What are the recommended medications for a patient with post-traumatic stress disorder (PTSD)?

Recommended Medications for Post-Traumatic Stress Disorder (PTSD)

First-Line Pharmacotherapy: SSRIs

Sertraline and paroxetine are the FDA-approved first-line medications for PTSD, with sertraline typically initiated at 25 mg daily for one week, then increased to 50-200 mg daily based on response. 1, 2

SSRI Selection and Dosing

• Sertraline is FDA-approved for PTSD treatment, started at 25 mg/day for the first week, then dosed in the range of 50-200 mg/day based on clinical response (mean effective dose 131-151 mg/day in clinical trials). 1, 3

• Paroxetine is FDA-approved for PTSD, with a recommended starting and established effective dose of 20 mg/day, though doses up to 50 mg/day were studied in clinical trials. 2, 3

• Fluoxetine is an alternative SSRI that has been extensively studied for PTSD, though it lacks FDA approval for this indication. 3, 4

• SSRIs demonstrate 53-85% treatment response rates in controlled trials and have a favorable adverse effect profile compared to other medication classes. 5

Duration of Treatment

Continue SSRI treatment for at least 6-12 months after symptom remission, as discontinuation leads to relapse rates of 26-52% when shifted to placebo compared to only 5-16% in patients maintained on medication. 6, 1

• Assess treatment response after 8 weeks of SSRI therapy; if inadequate response with good compliance, consider switching SSRIs or augmenting with trauma-focused therapy. 5

Second-Line Pharmacotherapy: Venlafaxine

• Venlafaxine (a serotonin-norepinephrine reuptake inhibitor) is recommended as second-line treatment when SSRIs are not tolerated or ineffective, dosed at 32.5-300 mg/day. 6, 3

• However, one pooled analysis of 687 participants showed no significant difference between venlafaxine ER and placebo specifically for distressing dreams in PTSD. 7

Adjunctive Medications for Specific Symptoms

For PTSD-Related Nightmares and Sleep Disturbance

Prazosin is strongly recommended (Level A evidence) for PTSD-associated nightmares, started at 1 mg at bedtime and increased by 1-2 mg every few days until effective (average dose 3 mg, range 1-13 mg), with monitoring for orthostatic hypotension. 8, 4

• Prazosin reduces elevated CNS noradrenergic activity that contributes to PTSD symptoms including arousal, irritability, and nightmares. 8

• Trazodone may be considered for PTSD-related sleep disturbances at doses of 25-600 mg (mean effective dose 212 mg/day), though 60% of patients experience side effects including daytime sedation, dizziness, or priapism. 7, 8

For Irritability, Anger, and Residual Symptoms

• Topiramate may be beneficial for PTSD symptoms including irritability and anger, started at 12.5-25 mg daily and increased in 25-50 mg increments every 3-4 days, with most responders achieving benefit at ≤100 mg/day. 8

• Topiramate reduced nightmares in 79% of patients in one study, with full suppression in 50%, though monitoring for cognitive impairment, weight loss, and paresthesias is necessary. 8

• Atypical antipsychotics should be considered when paranoia or flashbacks are prominent and in potentiating SSRIs in refractory cases. 3, 9

Critical Medications to AVOID

Benzodiazepines (including clonazepam and alprazolam) are absolutely contraindicated in PTSD treatment, as 63% of patients receiving benzodiazepines developed PTSD at 6 months compared to only 23% receiving placebo. 5, 6

• Clonazepam showed no improvements in either frequency or intensity of nightmares compared to placebo in a controlled trial of combat-related PTSD patients. 7

• Benzodiazepines have high abuse potential and evidence demonstrates worsening PTSD outcomes. 5

Important Clinical Considerations

Psychotherapy as Primary Treatment

• Trauma-focused psychotherapy (Prolonged Exposure, Cognitive Processing Therapy, or EMDR) should be offered as first-line treatment, with 40-87% of patients no longer meeting PTSD criteria after 9-15 sessions. 5, 6

• Medication should be considered when psychotherapy is unavailable, the patient refuses psychotherapy, or residual symptoms persist after psychotherapy. 5, 6

• Relapse rates are substantially lower after completing CBT compared to medication discontinuation, suggesting psychotherapy provides more durable benefits. 5, 6

Treatment Algorithm

1. Initiate trauma-focused psychotherapy as first-line treatment 6
2. If psychotherapy unavailable or refused, start sertraline 25 mg daily for one week, then increase to 50-200 mg daily 1
3. Assess response at 8 weeks; if inadequate, switch to paroxetine 20 mg daily or add trauma-focused therapy 5, 2
4. For persistent nightmares, add prazosin 1 mg at bedtime, titrating to effect 8
5. For residual irritability/anger, consider topiramate 12.5-25 mg daily, titrating slowly 8
6. Continue effective medication for 6-12 months minimum after symptom remission 6

Common Pitfalls

• Avoid psychological debriefing immediately after trauma (within 24-72 hours), as it is not supported by evidence and may be harmful. 6

• Never use benzodiazepines for PTSD treatment despite their common use for anxiety disorders. 5, 6

• Do not discontinue SSRIs prematurely; high relapse rates occur with early discontinuation. 6, 1

• Assess for obstructive sleep apnea in patients with PTSD-related sleep disturbance, as many have this comorbid condition. 4