Protocol and rationale-the efficacy of minocycline as an adjunctive treatment for major depressive disorder: a double blind, randomised, placebo controlled trial

While current pharmacotherapies are efficacious, there remain a clear shortfall between symptom remission and functional recovery. With the explosion in our understanding of the biology of these disorders, the time is ripe for the investigation of novel therapies. Recently depression is conceptualized as an immune-inflammatory and nitro-oxidative stress related disorder. Minocycline is a tetracycline antibiotic that has anti-inflammatory, pro-oxidant, glutamatergic, neurotrophic and neuroprotective properties that make it a viable target to explore as a new therapy. This double blind, randomised, placebo controlled adjunctive trial will investigate the benefits of 200 mg/day of minocycline treatment, in addition to any usual treatment, as an adjunctive treatment for moderate-severe major depressive disorder. Sixty adults are being randomised to 12 weeks of treatment (with a 4 week follow-up post-discontinuation). The primary outcome measure for the study is mean change on the Montgomery-Asberg Depression Rating Scale (MADRS), with secondary outcomes including the Social and Occupational Functioning Assessment Scale (SOFAS), Clinical Global Impressions (CGI), Hamilton Rating Scale for Anxiety (HAM-A), Patient Global Impression (PGI), Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) and Range of Impaired Functioning Tool (LIFE-RIFT). Biomarker analyses will also be conducted at baseline and week 12. The study has the potential to provide new treatment targets, both by showing efficacy with a new class of 'antidepressant' but also through the analysis of biomarkers that may further inform our understanding of the pathophysiology of unipolar depression.

Optimizing delivery of recovery-oriented online self-management strategies for bipolar disorder : a review

Self-management is emerging as a viable alternative to difficult-to-access psychosocial treatments for bipolar disorder (BD), and has particular relevance to recovery-related goals around empowerment and personal meaning. This review examines data and theory on BD self-management from a recovery-oriented perspective, with a particular focus on optimizing low-intensity delivery of self-management tools via the web.

Oxidative stress markers, cognitive functions, and psychosocial functioning in bipolar disorder: an empirical cross-sectional study

This study aimed to evaluate the relationship between oxidative stress markers and cognitive functions and domains of psychosocial functioning in bipolar disorder.

Is implementation of the 2013 Australian treatment guidelines for posttraumatic stress disorder cost-effective compared to current practice? A cost-utility analysis using QALYs and DALYs

To assess, from a health sector perspective, the incremental cost-effectiveness of three treatment recommendations in the most recent Australian Clinical Practice Guidelines for posttraumatic stress disorder (PTSD). The interventions assessed are trauma-focused cognitive behavioural therapy (TF-CBT) and selective serotonin reuptake inhibitors (SSRIs) for the treatment of PTSD in adults and TF-CBT in children, compared to current practice in Australia.

N-acetylcysteine for therapy-resistant tobacco use disorder: a pilot study

Introduction N-Acetylcysteine (NAC) may have efficacy in treating tobacco use disorder (TUD) by reducing craving and smoking reward. This study examines whether treatment with NAC may have a clinical efficacy in the treatment of TUD. Methods A 12-week double blind randomized controlled trial was conducted to compare the clinical efficacy of NAC 3 g/day versus placebo. We recruited 34 outpatients with therapy resistant TUD concurrently treated with smoking-focused group behavioral therapy. Participants had assessments of daily cigarette use (primary outcome), exhaled carbon monoxide (COEXH) (secondary outcome), and quit rates as defined by COEXH<6 ppm. Depression was measured with the Hamilton Depression Rating Scale (HDRS). Data were analyzed using conventional and modified intention-to-treat endpoint analyses. Results NAC treatment significantly reduced the daily number of cigarettes used (Δ mean±SD = -10.9 ± 7.9 in the NAC-treated versus -3.2 ± 6.1 in the placebo group) and COEXH (Δ mean± SD = -10.4 ± 8.6 ppm in the NAC-treated versus -1.5 ± 4.5 ppm in the placebo group); 47.1% of those treated with NAC versus 21.4% of placebo-treated patients were able to quit smoking as defined by COEXH<6 ppm. NAC treatment significantly reduced the HDRS score in patients with tobacco use disorder. Conclusions These data show that treatment with NAC may have a clinical efficacy in TUD. NAC combined with appropriate psychotherapy appears to be an efficient treatment option for TUD.

Symptom screening scales for detecting major depressive disorder in children and adolescents: A systematic review and meta-analysis of reliability, validity and diagnostic utility.

Depression symptom screening scales are often used to determine a clinical diagnosis of major depressive disorder (MDD) in prevention research. The aim of this review is to systematically examine the reliability, validity and diagnostic utility of commonly used screening scales in depression prevention research among children and adolescents.

Observable essential fatty acid deficiency markers and autism spectrum disorder

Autism Spectrum Disorder (ASD) has been associated with essential fatty acid (EFA) deficiencies, with some researchers theorising that dysregulation of phospholipid metabolism may form part of the biological basis for ASD. This pilot study compared observable signs of fatty acid status of 19 children with an ASD diagnosis to 23 of their typically developing siblings. A pregnancy, birth and breastfeeding history was also obtained from their parents, which included a measure of infant intake of fatty acid rich colostrum immediately post-partum. When considered within their family group, those infants not breastfed (with colostrum) within the first hour of life and who had a history of fatty acid deficiency symptoms were more likely to have an ASD diagnosis. Other variables such as formula use, duration of breastfeeding, gestational age and Apgar scores were not associated with group membership. The results of this study are consistent with previous research showing a relationship between fatty acid metabolism, breastfeeding and ASD such that early infant feeding practices and the influence this has on the fatty acid metabolism of the child may be a risk factor for ASD.

A collaborative approach to the treatment alliance in bipolar disorder.

The treatment alliance is the arena in which psychopharmacological and other therapeutic interventions occur. The nature and quality of the treatment alliance may affect adherence to treatment and the realization of the benefits of effective pharmacological treatment in clinical practice. It is an area that has attracted little systematic study, despite the available evidence suggesting that it plays a measurable role in clinical outcomes.

A comparison of olanzapine with haloperidol in cannabis-induced psychotic disorder: a double-blind randomized controlled trial

Little controlled data exist on the treatment of substance induced psychotic disorders. In this study, 30 patients meeting DSM-IV criteria for cannabis induced psychotic disorder were randomly allocated to receive either olanzapine or haloperidol in a 4-week double-blind clinical trial. There were no significant outcome differences between the two groups on any of the primary outcome measures, the Brief Psychiatric Rating Scale (haloperidol 25.7; olanzapine 27.1; P = 0.70); Clinical Global Impression (CGI) severity scale (haloperidol 1.8, olanzapine 2.3; P = 0.21) or the CGI improvement scale (haloperidol 1.3, olanzapine 1.7; P = 0.16). The haloperidol group however, developed significantly more extrapyramidal side-effects as measured by the Simpson Angus Scale (haloperidol 11.4, olanzapine 2.5; P = 0.014). Significantly (P = 0.027) more biperidin was used for extrapyramidal side-effects in the haloperidol (7.143 mg) than in the olanzapine (0.357 mg) group. Olanzapine appears to be as effective as haloperidol in the treatment of cannabis induced psychotic disorder, but is associated with a lower rate of extrapyramidal side-effects.

The platelet intracellular calcium response to serotonin and thrombin in patients with panic disorder.

Serotonin is implicated in both the biology of depression and anxiety. The aim of this study was to examine the platelet intracellular calcium response to serotonin and thrombin using spectrofluorometry in 14 patients with DSM-4 panic disorder compared to 14 matched controls. Patients did not show significantly higher baseline platelet intracellular calcium levels and serotonin stimulated levels of intracellular calcium than control subjects. There was a much smaller standard deviation in the control subjects than in the panic patients. The intracellular calcium response to thrombin activation was however greater in panic patients than in control subjects (P<0.001). The failure of this study to find enhanced sensitivity of 5-HT2 receptors in panic disorder is compatible with the findings of previous challenge studies that found no consistent dysregulation of serotonin in panic disorder. The enhanced thrombin sensitivity, nevertheless suggests some receptor mediated second messenger changes independent of serotonin in the disorder.

The potential utility of a staging model as a course specifier: a bipolar disorder perspective.

Staging models are widely used in clinical medicine, and offer an insight into the progressive nature of many disorders. In general, the earlier stages of illness may be associated with a better prognosis and a higher treatment response. Once chronicity is reached, more complex and invasive treatments may be required, and the utility of treatments may decline. There is evidence that treatment response is greatest in the early phases of the disorder. There is also a progressive social and psychological burden of ongoing illness. This is paralleled by the twin notions of neuroprotection, which is supported by increasing evidence that structural changes in the disorder may be progressive and reversible with algorithm appropriate treatment, and that of early intervention, which posits that the optimal window for intervention is early in the illness course. A staging model compliments existing and proposed classifications of bipolar disorder, adding a temporal dimension to a cross sectional view. It may inform treatment choice and prognosis, and could have utility as a course specifier.

The role of lamotrigine in the management of bipolar disorder.

Lamotrigine has emerged with a distinct place in the pharmacological treatment of bipolar disorder, with the potential to treat and prevent bipolar depression, which is the dominant and arguably most disabling and under-treated phase of the illness. This review examines the published clinical trials of lamotrigine in bipolar treatment. While the data supports its tolerability and safety, the strongest evidence for its efficacy lies in the prevention of bipolar depression, with weaker evidence for the treatment of acute bipolar depression, refractory unipolar and bipolar depression, and rapid cycling bipolar disorder. The total number of published well designed trials is small, even the maintenance evidence is derived from two studies. However, this relative inadequacy compares favorably with the alternative treatment options for bipolar depression, which are marked by poor efficacy or risk of polarity switch. The designation of lamotrigine as first-line treatment for bipolar depression prophylaxis should be done in cognizance of this context, and it would seem prudent to await greater evidence of efficacy before designating lamotrigine as first-line treatment for other bipolar indications. Further randomized controlled trials are required to consolidate the available findings and to explore the boundaries of lamotrigine's efficacy, which may encompass the soft spectral disorders.