Should a middle-aged adult patient with a history of depression and obsessive-compulsive disorder (OCD), currently taking 200mg of one medication with 100mg of another to augment treatment, taper off one of the medications if the current regimen is ineffective?

Do Not Taper the Augmentation Agent—Optimize or Switch the Primary Antidepressant Instead

When augmentation therapy fails in depression/OCD, the augmenting medication should generally be maintained while the primary antidepressant is switched or optimized, not the reverse. 1

Clinical Reasoning for Medication Sequencing

The fundamental principle from pediatric psychopharmacology guidelines applies equally to adults: when two medications target the same disorder, remove the augmenting agent first only if the combination achieved remission. 1 However, in your case of treatment failure, this logic reverses—the primary treatment has failed, not the augmentation strategy.

Why Keep the Augmentation Agent

• The 100mg augmenting medication may be providing partial benefit that isn't immediately apparent, and removing it could precipitate worsening. 1
• Augmentation strategies in OCD often involve medications that address comorbid anxiety or depression, and abrupt discontinuation risks symptom rebound. 1
• For OCD specifically, treatment should focus on ameliorating OCD symptoms first, as successful OCD treatment typically leads to improvement in depressive symptoms without directly targeting depression. 2

Recommended Action Plan

Step 1: Switch the Primary Antidepressant (200mg medication)

Switch to a different mechanism of action rather than dose-escalating the failed medication. 1 The consensus definition of treatment-resistant depression requires failure of at least two antidepressants with different mechanisms of action at adequate doses (minimum licensed dose) for at least 4 weeks. 1

• For OCD with depression, consider switching to clomipramine if not already tried, as it has demonstrated efficacy for both conditions and may be particularly helpful when SSRIs fail. 1, 3
• Alternative: Switch to an SNRI (venlafaxine) if the current medication is an SSRI, ensuring different mechanism of action per Neuroscience-based Nomenclature. 1

Step 2: Maintain the Augmentation During Transition

Continue the 100mg augmenting medication throughout the switch to avoid destabilizing the patient during the transition period. 1

• Taper medications slowly when discontinuing to avoid withdrawal symptoms, but this applies to the failed primary agent, not the augmentation. 1, 4
• For SSRIs specifically, hyperbolic tapering over months down to very low doses minimizes withdrawal symptoms better than rapid tapers. 4

Step 3: Reassess After Adequate Trial

Allow 8-12 weeks on the new primary antidepressant at therapeutic dose before making decisions about the augmentation agent. 1

• If the new regimen achieves remission, consider tapering the augmentation agent after 12-24 months of stability. 1
• If partial response occurs, consider adding CBT/ERP rather than further medication changes, as psychotherapy combined with medication shows superior outcomes in OCD. 1, 5

Critical Safety Considerations

Avoid Common Pitfalls

• Do not continue ineffective treatment hoping for delayed response—lack of improvement by 4 weeks at adequate dose indicates treatment failure, not inadequate trial duration. 6
• Do not taper both medications simultaneously, as this prevents determining which change caused any clinical deterioration. 1
• If the augmenting agent is a benzodiazepine, exercise extreme caution with tapering, as withdrawal can be severe and protracted; reduce by 0.25mg/week after reaching 1mg/day. 7

Monitoring Requirements

Weekly contact during the first month of any medication change to assess tolerability, adherence, and suicidal ideation. 6

• Monitor for behavioral activation, particularly in patients with comorbid depression. 6
• Watch for drug interactions if combining medications, especially with clomipramine which has significant interaction potential. 3

Special Consideration for OCD-Depression Comorbidity

Depression in OCD should not be the primary treatment target—successful OCD treatment typically resolves comorbid depressive symptoms. 2 This means:

• Focus interventions on OCD symptoms using adequate-dose SRIs (often higher than depression doses) combined with ERP. 1
• Depressive symptoms often improve as OCD symptoms resolve, without requiring depression-specific interventions. 2
• If depression persists after OCD improvement, then address it separately with behavioral activation or cognitive therapy. 5