Chee H. Ng

Mental health system in China: history, recent service reform and future challenges.

This paper summarizes the history of the development of Chinese mental health system; the current situation in the mental health field that China has to face in its effort to reform the system, including mental health burden, workforce and resources, as well as structural issues; the process of national mental health service reform, including how it was included into the national public health program, how it began as a training program and then became a treatment and intervention program, its unique training and capacity building model, and its outcomes and impacts; the barriers and challenges of the reform process; future suggestions for policy; and Chinese experiences as response to the international advocacy for the development of mental health.

Sexual Side-Effects of Contemporary Antidepressants: Review:

The aim of the present study was to review the sexual side-effects of contemporary antidepressants in Australia, comparing the selective serotonin re-uptake inhibitors (SSRIs) with venlafaxine, reboxetine, mirtazepine, duloxetine, bupropion, desvenlafaxine and agomelatine. Double-blind, randomized comparative studies of these antidepressants that included assessment of sexual dysfunction with validated rating scales in patients with major depressive disorder were identified from the literature using MEDLINE, EMBASE and PsychINFO databases. Bupropion and duloxetine caused significantly less sexual dysfunction than the SSRIs in short-term studies and reboxetine significantly less in both short- and longer term studies. Bupropion and agomelatine caused significantly less sexual dysfunction than venlafaxine. The evidence for mirtazepine having an advantage over the SSRIs is lacking and there are currently insufficient data for desvenlafaxine. Well-designed comparative studies of contemporary antidepressants with direct assessment of sexual side-effects as the primary outcome measure are scarce. Future studies should be randomized, double-blind, active controlled trials in sexually active subjects with major depressive disorder. There should be direct assessment of sexual function and depression using reliable, validated rating scales before and during treatment. Studies should assess treatment-emergent effects in patients with normal function and resolution of baseline dysfunction over treatment, in both the short and long term. Further research should compare available instruments for measuring sexual function, and include separate analyses of both remitters/non-remitters and male/female subjects.

Prospective study of depressive symptoms and quality of life in acne vulgaris patients treated with isotretinoin compared to antibiotic and topical therapy.

There have been recent concerns about the possible association between isotretinoin therapy and depressive symptoms. We conducted a prospective study to evaluate depressive symptoms and quality of life in acne patients having either isotretinoin or antibiotics/topical treatments. There were 215 patients (mean age 20 years) included in the study. Depression, quality of life and acne severity ratings were administered at baseline, 1 month, 3 months and end of treatment or 6 months, and compared between both treatment groups. The changes in the mean depression scores did not differ significantly between both groups (P = 0.62). The incidence of isotretinoin patients with moderate depressive symptoms remained relatively unchanged from baseline. The changes in the quality‐of‐life measures scores between treatment groups showed no significant difference. No correlation between isotretinoin dose and depression score was found. Although five isotretinoin patients were withdrawn during the study because of worsening of mood, no definite causal relationship was established. This pilot study does not appear to support any direct link between depression and isotretinoin, apart from being a rare unpredictable idiosyncratic side‐effect. However, because of the study limitations, a larger study is needed to confirm the findings.

Efficacy and cognitive effects of right unilateral electroconvulsive therapy

The efficacy, memory, and cognitive effects of right unilateral (RUL) electroconvulsive therapy (ECT) at 2.5 times threshold in 32 inpatients with moderate to severe major depressive disorder were evaluated at baseline, during the course of treatment, and 1 month after treatment. Neuropsychological assessment included the Randt Memory Test, Personal Memory Test, short-version Wechsler Adult Intelligence Scale–Revised, and Self-Rating Scale of Memory Functions. At the treatment end point, although the Hamilton Depression Rating Scale mean score was decreased by 54.2%, the response rate of 2.5 times threshold RUL ECT using stringent criteria was only 31.2%. Treatment was associated with significant anterograde memory impairment in the short term. Mean total scores of the Randt Memory Test and Personal Memory Test were decreased from baseline by 14.8% and 32.5%, respectively, after six sessions of ECT. These memory deficits were significantly improved by the 1 month follow-up examination. Subjective memory scores increased consistently during treatment, correlating with improvements in mood. No adverse effects on nonmemory cognition were found. Although RUL ECT at 2.5 times threshold is not associated with marked or persistent cognitive disturbances, its efficacy may be insufficient in clinical practice.

ABCB1 polymorphism predicts escitalopram dose needed for remission in major depression

The ATP-binding cassette family of transporter proteins, subfamily B (MDR/TAP), member 1 (ABCB1) (P-glycoprotein) transporter is a key component of the blood–brain barrier. Many antidepressants are subject to ABCB1 efflux. Functional polymorphisms of ABCB1 may influence central nervous system bioavailability of antidepressants subject to efflux. Single-nucleotide polymorphisms (SNPs) at rs1045642 (C3435T) of ABCB1 have been associated with efflux pump efficiency. This may explain part of the interindividual variation in antidepressant dose needed to remit. Individuals (N=113) with DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) major depressive disorder (MDD) were treated with escitalopram (ESC) or venlafaxine (VEN) over 8 weeks. The17-item Hamilton Depression Rating Scale was assessed serially, blind to genotype. SNP rs1045642 of ABCB1 along with two SNPs previously reported to be in linkage disequilibrium with it (rs2032582 and rs1128503) were genotyped. Demographic features, clinical features, P450 metabolizer status and 5-HTTLPR (serotonin-transporter-linked promoter region) genotype were controlled for. Carriers of rs1045642 TT needed on average 11 mg of ESC to remit, whereas TC and CC carriers required 24 and 19 mg, respectively (P=0.0001). This equates to a 2.0- (95% confidence interval=1.5–3.4; P<0.001) fold greater ESC dose needed to remit for C carriers compared with TT carriers at rs1045642. Of VEN-treated subjects carrying TT genotype at rs1045642, 73.3% remitted compared with 12.5% for CC genotype (odds ratio=6.69; 95% confidence interval=1.72–25.9, P=0.006). These data suggest that antidepressant dose needed to remit can be predicted by an ABCB1 SNP. This has the potential clinical translation implications for dose selection and remission from MDD.

An inter-ethnic comparison study of clozapine dosage, clinical response and plasma levels

The present study investigated clozapine dosage, plasma clozapine and metabolite levels, clinical and side-effect profiles in Asian versus Caucasian patients with chronic schizophrenia who were on stable maintenance treatment. Twenty Asian patients from Singapore and 20 Caucasian patients from Australia were systematically evaluated with the following rating scales: Positive and Negative Syndrome Scale for Schizophrenia, drug attitude scale (DAI-10), drug adverse reaction profile (Liverpool University Neuroleptic Side-effect Rating Scale), extrapyramidal side-effects scales (Abnormal Involuntary Movement Scale, Simpson and Angus Scale). Cigarette and caffeine consumption were recorded and steady-state plasma clozapine and metabolites levels were measured. Although Asian patients received a significantly lower mean clozapine dose (176 mg/day) than the Caucasian group (433 mg/day, P<0.001), plasma clozapine levels were similar between the groups. As a result, Asian patients had more than twice the effective clozapine concentration to dose ratio (P<0.001). The findings remained significant even after controlling for gender, body mass index, cigarette, alcohol and caffeine use. Conversely, the plasma metabolites (desmethylclozapine and clozapine N-oxide) to clozapine ratios were higher in the Caucasian patients (P<0.01). Compared to Caucasian patients, Asian patients appeared to have a lower dosage requirement for clinical efficacy. Hence, appropriate dose adjustment should be considered in Asian patients receiving maintenance clozapine therapy in clinical practice.

Kava in the treatment of generalized anxiety disorder: a double-blind, randomized, placebo-controlled study

Abstract Kava (Piper methysticum) is a plant-based medicine, which has been previously shown to reduce anxiety. To date, however, no placebo-controlled trial assessing kava in the treatment of generalized anxiety disorder (GAD) has been completed. A total of 75 participants with GAD and no comorbid mood disorder were enrolled in a 6-week double-blind trial of an aqueous extract of kava (120/240 mg of kavalactones per day depending on response) versus placebo. &ggr;-Aminobutyric acid (GABA) and noradrenaline transporter polymorphisms were also analyzed as potential pharmacogenetic markers of response. Reduction in anxiety was measured using the Hamilton Anxiety Rating Scale (HAMA) as the primary outcome. Intention-to-treat analysis was performed on 58 participants who met inclusion criteria after an initial 1 week placebo run-in phase. Results revealed a significant reduction in anxiety for the kava group compared with the placebo group with a moderate effect size (P = 0.046, Cohen d = 0.62). Among participants with moderate to severe Diagnostic and Statistical Manual of Mental Disorders–diagnosed GAD, this effect was larger (P = 0.02; d = 0.82). At conclusion of the controlled phase, 26% of the kava group were classified as remitted (HAMA ⩽ 7) compared with 6% of the placebo group (P = 0.04). Within the kava group, GABA transporter polymorphisms rs2601126 (P = 0.021) and rs2697153 (P = 0.046) were associated with HAMA reduction. Kava was well tolerated, and aside from more headaches reported in the kava group (P = 0.05), no other significant differences between groups occurred for any other adverse effects, nor for liver function tests. Standardized kava may be a moderately effective short-term option for the treatment of GAD. Furthermore, specific GABA transporter polymorphisms appear to potentially modify anxiolytic response to kava.

Design and rationale of a 16-week adjunctive randomized placebo-controlled trial of mitochondrial agents for the treatment of bipolar depression

OBJECTIVE Bipolar disorder places a significant burden on individuals, caregivers and family, and the broader community. Current treatments are believed to be more effective against manic symptoms, leaving a shortfall in recovery during the depressive phase of the illness. The current study draws on recent evidence suggesting that, in addition to increased oxidative load, alterations in mitochondrial function occur in bipolar disorder. METHODS This 16-week study aims to explore the potential benefits of N-acetylcysteine (NAC) alone or in combination (CT) with selected nutraceuticals believed to enhance mitochondrial function. The study includes adults diagnosed with bipolar disorder currently experiencing an episode of depression. Participants are asked to take NAC, CT, or placebo in addition to any usual treatments. A post-discontinuation visit is conducted 4 weeks following the treatment phase. RESULTS The primary outcome of the study will be mean change on the Montgomery-Asberg Depression Rating Scale. Secondary outcomes include functioning, substance use, mania ratings, and quality of life. Blood samples will be collected at baseline and week 16 to explore biochemical alterations following treatment. CONCLUSION This study may provide a novel adjunctive treatment for bipolar depression. Analysis of biological samples may assist in understanding the therapeutic benefits and the underlying etiology of bipolar depression. TRIAL REGISTRATION Australian and New Zealand Clinical Trial Registry ACTRN12612000830897.

A Comparison of Propofol and Thiopentone Use in Electroconvulsive Therapy: Cognitive and Efficacy Effects

Objective: The purpose of this study was to compare thiopentone and propofol administration for electroconvulsive therapy (ECT) in terms of associated efficacy and cognitive side effects in the immediate and medium term. Method: Participants comprised 30 depressed patients who were administered either propofol or thiopentone as an anesthetic agent for ECT. Clinical rating scales and a battery of neuropsychological tests were administered at baseline, after 6 treatments, 1 to 3 days after treatment end point, and at 1-month follow-up. Results: Thiopentone administration was associated with advantages in efficacy and cognitive side effects compared with propofol administration. Conclusions: This study reports some serendipitous findings regarding the comparative effects of the anesthetic agents, propofol and thiopentone. Although limited by small sample size, results suggest that thiopentone has advantages for use as an anesthetic agent with ECT compared with propofol. It also highlights the need for further investigation of the impact of anesthetic agents on the cognitive side effects and efficacy of ECT.

N-acetyl cysteine in the treatment of obsessive compulsive and related disorders: a systematic review

Objective Obsessive compulsive and related disorders are a collection of debilitating psychiatric disorders in which the role of glutamate dysfunction in the underpinning neurobiology is becoming well established. N-acetyl cysteine (NAC) is a glutamate modulator with promising therapeutic effect. This paper presents a systematic review of clinical trials and case reports exploring the use of NAC for these disorders. A further objective was to detail the methodology of current clinical trials being conducted in the area. Methods PubMed, Web of Science and Cochrane Library Database were searched for human clinical trials or case reports investigating NAC in the treatment of obsessive compulsive disorder (OCD) or obsessive compulsive related disorders. Researchers with known involvement in NAC studies were contacted for any unpublished data. Results Four clinical trials and five case reports/series were identified. Study durations were commonly 12-weeks, using 2,400–3,000 mg/day of NAC. Overall, NAC demonstrates activity in reducing the severity of symptoms, with a good tolerability profile and minimal adverse effects. Currently there are three ongoing randomized controlled trials using NAC for OCD (two adults and one pediatric), and one for excoriation. Conclusion Encouraging results have been demonstrated from the few pilot studies that have been conducted. These results are detailed, in addition to a discussion of future potential research.