NAC for OCD: An Effective Treatment Option?

NAC has been suggested as a treatment for OCD.

It’s likely that NAC can improve OCD symptoms in a subset of persons with OCD – but not everyone.

This is because individuals differ in gene expression, brain morphology, neurochemistry, hormones, and general physiology (influencing OCD and reactions to NAC).

What is NAC?

N-acetylcysteine – or the N-acetyl derivative of Cysteine.

It is used as a pharmaceutical drug and nutritional supplement as:

• A mucolytic agent (in cases of acetaminophen overdose)
• Investigational adjunct treatment for various medical conditions (including OCD)

For this reason, we can assume that NAC will do one of 3 things (regarding OCD):

1. Have zero effect on OCD
2. Improve OCD
   
3. Worsen OCD
   

NAC for OCD (Research)

Included below are various studies and/or reports examining and discussing the effect(s) of NAC for the treatment of OCD.

Not every single study is included here – may update with newer studies if: (1) I remember or (2) am alerted.

N-Acetylcysteine augmentation in refractory OCD (2019) (R)

• Author: Bhaskara (MD)
• Design: Case report
• Case: 25-year-old male with nonverbal learning disorder and OCD (first diagnosed at age 12). (YBOCS score = 34 at time of referral).
• Details: OCD symptoms included checking and ordering rituals; symmetry; and washing/self-care rituals. He spent 8-10 hours a day on self-care/toilette routines – continuing until it felt “just right.”
• Past treatments: SSRIs (fluvoxamine, fluoxetine, paroxetine) monotherapy (limited response). Clomipramine with CBT (partial response). Clomipramine (150 mg/d) + aripiprazole (2 mg/d).
• NAC treatment: Patient was prescribed NAC at a dosage of 1000 mg (twice daily) – then, one week later, instructed to increase to 1500 mg (twice daily). (These were taken along with his clomipramine 75 mg/d and aripiprazole 2 mg/d).

Timeline of improvement

Results: The patient’s OCD symptoms gradually improved over a 6-month duration with the addition of NAC (3000 mg/d) as an adjunct.

• 4 weeks (1 month): The patient reported noticeable reductions in OCD symptoms after 4 weeks and remained hopeful.
• 12 weeks (3 months): At week 12, there were substantial improvements in the patient’s OCD symptoms (YBOCS score dropped to 28 – from 34). (Time spent on rituals dropped to 3 hours per day – from 8-10 hours, previously).
• 6 months: At his 6-month review, the patient’s OCD remained significantly improved (YBOCS score was 18). His functioning also dramatically improved over the ensuing months such that he was able to get a driver’s license and part-time job.
• 1 year: After one year, the patient has continued to do well – he’s employed full-time and intends to start a university degree.

Takeaway: NAC (1000-1500 mg, 2x per day) can clearly be an effective adjunct for some individuals in the treatment of refractory OCD.

In refractory OCD where treatment options are limited and responses are generally partial (and often accompanied by adverse effects) NAC (a low cost supplement with minimal side effects) is worth a trial.

Relevant notes:

N-Acetylcysteine for Pediatric OCD (2019) (R)

• Author: Li et al.
• Design: RCT (12 weeks)
• Methods: Pediatrics (ages 8-17) with OCD were assigned to receive either NAC (up to 2700 mg/d) or a placebo for 12 weeks. Children’s YBOCS was used to track change in OCD symptoms from baseline.
• Limitations: Extremely small sample (11)
• Results: NAC was associated with significant reduction on the Children’s YBOCS relative to the placebo (beginning at week 8).
  • Mean CY-BOCS scores changed from ~21.4 to 14.4 in the NAC group – whereas the placebo group experienced no change from ~21.3 at baseline.
  • The improvement in the NAC group was primarily attributable to a >35% reduction in CY-BOCS total score of 1 participant (of the 5 in this group).

Takeaway: There may be some initial improvement in OCD symptom severity with NAC treatment.

Oral N-acetylcysteine in the treatment of OCD (Systematic Review) (2018) (R)

• Author: Couto & Moreira
• Design: Systematic Review
• Methods: Searched for human clinical trials and case reports in which NAC was evaluated as a standalone or adjunct in the treatment of OCD. A total of 10 studies were included in the review. (5 RCTs; 3 case reports; 2 case series).
• Results: All case reports and case series (except 1) reported substantial improvement in OCD symptoms with NAC augmentation therapy. 3 of the 5 RCTs reported NAC as effective for OCD (as a standalone or adjunct).

Takeaway: Reviewers gave a GOR (grade of recommendation) rating of a “D” for NAC in the treatment of OCD.

The “D” rating (Level 5 evidence) indicates that results have been inconclusive and/or inconsistent.

However, authors did suggest that NAC is favorable over the use of a placebo (based on pooled results from 4/5 RCTs).

A Review of NAC in Grooming Disorders (2019) (R)

• Author: Braun et al.
• Design: Literature review
• Methods: Find studies in which NAC was administered to treat trichotillomania, onychophagia, and pathological skin picking. (Case reports, case series, and RCTs were included).
• Included: 10 case reports; 1 case series; 4 RCTs. (NAC dosing ranged from 450-2400 mg/d and treatment lasted 1-8 months).
• Results: Current data should be considered preliminary, however, case reports have documented mostly positive results and no major side effects.

Takeaway: Preliminary evidence suggests NAC may be beneficial in the treatment of OCD-related grooming disorders.

Efficacy of NAC Augmentation on OCD (2017) (R)

• Author: Ghanizadeh et al.
• Design: RCT (Multicenter)
• Participants: 34 pediatric outpatients with OCD
• Method: Assign patients at random to receive either NAC (up to 2400 mg/day) or a placebo – as augmentation to citalopram (SSRI). Document changes in YBOCS scores from baseline through 10 weeks.
• Results: Patients who received NAC as an adjunct exhibited significantly greater YBOCS score reductions from baseline (~21 to 11.3) after 10 weeks – than those who received a placebo.

Takeaway: This trial found that adjunct NAC to an SSRI (citalopram) provides significant therapeutic benefit in pediatrics with OCD (relative to a placebo) – and is well-tolerated.

Randomized, Double-Blind, Placebo-Controlled Trial of NAC Augmentation for Treatment-Resistant OCD (2017) (R)

• Author: Costa et al.
• Design: RCT (16-week)
• Participants: 40 adults (ages 18-65) with resistant OCD
• Method: Assign participants at random to receive either NAC (3000 mg/d) or a placebo – as an augmentation to preexisting OCD treatment – for a 16-week period. YBOCS score was used as the primary outcome measure.
• Limitations: Small sample size.
• Results: Both groups showed reduction of YBOCS scores at week 16. NAC recipients had reductions of ~4.3 points, placebo recipients had reductions of ~3 points.  Adding NAC was superior to the placebo in reducing anxiety but not depression or specific components of OCD.

Takeaway: This trial did NOT find any benefit of NAC (3000 mg/d) as an adjunct in the treatment of resistant OCD.  However, it did find that NAC may have some benefit in reducing anxiety in patients with resistant OCD.

NAC Augmentation Therapy for Moderate-to-Severe OCD (2016) (R)

• Author: Paydary et al.
• Design: RCT (10-week)
• Participants: 44 patients with OCD
• Method: Participants randomized into parallel groups and assigned randomly to receive either NAC (2000 mg/d) or a placebo – in addition to fluvoxamine (200 mg/d). YBOCS scores (baseline, week 4, week 8, week 10) were used to determine efficacy.
• Limitations: Small sample size
• Results: There was a significant effect for time (x) treatment interaction for both YBOCS total score and the YBOCS obsession subscale.

Takeaway: NAC might be effective as an augmentation strategy in the treatment of moderate-to-severe OCD.

N-Acetylcysteine in the Treatment of Excoriation Disorder (2016) (R)

• Author: Grant et al.
• Design: RCT (12-week)
• Participants: 66 adults with Skin Picking Disorder (SPD); 53 completed the study
• Methods: Participants were assigned at random to receive either placebo (31) or NAC (35) – at a dosage between 1200-3000 mg/d for 12 weeks. NE-YBOCS was used to assess symptom severity throughout the trial.
• Limitations: Mostly female participants (59/61), small sample.
• Results: NAC treatment led to significant improvements in NE-YBOCS scores (i.e. SPD symptoms) relative to the placebo.
  • Details: NAC recipients’ scores dropped from 18.9 (baseline) to 11.5 (12 weeks) – and CGI scores dropped from 3.5 to 3.0.
  • (No significant improvements were noted for placebo recipients).
  • 15 of the 32 (47%) NAC recipients were “much” or “very much” improved – relative to just 4 of the 21 (19%) placebo recipients.

Takeaway: NAC treatment appears beneficial in treating Skin Picking Disorder (SPD), a form of OCD, possibly via modulating glutamatergic neurotransmission.

N-Acetyl Cysteine (NAC) in the treatment of OCD (2015) (R)

• Author: Sarris et al.
• Design: RCT
• Participants: 44 (18-70 years old) with OCD
• Methods: Patients assigned at random to receive NAC (1.5 g, 2x per day) or a placebo over a 16-week period. YBOCS scores were documented at baseline and at 4 week intervals.
• Limitations: Small number of participants.
• Results: NAC recipients exhibited significant improvements in the YBOCS “compulsions” subscale at week 12 (relative to placebo recipients) – but this dissipated by week 16. NAC was NOT found superior to a placebo for OCD over a 16-week period.

Takeaway: This study supports the idea that NAC (1500 mg, twice daily) may not be very effective for OCD – as it didn’t provide any greater symptom reduction than a placebo.

N-Acetyl Cysteine in the Treatment of OCD and Related Disorders (Systematic Review) (2015) (R)

• Author: Oliver et al.
• Design: Systematic Review
• Methods: Searched for human clinical trials or case reports of NAC for OCD. 4 clinical trials and 5 case reports (i.e. series) were found.
• Results: NAC demonstrates activity in reducing the severity of OCD symptoms when administered for 12 weeks (2400-3000 mg/day) – with good tolerability and minimal adverse effects.

Takeaway: NAC appears safe, tolerable, and effective as a treatment for OCD in the majority of published research, but the data remains inconclusive (for a variety of reasons).

Relevant notes:

N-acetylcysteine Add-on Treatment in Refractory OCD (2012) (R)

• Author: Afshar et al.
• Design: RCT (12-week)
• Participants: 48 patients with refractory OCD
• Methods: Patients assigned at random to receive either NAC (up to 2400 mg/d) or a placebo – in addition to SSRI treatment – for 12 weeks. YBOCS and CGI scores were tracked to determine the effect of NAC.
• Limitations: Small sample size.
• Results: NAC recipients showed significantly improved YBOCS scores and CGI-Severity scores at study endpoint. (52% of the NAC recipients were “full-responders” relative to 15% of placebo recipients).

Takeaway: This trial supports the idea that NAC may be effective for some patients as an SSRI adjunct in the treatment of refractory OCD.

NAC augmentation in SSRI-refractory OCD (2006) (R)

• Author: Lafleur et al.
• Design: Case report
• Case: 58-year-old female with OCD (diagnosed in childhood). Previously hospitalized 5x for OCD symptoms. History of recurrent Major Depressive Disorder (MDD) but in remission for 12+ years.
• Details: Persistent and severe OCD symptoms. Contamination fears; ego-dystonic thoughts; hoarding; excessive hand washing; repetitive rituals associated with doing laundry.
• Past treatments: Stable but partial response to fluvoxamine (3000 mg/d) for 12 years. (Fluoxetine, clomipramine, alprazolam, and behavior modification – all failed).
• NAC treatment: Initiated at 600 mg (2x daily) and titrated upwards to 3000 mg daily over 6 weeks. After the first 6 weeks, NAC was continued at 3000 mg daily for 7 additional weeks.  (This was an adjunct to her fluvoxamine 300 mg/d).
• Results: After the addition of NAC to fluvoxamine, the patient’s intrusive thoughts of contamination gradually decreased. YBOCS score decreased dramatically over time – and she became better able to resist compulsive watching rituals.  Symptoms remained improved at a 2-month follow-up visit.

Takeaway: NAC (3000 mg/d) may prove beneficial for augmentation in a subset of patients with treatment-resistant OCD.

NAC for OCD (Big Picture Takeaways)

NAC for OCD (Mechanisms of action)

Lafleur et al. (2005) suggested that NAC probably helps some patients with OCD via 3 general mechanisms: reducing synaptic glutamate activity (via activation of metabotropic receptors); raising extrasynaptic glutamate levels; and increasing GSH. (R)

Couto & Moriera (2018) propose 2 “main mechanisms” by which NAC might exert a therapeutic effect in OCD: GSH increase and glutamate modulation. (R)

Dean et al. (2011) provide additional mechanisms by which NAC might provide benefit in OCD and other psychiatric conditions, including: modulation of inflammatory mediators and dopamine. (R)

GSH (glutathione) increase

NAC supplementation increases production of GSH by providing an additional concentration of cysteine.

Increased availability of GSH results in greater scavenging of toxic byproducts in glutamatergic and dopaminergic metabolism.

As a result, there’s lower oxidative and nitrosative stress – and ultimately reduced cellular damage.

Glutamate modulation

NAC is understood to significantly modulate glutamatergic neurotransmission.

Specifically, NAC activates “Group II” metabotropic glutamate receptors (mGluR2/3) – receptors which are predominantly presynaptic.

Activation of presynaptic mGluR2/3 receptors is thought to decrease glutamatergic transmission and excitotoxicity (i.e. toxicity caused by excessive excitatory neurotransmission – such as from too much glutamate).

Essentially, it is thought that in OCD subtypes wherein excessive glutamate within the CSTC (cortico-striato-thalamo-cortical) circuit is a contributing factor, NAC supplementation could provide substantial therapeutic benefit.

Modulation of inflammatory mediators

Inflammation in the CSTC (cortico-striato-thalamo-cortico) circuit has been documented in patients with OCD. (R)

It’s unclear as to whether the inflammation is causing the OCD – or a byproduct of the OCD. Nevertheless, there’s clearly increased inflammation in the CSTC.

NAC has potent anti-inflammatory properties – such that it might decrease concentrations of inflammatory mediators (IL-6, IL-1B, TNF-alpha) and ultimately lower inflammation in the CSTC.

The anti-inflammatory effect of NAC might be a downstream response to upregulated GSH and lower oxidative/nitrosative stress – but it could also be an independent mechanism.

Dopamine modulation

Dopaminergic abnormalities may be causally implicated in OCD for a subset of individuals. (R)

NAC appears to alter the release of dopamine in animal models.

In rats: NAC facilitates vesicular dopamine release at low doses in striatal neurons – and inhibits release at millimolar concentrations.

Glutathione upregulation (its chief mechanism) has also been shown to increase glutamate-agonist evoked dopamine release in striatal neurons of mice.

In monkeys: NAC protects against reductions in dopamine transporter levels following repeated administration of methamphetamine (neurotoxic).

Has NAC helped my OCD? (My Experience)

Firstly, I want to emphasize that I have mild OCD that tends to worsen with high arousal and caffeine intake.

My OCD themes vary: perfectionism, urges to document ideas (in fear of forgetting), checking locks on doors, cleaning, cracking toes, emptying bladder, etc.

Generally, as long as I get good sleep and don’t overdo the caffeine, my OCD is pretty much a non-factor.

That said, my still urges me to follow a nighttime routine: shutting down computer (fully), writing down what to do tomorrow, etc.

The worst my OCD has been: (1) SSRI withdrawal in early 2000s (paroxetine) – I never knew it could get so bad (nothing was as bad as this) and (2) chronic high-dose caffeine consumption (e.g. Bang, Reign, Monster, etc.).

Prior to starting NAC, my OCD was practically nonexistent.

I’ve gone through extended periods (years) wherein, for whatever reason, my mild OCD was in full remission and had zero effect on my life.

After starting NAC, I didn’t notice worsening of OCD.

NAC supplementation

I’ve been supplementing with 2000-2400 mg of NAC (in divided doses: 1000-1200 mg in the AM & 1000-1200 mg in the PM) for over 2 years now (maybe missing 7-14 days total throughout that period).

My primary reason for supplementing with NAC is to protect my hearing from loud noises and medication-related ototoxicity.

It allegedly does this by upregulating glutathione (a potent antioxidant produced by the body to scavenge free radicals and reduce inflammation).

Was recommended to take while on antibiotics by Neil Bauman (PhD) – hearing loss researcher – to reduce risk of ototoxicity.

Any effect on OCD though?

In my specific case, I’ve noticed zero substantial effect of NAC on my OCD.

In fact, I’ve become “OCD about taking NAC” (haha) – such that if I think about discontinuing NAC as a core supplement – my brain reacts harshly (making me think I’m missing out on a supplement that may optimize health – even if this thinking is erroneous).

So in my personal experience, NAC has had zero significant impact on my OCD.

At one point I did 7 days off of all supplements – and noticed no substantial effect of going without NAC on my OCD (there was no increase in my OCD) – leading me to conclude that it does nothing for me with regard to OCD.

Maybe if I took a smaller or larger dose the effect would be different?

I have experimented with just 600 mg in the AM and 600 mg in the PM (total of 1200 mg/day) – but never have regularly gone above 2400 mg dose per day.

I’m considering another experiment wherein I take a total of 3000 mg/day (1500 mg in AM, 1500 mg in PM) – mostly to determine whether it can prevent caffeine-induced OCD.

Will NAC treat your OCD?

Unknown until you try. It’s a relatively inexpensive supplement to try with virtually zero side effects for most people – and it doesn’t interact with many medications.

NAC for OCD Experiment

You could run a low-risk, self-experiment testing the effect of NAC on your OCD.

Note: Before trying NAC, verify with a medical doctor and pharmacist (I recommend both) that it’s safe for you to take (given your current health status and medication regimen).

Also make sure you’re getting a quality NAC supplement (not some pseudo-NAC or contaminated NAC).

NAC dosage: 2000-3000 mg/day (in divided doses).  Most studies recommend taking 1000-1500 mg NAC twice per day (for a total of 2000-3000 mg) in the treatment of OCD.

How to take: Empty stomach. Once (AM) or twice per day (AM & PM).

Experiment duration: 8-12 weeks.

• Studies suggest that NAC may require 8+ weeks to provide therapeutic benefit in OCD.
• You may want to extend the experiment duration by double if you started with a low dose (e.g. 600 mg/day) and are now trialing a higher dose (e.g. 2400 mg/day).

Drew’s final thoughts (NAC for OCD)

NAC is an inexpensive, low risk supplement to try if you have OCD.

Side effects associated with NAC are generally minimal or nonexistent for most.

I would start with a lower dose (1000 mg, 2x daily – for a daily total of 2000 mg) for ~4-8 weeks before trying a higher dose (e.g. 1500 mg, 2x daily). (Lower doses are more tolerable).

NAC does work well for some cases of OCD – but clearly not all. It’ll depend upon the physiological underpinnings of your specific OCD.

NAC may work best when administered as an adjunct to an FDA-approved, serotonergic agent (e.g. fluvoxamine).

Individuals with glutamatergic abnormalities and/or excessive oxidative/nitrosative stress may be more likely to benefit from NAC (due to the fact that it modulates glutamate and reduces free radicals) – than those without these abnormalities.

Have you tried NAC for OCD?

If you have either clinically-verified OCD or OCD-like symptoms, have you tested NAC supplementation as a potential treatment?

If you tested NAC for your OCD, did it: (1) improve your symptoms; (2) have no effect; or (3) worsen your symptoms?

Provide additional details such as: (1) NAC trial duration; (2) NAC dosage; (3) whether you used other medications/supplements with NAC.

Additional reading (NAC for OCD)

• In Adult Patients with OCD, Is the Amino Acid N-Acetyl Cysteine (NAC) Effective in Reducing Severity of OCD? (2019) (R)
• Evidence Review of NAC for OCD (Advanced Interventions) (R)
• N-Acetylcysteine for the Treatment of Psychiatric Disorders (Review of Current Evidence) (2018) (R)
• NAC and Vitamin D Supplementation in Resistant OCD (2018) (R)
• NAC Blocks Serotonin 1B Agonist-Induced OCD-related Behavior in Mice (2018) (R)
• What Future Role Might NAC Have in the Treatment of OCD and Grooming Disorders? (2016) (Systematic Review) (R)
• Clinical Trials of NAC in Psychiatry and Neurology (Systematic Review) (2015) (R)