Youth Depression Alleviation with Anti-inflammatory Agents (YoDA-A): a randomised clinical trial of rosuvastatin and aspirin.

BACKGROUND: Inflammation contributes to the pathophysiology of major depressive disorder (MDD), and anti-inflammatory strategies might therefore have therapeutic potential. This trial aimed to determine whether adjunctive aspirin or rosuvastatin, compared with placebo, reduced depressive symptoms in young people (15-25 years). METHODS: YoDA-A, Youth Depression Alleviation with Anti-inflammatory Agents, was a 12-week triple-blind, randomised, controlled trial. Participants were young people (aged 15-25 years) with moderate to severe MDD (MADRS mean at baseline 32.5 ± 6.0; N = 130; age 20.2 ± 2.6; 60% female), recruited between June 2013 and June 2017 across six sites in Victoria, Australia. In addition to treatment as usual, participants were randomised to receive aspirin (n = 40), rosuvastatin (n = 48), or placebo (n = 42), with assessments at baseline and weeks 4, 8, 12, and 26. The primary outcome was change in the Montgomery-Åsberg Depression Rating Scale (MADRS) from baseline to week 12. RESULTS: At the a priori primary endpoint of MADRS differential change from baseline at week 12, there was no significant difference between aspirin and placebo (1.9, 95% CI (- 2.8, 6.6), p = 0.433), or rosuvastatin and placebo (- 4.2, 95% CI (- 9.1, 0.6), p = 0.089). For rosuvastatin, secondary outcomes on self-rated depression and global impression, quality of life, functioning, and mania were not significantly different from placebo. Aspirin was inferior to placebo on the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q-SF) at week 12. Statins were superior to aspirin on the MADRS, the Clinical Global Impressions Severity Scale (CGI-S), and the Negative Problem Orientation Questionnaire scale (NPOQ) at week 12. CONCLUSIONS: The addition of either aspirin or rosuvastatin did not to confer any beneficial effect over and above routine treatment for depression in young people. Exploratory comparisons of secondary outcomes provide limited support for a potential therapeutic role for adjunctive rosuvastatin, but not for aspirin, in youth depression. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12613000112763. Registered on 30/01/2013.

The Youth Mood Clinic: an innovative service for the treatment of severe and complex depression.

OBJECTIVE: Depression is the leading cause of disability for Australians from late adolescence through mid-adulthood, and effective treatments can positively impact subsequent life course trajectories. A treatment model for the management of complex youth depression, characterised by symptom severity, multi-morbidity and ongoing suicidality is presented. CONCLUSIONS: The Youth Mood Clinic (YMC) provides multidisciplinary, team-based treatment for young people aged 15-25 years. The YMC model utilises a phased treatment approach, drawing on elements of cognitive and interpersonal psychotherapy embedded within case management and psychiatry review. Particular attention is given to developmental factors, engagement, assessment, suicide risk, caregiver input and pharmacotherapy. Key tasks of the YMC treatment phases are outlined, reflecting initial stages, recovery planning and treatment, continuation, consolidation and future planning.

Herpes zoster infection, vaccination and immunocompromised rheumatology patients.

Varicella is a self-limiting and relatively mild disease of childhood, although it is frequently more severe and complicated among the immunocompromised rheumatology patients on immunomodulator therapies. In addition, future reactivation of the dormant virus in dorsal root ganglia may cause herpes zoster infection, which can be very debilitating. In this manuscript, we discuss the nature of this infection along with its potential vaccine especially among rheumatology patients.

Interventions for preventing relapse and recurrence of a depressive disorder in children and adolescents.

BACKGROUND: Depressive disorders often begin during childhood or adolescence. There is a growing body of evidence supporting effective treatments during the acute phase of a depressive disorder. However, little is known about treatments for preventing relapse or recurrence of depression once an individual has achieved remission or recovery from their symptoms. OBJECTIVES: To determine the efficacy of early interventions, including psychological and pharmacological interventions, to prevent relapse or recurrence of depressive disorders in children and adolescents. SEARCH METHODS: We searched the Cochrane Depression, Anxiety and Neurosis Review Group's Specialised Register (CCDANCTR) (to 1 June 2011). The CCDANCTR contains reports of relevant randomised controlled trials from The Cochrane Library (all years), EMBASE (1974 to date), MEDLINE (1950 to date) and PsycINFO (1967 to date). In addition we handsearched the references of all included studies and review articles. SELECTION CRITERIA: Randomised controlled trials using a psychological or pharmacological intervention, with the aim of preventing relapse or recurrence from an episode of major depressive disorder (MDD) or dysthymic disorder (DD) in children and adolescents were included. Participants were required to have been diagnosed with MDD or DD according to DSM or ICD criteria, using a standardised and validated assessment tool. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed all trials for inclusion in the review, extracted trial and outcome data, and assessed trial quality. Results for dichotomous outcomes are expressed as odds ratio and continuous measures as mean difference or standardised mean difference. We combined results using random-effects meta-analyses, with 95% confidence intervals. We contacted lead authors of included trials and requested additional data where possible. MAIN RESULTS: Nine trials with 882 participants were included in the review. In five trials the outcome assessors were blind to the participants' intervention condition and in the remainder of trials it was unclear. In the majority of trials, participants were either not blind to their intervention condition, or it was unclear whether they were or not. Allocation concealment was also unclear in the majority of trials. Although all trials treated participants in an outpatient setting, the designs implemented in trials was diverse, which limits the generalisability of the results. Three trials indicated participants treated with antidepressant medication had lower relapse-recurrence rates (40.9%) compared to those treated with placebo (66.6%) during a relapse prevention phase (odds ratio (OR) 0.34; 95% confidence interval (CI) 0.18 to 0.64, P = 0.02). One trial that compared a combination of psychological therapy and medication to medication alone favoured a combination approach over medication alone, however this result did not reach statistical significance (OR 0.26; 95% CI 0.06 to 1.15). The majority of trials that involved antidepressant medication reported adverse events including suicide-related behaviours. However, there were not enough data to show which treatment approach results in the most favourable adverse event profile. AUTHORS' CONCLUSIONS: Currently, there is little evidence to conclude which type of treatment approach is most effective in preventing relapse or recurrence of depressive episodes in children and adolescents. Limited trials found that antidepressant medication reduces the chance of relapse-recurrence in the future, however, there is considerable diversity in the design of trials, making it difficult to compare outcomes across studies. Some of the research involving psychological therapies is encouraging, however at present more trials with larger sample sizes need to be conducted in order to explore this treatment approach further.

The impact of HSV for inflammatory arthropathy patients.

Herpes simplex virus type 1 (HSV-1), also known as herpes labialis, is the etiologic agent of vesicular lesions of the oral mucosa commonly referred to as "cold sores". HSV-1 can also cause clinical disease in a wide variety of other anatomic locations including the genitalia, liver, lung, eye, and central nervous system. These infections can be severe, particularly in the setting of immunosuppression, such as inflammatory arthropathy patients on Methotrexate ± biological therapies. Here, we highlight the importance of physician awareness of HSV due to its potential impact for rheumatology patients.

Osteonecrosis following alcohol, cocaine, and steroid use.

Alcohol, steroids and cocaine have all been shown to be independent risk factors for osteonecrosis when taken in excess. Here we present a case of a young girl who developed debilitating osteonecrosis secondary to low doses of alcohol, steroids and cocaine. We feel it is important to highlight to those caring for such patients of the potential devastating complication of these three agents.

An Enhanced Social Networking Intervention for Young People with Active Suicidal Ideation: Safety, Feasibility and Acceptability Outcomes.

Online social networking interventions have potential to support young people who experience suicidal thoughts by specifically addressing interpersonal risk factors for suicide, but may also pose a risk of harm. This uncontrolled, single-group pilot study aimed to evaluate the safety, feasibility, and acceptability of an enhanced online social networking intervention ("Affinity") among a sample of young people who experienced active suicidal ideation, and to explore potential changes in clinical outcomes and the therapeutic targets of the intervention. Twenty young people with current or recent suicidal ideation who were receiving treatment for depression at a tertiary-level mental health service were given access to Affinity for two months. Participants were assessed at baseline and 8-week follow-up; 90 percent reported clinical suicidal ideation at baseline. A priori criteria related to feasibility, safety and acceptability were satisfied. In terms of potential clinical effects, significant and reliable pre-post improvements were found on self-report outcomes including suicidal ideation. This study provides initial world-first evidence to support the use of an online intervention incorporating social networking as an adjunct to treatment for young people who experience suicidal ideation. The effectiveness of Affinity needs to be evaluated in a randomised controlled trial.

Early intervention for bipolar disorder - Do current treatment guidelines provide recommendations for the early stages of the disorder?

BACKGROUND: Interventions early in the course of bipolar disorder (BD) may have the potential to limit its functional and symptomatic impact. However, the implementation of specific early interventions for BD has been limited which may at least partly be due to the lack of guidelines focused on the early illness stages. We therefore aimed to review the current recommendations for early stage BD from clinical practice guidelines. METHODS: We searched PubMED and PsychINFO for clinical guidelines for BD published in the ten years prior to 1 November 2018. Recommendations from identified guidelines that addressed early stage BD or first episode mania were consolidated and compared. We also reviewed the guidelines relating to adolescents with BD to complement the guidelines related to those in the early illness course. RESULTS: We identified fourteen international and national guidelines on BD or affective psychoses. Most guidelines contained a separate section on adolescents, but only a few referred specifically to early stage BD. There were no consistent recommendations for early stage disorder, except with respect to the indications for maintenance medication treatments. For adolescents, there was a consistent recommendation for the use of second generation antipsychotics for treating acute mania. LIMITATION: The main limitation is that the identified guidelines did not include primary data that clearly separated illness and developmental stages. CONCLUSIONS: There is a lack of emphasis on early BD among widely-respected current clinical guidelines, likely reflecting the dearth of primary data. Future evidence or consensus-based recommendations could significantly inform clinical practice for this population.

The addition of fluoxetine to cognitive behavioural therapy for youth depression (YoDA-C): a randomised, double-blind, placebo-controlled, multicentre clinical trial.

BACKGROUND: Medication is commonly used to treat youth depression, but whether medication should be added to cognitive behavioural therapy (CBT) as first-line treatment is unclear. We aimed to examine whether combined treatment with CBT and fluoxetine was more effective than CBT and placebo in youth with moderate-to-severe major depressive disorder. METHODS: The Youth Depression Alleviation-Combined Treatment (YoDA-C) trial was a randomised, double-blind, placebo-controlled, multicentre clinical trial. Participants were aged 15-25 years with moderate-to-severe MDD and had sought care at one of four clinical centres in metropolitan Melbourne, Australia. Patients were randomly assigned (1:1) to receive CBT for 12 weeks, plus either fluoxetine or placebo. Participants began on one 20 mg capsule of fluoxetine or one placebo pill per day. All participants received CBT, delivered by therapists in weekly 50-minute sessions and attended interviews at baseline, and at weeks 4, 8, and 12, during which they completed assessments with research assistants. Participants saw a psychiatrist or psychiatry trainee to complete medical assessments at the same timepoints. The primary outcome was change in the interviewer-rated Montgomery-Åsberg Depression Rating Scale (MADRS) score at 12 weeks. The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12612001281886). FINDINGS: 153 participants (mean age 19·6 years [SD 2·7]) were enrolled from Feb 20, 2013, to Dec 13, 2016. 77 (50%) patients were allocated to CBT and placebo and 76 (50%) to CBT and fluoxetine. Participants had severe depression at baseline (mean MADRS score 33·6 [SD 5·1] in the CBT and placebo group and 32·2 [5·6] in the CBT and fluoxetine group), with high proportions of participants with anxiety disorder comorbidity (47 [61%] in the CBT and placebo group and 49 [64%] in the CBT and fluoxetine group) and past-month suicidal ideation (55 [71%] in the CBT and placebo group and 59 [78%] in the CBT and fluoxetine group). 59 (77%) participants in the CBT and placebo group and 64 (84%) in the CBT and fluoxetine group completed follow-up at week 12. After 12 weeks of treatment both groups showed a reduction in MADRS scores (-13·7, 95% CI -16·0 to -11·4, in the CBT and placebo group and -15·1, -17·4 to -12·9, in the CBT and fluoxetine group). There was no significant between-group difference in MADRS scores (-1·4, -4·7 to 1·8; p=0·39). There were five suicide attempts in the CBT and placebo group and one suicide attempt in the CBT and fluoxetine group (odds ratio 0·2, 0·0-1·8; p=0·21), and no significant between-group differences for other suicidal behaviours. INTERPRETATION: We did not find evidence that the addition of fluoxetine (rather than placebo) to CBT further reduced depressive symptoms in young people with moderate-to-severe MDD. Exploratory analyses showed that the addition of medication might be helpful for patients with comorbid anxiety symptoms and for older youth. FUNDING: Australian National Health and Medical Research Council.

Sinusitis: a possible link with adalimumab.

The experience with anti-TNF agents is relatively short; and with time, we are learning more about the frequency of occurrence of different adverse events as the original trials were either too small or too brief. We report a case series of four patients who suffered from chronic inflammatory arthritis [rheumatoid arthritis (n = 3) and psoriatic arthritis (n = 1)]. Their inflammatory arthritis remained refractory to increasing doses of methotrexate up to 20 mg weekly and required an advance in treatment to TNF antagonists. However, within a few weeks of commencing these patients on adalimumab, they developed newly diagnosed recurring sinusitis. All these patients were assessed by otorhinolaryngologists, and had clinically confirmed diagnosis. The sinusitis remained refractory to standard medications; however, it resolved after the discontinuation of adalimumab. Although FDA and Irish Pharmaceutical Health Association describe that adalimumab use increases the risk of non-serious infections marginally and most of the patients continued on Humira (adalimumab) after the infection was resolved, however, our recent observation raises the concern of probable higher incidence.

A paraneoplastic case of palmar fasciitis and polyarthritis syndrome.

BACKGROUND: A 58-year-old woman presented with arthritis of the small joints of her hands and rapidly progressive joint contractures. She was wheelchair bound within 2 months of the onset of her symptoms. Physical examination revealed synovitis of the small joints of her hands and palmar fasciitis. The patient had been diagnosed with pancreatic carcinoma approximately 1 year before the presentation of her rheumatic symptoms, and had undergone radical pancreatico-duodenectomy. INVESTIGATIONS: Physical examination; routine laboratory work, including full blood count and measurement of erythrocyte sedimentation rate and C-reactive protein; serological tests for rheumatoid factor, antinuclear antibodies and extractable nuclear antibodies; measurement of serum tumor markers; radiological investigations, including X-rays of her hands and feet, whole-body CT-scans and radioisotope bone scan. DIAGNOSIS: The patient's rheumatic presentation was diagnosed as a paraneoplastic syndrome associated with pancreatic carcinoma. MANAGEMENT: The patient's condition was managed with corticosteroids and methotrexate. No residual tumor or evidence of metastatic disease have been detected in the 1.5 years since the initial presentation of her rheumatic symptoms.

Integrating family work into the treatment of young people with severe and complex depression: a developmentally focused model.

AIM: Although models of family intervention are clearly articulated in the child and early adolescent literature, there is less clarity regarding family intervention approaches in later adolescence and emerging adulthood. METHODS: This study provides the rationale and intervention framework for a developmentally sensitive model of time-limited family work in the outpatient treatment of complex youth depression (15-25 years). RESULTS: Derived from current practice in the Youth Mood Clinic (YMC) at Orygen Youth Health, Melbourne, a stepped model of family intervention is discussed. YMC aims to provide comprehensive orientation, assessment and education to all families. For some, a family-based intervention, delivered either by the treating team or through the integration of a specialist family worker, offers an important adjunct in supporting the recovery of the young person. Developmental phases and challenges experienced by the young person with respect to family/caregiver involvement are discussed in the context of two case studies. CONCLUSIONS: A developmentally sensitive model is presented with particular attention to the developmental needs and preferences of young people. Formal evaluation of this model is required. Evaluation perspectives should include young people, caregivers, the broader family system (i.e. siblings) and the treating team (i.e. case manager, doctor and family worker) incorporating outcome measurement. Such work determines how best to apply a time-limited family-based intervention approach in strengthening family/caregiver relationships as part of the young person's recovery from severe and complex depression.

Youth Depression Alleviation-Augmentation with an anti-inflammatory agent (YoDA-A): protocol and rationale for a placebo-controlled randomized trial of rosuvastatin and aspirin.

AIM: There is growing support for the role of inflammation and oxidative stress in the pathophysiology of major depressive disorder (MDD). This has led to the development of novel strategies targeting inflammation in the treatment of depression. Rosuvastatin and aspirin have well-documented, anti-inflammatory and antioxidant properties. The aim of the Youth Depression Alleviation: Augmentation with an anti-inflammatory agent (YoDA-A) study is to determine whether individuals receiving adjunctive anti-inflammatory agents, aspirin and rosuvastatin experience a reduction in the severity of MDD compared with individuals receiving placebo. METHODS: YoDA-A is a 12-week triple-blind, randomized controlled trial funded by the National Health and Medical Research Council, Australia. Participants aged 15-25, with moderate-to-severe MDD, are allocated to receive either 10 mg/day rosuvastatin, 100 mg/day aspirin, or placebo, in addition to treatment as usual. Participants are assessed at baseline and at weeks 4, 8, 12 and 26. The primary outcome is change in the Montgomery-Åsberg Depression Rating Scale (MADRS) from baseline to week 12. RESULTS: The study is planned to be completed in 2017. At date of publication, 85 participants have been recruited. CONCLUSION: Timely and targeted intervention for youth MDD is crucial. Given the paucity of new agents to treat youth MDD, adjunctive trials are not only pragmatic and 'real-world', but additionally aim to target shortfalls in conventional medications. This study has the potential to first provide two new adjunctive treatment options for youth MDD; aspirin and rosuvastatin. Second, this study will serve as proof of principle of the role of inflammation in MDD.

Successful treatment of Takayasu arteritis with rituximab as a first-line immunosuppressant.

Takayasu arteritis is a rare large vessel vasculitis which has traditionally been treated with high-dose steroids. There have been a small number of publications where biological agents have been used to manage refractory cases. To the authors knowledge, there are no publications using biological agents in combination with steroids as a first-line treatment in Takayasu arteritis. In this publication, we document the case of Takayasu arteritis, in a 39-year-old woman, where rituximab was used in combination with steroids as a first-line agent in the setting of poorly controlled bipolar affective disorder.