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Limitations of available conventional treatments of OCD invite consideration of non-drug treatments.
Obsessive-compulsive disorder (OCD) is one of the leading causes of psychiatric disability globally and can result in severe impairment in social and occupational functioning. Available pharmacologic treatments of obsessive-compulsive disorder (OCD) are often beneficial, however, roughly one-third of individuals diagnosed with OCD do not respond to SSRIs and other first-line drug treatments or discontinue treatment due to side effects resulting in a significant reduction in quality of life.
Many individuals diagnosed with OCD benefit from a specialized form of cognitive-behavioral therapy called exposure and response prevention. However, CBT is not effective for everyone who struggles with OCD. In the context of the limitations of conventional treatment choices, emerging research findings suggest that select natural products may reduce the severity of symptoms of OCD (Camfield, Sarris & Berk 2011). A systematic review of studies on complementary and alternative medicine (CAM) approaches used to treat OCD found preliminary evidence for the natural products glycine, borage, and N-acetylcysteine (Sarris, Camfield & Berk 2012).
This post is offered as a concise review of recent research highlights on natural products that are being investigated as potential treatments of OCD, either alone or in combination with medications.
N-acetylcysteine: A promising augmentation treatment of OCD
An important new direction in OCD research has been the investigation of augmentation strategies using both drugs and natural products, including n-acetylcysteine and others, that stimulate the brain’s glutamate receptors (Sheshachala & Narayanaswamy 2019).
Findings of animal and human studies suggest that the brain’s glutamatergic system plays a role in etiology of OCD and related disorders (e.g. trichotillomania and compulsive nail-biting), and that reported therapeutic effects of the amino acid n-acetylcysteine (NAC) in individuals diagnosed with these disorders may be due to its role in reducing oxidative stress in the brain as well as its direct actions on the brain’s glutamatergic neurons (Smith, Treacy & Giaroli 2016).
However, to date, few studies investigating NAC as a treatment of OCD have been done and research findings are inconsistent (Paydary et al 2016). In a double-blind randomized placebo-controlled trial, 44 individuals with moderate to severe OCD were randomized to receive daily doses of the anti-OCD drug fluvoxamine (Luvox™) 200mg vs fluvoxamine 200mg plus NAC 2000mg. All subjects rated the severity of their symptoms using the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) at baseline and at weeks 4, 8 and 10. The authors remarked that NAC “might be effective as an augmentative agent” for the treatment of moderate to severe OCD.
In a 16-week placebo-controlled augmentation study, 40 individuals with severe treatment-resistant OCD were randomized to receive a serotonin selective reuptake inhibitor (SSRI) plus NAC 3000mg daily vs an SSRI plus a placebo (Costa et al 2017). At the study's end, individuals in both groups reported significant and equivalent reductions in OCD symptom severity. Individuals receiving adjunctive NAC reported greater reductions in anxiety (but not depressed mood) compared to subjects treated with an SSRI plus a placebo.
A systematic review of studies on NAC as a treatment of OCD included five randomized placebo-controlled trials, three case reports, and two case series and found provisional evidence that NAC may be more effective than a placebo (Couto & Moreira 2018). Findings of a separate systematic review of placebo-controlled studies on NAC in individuals diagnosed with OCD and the so-called OCD-related disorders (i.e. trichotillomania and compulsive nail biting) were largely inconclusive (Smith, Treacy & Giaroli 2016). NAC is generally well tolerated at doses used to treat OCD, however, some individuals report mild nausea, constipation, or skin rash.
Glycine and sarcosine
Glycine and sarcosine are two other amino acids that have been investigated as potential treatments of OCD. Like NAC, glycine affects glutamate but via an indirect mechanism of action. Sarcosine acts as a co-agonist at NMDA receptors, which play an essential role in the brain's glutamate signaling.
In a small 12-week placebo-controlled double-blind study, 24 adults with OCD were randomized to receive glycine up to 60gm/day versus placebo while taking their usual OCD medications (Greenberg 2009). OCD symptom severity was self-rated using the Y-BOCS at weeks 4, 8 and 12. Only 14 individuals completed the study due to a high dropout rate caused by poor side effect tolerance (mainly bad taste and nausea). Two individuals in the glycine group experienced significant reductions in OCD symptom severity but no one in the placebo group improved. A larger study is needed to investigate the potential role of glycine as a viable treatment of OCD.
Sarcosine is derived from glycine and acts as a reuptake inhibitor of glycine. In a small, uncontrolled study, 26 adults diagnosed with OCD taking sarcosine between 500mg and 2gm/day without taking other OCD medications experienced statistically significant reductions in symptom severity (Wu et al 2011). For unclear reasons, medication naïve subjects enrolled in the study showed a better and more sustained response compared to those who had previously been treated with medications. Sarcosine was well tolerated and only one person dropped out of the study due to headaches.
Myo-inositol
Myo-inositol (MI) is an important signaling molecule in the brain and interacts with serotonin, glutamate, and other neurotransmitter systems.
Several small studies have investigated MI as a potential treatment of OCD with largely inconsistent findings. In a small six-week placebo-controlled study, 13 adults with OCD were randomized to receive MI 18gm/day or a placebo (Fux et al 1996). Individuals taking MI reported significantly greater reductions in symptom severity compared to the placebo group. In contrast to these findings, the authors of a small augmentation study in which 10 adults with OCD were randomized to MI versus placebo (i.e., while continuing on their usual medications) found no evidence supporting the efficacy of MI against OCD (Fux 1999).
Borage extract
The dried flower of the herbal Echium amoenum (also called borage or starflower) is widely used in traditional Persian medicine to treat anxiety and depressed mood. The bioactive constituents of borage extract are known to affect serotonin activity in the brain.
In a small six-week double-blind study, 44 adults with OCD were randomized to receive an aqueous extract of borage 500mg/day or a placebo (Sayyah et al 2009). Individuals treated with the borage extract reported reductions in symptoms of both OCD and generalized anxiety that were significantly greater than the placebo group. Some individuals treated with borage extract reported headaches.
It is important to note that some over-the-counter preparations of borage contain bioactive agents that are known to increase the risk of cancer (i.e. the pyrrolizidine alkaloids), hence caution should be exercised when selecting a brand that is both reputable and safe.
Milk thistle
Milk thistle (Silybum marianum) is widely used in traditional Persian medicine for treating gastrointestinal ailments and cancer. In a small eight-week double-blind pilot study, 35 adults with OCD were randomized to receive 600mg of a standardized preparation of milk thistle extract or fluoxetine (Prozac) 30mg (Sayyah et al 2010). At the study's end, no significant differences in OCD symptom severity were found between the two groups. Similar side effects reported in both groups included nausea, sexual dysfunction, and insomnia.
Finding safe reliable natural product supplements
As natural product supplements are not regulated in the U.S. and many other countries, finding affordable quality products that are safe for human consumption, contain the desirable active ingredients in appropriate strengths, and have good bioavailability poses complex challenges. Efforts are currently ongoing to address issues of natural supplement quality and safety, including by a non-governmental organization called the US Pharmacopeial Convention and other organizations.
Bottom line
It is estimated that approximately one-third of individuals diagnosed with OCD do not respond to conventional drug treatments resulting in a significant reduction in quality of life. In the context of limitations of available conventional treatments, there is emerging evidence that select natural products may help reduce symptoms of OCD, however, most findings are limited by the small number of studies and small study sizes.
Some findings suggest the amino acid NAC may be an effective adjunctive treatment of OCD, however, only a few studies small have been done and findings are largely inconsistent. Findings of two small studies suggest that some individuals with OCD improve in response to large doses of the amino acid glycine, however, poor side-effect tolerance has resulted in a loss of interest in investigating this substance as a potential treatment of OCD. Findings of a single small study suggest that the glycine derivative sarcosine may significantly reduce the severity of OCD symptoms. A few small studies on myo-inositol do not support its use as a treatment of OCD. Finally, preliminary findings suggest that the aqueous extract of borage may be an effective stand-alone treatment of OCD.
In sum, the evidence supporting the use of the natural products reviewed in this post as treatments of OCD should be viewed as preliminary. Large well-designed placebo-controlled studies are needed to elucidate the potential clinical benefits of natural products for OCD (and related disorders such as trichotillomania and compulsive nail-biting) and to determine appropriate, safe dosing strategies when a particular natural product is used alone or as adjunctive to conventional drug therapy.
