What is the recommended treatment with Prozac (fluoxetine) vs Paxil (paroxetine) for Obsessive-Compulsive Disorder (OCD) and Post-Traumatic Stress Disorder (PTSD)?

Prozac vs Paxil for OCD and PTSD

For OCD, both Prozac (fluoxetine) and Paxil (paroxetine) are FDA-approved first-line treatments with comparable efficacy at higher doses (fluoxetine 60-80 mg, paroxetine 60 mg), but Paxil carries higher risks of discontinuation syndrome, increased suicidality compared to other SSRIs, and significantly greater toxicity in CYP2D6 poor metabolizers, making Prozac the safer initial choice for most patients. 1, 2

For PTSD, Paxil is FDA-approved while Prozac is not, and Paxil has demonstrated superior evidence in controlled trials, making it the preferred SSRI for PTSD despite its tolerability concerns. 1, 3, 4

OCD Treatment Algorithm

First-Line SSRI Selection

• Fluoxetine is preferred over paroxetine for initial OCD treatment due to its superior safety profile, particularly regarding discontinuation syndrome and suicidality risk 1

• Both medications require higher doses than depression treatment: fluoxetine 60-80 mg daily and paroxetine 60 mg daily for optimal OCD efficacy 1, 2

• Treatment duration must be at least 12-24 months after achieving remission due to high relapse risk 2

• Do not assess efficacy before 8 weeks of adequate dosing, as therapeutic effects require this minimum duration 5

Critical Safety Considerations for OCD Dosing

• CYP2D6 poor metabolizers face severe toxicity risk: paroxetine AUC increases 7-fold and fluoxetine 11.5-fold (at 60 mg) in poor metabolizers versus extensive metabolizers 2

• Consider pharmacogenetic testing before initiating high-dose therapy in patients with family history of sudden cardiac death or known CYP2D6 poor metabolizer status 2

• Fluoxetine carries FDA warnings for QT prolongation in CYP2D6 poor metabolizers, with documented fatal cases on high-dose therapy 2

• Paroxetine has increased suicidality risk compared to other SSRIs according to pediatric and young adult data 1

Paroxetine-Specific Warnings

• Paroxetine causes more severe discontinuation syndrome than other SSRIs, characterized by dizziness, sensory disturbances, paresthesias, anxiety, and agitation 1

• Paroxetine has greater anticholinergic effects than fluoxetine, which may be problematic in elderly patients or those with comorbid conditions 1

• Taper paroxetine over 10-14 days minimum when discontinuing to limit withdrawal symptoms 1

PTSD Treatment Algorithm

First-Line Selection

• Paroxetine is FDA-approved for PTSD and has the most extensive controlled trial evidence among SSRIs for this indication 1, 3, 4, 6

• Fluoxetine is not FDA-approved for PTSD but has shown efficacy in open-label studies 3

• Sertraline and paroxetine are the only FDA-approved SSRIs for PTSD, with sertraline being an alternative if paroxetine is not tolerated 3

PTSD Dosing Strategy

• Standard SSRI doses are effective for PTSD (paroxetine 20-60 mg daily), unlike OCD which requires higher dosing 4, 6

• Treatment duration of 6-12 months after initial response decreases relapse rates significantly 3

• Continuation therapy prevents relapse for 24 weeks to 1 year in controlled trials 4

When Paroxetine Fails in PTSD

• Venlafaxine (SNRI) is second-line with promising open-label data and better tolerability than paroxetine in some patients 3, 6

• Augmentation with atypical antipsychotics should be considered when paranoia or flashbacks are prominent 3

• Avoid benzodiazepines as they were ineffective in controlled trials and may worsen PTSD 3

Drug-Drug Interaction Considerations

• Fluoxetine is a potent CYP2D6 inhibitor, creating more drug-drug interactions than paroxetine, particularly with medications metabolized by CYP2D6 1, 2

• Paroxetine also inhibits CYP2D6 but to a lesser extent than fluoxetine 1

• Both drugs are contraindicated with MAOIs due to serotonin syndrome risk 1

Comorbid OCD and PTSD

• When both conditions coexist, prioritize paroxetine as it is FDA-approved for both disorders and has demonstrated efficacy in both conditions 1, 4, 6

• Use OCD dosing strategy (paroxetine 60 mg) as higher doses will also address PTSD symptoms 1, 2

• Monitor closely for discontinuation syndrome given the high dose and dual indication 1

Predictors of Response

Favorable Response Indicators for Fluoxetine in OCD

• Nervousness or insomnia at treatment initiation predicts good response 5

• Presence of remissions in illness course and absence of prior pharmacologic therapy 5

• High impulsiveness scores correlate with better fluoxetine response 5

Poor Response Indicators

• Long illness duration, severe symptoms, collection obsessions, washing compulsions, and obsessional slowness predict poorer response to both medications 5

• Comorbid schizotypic personality or vocal/motor tics reduce treatment efficacy 5