N-acetyl cysteine (NAC) augmentation in the treatment of obsessive-compulsive disorder: A phase III, 20-week, double-blind, randomized, placebo-controlled trial.

OBJECTIVE: Preliminary evidence has suggested that adjunctive N-acetylcysteine (NAC), an antioxidant precursor to glutathione, may reduce symptoms of obsessive-compulsive disorder (OCD). We conducted a 20-week, multi-site, randomized controlled trial to investigate the safety and efficacy of the adjunctive use of NAC in OCD. METHODS: The study was a phase III, 20-week, double-blind, randomized controlled trial across multiple sites in Australia investigating 2 g to 4 g per day of NAC (titrated according to response) in 98 participants with DSM-5 diagnosed OCD. Data were analysed using linear mixed effects models for the 89 participants who attended at least one follow-up visit. RESULTS: A modified intention-to-treat analysis of the primary outcome found no evidence that NAC reduced symptoms of OCD measured on the Yale-Brown Obsessive-Compulsive Scale, relative to placebo (mean difference at week 20 = 0.53, 95% compatibility interval = -2.18, 3.23; p = 0.70; favouring placebo). There was also no evidence that NAC, compared to placebo, improved outcomes on the secondary measures including anxiety, depression, quality of life, functioning, or clinician/participant impression. NAC was well-tolerated with only mild gastrointestinal adverse events associated with the treatment. CONCLUSION: We found no evidence supporting the efficacy of the adjunctive use of NAC in OCD.

The impact of COVID-19 on benzodiazepine usage in psychiatric inpatient units.

OBJECTIVE: This study aims to investigate whether COVID-19 has led to increased usage of benzodiazepines in acute psychiatric settings. METHOD: We evaluated the rates of benzodiazepine usage in two acute psychiatric inpatient units over a period of two years, 2019 and 2020 (the year of the pandemic). Rates of oral atorvastatin usage over the same period were used as a comparator. RESULTS: We saw a significant increase in the usage of benzodiazepines in the period between April and December 2020 compared to the same period in 2019 despite a decline in the total number of admissions in 2020. Usage peaked further at the time of eased pandemic restrictions which coincided with higher rates of emergency department mental health (MH) presentations and acute MH hospital admissions. We also noticed higher rates of substance use disorder recorded on admission. Hospital leave restrictions due to COVID-19 also led to further restrictions on smoking. CONCLUSION: Benzodiazepine usage increased in the context of the COVID-19 pandemic. The study encourages more research to better understand the impact of the pandemic on acute psychiatric settings.

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

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.

Polypharmacy as maintenance treatment in bipolar illness: A systematic review.

OBJECTIVES: Polypharmacy is common in maintenance treatment of bipolar illness, but proof of greater efficacy compared to monotherapy is assumed rather than well known. We systematically reviewed the evidence from the literature to provide recommendations for clinical management and future research. METHOD: A systematic review was conducted on the use of polypharmacy in bipolar prophylaxis. Relevant papers published in English through 31 December 2019 were identified searching the electronic databases MEDLINE, Embase, PsycINFO, and the Cochrane Library. RESULTS: Twelve studies matched inclusion criteria, including 10 randomized controlled trials (RCTs). The best drug combination in prevention is represented by lithium + valproic acid which showed a significant effect on time to mood relapses (HR = 0.57) compared to valproic acid monotherapy, especially for manic episodes (HR = 0.51). The effect was significant in terms of time to new drug treatment (HR = 0.51) and time to hospitalization (HR = 0.57). A significant reduction in the frequency of mood relapses was also reported for lithium + valproic acid vs. lithium monotherapy (RR=0.12); however, the trial had a small sample size. Lamotrigine + valproic acid reported significant efficacy in prevention of depressive episodes compared to lamotrigine alone. CONCLUSIONS: The literature to support a generally greater efficacy with polypharmacy in bipolar illness is scant and heterogeneous. Within that limited evidence base, the best drug combination in bipolar prevention is represented by lithium + valproic acid for manic, but not depressive episodes. Clinical practice should focus more on adequate monotherapy before considering polypharmacy.

Screening for depression in primary care with Patient Health Questionnaire-9 (PHQ-9): A systematic review.

BACKGROUND: Depression is a leading cause of disability. International guidelines recommend screening for depression and the Patient Health Questionnaire 9 (PHQ-9) has been identified as the most reliable screening tool. We reviewed the evidence for using it within the primary care setting. METHODS: We retrieved studies from MEDLINE, Embase, PsycINFO, CINAHL and the Cochrane Library that carried out primary care-based depression screening using PHQ-9 in populations older than 12, from 1995 to 2018. RESULTS: Forty-two studies were included in the systematic review. Most of the studies were cross-sectional (N=40, 95%), conducted in high-income countries (N=27, 71%) and recruited adult populations (N=38, 90%). The accuracy of the PHQ-9 was evaluated in 31 (74%) studies with a two-stage screening system, with structured interview most often carried out by primary care and mental health professionals. Most of the studies employed a cut-off score of 10 (N=24, 57%, total range 5 - 15). The overall sensitivity of PHQ-9 ranged from 0.37 to 0.98, specificity from 0.42 to 0.99, positive predictive value from 0.09 to 0.92, and negative predictive value from 0.8 to 1. LIMITATIONS: Lack of longitudinal studies, small sample size, and the heterogeneity of primary-care settings limited the generalizability of our results. CONCLUSIONS: PHQ-9 has been widely validated and is recommended in a two-stage screening process. Longitudinal studies are necessary to provide evidence of long-term screening effectiveness.

Treatments used for obsessive-compulsive disorder-An international perspective.

OBJECTIVE: The objective of this study was to characterise international trends in the use of psychotropic medication, psychological therapies, and novel therapies used to treat obsessive-compulsive disorder (OCD). METHODS: Researchers in the field of OCD were invited to contribute summary statistics on the characteristics of their samples. Consistency of summary statistics across countries was evaluated. RESULTS: The study surveyed 19 expert centres from 15 countries (Argentina, Australia, Brazil, China, Germany, Greece, India, Italy, Japan, Mexico, Portugal, South Africa, Spain, the United Kingdom, and the United States) providing a total sample of 7,340 participants. Fluoxetine (n = 972; 13.2%) and fluvoxamine (n = 913; 12.4%) were the most commonly used selective serotonin reuptake inhibitor medications. Risperidone (n = 428; 7.3%) and aripiprazole (n = 415; 7.1%) were the most commonly used antipsychotic agents. Neurostimulation techniques such as transcranial magnetic stimulation, deep brain stimulation, gamma knife surgery, and psychosurgery were used in less than 1% of the sample. There was significant variation in the use and accessibility of exposure and response prevention for OCD. CONCLUSIONS: The variation between countries in treatments used for OCD needs further evaluation. Exposure and response prevention is not used as frequently as guidelines suggest and appears difficult to access in most countries. Updated treatment guidelines are recommended.

Multiple cerebral infarcts following septic shock.

A 60-year-old female in septic shock developed neurological signs and symptoms. She had left-sided hemiparesis, left homonymous hemianopia, bimanual coordination disorder, a language dysfunction of anomic aphasic type and a non-aphasic right hemispheric communication disorder. Computer tomography demonstrated bilateral anterior and posterior watershed as well as territorial infarctions. Risk factors included chronic airways limitation, cardiac failure and heavy smoking. Carotid duplex studies were normal. The mechanisms can be explained by flow changes and thrombus formation.