To save content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about saving content to .
To save content items to your Kindle, first ensure no-reply@cambridge.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Bipolar depression remains difficult to treat, and people often experience ongoing residual symptoms, decreased functioning and impaired quality of life. Adjunctive therapies targeting novel pathways can provide wider treatment options and improve clinical outcomes. Garcinia mangostana Linn. (mangosteen) pericarp has serotonogenic, antioxidant anti-inflammatory and neurogenic properties of relevance to the mechanisms of bipolar depression.
Aims
The current 28-week randomised, multisite, double-blind, placebo-controlled trial investigated mangosteen pericarp extract as an adjunct to treatment-as-usual for treatment of bipolar depression.
Method
This trial was prospectively registered on the Australia New Zealand Clinical Trials Registry (no. ACTRN12616000028404). Participants aged 18 years and older with a diagnosis of bipolar I or II and with at least moderate depressive symptoms were eligible for the study. A total of 1016 participants were initially approached or volunteered for the study, of whom 712 did not progress to screening, with an additional 152 screened out. Seventy participants were randomly allocated to mangosteen and 82 to a placebo control. Fifty participants in the mangosteen and 64 participants in the placebo condition completed the treatment period and were analysed.
Results
Results indicated limited support for the primary hypothesis of superior depression symptom reduction following 24 weeks of treatment. Although overall changes in depressive symptoms did not substantially differ between conditions over the course of the trial, we observed significantly greater improvements for the mangosteen condition at 24 weeks, compared with baseline, for mood symptoms, clinical impressions of bipolar severity and social functioning compared with controls. These differences were attenuated at week 28 post-discontinuation assessment.
Conclusions
Adjunctive mangosteen pericarp treatment appeared to have limited efficacy in mood and functional symptoms associated with bipolar disorder, but not with manic symptoms or quality of life, suggesting a novel therapeutic approach that should be verified by replication.
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.
Aims
This study aims to explore the relationship between OCD severity, nutrient intake and dietary quality.
Method
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.
Results
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.
Conclusions
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.
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.
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.
Methods
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.
Results
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.
Conclusion
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.
Methods
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.
Results
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.
Conclusions
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.
Methods
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.
Results
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.
Conclusions
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.
Methods
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.
Results
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.
Conclusion
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.
Methods:
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.
Results:
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.
Conclusions:
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).