What is the first‑line treatment for obsessive‑compulsive disorder in an adult, including recommended selective serotonin reuptake inhibitors (SSRIs) with dosing and cognitive‑behavioral therapy (CBT) with exposure and response prevention (ERP)?

First-Line Treatment for Obsessive-Compulsive Disorder in Adults

The first-line treatment for OCD in adults is combined therapy with an SSRI at higher-than-typical doses (fluoxetine 60-80 mg daily, sertraline 150-200 mg daily, or paroxetine 60 mg daily) plus cognitive-behavioral therapy with exposure and response prevention (ERP). 1

Pharmacological Treatment: SSRI Selection and Dosing

Preferred First-Line SSRIs

Fluoxetine is the preferred initial SSRI for OCD due to its superior safety profile, particularly regarding discontinuation syndrome and lower suicidality risk compared to paroxetine. 1 Alternative first-line options include sertraline, fluvoxamine, and escitalopram. 1

Required Dosing for OCD

Higher doses than depression treatment are mandatory for OCD efficacy:

• Fluoxetine: 60-80 mg daily 1
• Sertraline: 150-200 mg daily 1
• Paroxetine: 60 mg daily 1
• Escitalopram: 20 mg daily 1
• Citalopram: 40-60 mg daily 1

Titrate doses upward every 1-2 weeks in small increments (5-10 mg for citalopram, 5 mg for escitalopram) to minimize adverse effects while achieving steady-state concentrations. 1

Critical Timing Considerations

Allow 8-12 weeks at maximum tolerated dose before declaring treatment failure, with maximal improvement typically occurring by week 12 or later. 1, 2 Early response by weeks 2-4 predicts ultimate treatment success. 1, 3

Full therapeutic effect may be delayed until 5 weeks of treatment or longer. 1

Cognitive-Behavioral Therapy with Exposure and Response Prevention

CBT with ERP should be implemented from the outset alongside pharmacotherapy, as combined treatment yields larger effect sizes than either monotherapy alone. 3 CBT alone has a number needed to treat of 3 compared to 5 for SSRIs. 3

Patient adherence to between-session ERP homework is the strongest predictor of treatment success. 2, 3 The therapeutic approach involves systematic exposure to feared stimuli while preventing compulsive responses.

Treatment Duration

Maintain treatment for a minimum of 12-24 months after achieving remission due to high relapse risk after discontinuation. 1, 2, 3 Sertraline demonstrates significantly lower relapse rates during 28-week continuation compared to placebo. 1

Special Pharmacogenetic Considerations

Consider pharmacogenetic testing for CYP2D6 poor metabolizers before initiating high-dose fluoxetine or paroxetine, as poor metabolizers have 3.9-fold to 11.5-fold higher drug exposure and increased risk for QT prolongation and sudden cardiac death. 1 The FDA has issued specific warnings about QT prolongation risk in CYP2D6 poor metabolizers taking fluoxetine, with documented fatal cases. 1

For citalopram doses above 40 mg (such as 52 mg for OCD), ECG monitoring is indicated due to increased risk of QT prolongation, Torsades de Pointes, and sudden death. 1

Critical Pitfalls to Avoid

Never conclude treatment failure without documenting at least one adequate trial: proper dose for 8-12 weeks with confirmed adherence. 2 Inadequate medication trials—characterized by insufficient dose or duration—are the most common cause of apparent treatment resistance and lead to unnecessary medication switches and polypharmacy. 2

Do not switch medications based on early side effects or lack of response before week 8-12. 2 SSRIs can cause increased anxiety, agitation, and worsening of symptoms in the first 24-48 hours after dose changes, particularly in OCD patients. 1

Management of Partial or Non-Response

If inadequate response after 12 weeks at maximum tolerated SSRI dose:

1. Add CBT with ERP if not already implemented—this has larger effect sizes than medication augmentation alone. 1, 2, 3

2. Consider augmentation with atypical antipsychotics: risperidone or aripiprazole 10-15 mg have the strongest evidence for SSRI-resistant OCD. 1, 2 Approximately one-third of patients with SSRI-resistant OCD show clinically meaningful response to antipsychotic augmentation. 2

3. Alternative augmentation: N-acetylcysteine has the strongest evidence among glutamatergic agents, with three out of five randomized controlled trials showing superiority to placebo. 2

4. Consider switching to a different SSRI or clomipramine 150-250 mg daily, though clomipramine is reserved for patients who fail at least one adequate SSRI trial due to inferior safety and tolerability profile. 1, 2

EX/RP remains effective even for patients who have failed SRI augmentation with risperidone or placebo, showing significant reductions in OCD symptoms. 4