Can adding memantine, buspirone, or N-acetylcysteine (NAC) be an alternative to aid social flatness in a patient sensitive to stimulants and their side effects, particularly with obsessive-compulsive disorder (OCD) and mood dysregulation, instead of discontinuing viloxazine (serotonin-norepinephrine reuptake inhibitor)?

Augmentation for Social Flatness on Viloxazine in OCD with Mood Dysregulation

Adding memantine or NAC as augmentation to viloxazine is a reasonable strategy for addressing social flatness while managing OCD symptoms, particularly given your sensitivity to stimulants and concerns about mood dysregulation. Buspirone should be avoided as it has demonstrated no benefit for OCD symptoms. 1

Why Not Discontinue Viloxazine

• Viloxazine (a selective norepinephrine reuptake inhibitor) may be providing benefit for ADHD symptoms without the stimulant-related side effects you're trying to avoid 2
• Stimulants can worsen OCD symptoms and cause mood dysregulation in vulnerable patients, making them problematic for your specific presentation 2
• Social flatness may be a side effect of viloxazine or could represent undertreated OCD/mood symptoms rather than requiring viloxazine discontinuation 3

Recommended Augmentation Strategy: Prioritize Memantine or NAC

First Choice: Memantine

• Memantine has demonstrated efficacy in multiple randomized controlled trials for treatment-resistant OCD, with 81% response rates in augmentation studies 3, 4, 5
• Memantine is positioned as a third-line augmentation agent for OCD in current treatment algorithms, specifically for patients who have failed first-line treatments 4
• Dosing typically starts at 5mg daily and titrates up to 10-20mg daily over several weeks 3, 5
• Memantine may improve both OCD symptoms and associated social withdrawal without worsening mood dysregulation 5, 6
• The medication is generally well-tolerated with minimal side effects 6

Critical caveat: One 2019 analysis questioned the validity of memantine studies due to methodological concerns, though the evidence base has expanded since then 7

Second Choice: N-Acetylcysteine (NAC)

• NAC has the strongest evidence among glutamatergic agents for treatment-resistant OCD, with three out of five randomized controlled trials showing superiority to placebo 3, 4
• NAC modulates glutamate neurotransmission and may address both OCD symptoms and associated social/emotional blunting 3, 8
• Typical dosing is 1200-2700mg daily, divided into 2-3 doses 3, 8
• NAC is extremely well-tolerated with minimal adverse effects and no risk of worsening mood dysregulation 8
• Effects may take 8-12 weeks to manifest, with separation from placebo beginning around week 8 8

Avoid: Buspirone

• Buspirone added to SSRI therapy showed no benefit over placebo for OCD symptoms in a controlled trial of 33 patients 1
• While buspirone is sometimes used for anxiety, it has no established role in treating OCD or augmenting OCD treatment 1

Implementation Algorithm

Step 1: Optimize Current Treatment

• Ensure viloxazine is at an adequate dose and has been trialed for at least 8-12 weeks 3, 4
• Confirm you're receiving or have received adequate trials of CBT with Exposure and Response Prevention (ERP), as this has larger effect sizes than medication augmentation alone 3, 4

Step 2: Choose Augmentation Agent

• Start with memantine 5mg daily, increasing by 5mg weekly to target dose of 10-20mg daily 3, 5
• If memantine is not tolerated or unavailable, start NAC 600mg twice daily, increasing to 1200-1800mg twice daily over 2-4 weeks 3, 8

Step 3: Monitor Response

• Allow 8-12 weeks at target dose before declaring treatment failure 3, 4
• Monitor for improvement in both OCD symptoms and social engagement/emotional responsiveness 3
• Watch for any worsening of mood dysregulation, though this is unlikely with either agent 5, 8

Step 4: If Inadequate Response

• Consider switching to the alternative glutamatergic agent (NAC if started with memantine, or vice versa) 3, 4
• Consider antipsychotic augmentation with aripiprazole 5-15mg daily, which has strong evidence for treatment-resistant OCD but requires metabolic monitoring 3, 9, 4
• Consider deep repetitive transcranial magnetic stimulation (FDA-approved for treatment-resistant OCD) 3, 4

Critical Monitoring Points

• Monitor for serotonin syndrome if viloxazine is combined with any serotonergic agents, though risk is low with memantine or NAC 3
• If mood dysregulation worsens, prioritize mood stabilization before further OCD treatment optimization 9
• Assess for emergence of hypomania or mood instability at each visit, particularly if there's any underlying bipolar spectrum pathology 9

Common Pitfalls to Avoid

• Do not add buspirone - it has no demonstrated efficacy for OCD and will not address your symptoms 1
• Do not rush to discontinue viloxazine - social flatness may improve with augmentation rather than requiring medication discontinuation 3
• Do not use stimulants given your sensitivity and concerns about OCD/mood worsening 2
• Do not expect immediate results - glutamatergic agents require 8-12 weeks for full effect 3, 8