Review article
Nutraceuticals in the treatment of Obsessive Compulsive Disorder (OCD): A review of mechanistic and clinical evidence

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Abstract

Obsessive–Compulsive Disorder (OCD) is a debilitating mental illness which has a significant impact on quality of life. First-line SSRI treatments for OCD typically are of limited benefit to only 40–60% of patients, and are associated with a range of adverse side effects. Current preclinical research investigating nutraceuticals (natural products) for OCD, reveals encouraging novel activity in modulating key pathways suggested to be involved in the pathogenesis of OCD (glutamatergic and serotonergic pathway dysregulation). Emerging clinical evidence also appears to tentatively support certain nutrients and plant-based interventions with known active constituents which modulate these pathways: N-acetlycysteine, myo-inositol, glycine, and milk thistle (Silybum marianum). The serotonin precursor tryptophan is unlikely to be of use in treating OCD while 5-HTP may possibly be a more effective precursor strategy. However, there is currently no clinical evidence to test the efficacy of either of these substances. Currently the balance of clinical evidence does not support the use of St. John's wort (Hypericum perforatum) in OCD. While clinical research in this area is in its infancy, further research into nutraceuticals is warranted in light of the promising preclinical data regarding their mechanisms of action and their favourable side effect profiles in comparison to current SSRI treatments. It is recommended that future clinical trials of nutraceutical treatments for OCD utilize randomized placebo-controlled study designs and considerably larger sample sizes in order to properly test for efficacy.

Research highlights

► Glutamatergic and Serotonergic mechanisms of action of nutraceutical substances with the potential to treat OCD are reviewed. ► Clinical evidence from preliminary human trials using nutraceuticals for OCD are also reviewed, together with side effect profiles. ► N-acetylcysteine and glycine are found to be substances with a glutamatergic mechanism of action which are worthy of further clinical investigation in OCD treatment. ► Myo-Inositol may also potentially have efficacy as a monotherapy for OCD due to serotonergic modulation, although larger-sized clinical trials are required.

Introduction

Obsessive Compulsive Disorder (OCD) is a debilitating illness that if left untreated often follows a chronic course. The World Health Organization (WHO) has identified OCD as one of the top 10 disabling illnesses by lost income and decreased quality of life (Bobes et al., 2001). Obsessions are recurrent and persistent thoughts, impulses, or images that are experienced as intrusive and inappropriate and that cause marked anxiety or distress, while compulsions are repetitive behaviors (e.g., hand washing, ordering, checking) or mental acts (e.g., praying, counting, repeating words silently) that the person feels driven to perform in response to an obsession, or according to rules that must be applied rigidly (American Psychiatric Association, 2000).

The prevalence of OCD in the USA has been estimated to be 2.3% for lifetime prevalence and 1.2% for 12-month prevalence according to DSM-IV criteria (Ruscio et al., 2010). A similar 12-month prevalence rate has been noted in Australia, with OCD prevalence estimated to be 1.9% (CI 1.5–2.3) according to ICD-10 criteria (Slade et al., 2009). A high degree of comorbidity of OCD with other psychiatric disorders (affective, anxiety, substance use or personality disorders) has also been reported in Australia (79%) (Crino et al., 2005). The burden of disease associated with OCD is high, with financial costs associated with health care in the USA estimated to be around $10.6 billion per annum (Eaton et al., 2008).

Section snippets

The neurobiology of OCD

Neuroimaging and neuropsychological studies suggest that the etiology of OCD may be related to abnormalities in orbito-striatal circuitry (Menzies et al., 2008). In particular, the finding of increased radiotracer uptake in the head of the caudate nucleus suggests increased activity in this area for OCD patients in comparison to controls (Whiteside et al., 2004). In relating these brain abnormalities to OCD symptomology, Saxena et al., 2001, Saxena et al., 1998 propose that an imbalance in

Current pharmacotherapy for OCD

The current first line treatments for OCD are behavioural therapy using Exposure and Response Prevention (ERP) and/or pharmacotherapy with the tricyclic antidepressant clomipramine, Selective Serotonin Re-uptake Inhibitors (SSRIs) such as fluvoxamine, fluoxetine, sertraline, paroxetine, citalopram and escitalopram, or dual reuptake inhibitors such as venlafaxine or duloxetine (Dell'Osso et al., 2006, Denys et al., 2007, Fineberg and Gale, 2005, Jenike, 2004). It has been estimated that only

Nutraceuticals in the treatment of OCD

In consideration of the shortfalls of traditional antidepressant treatments for OCD and the adverse side-effects associated with their use, it is critically important that new treatment options be identified that may be efficacious in ameliorating OCD symptoms. In this capacity, nutraceuticals (natural products) have received comparatively little research focus when compared to pharmaceutical substances. A nutraceutical may be defined as any substance which is considered a food, a part of a

Discussion

In light of the continuing challenges concerning the use of pharmacotherapies such as clomipramine, the SSRIs and SNRIs for the treatment of OCD, it is timely to consider the use of alternative nutraceutical and plant-based treatments used either as monotherapy or in augmentation strategies. The recent research focus on glutamatergic treatments for OCD is a treatment avenue which holds potential. N-acetylcysteine (NAC), through its effects on cystine-glutamate exchange and antioxidant pathways,

Acknowledgements

Dr. Jerome Sarris is funded by an Australian National Health & Medical Research Council fellowship (NHMRC funding ID 628875), in a strategic partnership with The University of Melbourne and the Brain Sciences Institute at Swinburne University of Technology.

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