Treatment of refractory obsessive–compulsive disorder with nutraceuticals (TRON): a 20-week, open label pilot study

Abstract

Background Obsessive–compulsive disorder (OCD) is often challenging to treat and resistant to psychological interventions and prescribed medications. The adjunctive use of nutraceuticals with potential neuromodulatory effects on underpinning pathways such as the glutamatergic and serotonergic systems is one novel approach. Objective To assess the effectiveness and safety of a purpose-formulated combination of nutraceuticals in treating OCD: N-acetyl cysteine, L-theanine, zinc, magnesium, pyridoxal-5′ phosphate, and selenium. Methods A 20-week open label proof-of-concept study was undertaken involving 28 participants with treatment-resistant DSM-5-diagnosed OCD, during 2017 to 2020. The primary outcome measure was the Yale-Brown Obsessive–Compulsive Scale (YBOCS), administered every 4 weeks. Results An intention-to-treat analysis revealed an estimated mean reduction across time (baseline to week-20) on the YBOCS total score of −7.13 (95% confidence interval = −9.24, −5.01), with a mean reduction of −1.21 points per post-baseline visit (P ≤ .001). At 20-weeks, 23% of the participants were considered “responders” (YBOCS ≥35% reduction and “very much” or “much improved” on the Clinical Global Impression-Improvement scale). Statistically significant improvements were also revealed on all secondary outcomes (eg, mood, anxiety, and quality of life). Notably, treatment response on OCD outcome scales (eg, YBOCS) was greatest in those with lower baseline symptom levels, while response was limited in those with relatively more severe OCD. Conclusions While this pilot study lacks placebo-control, the significant time effect in this treatment-resistant OCD population is encouraging and suggests potential utility especially for those with lower symptom levels. Our findings need to be confirmed or refuted via a follow-up placebo-controlled study.

Dietary quality and nutrient intake in adults with obsessive–compulsive disorder

“…48,49 Additionally, in our recently completed open-label Treatment of Refractory Obsessive-Compulsive Disorder with Nutraceuticals (TRON) trial, we found that treatment response to a nutraceutical combination was substantially higher in participants with high levels of caffeine intake relative to those with low caffeine intake in a treatment resistant OCD sample. 26 It has been hypothesised that caffeine's modulation of tryptophan, serotonin and noradrenaline production via adenosine A1 and A2 receptor antagonism is also implicated in the pathophysiology of OCD. 49 However, larger samples and longer-term follow-up trials are required to determine whether a dose-response relationship exists.…”

“…The second study (n = 28) was a 20-week, open-label pilot study that assessed the effectiveness and safety of a nutraceutical formulation for patients with treatment-resistant DSM-5-diagnosed OCD. 26 Participants were recruited at the same sites as the first study described above, between 2017 and 2020. Eligibility criteria included being aged 18-75 years, capacity as well as desire to consent to the study and follow its procedures, a primary DSM-5 diagnosis of moderate-to-extreme OCD (Y-BOCS ≥ 16), inadequate responses to at least three trials of serotonin reuptake inhibitors and at least one augmentation strategy as well as engagement in adequate OCD-specific cognitive-behavioural therapy.…”

“…time spent on obsessions) on a five-point Likert scale from 0 (none or minimal severity) to 4 (greatest severity). 28 The sum of these ten items allows an individual's OCD to be categorised as either subclinical (0-7), mild (8)(9)(10)(11)(12)(13)(14)(15), moderate (16)(17)(18)(19)(20)(21)(22)(23), severe (24)(25)(26)(27)(28)(29)(30)(31) or extreme (32)(33)(34)(35)(36)(37)(38)(39)(40). The Y-BOCS-SS demonstrates good psychometric properties and is considered to be the gold standard in assessing OCD symptom severity.…”

Use of Nutritional Supplements Based on L-Theanine and Vitamin B6 in Children with Tourette Syndrome, with Anxiety Disorders: A Pilot Study

“…Recently, a 20-week open label proof-of-concept study was undertaken involving 28 participants with pharmacologicalresistant OCD treated with a nutraceutical combination: N-acetyl cysteine, L-theanine, zinc, magnesium, pyridoxal-50 phosphate, and selenium. Statistically significant improvements were revealed on the YBOCS total score and secondary outcomes, suggesting the potential usefulness of this treatment option especially for patients with lower symptom levels [24].…”

“…Participants were randomly assigned into two groups using a simple randomization plan based on a random number list in a ratio of 1:1, the "N-group" (n = 17), which didn't receive the nutritional supplement for two months, and the "THE-group" (n = 17), which received the nutritional supplements L-Theanine (200 mg/day) and vitamin B6 (2.8 mg/day) for two months. Based on the previous clinical trials on neurodevelopmental disorders, dose selection for L-Theanine and vitamin B6 was considered safe and well tolerated to our patients [19,[21][22][23][24][25][26][27].…”