For a patient with post‑traumatic stress disorder and a co‑occurring substance use disorder, what are the appropriate first‑line and second‑line pharmacologic and psychotherapeutic treatments, which medications should be avoided, and how should a psychiatric‑mental‑health nurse practitioner prioritize and sequence community referrals to prevent overwhelming the patient?

Treatment of PTSD with Co-occurring Substance Use Disorder

For a patient with PTSD and co-occurring substance use disorder, initiate trauma-focused psychotherapy immediately—specifically Prolonged Exposure (PE), Cognitive Processing Therapy (CPT), or Eye Movement Desensitization and Reprocessing (EMDR)—combined with an SSRI (sertraline 50-200 mg/day or paroxetine 20-50 mg/day), and avoid benzodiazepines entirely as they worsen PTSD outcomes. 1, 2, 3

First-Line Treatment: Integrated Trauma-Focused Psychotherapy

Patients do not need to be abstinent from substances to begin trauma-focused therapy. 4 The evidence demonstrates that:

• Trauma-focused psychotherapies (PE, CPT, or EMDR) should be initiated immediately without requiring prolonged stabilization, even with active substance use, as these approaches are both safe and effective for complex presentations with co-occurring SUDs 1, 5, 3
• 40-87% of patients no longer meet PTSD criteria after 9-15 sessions of trauma-focused therapy, with no increased dropout rates in patients with co-occurring SUDs 1, 2, 4
• Concurrent Treatment of PTSD and Substance Use Disorders using Prolonged Exposure (COPE) is a manualized approach specifically designed for this population, combining imaginal and in vivo exposure techniques with cognitive behavioral techniques for substance use 3, 6, 7
• Individual, manualized, trauma-focused treatments are the most efficacious psychotherapies for PTSD/SUD comorbidity, with improvement in PTSD symptoms positively impacting substance use outcomes 3, 6, 4

First-Line Pharmacotherapy: SSRIs

Initiate an SSRI concurrently with psychotherapy:

• Sertraline 50-200 mg/day or paroxetine 20-50 mg/day are first-line pharmacological agents recommended by the American Psychiatric Association 1, 2
• Continue SSRI treatment for a minimum of 6-12 months after symptom remission, as discontinuation leads to 26-52% relapse rates compared to only 5-16% when maintained on medication 1, 2, 5
• SSRIs address both PTSD and generalized anxiety symptoms that commonly co-occur, eliminating the need for separate anxiety interventions 1
• Sertraline is often used in combination with anticonvulsants, antipsychotics, or adrenergic blockers when treating comorbid PTSD and SUD, though monotherapy should be attempted first 8

Second-Line Pharmacotherapy Options

If SSRIs are ineffective or not tolerated after 8-12 weeks at adequate doses:

• Venlafaxine (SNRI) 32.5-300 mg/day is recommended as second-line treatment 2, 8
• Prazosin for PTSD-related nightmares and sleep disturbances (Level A evidence): start 1 mg at bedtime, titrate by 1-2 mg every few days to average effective dose of 3 mg (range 1-13 mg), monitoring for orthostatic hypotension 2, 5
• For comorbid alcohol use disorder: naltrexone, acamprosate, or disulfiram may be combined with PTSD treatments, with disulfiram alone potentially treating both PTSD and alcohol use disorder 9, 8
• For comorbid opioid use disorder: methadone or buprenorphine combined with sertraline 9, 8

Medications to ABSOLUTELY AVOID

Benzodiazepines (including alprazolam, clonazepam, diazepam) are contraindicated:

• 63% of patients receiving benzodiazepines developed PTSD at 6 months compared to only 23% receiving placebo, demonstrating clear harm 1, 2, 5
• The 2023 VA/DoD guideline strongly recommends AGAINST benzodiazepines for PTSD treatment 2
• Benzodiazepines worsen PTSD outcomes and should be avoided entirely, even for anxiety or insomnia management 1, 2
• Clonazepam showed no improvements in nightmare frequency or intensity compared to placebo in controlled trials 2

Other medications to avoid:

• Propranolol and other beta-blockers have no evidence supporting use as monotherapy for established PTSD (only studied for immediate post-trauma prevention, not chronic PTSD) 2
• Psychological debriefing within 24-72 hours post-trauma is not recommended and may be harmful 2

Pacing and Prioritizing Community Referrals

As a PMHNP, implement a staged referral approach to prevent overwhelming the patient:

Immediate Priority (Week 1-2):

• Establish one primary trauma-focused therapist trained in PE, CPT, or EMDR for individual weekly sessions 1, 3, 4
• Initiate SSRI pharmacotherapy with close monitoring for side effects and substance use interactions 1, 8
• Develop a safety plan identifying warning signs, coping strategies, social supports, means restriction, and emergency contacts 5

Secondary Priority (Week 2-4):

• Connect to mutual help meetings (Alcoholics Anonymous, Narcotics Anonymous, SMART Recovery) as these are appropriate for patients at any stage of readiness, including ongoing substance use, and are free and available in most communities 9
• Assess need for medically supervised withdrawal if physical dependence on alcohol, opioids, or benzodiazepines is present 9

Tertiary Priority (Week 4-8):

• Consider outpatient substance use treatment with dual diagnosis services once trauma-focused therapy is established, as services can include group and individual counseling while patients continue to work and participate in family life 9
• Evaluate for residential treatment only if the patient lacks a stable and safe living environment or if outpatient treatment has been ineffective 9

Critical Implementation Principles:

• Introduce one new referral at a time, allowing 2-4 weeks for the patient to establish rapport and routine before adding additional services 9
• Prioritize trauma-focused individual therapy over group interventions initially, as individual therapy has stronger evidence and allows for personalized pacing 2
• Coordinate care between all providers to ensure integrated treatment rather than parallel or sequential approaches 3, 4, 7
• Monitor for practical barriers (transportation, childcare, work schedules) that are the most common reasons for treatment dropout, not trauma characteristics or treatment intensity 2
• Use telehealth when appropriate, as video or computerized interventions produce similar effect sizes to in-person treatment and may improve access 2

Common Pitfalls to Avoid

• Never delay trauma-focused therapy for prolonged stabilization or require abstinence first, as this communicates the patient is "too fragile" and has iatrogenic effects 1, 5, 4
• Do not refer to multiple simultaneous programs in the first month, as this creates competing demands and increases dropout risk 9
• Avoid referring to substance use treatment that does not have dual diagnosis capability, as PTSD symptoms will interfere with SUD treatment success 9, 3
• Do not prescribe benzodiazepines for anxiety or insomnia, even temporarily, given the clear evidence of harm in PTSD 1, 2, 5
• Recognize that depression, anxiety, and emotion dysregulation generally improve following trauma-focused psychotherapy without requiring separate interventions 1, 2

Expected Treatment Outcomes

• PTSD symptoms: 40-87% remission after completing trauma-focused therapy 1, 2
• Substance use: Improvement in PTSD symptoms positively impacts substance use outcomes 3, 6, 7
• Relapse prevention: Lower relapse rates after completing psychotherapy compared to medication discontinuation (5-16% vs. 26-52%) 1, 2
• Treatment duration: Adequate dose is 9-15 sessions of trauma-focused therapy, with SSRI continuation for 6-12 months minimum after symptom remission 1, 2, 5