Best Antidepressant for Obsessive-Compulsive Disorder (OCD)

Fluoxetine (Prozac) is the best first-line antidepressant for treating OCD, with a recommended dose range of 20-60 mg/day for adults. 1

Dosing and Administration

For adults with OCD:
- Start with 20 mg/day in the morning
- After several weeks, if insufficient clinical improvement is observed, dose can be increased
- Effective dose range: 20-60 mg/day
- Maximum dose: 80 mg/day (well-tolerated in open studies) 1
For children and adolescents with OCD:
- Higher weight children/adolescents: Start with 10 mg/day, increase to 20 mg/day after 2 weeks
- Lower weight children: Start with 10 mg/day, with a recommended range of 20-30 mg/day 1

Fluoxetine efficacy was established in 13-week trials with OCD outpatients 1
Clinical improvement may be delayed until 5 weeks of treatment or longer 1
Fluoxetine has demonstrated good efficacy in all published open-label studies and placebo-controlled trials 2
The optimal dose for efficacy is approximately 40 mg fluoxetine equivalent, as shown in dose-response meta-analysis 3

Fluoxetine has a very long half-life, making it more forgiving if doses are missed 4
CYP2D6 genetic variations can significantly affect fluoxetine metabolism:
- Poor metabolizers (PMs) may have 3.9-fold higher area under the curve (AUC) at 20 mg doses
- At 60 mg doses, PMs may have 11.5-fold higher AUCs for S-fluoxetine 5
Long-term fluoxetine use can convert approximately 43% of extensive metabolizers to poor metabolizers 5

Fluoxetine should be used with caution in patients with:
- Congenital long QT syndrome
- Previous history of QT prolongation
- Family history of long QT syndrome or sudden cardiac death 5
Higher dosing of SSRIs (including fluoxetine) for OCD has been associated with higher dropout rates due to adverse effects 5
Common side effects include insomnia, headache, and diminished libido 2
Fatalities associated with CYP2D6 poor metabolizer status have been reported, including a case of a 9-year-old child with OCD treated with high-dose fluoxetine 5

Efficacy should not be evaluated before 8 weeks due to delayed onset of therapeutic effects 2
Minimum treatment duration recommendation: 1-2 years 2
Long-term use should be periodically reevaluated 1

Escitalopram has shown significant symptom relief and prevention of relapse during long-term use 6
Clomipramine has comparable efficacy to fluoxetine but with more anticholinergic side effects and greater cardiotoxicity risk 2
Sertraline has shown similar efficacy to fluoxetine in comparative studies 2
Paroxetine is another option but is more sedating with anticholinergic effects 4

For patients with inadequate response to fluoxetine:
- Antipsychotics (risperidone, aripiprazole) can be considered, though only about one-third of patients show meaningful response 4
- Glutamatergic agents like N-acetylcysteine have strong evidence for SSRI augmentation 4
- Cognitive Behavioral Therapy (CBT) has the strongest evidence for SSRI augmentation, with larger effect sizes compared to medication augmentation alone 4

Nervousness or insomnia at the start of therapy may predict good response to fluoxetine 2
Poor response predictors include:
- Long history of OCD
- Severe symptoms
- Collection obsessions
- Washing compulsions
- Obsessional slowness
- Comorbidity with schizotypic personality or tics 2
Fluoxetine also alleviates collateral depressive symptoms by reducing suicidal ideation and impulsiveness in OCD patients 2