What to do if symptoms persist after increasing sertraline (selective serotonin reuptake inhibitor) to 200mg for a couple of months?

Management of Persistent OCD Symptoms on Sertraline 200mg

If symptoms persist after a couple of months on sertraline 200mg, the most effective next step is to add cognitive-behavioral therapy with exposure and response prevention (CBT-ERP), which has demonstrated larger effect sizes than pharmacological augmentation strategies. 1

First-Line Augmentation Strategy

Augment with CBT-ERP as the priority intervention for SSRI-resistant OCD:

• CBT-ERP augmentation of SSRIs produces larger effect sizes compared to antipsychotic augmentation 2
• This combination addresses treatment resistance more effectively than medication adjustments alone 1
• Consider 10-20 sessions delivered in-person, remotely via internet protocols, or in group format 2

If CBT-ERP is Unavailable or Not Tolerated

When CBT is not accessible or the patient cannot tolerate exposure therapy 2, consider these evidence-based pharmacological strategies in order:

Option 1: Switch to Different SSRI or Clomipramine

• Switch to a different SSRI as second-line monotherapy 2
• Switch to clomipramine (a non-selective serotonin reuptake inhibitor), which may have superior efficacy though with more side effects 2
• Trial a serotonin-noradrenaline reuptake inhibitor (SNRI) 2

Option 2: Pharmacological Augmentation

Antipsychotic augmentation is the most commonly used strategy for SSRI-resistant OCD:

• Risperidone or aripiprazole have the strongest evidence for augmentation 2, 1
• Only one-third of SSRI-resistant patients show clinically meaningful response to antipsychotic augmentation 2
• Critical monitoring required: Watch closely for weight gain and metabolic dysregulation 2
• Effect size is smaller than CBT-ERP augmentation 2

Clomipramine augmentation as alternative:

• In the only head-to-head trial, fluoxetine plus clomipramine was significantly superior to fluoxetine plus quetiapine 2
• Major safety concern: Risk of severe and potentially life-threatening events including seizures, heart arrhythmia, and serotonin syndrome due to increased blood levels of both drugs 2
• This combination requires careful monitoring and should only be attempted by experienced clinicians 2

Glutamatergic agents as emerging options:

• N-acetylcysteine has the largest evidence base (3 out of 5 RCTs positive) 2
• Memantine has demonstrated efficacy in several trials 2
• Other agents (lamotrigine, topiramate, riluzole, ketamine) have some evidence but require further study 2

Important Timing Considerations

• The optimal SSRI trial duration is 8-12 weeks at maximum tolerated dose before declaring treatment resistance 2, 1
• You have met this threshold at 200mg for "a couple of months" 2
• Notably, in one trial, time spent on SSRI monotherapy (6 months) was the most important factor associated with response, suggesting some patients may benefit from longer trials 2

Common Pitfalls to Avoid

Do not prematurely abandon sertraline if the patient has only been at 200mg for 8-10 weeks—maximal improvement may not occur until week 12 or later 1

Avoid combining clomipramine with sertraline without specialist consultation due to serious drug interaction risks including potentially fatal cardiac arrhythmias and serotonin syndrome 2

Monitor risk-benefit ratio continuously when using antipsychotic augmentation, as metabolic side effects can significantly impact quality of life 2

Advanced Treatment Options

If multiple medication trials and adequate CBT fail:

• Consider intensive outpatient or residential treatment 2
• Deep repetitive transcranial magnetic stimulation (rTMS) with individualized symptom provocation has FDA approval for OCD 2
• Neurosurgery including deep brain stimulation only after failure of three serotonin reuptake inhibitors (including clomipramine), adequate CBT trial, and disease incapacitation 2