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N-Acetyl Cysteine (NAC) for OCD

Amino acid supplement for symptoms of Obsessive Compulsive Disorder


Obsessive-compulsive disorder (OCD) is a relatively common psychiatric disorder in which a person has recurrent intrusive thoughts, images, or urges (called obsessions) that cause significant distress. These thoughts may be accompanied by behaviors (called compulsions) as an attempt to reduce anxiety related to these thoughts.


Reoccurring thoughts and behaviors of OCD often start in childhood can have mild to severe impact on a person’s quality of life. Approximately 2.3% of the population has been diagnosed with OCD at some point in their lifetime, or 1 in 42 people. At any one time about 1 in 100 people are currently struggling with OCD symptoms (Up to Date 2021).


What’s happening in the brain in OCD?


Pharmacological studies have suggested that a dysfunction in the brain’s serotonin signaling system plays a role in OCD, shown by some patients with OCD responding to serotonin-supporting medications (Ooi et al., 2018). Newer evidence, however, suggests that OCD may also be associated with abnormal levels of the neurotransmitter glutamate (Karthik et al, 2020) in a particular neuron pathway called the cortico-striato-thalamo-cortical loop (CTSC). Glutamate is an excitatory molecule that, at high levels, can cause neuron damage via oxidative stress, and can not only cause OCD symptoms in animal models, but also cause dysfunction in the CTSC of humans (Balmus et al, 2016; Karthik et all, 2020). Another less common type of OCD is caused by PANDAS, or Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections, which is an immune overreaction to certain bacterial infections in childhood and is managed differently than other types of OCD.


The standard pharmaceutical treatment for common OCD in children and adults is SSRI medication, often in combination with a type of cognitive behavioral therapy called Exposure and Response Prevention (ERP) for managing anxiety caused by intrusive thoughts and urges (Kotapati et al., 2019). While an estimated 30% of people respond fully to this treatment, a summary article from 2019 reported that this approach does not adequately help roughly 50% of patients with OCD (Stein et al., 2019), and these people are left with residual symptoms and reduced quality of life. Risk factors for poor treatment response have been identified by Stein et al., 2019 (below). The generally low response rate to SSRIs, along with emerging evidence on the role of glutamate, has inspired new treatment and augmentation strategies, including the use of N-Acetyl Cysteine (NAC) for OCD.


Factors associated with poor treatment outcome in OCD (Stein et al., 2019).

Clinical characteristics

·    More severe obsessive–compulsive disorder (OCD)

·    Greater functional impairment

·    Sexual, religious, and hoarding symptoms

·    Poor insight

·    Higher number of comorbidities

·    Comorbid major depression, agoraphobia or social anxiety disorder

·    Lower willingness to fully experience unpleasant thoughts

·    Greater resistance to change

·    Lower adherence to treatment

Other characteristics

·    Family history of OCD

·    Poor therapeutic alliance with providers

·    Greater family accommodation of OCD symptoms

·    Absence of early response to SSRI treatment


NAC as treatment/augmentation for OCD


NAC, or N-Acetyl Cysteine, is an oral over-the-counter supplement that is being studied both as a stand-alone treatment for OCD and as an augmentation strategy to improve response to SSRI treatment for OCD.


The molecule NAC is a precursor to one of the brain’s most important antioxidant molecules, glutathione. Glutathione works to counteract the oxidative stress associated with OCD and other psychiatric disorders. Beyond its role in forming glutathione, NAC also works to directly regulate glutamate within the brain, reducing its release and excitatory effect in neurons. Furthermore, NAC has also been shown to reduce non-specific inflammatory pathways associated with several psychiatric disorders. Fortunately, NAC also has an excellent safety profile with low adverse events and minimal pharmaceutical interactions.


A 2016 trial showed that giving NAC with the SSRI fluoxetine improved response to treatment over fluoxetine alone in patients with moderate-to-severe OCD, a population known to have typically poor treatment response (Paydary et al., 2016). Another trial from 2017 using NAC as an add-on to the SSRI citalopram in children and adolescents showed significant improvement over the SSRI alone in the Yale-Brown Obsessive Compulsive Scale (YBOCS) and in the control of compulsions (Ganazideh et al., 2017).  NAC has also shown some preliminary evidence in treatment of grooming disorders, which are OCD-related symptoms of compulsive nail biting (onychophagia), hair pulling (trichotillomania), and skin picking (excoriation disorder) (Schwalfenberg et al., 2021).


NAC is not always effective when added to SSRIs for OCD symptoms, however; another trial from 2017 showed that NAC added on to SSRI therapy for treatment-resistant OCD did not have significant benefit on OCD symptoms, but did show improvement in anxiety in these patients (Costa et. al., 2017).


In addition, NAC has been used on its own as treatment for OCD. Afshar et al., (2012) published a small study wherein patients who had previously not responded to SSRI treatment showed significant improvement with NAC alone, but evidence in this area of NAC as monotherapy is still in its early stages.


What you should know before you start NAC for OCD


An important point to note is that most studies find that response to NAC can begin within a week or two, but can take up to 12 weeks to fully appear, something that patients should know and discuss with their providers before considering NAC treatment. In addition, oral NAC may cause digestive upset, diarrhea, fever, and may also affect reproductive hormones (NAC is being studied as a treatment for PCOS as well). Always consult with a provider before taking any new supplement, since "natural" does not always mean safe.


Generally, however, the current body of research suggests that treatment with N-Acetyl Cysteine may help to reduce the severity of OCD symptoms and show good tolerability with minimal adverse effects, mostly as an add-on to SSRI therapy but also possibly when used on its own. It is especially promising for populations who have not responded to SSRI therapy in the past, or for those with risk factors for poor treatment response.


To learn more about NAC and other integrative therapies for mental health conditions, make an appointment with Dr. Crawford or reach out to an integrative practitioner near you.


1.  Up to Date (2021) Obsessive-compulsive disorder in adults: Epidemiology, pathogenesis, clinical manifestations, course, and diagnosis.

2.  Ooi, S. L., Green, R., & Pak, S. C. (2018). N-acetylcysteine for the treatment of psychiatric disorders: A review of current evidence. BioMed research international, 2018

3.  Karthik, S., Sharma, L. P., & Narayanaswamy, J. C. (2020). Investigating the role of glutamate in obsessive-compulsive disorder: current perspectives. Neuropsychiatric disease and treatment, 16, 1003

4.  Balmus, I. M., Ciobica, A., Antioch, I., Dobrin, R., & Timofte, D. (2016). Oxidative stress implications in the affective disorders: main biomarkers, animal models relevance, genetic perspectives, and antioxidant approaches. Oxidative medicine and cellular longevity, 2016

5.  Kotapati, V. P., Khan, A. M., Dar, S., Begum, G., Bachu, R., Adnan, M., ... & Ahmed, R. A. (2019). The effectiveness of selective serotonin reuptake inhibitors for treatment of obsessive-compulsive disorder in adolescents and children: a systematic review and meta-analysis. Frontiers in psychiatry, 10, 523

6.  Simpson, B. (2014). The Relative Efficacy of Current Medication and Therapy for OCD. Psychiatric Times.

7.  Stein, D. J., Costa, D., Lochner, C., Miguel, E. C., Reddy, Y., Shavitt, R. G., van den Heuvel, O. A., & Simpson, H. B. (2019). Obsessive-compulsive disorder. Nature reviews. Disease primers, 5(1), 52.

8.  Paydary, K., Akamaloo, A., Ahmadipour, A., Pishgar, F., Emamzadehfard, S., & Akhondzadeh, S. (2016). N‐acetylcysteine augmentation therapy for moderate‐to‐severe obsessive–compulsive disorder: Randomized, double‐blind, placebo‐controlled trial. Journal of clinical pharmacy and therapeutics, 41(2), 214-219.

9.  Ghanizadeh, A., Mohammadi, M. R., Bahraini, S., Keshavarzi, Z., Firoozabadi, A., & Shoshtari, A. A. (2017). Efficacy of N-acetylcysteine augmentation on obsessive compulsive disorder: A multicenter randomized double blind placebo controlled clinical trial. Iranian Journal of Psychiatry, 12(2), 134

10.  Schwalfenberg, G. K. (2021). N-Acetylcysteine: A Review of Clinical Usefulness (an Old Drug with New Tricks). Journal of Nutrition and Metabolism, 2021

11.  Afshar, H., Roohafza, H., Mohammad-Beigi, H., Haghighi, M., Jahangard, L., Shokouh, P., ... & Hafezian, H. (2012). N-acetylcysteine add-on treatment in refractory obsessive-compulsive disorder: a randomized, double-blind, placebo-controlled trial. Journal of clinical psychopharmacology, 32(6), 797-803

12.  Costa, D. L., Diniz, J. B., Requena, G., Joaquim, M. A., Pittenger, C., Bloch, M. H., ... & Shavitt, R. G. (2017). Randomized, double-blind, placebo-controlled trial of N-acetylcysteine augmentation for treatment-resistant obsessive-compulsive disorder. The Journal of clinical psychiatry, 78(7), 0-0

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