Adjunctive minocycline treatment for major depressive disorder: A proof of concept trial.

OBJECTIVE: Conventional antidepressant treatments result in symptom remission in 30% of those treated for major depressive disorder, raising the need for effective adjunctive therapies. Inflammation has an established role in the pathophysiology of major depressive disorder, and minocycline has been shown to modify the immune-inflammatory processes and also reduce oxidative stress and promote neuronal growth. This double-blind, randomised, placebo-controlled trial examined adjunctive minocycline (200 mg/day, in addition to treatment as usual) for major depressive disorder. This double-blind, randomised, placebo-controlled trial investigated 200 mg/day adjunctive minocycline (in addition to treatment as usual) for major depressive disorder. METHODS: A total of 71 adults with major depressive disorder ( Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition) were randomised to this 12-week trial. Outcome measures included the Montgomery-Asberg Depression Rating Scale (primary outcome), Clinical Global Impression-Improvement and Clinical Global Impression-Severity, Hamilton Anxiety Rating Scale, Quality of Life Enjoyment and Satisfaction Questionnaire, Social and Occupational Functioning Scale and the Range of Impaired Functioning Tool. The study was registered on the Australian and New Zealand Clinical Trials Register: www.anzctr.org.au , #ACTRN12612000283875. RESULTS: Based on mixed-methods repeated measures analysis of variance at week 12, there was no significant difference in Montgomery-Asberg Depression Rating Scale scores between groups. However, there were significant differences, favouring the minocycline group at week 12 for Clinical Global Impression-Improvement score - effect size (95% confidence interval) = -0.62 [-1.8, -0.3], p = 0.02; Quality of Life Enjoyment and Satisfaction Questionnaire score - effect size (confidence interval) = -0.12 [0.0, 0.2], p < 0.001; and Social and Occupational Functioning Scale and the Range of Impaired Functioning Tool score - 0.79 [-4.5, -1.4], p < 0.001. These effects remained at follow-up (week 16), and Patient Global Impression also became significant, effect size (confidence interval) = 0.57 [-1.7, -0.4], p = 0.017. CONCLUSION: While the primary outcome was not significant, the improvements in other comprehensive clinical measures suggest that minocycline may be a useful adjunct to improve global experience, functioning and quality of life in people with major depressive disorder. Further studies are warranted to confirm the potential of this accessible agent to optimise treatment outcomes.

Medication attitudes and beliefs in patients with psychotic and affective disorders on maintenance treatment.

RATIONALE: Patient attitudes and beliefs regarding the cost-benefits of medications may influence treatment adherence. However, beliefs and attitudes about psychotropic medications have not been well studied across different clinical populations. OBJECTIVE: This study sought to compare medication attitudes, beliefs, and clinical characteristics in patients with psychotic disorders versus those with affective disorders. METHOD: Clinician-rated and self-report measures were used to assess the drug attitudes, beliefs, and clinical features of outpatients with affective and psychotic disorders on stable medications. RESULTS: There were no significant differences in the overall medication attitudes and beliefs scores between the clinical groups. The affective group, however, were less likely to believe that medications would prevent hospitalisation (p < 0.05) and were less likely to use an aid as a reminder to take their medication (p < 0.05). Medication attitudes and beliefs were found to have significant correlation with reported side effects (p < 0.01) but not with educational level and duration or severity of illness. CONCLUSIONS: Patients with psychotic disorders did not show more negative attitudes or beliefs about medication than those with affective disorders. It would be clinically important that equal care is taken to assess perceived drug side effects, and attitudes and beliefs about medications across diagnostic groups.

'Omic' genetic technologies for herbal medicines in psychiatry.

The field of genetics, which includes the use of 'omic' technologies, is an evolving area of science that has emerging application in phytotherapy. Omic studies include pharmacogenomics, proteomics and metabolomics. Herbal medicines, as monotherapies, or complex formulations such as traditional Chinese herbal prescriptions, may benefit from omic studies, and this new field may be termed 'herbomics'. Applying herbomics in the field of psychiatry may provide answers about which herbal interventions may be effective for individuals, which genetic processes are triggered, and the subsequent neurochemical pathways of activity. The use of proteomic technology can explore the differing epigenetic effects on neurochemical gene expression between individual herbs, isolated constituents and complex formulae. The possibilities of side effects or insufficient response to the herb can also be assessed via pharmacogenomic analysis of polymorphisms of cytochrome P450 liver enzymes or P-glycoprotein. While another novel application of omic technology is for the validation of the concept of synergy in individual herbal extracts and prescriptive formulations. Chronic administration of psychotropic herbal medicines may discover important effects on chromatin remodelling via modification of histone and DNA methylation. This paper focuses on the emerging field of herbomics, and is to our knowledge the first publication to explore this in the area of psychiatry.

The national community mental health care project in Vietnam: a review for future guidance.

OBJECTIVES: The aim of this paper is to review the national community mental health care (CMHC) project in Vietnam and recommend improvements to the model based on findings reported at a national workshop of major service providers, and supplemented by information gathered from site visits and discussions with mental health leaders, professionals and stakeholders in the hospital and community mental health services. CONCLUSION: Since 2000, the CMHC project has been carried out in all 63 provinces with an overall national district coverage of around 64% and a total registry of 145 160 patients. It demonstrates a commitment by the government to integrate mental health into primary health care, in line with the World Health Organization recommendations, and set up a national community mental health network. Free treatment is provided for patients, mostly with schizophrenia (62.83%) and epilepsy (34.78%), at the local community level, and a national monitoring system is well established. However, the limitations include the lack of project funds, human resources and facilities, treatment scope, and linkages with families and community. A revised model of CMHC that builds on the strengths of existing services is proposed. While progress in community mental health care in Vietnam has been significant, many challenges facing the CMHC project need addressing.

Serotonin transporter polymorphisms and clinical response to sertraline across ethnicities.

The aim of this pilot study was to examine the relationship between clinical response, adverse effects, sertraline (SERT) plasma concentrations and the genetic polymorphism of the serotonin transporter gene-linked polymorphic region (5HTTLPR) in 2 ethnic patient groups. The study involved 45 patients in a clinical trial who received a fixed dose regimen of 50 mg SERT for one week, then a variable-dose regimen for a further 6 weeks for major depressive disorder. At weeks 1 and 6, the following assessments were completed: Hamilton Depression Rating Scale (HDRS), Clinical Global Impression (CGI), drug adverse reaction scale and measurement of plasma SERT levels. Genomic analysis for the long and short allele variants of the 5HTTLPR polymorphism was also carried out. Caucasian subjects had a higher rate of l/l genotype while Chinese subjects had higher frequencies of l/s and s/s genotypes. Comparison of the subjects with the 5HTTLPR s/s genotype and those with the l/l and l/s genotypes found no significant differences in the HDRS scores, CGI scores, response rates, adverse effects and SERT plasma concentrations at week 6.

Effects of persisting emotional impact from child abuse and norepinephrine transporter genetic variation on antidepressant efficacy in major depression: a pilot study.

OBJECTIVE: Previous studies suggest child abuse and serotonergic polymorphism influence depression susceptibility and antidepressant efficacy. Polymorphisms of the norepinephrine transporter (NET) may also be involved. Research in the area is possibly clouded by under reporting of abuse in researcher trials. METHODS: Adults (n=51) with major depressive disorder has 8 weeks treatment with escitalopram or venlafaxine. Abuse history was obtained, the ongoing emotional impact of which was measured with the 15-item impact of event scale (IES-15). The 17-item Hamilton Depression Rating Scale (HDRS) was applied serially. Two NET polymorphisms (rs2242446 and rs5569) were assayed, blinded to HDRS ratings and abuse history. RESULTS: No subjects reporting abuse with high impact in adulthood (IES-15 ≥26, n=12) remitted; whereas 77% reporting low impact (IES-15 <26; n=26) remitted (p<0.001). Subjects reporting high impact abuse (n=12) had a 50-fold (95% confidence interval=4.85-514.6) greater odds of carrying rs2242446-TT genotype, but the small sample size leaves this finding vulnerable to type I error. CONCLUSIONS: The level of persisting impact of child abuse appears relevant to antidepressant efficacy, with susceptibility to such possibly being influence by NET rs2242446 polymorphism. Larger studies may be merited to expand on this pilot level finding given potential for biomarker utility.

Implementation of psychiatric-focused lifestyle medicine programs in Asia.

Lifestyle-focused health programs are growing in interest throughout Western society, and a range of lifestyle factors are known to enhance both physical and mental health. However, it remains largely unknown as to whether this approach is salient for the Asian context. The major components of integrative lifestyle-focused health programs to enhance mental and physical health are considered to include the evidence-based adoption of physical activity and exercise, dietary modification, general psychoeducation, adequate relaxation/sleep and social interaction, use of mindfulness techniques, the reduction of substance use, attention of intersecting environmental factors, and the potential use of motivation and goal-setting techniques. This paper outlines an overview of the evidence underpinning these elements, and discusses potential barriers and challenges, and what logistical considerations may need to be addressed in the implementation of such programs within the context of Asian cultures.

The association between depression and isotretinoin use in acne.

OBJECTIVE: The association between isotretinoin and depression has received little attention in the psychiatric literature despite an increasing number of reports in medical journals. The purpose of this paper is to highlight this association, examine the possible link and review the clinical implications. METHOD: A critical review of the literature pertaining to depression in patients with acne who were treated with isotretinoin was conducted. RESULTS AND CONCLUSIONS: The causal relationship between isotretinoin therapy and depression has not been clearly established and needs further study. Isotretinoin is likely to have a positive psychological impact for the majority of patients who benefit from such a highly efficacious anti-acne treatment. However, it is important to recognize that depression can occur as an idiosyncratic side-effect that requires urgent and appropriate treatment. Therefore, having a low threshold for detection of this uncommon complication and early psychiatric referral to address both the depression and its contributing factors may prevent serious consequences.

The emerging role of pharmacogenetics: implications for clinical psychiatry.

OBJECTIVE: This article aims to review the implications of pharmacogenetics for clinical psychiatry; these are discussed in the context of environmental and sociocultural factors. METHOD: A selective literature review was conducted using Medline search and other relevant references available to the authors. RESULTS: The individual differences in therapeutic and adverse effects of psychotropic drugs are largely determined by genetic factors. Recent advances in pharmacogenetics have highlighted the potential utility in predicting metabolic phenotypes, risks for side-effects and likelihood of drug response for the individual patient. CONCLUSIONS: Genotyping, especially for drug metabolizing enzymes, could enable more rational, cost-effective and optimal prescribing in future psychopharmacotherapy. Although the advances of pharmacogenetics may have many benefits in clinical practice, the importance of non-genetic factors must also be considered as cultural and environmental factors significantly impinge on response to medications. To clarify the extent pharmacogenetics can be adopted in clinical practice to predict drug response in patients from diverse backgrounds, further studies in different ethnic groups and clinical settings are required.