Combination pharmacotherapy in unipolar depression

It is estimated that between 60 and 80% of those with major depressive disorder do not achieve full symptomatic remission from first-line antidepressant monotherapy. Residual depressive symptoms substantially impair quality of life and add to the risk of recurrence. It is now clear that depression would benefit from more vigorous treatment, in order to ameliorate its disease burden. While there are established algorithms in situations of treatment resistance, the use of combination pharmacotherapy in unipolar depression is a relatively under-investigated area of treatment and may be an effective and tolerable strategy that maximizes the available resources. This paper reviews the current evidence for combination pharmacotherapy in unipolar depression and discusses its clinical applications.

Atypical antipsychotics for bipolar disorder : overblown or blown over?

Objective：Developments in the pharmacological treatment of bipolar disorder are of much interest, as the chronicity and disability of the disorder become better understood, and as treatment goals have shifted to emphasise early control of illness course and maintenance of euthymia in addition to acute episodic remission. Atypical antipsychotics have emerged as treatment options, and this paper aims to review the evidence for their role in bipolar disorder.

Methods：A MEDLINE search was conducted for publications up till October 2006.

Results：The search yielded a number of randomised, controlled clinical trials of various atypical antipsychotics as monotherapy or adjunctive therapy in bipolar disorder. The majority of such trials have investigated their efficacy in acute mania, with fewer studies devoted to acute bipolar depression or maintenance treatment. There are no specific trials on mixed states, which have mainly been studied together with bipolar mania. The most robust evidence supports a class effect of atypical agents in the treatment of mania.

Conclusions：There are placebo-controlled trials that support the efficacy of olanzapine and quetiapine in bipolar depression, and of olanzapine and aripiprazole as maintenance treatment. There is strong support for the role of atypical antipsychotics in bipolar disorder management despite a relatively narrow literature base, chiefly for the treatment of mania. However, these findings need to be replicated, and further investigation is warranted to clarify their spectrum of efficacy in bipolar disorder.

Development of the teenage cancer peer support program - Canteen

With current medical technology, many young people diagnosed with cancer are able to be cured or given extended periods of disease remission. White treatment regimes are meeting with considerable success, the diagnosis and treatment of cancer is nevertheless often met with experiences of anxiety and despair. This paper discusses the advantages and disadvantages of referring patients to cancer peer support groups to assist those adjusting to a diagnosis of cancer. For others, Cancer is a chronic and debilitating illness, causing family dislocation, financial difficulties, social isolation and chronic uncertainty about the future. Contemporary attitudes towards cancer and adjunctive therapies are characterized by contradictory and confusing information and engender a range of emotions in patients and relatives ranging from suspicion to overt hostility.

Treatment and outcomes of an Australian cohort of outpatients with bipolar 1 or schizoaffective disorder over twenty-four months : implications for clinical practice

Background The Bipolar Comprehensive Outcomes Study (BCOS) is a 2-year, prospective, non-interventional, observational study designed to explore the clinical and functional outcomes associated with ‘real-world’ treatment of participants with bipolar I or schizoaffective disorder. All participants received treatment as usual. There was no study medication.

Methods Participants prescribed either conventional mood stabilizers (CMS; n = 155) alone, or olanzapine with, or without, CMS (olanzapine ± CMS; n = 84) were assessed every 3 months using several measures, including the Young Mania Rating Scale, 21-item Hamilton Depression Rating Scale, Clinical Global Impressions Scale – Bipolar Version, and the EuroQol Instrument. This paper reports 24-month longitudinal clinical, pharmacological, functional, and socioeconomic data.

Results On average, participants were 42 (range 18 to 79) years of age, 58%; were female, and 73%; had a diagnosis of bipolar I. Polypharmacy was the usual approach to pharmacological treatment; participants took a median of 5 different psychotropic medications over the course of the study, and spent a median proportion of time of 100%; of the study on mood stabilizers, 90%; on antipsychotics, 9%; on antidepressants, and 5%; on benzodiazepines/hypnotics. By 24 months, the majority of participants had achieved both symptomatic and syndromal remission of both mania and depression. Symptomatic relapse rates were similar for both the CMS alone (65%;) and the olanzapine ± CMS (61%;) cohorts.

Conclusions Participants with bipolar I or schizoaffective disorder in this study were receiving complex medication treatments that were often discordant with recommendations made in contemporary major treatment guidelines. The majority of study participants demonstrated some clinical and functional improvements, but not all achieved remission of symptoms or syndrome.

A distinct DNA methylation signature defines pediatric pre-B cell acute lymphoblastic leukemia

Pre-B cell acute lymphoblastic leukemia (ALL) is the most prevalent childhood malignancy and remains one of the highest causes of childhood mortality. Despite this, the mechanisms leading to disease remain poorly understood. We asked if recurrent aberrant DNA methylation plays a role in childhood ALL and have defined a genome-scale DNA methylation profile associated with the ETV6-RUNX1 subtype of pediatric ALL. Archival bone marrow smears from 19 children collected at diagnosis and remission were used to derive a disease specific DNA methylation profile. The gene signature was confirmed in an independent cohort of 86 patients. A further 163 patients were analyzed for DNA methylation of a three gene signature. We found that the DNA methylation signature at diagnosis was unique from remission. Fifteen loci were sufficient to discriminate leukemia from disease-free samples and purified CD34+ cells. DNA methylation of these loci was recurrent irrespective of cytogenetic subtype of pre-B cell ALL. We show that recurrent aberrant genomic methylation is a common feature of pre-B ALL, suggesting a shared pathway for disease development. By revealing new DNA methylation markers associated with disease, this study has identified putative targets for development of novel epigenetic-based therapies.

A preliminary investigation on the efficacy of N-acetyl cysteine for mania or hypomania

Objective: Oxidative imbalance has emerged as a treatment target in bipolar disorder. As very limited data are available on the clinical use of antioxidants for mania, we report here results from a post hoc and exploratory subgroup analysis of a randomized, placebo-controlled trial of N-acetyl cysteine (NAC).

Methods: This was a placebo-controlled, randomized, clinical trial assessing the effect of NAC over 24 weeks in mania or hypomania. Symptomatic and functional outcomes were collected over the study period.

Results: Fifteen participants were available for this report; two participants in each group failed to complete all assessments. Within-group analyses pointed to an improvement in the NAC group on manic symptoms and worsening in the placebo group on depressive symptoms at endpoint.

Conclusions: Although the sample size was small, these results indicated within-group efficacy for this glutathione precursor as compared to placebo. Future trials specifically designed to demonstrate the efficacy of NAC in mania are needed.

DSM-5 mixed specifier for manic episodes: evaluating the effect of depressive features on severity and treatment outcome using asenapine clinical trial data

Background:
To describe the frequency of mixed specifier as proposed in DSM-5 in bipolar I patients with manic episodes, and to evaluate the effect of mixed specifier on symptom severity and treatment outcome.

Methods:
This post-hoc analysis used proxies for DSM-5 mixed features specifier by using MADRS or PANSS items.

Results:
Of the 960 patients analysed, 34%, 18% and 4.3% of patients, respectively, had ≥3 depressive features with mild (score ≥1 for MADRS items and ≥2 for PANSS item), moderate (score ≥2 MADRS, ≥3 PANSS) and severe (score ≥3 MADRS, ≥4 PANSS) symptoms. In patients with ≥3 depressive features and independent of treatment: MADRS remission (score ≤12) rate decreased with increasing severity (61–43%) and YMRS remission (score ≤12) was similar for mild and moderate patients (36–37%), but higher for severe (54%). In asenapine-treated patients, the MADRS remission rate was stable regardless of baseline depressive symptom severity (range 64–67%), whereas remission decreased with increasing severity with olanzapine (63–38%) and placebo (49–25%). Reduction in YMRS was significantly greater for asenapine compared with placebo at day 2 across the 3 severity cut-offs and continued to decrease throughout the treatment period. The difference between olanzapine and placebo was statistically significant in mild and moderate patients.

Limitations:
Results are from post-hoc analyses.

Conclusions:
These analyses support the validity of proposed DSM-5 criteria. They confirm that depressive features are frequent in bipolar patients with manic episodes. With increasing baseline severity of depressive features, treatment outcome was poorer with olanzapine and placebo, but remained stable with asenapine.

Post-traumatic stress disorder and quality of life in sexually abused Australian children

The study used publicly available data on post-traumatic stress disorder in a sample of the Australian population with a history of sexual abuse to demonstrate how this evidence can inform economic analyses. The 2007 Australian Mental Health Survey revealed that 8.3% of 993 adolescents experienced childhood sexual abuse, of which 40.2% were diagnosed with post-traumatic stress disorder. Post-traumatic stress disorder diagnosis corresponded to a significant loss of quality of life. Survival analysis was used to estimate the lifetime persistence of post-traumatic stress disorder symptoms. The average time between post-traumatic stress disorder onset and remission was 11.4 years. Results suggest that successful treatment of post-traumatic stress disorder will save 2.05 quality adjusted life years per child or adolescent with post-traumatic stress disorder.

The International Society for Bipolar Disorders (ISBD) Task Force report on the nomenclature of course and outcome in bipolar disorders

Objectives:  Via an international panel of experts, this paper attempts to document, review, interpret, and propose operational definitions used to describe the course of bipolar disorders for worldwide use, and to disseminate consensus opinion, supported by the existing literature, in order to better predict course and treatment outcomes. Methods:  Under the auspices of the International Society for Bipolar Disorders, a task force was convened to examine, report, discuss, and integrate findings from the scientific literature related to observational and clinical trial studies in order to reach consensus and propose terminology describing course and outcome in bipolar disorders. Results:  Consensus opinion was reached regarding the definition of nine terms (response, remission, recovery, relapse, recurrence, subsyndromal states, predominant polarity, switch, and functional outcome) commonly used to describe course and outcomes in bipolar disorders. Further studies are needed to validate the proposed definitions. Conclusion:  Determination and dissemination of a consensus nomenclature serve as the first step toward producing a validated and standardized system to define course and outcome in bipolar disorders in order to identify predictors of outcome and effects of treatment. The task force acknowledges that there is limited validity to the proposed terms, as for the most part they represent a consensus opinion. These definitions need to be validated in existing databases and in future studies, and the primary goals of the task force are to stimulate research on the validity of proposed concepts and further standardize the technical nomenclature.

Escitalopram efficacy in depression a cross-ethnicity examination of the serotonin transporter promoter polymorphism

Current evidence suggests that polymorphism in the serotonin transporter gene (5-HTTLPR) predicts antidepressant efficacy in whites but less so in Asians. However, it is not clear whether this effect can be observed for specific types of antidepressant drugs. White (n = 47) and Korean (n = 118) participants with major depressive disorder were treated with escitalopram and assessed over 8 weeks. Among those with the l/l but not l/s or s/s genotypes, whites had greater depression score reductions, response rates, and remission rates compared with Koreans. Our results suggest that 5-HTTLPR predicts escitalopram efficacy in an ethnicity-dependent manner.