Prozac (Fluoxetine) for PTSD
Fluoxetine is an effective second-line treatment for PTSD when trauma-focused psychotherapy is unavailable, ineffective, or strongly not preferred by the patient, with dosing typically requiring 20-80 mg/day (often in the upper range of 57-80 mg/day) for 6-12 weeks to achieve optimal response. 1, 2
Treatment Hierarchy
Psychotherapy Remains First-Line
- Trauma-focused psychotherapies (exposure therapy, cognitive therapy, EMDR, stress inoculation training) should be offered first, showing 40-87% of patients no longer meeting PTSD criteria after 9-15 sessions 1
- Psychotherapy provides more durable benefits with lower relapse rates (5-16%) compared to medication discontinuation (26-52% relapse rate) 1
- Many PTSD patients prefer psychotherapy when given a choice 1
When to Use Fluoxetine
- Consider fluoxetine when psychotherapy is unavailable, ineffective, or the patient strongly prefers medication 1
- Fluoxetine can be used as adjunctive treatment for residual symptoms after psychotherapy 3
- Medication is more widely available than trauma-focused psychotherapy, which is typically limited to large cities and medical schools 1
Fluoxetine Dosing Protocol
Starting and Titration
- Begin with 20 mg/day 4, 2
- Increase gradually to 80 mg/day until response is optimal or side effects prohibit further increase 4
- Most patients require doses in the upper normal range (mean endpoint dose 57 mg/day) for satisfactory response 2
Timeline for Response
- Appreciable improvement typically occurs after 6 weeks of treatment 4
- Full acute treatment course is 12 weeks 2, 5
- Higher doses and longer duration than typically used for depression may be necessary 4
Expected Outcomes with Fluoxetine
Symptom Improvement
- Fluoxetine significantly reduces all three PTSD symptom clusters: reexperiencing, avoidance/numbing, and hyperarousal 4, 2
- In controlled trials, 85% showed much or very much improvement (versus 62% with placebo), and 59% showed very much improvement (versus 19% with placebo) 5
- Clinician-Administered PTSD Scale scores decreased from mean 64.5 at baseline to 42.7 at endpoint 4
- Fluoxetine also reduces comorbid depression, anxiety, and panic attacks (50% reduction in panic frequency in 75% of patients with panic diaries) 4
Limitations
- Improvement in social and occupational functioning is minimal 4
- High dropout rates occur due to side effects, anxiety symptoms, external events, and substance abuse 4
Evidence Quality
The evidence supporting fluoxetine is robust, with multiple placebo-controlled trials showing consistent positive results 1, 6. Fluoxetine, along with paroxetine, sertraline, and venlafaxine, represents the best-evidenced pharmacological treatments for PTSD 3, 6. The 2002 European/Israeli/South African trial (N=301) and 1999 civilian trial (N=53) provide Level A evidence for efficacy 2, 5.
Critical Pitfalls to Avoid
Relapse Prevention
- Relapse is common after medication discontinuation (26-52% when shifted to placebo versus 5-16% maintained on medication) 1
- Longer-term treatment may be necessary beyond the acute 12-week phase 1
- Do not abruptly discontinue fluoxetine without a plan for ongoing treatment 1
What NOT to Do
- Never use benzodiazepines (like alprazolam) for PTSD—63% of patients receiving benzodiazepines developed PTSD at 6 months versus only 23% receiving placebo 1
- Do not perform psychological debriefing within 24-72 hours after trauma, as this may be harmful 1, 7
- Avoid delaying trauma-focused treatment by insisting on prolonged stabilization phases, as this reduces motivation for active trauma processing 8
Adjunctive Treatments
For Nightmares and Sleep Disturbance
- Add prazosin (Level A evidence) starting at 1 mg at bedtime, increased by 1-2 mg every few days until effective 7
- Consider screening for obstructive sleep apnea, which is common in PTSD patients with sleep disturbance 3
For Residual Symptoms
- Atypical antipsychotics or topiramate may be helpful for symptoms not fully responsive to fluoxetine alone 3