For an adult with obsessive‑compulsive disorder already on a high‑dose selective serotonin reuptake inhibitor, is a 5 mg daily dose of olanzapine an adequate adjunctive augmentation?

Is 5mg Olanzapine Adequate for OCD Augmentation?

No, 5 mg olanzapine is likely insufficient as adjunctive therapy for treatment-resistant OCD in most adults, though it may serve as a reasonable starting dose with planned titration to higher doses based on response and tolerability.

Evidence for Olanzapine Dosing in OCD Augmentation

The evidence base for olanzapine augmentation in SSRI-resistant OCD shows mixed results, with dosing being a critical variable:

• Risperidone and aripiprazole have the strongest evidence for efficacy in SSRI-resistant OCD, with approximately one-third of treatment-refractory patients showing clinically meaningful response to antipsychotic augmentation 1.

• In open-label trials, olanzapine doses ranged from 5-10 mg daily (mean 6.1 mg), with some studies using doses up to 10 mg for adequate trials 2, 3.

• A double-blind, placebo-controlled trial found no advantage of adding olanzapine (5-10 mg, mean 6.1 mg) to fluoxetine over 6 weeks compared to continuing fluoxetine monotherapy 4.

• However, open-label studies showed more promising results with longer treatment durations (8 weeks to 1 year), suggesting that 6 weeks may be insufficient to assess response 2, 5.

Recommended Dosing Strategy

Start with 5 mg daily but plan to titrate upward based on response:

• Begin olanzapine at 2.5-5 mg daily to assess tolerability, particularly sedation 3.

• If no response after 2 weeks and side effects are tolerable, increase to 5 mg daily 3.

• If still no response after 2 more weeks, increase to 10 mg daily for at least 4 weeks to complete an adequate 8-week augmentation trial 3.

• The target therapeutic range appears to be 5-10 mg daily, with mean effective doses around 6 mg in published trials 2, 4.

Critical Treatment Considerations

Ensure adequate SSRI trial first:

• Patients should have received at least 3 months (12 weeks) of maximum-tolerated SSRI dosing before initiating antipsychotic augmentation, as 25.6% of patients respond to continued SSRI monotherapy during this period 6.

• For OCD, SSRIs require higher doses than depression treatment: fluoxetine 60-80 mg, sertraline 150-200 mg, or paroxetine 60 mg daily 1.

Prioritize evidence-based alternatives:

• Aripiprazole (10-15 mg) or risperidone have superior evidence compared to olanzapine for OCD augmentation 1.

• Adding CBT with exposure and response prevention (ERP) produces larger effect sizes than antipsychotic augmentation alone and should be strongly considered first 1.

Monitoring for Adverse Effects

Weight gain and metabolic effects are the primary concerns:

• 60% of patients experienced significant weight gain in one trial of olanzapine augmentation 3.

• Monitor weight, fasting glucose, and lipid profiles regularly when using olanzapine 1.

• Sedation is common but typically does not require discontinuation; only 1 of 10 patients discontinued due to excessive sedation in one series 2.

Special Populations

For patients with comorbid tic disorders:

• Antipsychotic augmentation shows particularly robust response (ARD=0.43) in OCD patients with comorbid tics 6.

• This subgroup may justify earlier use of antipsychotic augmentation strategies 6.

For elderly or oversedated patients:

• A 5 mg dose may be appropriate as a maintenance dose in elderly patients or those experiencing excessive sedation 7.

Treatment Algorithm

1. Verify adequate SSRI trial: Maximum tolerated dose for 12 weeks minimum 6.
2. Add or intensify CBT with ERP if not already implemented (strongest evidence) 1.
3. If augmentation needed, consider aripiprazole or risperidone first (stronger evidence than olanzapine) 1.
4. If olanzapine chosen, start 2.5-5 mg and titrate to 10 mg over 4 weeks based on response and tolerability 3.
5. Continue for minimum 8 weeks at target dose before declaring treatment failure 2, 3.
6. If response achieved, maintain for 12-24 months given high OCD relapse rates 1.

Common Pitfalls to Avoid

• Do not conclude treatment failure with 5 mg alone—most studies used 5-10 mg with titration protocols 2, 4, 3.

• Do not add olanzapine before ensuring adequate SSRI duration and dosing—25.6% respond to continued SSRI monotherapy 6.

• Do not neglect CBT/ERP, which has superior effect sizes to medication augmentation 1.

• Do not ignore metabolic monitoring—weight gain occurs in the majority of patients 3.