrexone: Standard dosing for alcohol/opioid dependence 1
• Chlordiazepoxide: Use lowest effective dose given substance abuse history 1

Critical Pitfalls to Avoid

• Do not initiate naltrexone without confirming complete opioid detoxification 1
• Avoid long-term benzodiazepine use in patients with substance use disorders due to high abuse potential 1
• Do not abruptly discontinue chlordiazepoxide, as withdrawal can be life-threatening 1
• Do not ignore the need for psychosocial interventions and addiction treatment/psychotherapy alongside pharmacotherapy 4
• Ensure parental oversight of medication regimens in adolescents 1

Alternative Considerations

If benzodiazepine use is concerning given substance dependence history:

• Consider SSRIs or SNRIs for anxiety disorders instead of benzodiazepines 1
• SSRIs have moderate-to-high evidence for treating anxiety disorders in this population 1
• Buspirone is another non-addictive option for generalized anxiety disorder 6