Is glycine (amino acid) a suitable treatment for patients with obsessive-compulsive disorder (OCD)?

Glycine for OCD: Limited Evidence Does Not Support Routine Use

Glycine is not a suitable first-line, second-line, or established treatment for OCD and should not be used outside of research settings. The evidence base consists of only small, preliminary studies with significant methodological limitations, while established treatments with robust efficacy data remain the standard of care 1, 2.

Why Glycine Is Not Recommended

Insufficient Evidence Base

• Only one small randomized controlled trial (n=14 evaluable patients) showed a trend toward efficacy that did not reach statistical significance (p=0.053), with high dropout rates due to palatability issues and nausea 3.
• The study showed a mean Y-BOCS decrease of 6.04 points in the glycine group versus 1.00 point in placebo, but the 58% dropout rate severely limits interpretation 3.
• A systematic review of complementary treatments for OCD rated glycine with a moderate effect size (d=1.10) but noted the study was un-replicated with a small sample, precluding confidence in clinical effect 4.

Practical Barriers to Use

• The required dose of 60g/day is extremely high, causing significant palatability problems and gastrointestinal side effects that led to treatment discontinuation in the majority of patients 3.
• No standardized formulation or dosing protocol exists for clinical use 3.

Case Reports Are Not Sufficient

• Individual case reports describe improvement over 5 years in treatment-refractory patients, but these uncontrolled observations cannot establish causation or guide clinical practice 5.
• Open-label studies with sarcosine (a related compound) showed some promise but lack the rigor needed to change practice 6.

What You Should Use Instead

First-Line Treatment: SSRIs Plus CBT

• SSRIs are the established first-line pharmacological treatment, with robust evidence from multiple meta-analyses showing efficacy, tolerability, and safety 1, 2.
• Higher doses than used for depression are required: fluoxetine 60-80mg, sertraline 150-200mg, or paroxetine 60mg daily 1, 2.
• Cognitive-behavioral therapy with exposure and response prevention (ERP) has larger effect sizes than pharmacotherapy alone and should be initiated immediately if available 1, 2.
• Allow 8-12 weeks at maximum tolerated SSRI dose before declaring treatment failure 1, 2.

Second-Line Treatment: Augmentation Strategies

• Risperidone and aripiprazole have the strongest evidence for SSRI-resistant OCD, with approximately one-third of patients showing clinically meaningful response 2.
• N-acetylcysteine has the strongest evidence among glutamatergic agents, with three out of five randomized controlled trials showing superiority to placebo 2.
• Memantine has demonstrated efficacy in several trials and can be considered 2.
• Clomipramine 150-250mg daily should be reserved for patients who fail at least one adequate SSRI trial, despite potential superior efficacy, due to safety concerns 2.

Third-Line Treatment: Neuromodulation

• Deep repetitive transcranial magnetic stimulation (rTMS) has FDA approval for treatment-resistant OCD with moderate effect size (0.65) and 3-fold increased likelihood of response versus sham 2.
• Deep brain stimulation (DBS) may be considered for severe, highly treatment-resistant cases 2.

Critical Clinical Pitfalls

Don't Mistake Inadequate Trials for Treatment Resistance

• Many patients receive insufficient SSRI doses or durations before being labeled "treatment-resistant" 2.
• Verify that the patient has completed at least 8-12 weeks at maximum tolerated dose with confirmed adherence before moving to augmentation 2.

Prioritize Evidence-Based Augmentation

• When SSRIs fail, add CBT with ERP first if not already implemented—this has larger effect sizes than antipsychotic augmentation 2.
• If glutamatergic modulation is desired, use N-acetylcysteine, which has substantially more evidence than glycine 2.

Long-Term Management Matters

• Maintain treatment for 12-24 months after achieving remission due to high relapse rates after discontinuation 1, 2.
• Patient adherence to between-session ERP homework is the strongest predictor of good outcomes 1.

Bottom Line

Glycine remains an experimental intervention with preliminary, inconclusive evidence that does not justify clinical use outside research protocols. Stick with established treatments that have robust efficacy data and prioritize CBT with ERP, which consistently demonstrates superior outcomes 1, 2, 4, 3.