Feasibility, acceptability and practicality of transcranial stimulation in obsessive compulsive symptoms (FEATSOCS): A randomised controlled crossover trial.

BACKGROUND: Transcranial direct current stimulation (tDCS) is a non-invasive form of neurostimulation with potential for development as a self-administered intervention. It has shown promise as a safe and effective treatment for obsessive compulsive disorder (OCD) in a small number of studies. The two most favourable stimulation targets appear to be the left orbitofrontal cortex (L-OFC) and the supplementary motor area (SMA). We report the first study to test these targets head-to-head within a randomised sham-controlled trial. Our aim was to inform the design of future clinical research studies, by focussing on the acceptability and safety of the intervention, feasibility of recruitment, adherence to and tolerability of tDCS, and the size of any treatment-effect. METHODS: FEATSOCS was a randomised, double-blind, sham-controlled, cross-over, multicentre study. Twenty adults with DSM-5-defined OCD were randomised to treatment, comprising three courses of clinic-based tDCS (SMA, L-OFC, Sham), randomly allocated and delivered in counterbalanced order. Each course comprised four 20-min 2 mA stimulations, delivered over two consecutive days, separated by a 'washout' period of at least four weeks. Assessments were carried out by raters who were blind to stimulation-type. Clinical outcomes were assessed before, during, and up to four weeks after stimulation. Patient representatives with lived experience of OCD were actively involved at all stages. RESULTS: Clinicians showed willingness to recruit participants and recruitment to target was achieved. Adherence to treatment and study interventions was generally good, with only two dropouts. There were no serious adverse events, and adverse effects which did occur were transient and mostly mild in intensity. Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) scores were numerically improved from baseline to 24 h after the final stimulation across all intervention groups but tended to worsen thereafter. The greatest effect size was seen in the L-OFC arm, (Cohen's d = -0.5 [95% CI -1.2 to 0.2] versus Sham), suggesting this stimulation site should be pursued in further studies. Additional significant sham referenced improvements in secondary outcomes occurred in the L-OFC arm, and to a lesser extent with SMA stimulation. CONCLUSIONS: tDCS was acceptable, practicable to apply, well-tolerated and appears a promising potential treatment for OCD. The L-OFC represents the most promising target based on clinical changes, though the effects on OCD symptoms were not statistically significant compared to sham. SMA stimulation showed lesser signs of promise. Further investigation of tDCS in OCD is warranted, to determine the optimal stimulation protocol (current, frequency, duration), longer-term effectiveness and brain-based mechanisms of effect. If efficacy is substantiated, consideration of home-based approaches represents a rational next step. TRIAL REGISTRATION: ISRCTN17937049. https://doi.org/10.1186/ISRCTN17937049.

Investigating Transcranial Direct Current Stimulation (TDCS) in obsessive compulsive disorder (OCD): a double-blind, sham-controlled, cross-over randomised trial

Aims Obsessive Compulsive Disorder is a disabling and difficult-to-treat condition, new treatment options are needed to improve health outcomes. Transcranial Direct Current Stimulation, a non-invasive form of neurostimulation, has shown positive results in a small number of studies as a safe and potentially efficacious treatment for OCD. There nevertheless remains uncertainty about the optimal stimulation protocol, magnitude and duration of effect, acceptability, tolerability and practicality of applying tDCS clinical settings. As existing data are inadequate to support a full-scale trial, we will deliver a feasibility study to address key research questions and knowledge gaps to enable the design and the development of the most efficient, cost effective, definitive trial. Method We designed Feasibility And Acceptability Of Transcranial Stimulation In Obsessive Compulsive Symptoms (FEATSOCS), a double-blind, sham-controlled, cross-over randomised multicentre study in 25 adults with OCD. We will stimulate the two most promising cortical sites, the orbitofrontal cortex (OFC) and the supplementary motor area (SMA). Each participant will receive three courses of tDCS (SMA, OFC and sham), randomly allocated, given in counterbalanced order. Each course comprises four 20 minutes-stimulations, delivered over two consecutive days, separated by at least four weeks’ washout period. Blinded raters will regularly assess clinical outcomes before, during and up to four weeks after stimulation using validated scales. We will include relevant neurocognitive tasks, testing cognitive flexibility, motor disinhibition, cooperation and habit learning. Result FEATSOCS trial is currently underway and recruiting. Owing to the impact of COVID-19, a recruitment extension has been granted. At the study end, we will analyse the feasibility outcomes, magnitude of the effect of the interventions on OCD symptoms alongside the standard deviation of the outcome measure to estimate effect size, and determine the optimal stimulation target. We will also measure the duration of the effect of stimulation, to provide information on spacing treatments efficiently. We will evaluate the usefulness and limitations of specific neurocognitive tests to determine a definitive test battery. Qualitative data will be collected from participants to better understand their experience of taking part in a tDCS intervention, the impact on their overall quality of life and their views on the potential of tDCS as home based-intervention. Conclusion Further evidence is needed to establish whether tDCS could join the treatment armamentarium of OCD. The clinical outcomes in FEATSOCS will enable to further refine the methodology to ensure optimal efficiency in terms of both delivering and assessing the tDCS in OCD in a full scale trial. The funder for this study is the National Institute for Health Research Programme, Research for Patient Benefit (RfPB) [Ref. no PB-PG-1216-20005]. Extra funding to allow study extension was provided by Orchard OCD. This study has received full ethics committee approval and protocol amendments approval form the Cambridge and Hertfordshire NHS Research Ethics Committee, IRAS Project ID 254507, REC ref: 19/EE/0046.

Current and Future Potential Impact of COVID-19 on Kratom (Mitragyna speciosa Korth.) Supply and Use.

Kratom (Mitragyna speciosa Korth., Rubiaceae) is native to and has traditional use in Southeast Asia. The number of kratom users outside of Southeast Asia has increased significantly in recent decades with use spreading to the Unites States (US) and Europe. Because of its reputed opioid-like psychoactive effects at higher doses, kratom has been regulated in several countries and is subject to an import ban by the US Food and Drug Administration. Nonetheless, in the US it is estimated that 10-15 million people consume kratom primarily for the self-treatment of pain, psychiatric disorders, to mitigate withdrawal from or dependence on opioids, and to self-treat opioid use disorder or other substance use disorders (SUDs). Due to the global COVID-19 pandemic, a shortage in the supply of kratom products may place unexpected burdens on kratom users, potentially influencing some who use kratom for SUD self-treatment to regress to harmful drug use, hence increasing the likelihood of adverse outcomes, including overdose. Inadequate treatment, treatment barriers, and increases in the sales of adulterated kratom products on the internet or in convenience stores could exacerbate circumstances further. Although there are currently no verified indications of kratom scarcity, researchers and clinicians should be aware of and remain vigilant to this unanticipated possibility.