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This study aimed to explore effects of adjunctive minocycline treatment on inflammatory and neurogenesis markers in major depressive disorder (MDD). Serum samples were collected from a randomised, placebo-controlled 12-week clinical trial of minocycline (200 mg/day, added to treatment as usual) for adults (n = 71) experiencing MDD to determine changes in interleukin-6 (IL-6), lipopolysaccharide binding protein (LBP) and brain derived neurotrophic factor (BDNF). General Estimate Equation modelling explored moderation effects of baseline markers and exploratory analyses investigated associations between markers and clinical outcomes. There was no difference between adjunctive minocycline or placebo groups at baseline or week 12 in the levels of IL-6 (week 12; placebo 2.06 ± 1.35 pg/ml; minocycline 1.77 ± 0.79 pg/ml; p = 0.317), LBP (week 12; placebo 3.74 ± 0.95 µg/ml; minocycline 3.93 ± 1.33 µg/ml; p = 0.525) or BDNF (week 12; placebo 24.28 ± 6.69 ng/ml; minocycline 26.56 ± 5.45 ng/ml; p = 0.161). Higher IL-6 levels at baseline were a predictor of greater clinical improvement. Exploratory analyses suggested that the change in IL-6 levels were significantly associated with anxiety symptoms (HAMA; p = 0.021) and quality of life (Q-LES-Q-SF; p = 0.023) scale scores. No other clinical outcomes were shown to have this mediation effect, nor did the other markers (LBP or BDNF) moderate clinical outcomes. There were no overall changes in IL-6, LBP or BDNF following adjunctive minocycline treatment. Exploratory analyses suggest a potential role of IL-6 on mediating anxiety symptoms with MDD. Future trials may consider enrichment of recruitment by identifying several markers or a panel of factors to better represent an inflammatory phenotype in MDD with larger sample size.
Many mental disorders, including depression, bipolar disorder and schizophrenia, are associated with poor dietary quality and nutrient intake. There is, however, a deficit of research looking at the relationship between obsessive–compulsive disorder (OCD) severity, nutrient intake and dietary quality.
This study aims to explore the relationship between OCD severity, nutrient intake and dietary quality.
A post hoc regression analysis was conducted with data combined from two separate clinical trials that included 85 adults with diagnosed OCD, using the Structured Clinical Interview for DSM-5. Nutrient intakes were calculated from the Dietary Questionnaire for Epidemiological Studies version 3.2, and dietary quality was scored with the Healthy Eating Index for Australian Adults – 2013.
Nutrient intake in the sample largely aligned with Australian dietary guidelines. Linear regression models adjusted for gender, age and total energy intake showed no significant associations between OCD severity, nutrient intake and dietary quality (all P > 0.05). However, OCD severity was inversely associated with caffeine (β = −15.50, 95% CI −28.88 to −2.11, P = 0.024) and magnesium (β = −6.63, 95% CI −12.72 to −0.53, P = 0.034) intake after adjusting for OCD treatment resistance.
This study showed OCD severity had little effect on nutrient intake and dietary quality. Dietary quality scores were higher than prior studies with healthy samples, but limitations must be noted regarding comparability. Future studies employing larger sample sizes, control groups and more accurate dietary intake measures will further elucidate the relationship between nutrient intake and dietary quality in patients with OCD.
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.
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.
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.
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.
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.
Bipolar disorder (BD) is a severe psychiatric disorder associated with a high risk of suicide. This meta-analysis examined the prevalence of suicide attempts (SA) in patients with BD and its associated factors.
A systematic literature search was conducted in the PubMed, PsycINFO, EMBASE and Web of Science databases from their inception to 11 June 2018. The prevalence of SA in BD was synthesised using the random-effects model.
The search identified 3451 articles of which 79 studies with 33 719 subjects met the study entry criteria. The lifetime prevalence of SA was 33.9% (95% CI 31.3–36.6%; I2 = 96.4%). Subgroup and meta-regression analyses revealed that the lifetime prevalence of SA was positively associated with female gender, BD-I, BD Not Otherwise Specified and rapid cycling BD subtypes, income level and geographic region.
This meta-analysis confirmed that SA is common in BD and identified a number of factors related to SA. Further efforts are necessary to facilitate the identification and prevention of SA in BD. Long-term use of mood stabilisers coupled with psycho-social interventions should be available to BD patients to reduce the risk of suicidal behaviour.
Suicide attempt is an important indicator of suicide and potential future mortality. However, the prevalence of suicide attempts has been inconsistent across studies. This meta-analysis aimed to examine the prevalence of suicide attempts in individuals with schizophrenia and associated correlates.
Relevant publications in Embase, PsycINFO, PubMed, Web of science and Cochrane were systematically searched. Data on the prevalence of suicide attempts in individuals with schizophrenia were pooled using a random-effects model.
Thirty-five studies with 16 747 individuals with schizophrenia were included. The pooled lifetime prevalence of suicide attempts was 26.8% (95% CI 22.1–31.9%; I2 = 97.0%), while the 1-year prevalence, 1-month prevalence and the prevalence of suicide attempts from illness onset were 3.0% (95% CI 2.3–3.7%; I2 = 95.6%), 2.7% (95% CI 2.1–3.4%; I2 = 78.5%) and 45.9% (95% CI 42.1–49.9%; I2 = 0), respectively. Earlier age of onset (Q = 4.38, p = 0.04), high-income countries (Q = 53.29, p < 0.001), North America and Europe and Central Asia (Q = 32.83, p < 0.001) were significantly associated with a higher prevalence of suicide attempts.
Suicide attempts are common in individuals with schizophrenia, especially those with an early age of onset and living in high-income countries and regions. Regular screening and effective preventive measures should be implemented as part of the clinical care.
Clozapine treatment increases the risk of agranulocytosis, but findings on the epidemiology of agranulocytosis have been inconsistent. This meta-analysis examined the prevalence of agranulocytosis and related death in clozapine-treated patients.
A literature search in the international (PubMed, PsycINFO, and EMBASE) and Chinese (WanFang, Chinese National Knowledge Infrastructure, and Sinomed) databases was conducted. Prevalence estimates of agranulocytosis and related death in clozapine-treated patients were synthesized with the Comprehensive Meta-Analysis program using the random-effects model.
Thirty-six studies with 260 948 clozapine-treated patients published between 1984 and 2018 were included in the meta-analysis. The overall prevalence of agranulocytosis and death caused by agranulocytosis were 0.4% (95% CI 0.3–0.6%) and 0.05% (95% CI 0.03–0.09%), respectively. The prevalence of agranulocytosis was moderated by sample size, study quality, year of publication, and that of data collection.
The prevalence of clozapine-associated agranulocytosis is low. Agranulocytosis-related death appears rare.
Suicide attempt (SA), which is one of the strongest predictors of completed suicide, is common in major depressive disorder (MDD) but its prevalence across epidemiological studies has been mixed. The aim of this comprehensive meta-analysis was to examine the pooled prevalence of SA in individuals with MDD.
A systematic literature search was conducted in PubMed, Embase, PsycINFO, Web of Science and Cochrane Library from their commencement date until 27 December 2017. Original studies containing data on prevalence of SA in individuals with MDD were analyzed.
In all, 65 studies with a total of 27 340 individuals with MDD were included. Using the random effects model, the pooled lifetime prevalence of SA was 31% [95% confidence interval (CI) 27–34%], 1-year prevalence was 8% (95% CI 3–14%) and 1-month prevalence was 24% (95% CI 15–34%). Subgroup analyses revealed that the lifetime prevalence of SA was significantly associated with the patient setting, study region and income level, while the 1-month prevalence of SA was associated with only the patient setting.
This meta-analysis confirmed that SA was common in individuals with MDD across the world. Careful screening and appropriate interventions should be implemented for SA in the MDD population.
The APEC Mental Health Roadmap has a vision to strengthen mental health and reduce the economic impact of mental illness in the Asia Pacific. To facilitate its implementation, the APEC Digital Hub will heighten exchange and dissemination of best practices in Asia Pacific mental health partnerships, and increase multi-sectoral recognition to invest in mental health to support economic growth.
This brief report examines the extent to which community-based treatment and integration support are provided for people living with mental illness across 15 selected Asia-Pacific economies. Some of the key findings are discussed in light of the diversity of economies and cultural contexts.
Little is known about the combined use of benzodiazepines and antidepressants in older psychiatric patients. This study examined the prescription pattern of concurrent benzodiazepines in older adults treated with antidepressants in Asia, and explored its demographic and clinical correlates.
The data of 955 older adults with any type of psychiatric disorders were extracted from the database of the Research on Asian Psychotropic Prescription Patterns for Antidepressants (REAP-AD) project. Demographic and clinical characteristics were recorded using a standardized protocol and data collection procedure. Both univariate and multiple logistic regression analyses were performed.
The proportion of benzodiazepine and antidepressant combination in this cohort was 44.3%. Multiple logistic regression analysis revealed that higher doses of antidepressants, younger age (<65 years), inpatients, public hospital, major comorbid medical conditions, antidepressant types, and country/territory were significantly associated with more frequent co-prescription of benzodiazepines and antidepressants.
Nearly, half of the older adults treated with antidepressants in Asia are prescribed concurrent benzodiazepines. Given the potentially adverse effects of benzodiazepines, the rationale of benzodiazepines and antidepressants co-prescription needs to be revisited.
No one reacts or responds to a drug in exactly the same way, just as no two persons are exactly alike. Individual and ethnic differences in drug response have been consistently found in clinical practice. This book covers all the important factors that explain how and why drug treatments used in psychiatry affect individuals and ethnic groups differently. It will increase understanding of how biological differences interact with social, cultural and environmental factors to bring about overall effects of medications, particularly in individuals from various ethnicities. This book uniquely brings these varied aspects together to consider a holistic approach to drug therapy across diverse biological make-up and cultures. This information has direct practical use in the clinical setting.
Inter-individual and inter-ethnic differences in drug response have been regularly found in clinical practice. This is not surprising given the remarkable diversity in genetic polymorphisms, environmental factors, cultural contexts, and treatment settings. Although some of the key research reports and pertinent data have been summarized in previous chapters, systematically conducted studies in this field remain scarce, sporadic, and lacking in consistency (Lin et al., 1999). Ethnic and sociocultural variables are rarely analyzed or controlled in published studies on drug effects. Such paucity of cross-ethnic data exists even though there is widespread use of psychotropics to treat people with mental disorders globally. There are compelling reasons why research in this area is very much needed to understand cross-cultural differences in psychopharmacology better. There is significant demographic shift with increasing multicultural populations in both Western and non-Western societies. As a consequence, there has been a significant growth of cultural psychiatry internationally. For instance, Asians represent more than half of the global population, and all the major psychotropics are widely prescribed in Asia. With increasing pressure on the health dollar, there is a need to improve the cost-effectiveness of pharmacotherapeutic agents by reducing the morbidity and mortality of medication side effects occurring in drug-sensitive individuals and populations (e.g., in many parts of Asia). Given that factors involved in determining inter-ethnic differences in drug response are often similar to those responsible for inter-individual variations, advances in cross-ethnic psychopharmacology can contribute to greater understanding of individual differences as well (Lin et al., 1993).
Chee H. Ng, Department of Psychiatry, The University of Melbourne, St Vincent Hospital & The Melbourne Clinic, Victoria, Australia,
Steven Klimidis, Centre for International Mental Health, School of Population Health, The University of Melbourne, Victoria, Australia
The prescription and use of medications fundamentally involves a social transaction that carries both symbolic and social meanings based on the interactions between the patient, doctor, and their social environment (Moerman, 1979). Consequently medication uptake and use is considerably influenced by sociocultural factors, ultimately influencing therapeutic benefit, as first surmised by Murphy (1969). Cross-cultural and cross-ethnic differences in drug response are considerable, and beyond explanations based simply on the biological effects of the medication. Sociocultural factors include beliefs and expectations concerning the illness, the treatment and its mechanisms of action, compliance behavior, the role of the social network in using medicines, propensity to placebo effects, and use of alternative or concurrent herbal and other strategies from traditional medicines. The patient's willingness to accept medication is related to cross-cultural variability in drug tolerance and metabolism, as well as past experiences and current beliefs and perceptions held about psychiatric drugs.
Sociocultural, illness, and biological factors affect individual attitudes towards psychotropic medications. Health beliefs or explanatory models, particularly causal attributions regarding the illness and the treatment options afforded within such models, exert a profound influence on patients' attitudes and behavior regarding medications (Smith, Lin & Mendoza, 1993). Such effects can be subtle and can occur during the course of treatment even if there has been initial successful negotiation about the nature of the illness and treatment.