Anxiety disorders and treatment-resistant major depressive disorder (TRD) are often comorbid. Studies suggest ketamine has anxiolytic and antidepressant properties.

To investigate if subcutaneous racemic ketamine, delivered twice weekly for 4 weeks, reduces anxiety in people with TRD.

The Ketamine for Adult Depression Study was a multisite 4-week randomised, double-blind, active (midazolam)-controlled trial. The study initially used fixed low dose ketamine (0.5 mg/kg, cohort 1), before protocol revision to flexible, response-guided dosing (0.5–0.9 mg/kg, cohort 2). This secondary analysis assessed anxiety using the Hamilton Anxiety (HAM-A) scale (primary measure) and ‘inner tension’ item 3 of the Montgomery–Åsberg Depression Rating Scale (MADRS), at baseline, 4 weeks (end treatment) and 4 weeks after treatment end. Analyses of change in anxiety between ketamine and midazolam groups included all participants who received at least one treatment (n = 174), with a mixed effects repeated measures model used to assess the primary anxiety measure. The trial was registered at www.anzctr.org.au (ACTRN12616001096448).

In cohort 1 (n = 68) the reduction in HAM-A score was not statistically significant: −1.4 (95% CI [−8.6, 3.2], P = 0.37), whereas a significant reduction was seen for cohort 2 (n = 106) of −4.0 (95% CI [−10.6, −1.9], P = 0.0058), favouring ketamine over midazolam. These effects were mediated by total MADRS and were not maintained at 4 weeks after treatment end. MADRS item 3 was also significantly reduced in cohort 2 (P = 0.026) but not cohort 1 (P = 0.96).

Ketamine reduces anxiety in people with TRD when administered subcutaneously in adequate doses.

Epilepsy is the third most common neurological disorder among older adults, and as adults are living longer, the incidence of epilepsy is increasing (Kun Lee, 2019). The purpose of this study is to examine 1. differences in quality of life (QOL) between older and younger adults with medically intractable epilepsy and 2. the impact of seizure frequency, seizure duration, depression, sex, and marital status on QOL. Given differences in the prevalence rates of depression between men and women and importance of depression in QOL, we predicted that sex and marital status would moderate the effect of depression on total QOL (TQOL).

Hypothesis I: Compared to younger adults, older adults with epilepsy will report lower TQOL scores and lower scores on subscales measuring energy/fatigue, cognition, and medication effects. Hypothesis II: Seizure variables and depression will significantly account for TQOL scores in both groups (younger and older) above demographic variables (sex, marital status, and education). Hypothesis III: Sex will moderate the effect of depression in both groups and marital status will moderate the effect of depression only in the older adults.

Participants were 607 adults (> 18 years old) who were prospective candidates for epilepsy surgery and underwent a comprehensive neuropsychological evaluation including QOL assessment using the Quality of Life in Epilepsy Scale-31 (QOLIE-31). Individuals were grouped by older (> 50 years old; N = 122) and younger adults (< 50 years old; N = 485). Hierarchical regression was used to examine the proposed associations.

Hypothesis I: In contrast to our hypothesis, a one-way ANOVA did not reveal significant differences between the older and younger groups on the QOL subscales, TQOL, or depression.

Hypothesis II: For older adults, longer seizure duration was associated with better TQOL; bivariate correlations showed no evidence of statistical suppression. Higher depression scores were associated with worse TQOL. Overall, the model accounted for 39.6% of variance among older adults. For younger adults, only depression was a significant predictor of TQOL wherein higher depression scores were associated with worse TQOL. Overall, the model accounted for 36.1% of the variance among younger adults. Hypothesis III: There was no moderation between depression and marital status in older or younger adults (b = -.009, p > .05). There was multicollinearity evidenced by VIF (variance inflation factor) greater than 10, so the associations between depression and sex could not be examined.

Overall, there were no significant differences between QOL in younger versus older adults. Greater depression symptoms were associated with lower TQOL in both groups. Longer seizure duration was a significant predictor of better TQOL in older adults only, perhaps indicating better adjustment to having a seizure disorder with longer duration of epilepsy. Lastly, marital status did not moderate the effects of depression on TQOL and the moderating effects of sex on TQOL could not be assessed due to multicollinearity. Study limitations include dichotomizing the sample into these particular age groups and the heterogeneity of seizure types.

Prior trials suggest that intravenous racemic ketamine is a highly effective for treatment-resistant depression (TRD), but phase 3 trials of racemic ketamine are needed.

To assess the acute efficacy and safety of a 4-week course of subcutaneous racemic ketamine in participants with TRD. Trial registration: ACTRN12616001096448 at www.anzctr.org.au.

This phase 3, double-blind, randomised, active-controlled multicentre trial was conducted at seven mood disorders centres in Australia and New Zealand. Participants received twice-weekly subcutaneous racemic ketamine or midazolam for 4 weeks. Initially, the trial tested fixed-dose ketamine 0.5 mg/kg versus midazolam 0.025 mg/kg (cohort 1). Dosing was revised, after a Data Safety Monitoring Board recommendation, to flexible-dose ketamine 0.5–0.9 mg/kg or midazolam 0.025–0.045 mg/kg, with response-guided dosing increments (cohort 2). The primary outcome was remission (Montgomery-Åsberg Rating Scale for Depression score ≤10) at the end of week 4.

The final analysis (those who received at least one treatment) comprised 68 in cohort 1 (fixed-dose), 106 in cohort 2 (flexible-dose). Ketamine was more efficacious than midazolam in cohort 2 (remission rate 19.6% v. 2.0%; OR = 12.1, 95% CI 2.1–69.2, P = 0.005), but not different in cohort 1 (remission rate 6.3% v. 8.8%; OR = 1.3, 95% CI 0.2–8.2, P = 0.76). Ketamine was well tolerated. Acute adverse effects (psychotomimetic, blood pressure increases) resolved within 2 h.

Adequately dosed subcutaneous racemic ketamine was efficacious and safe in treating TRD over a 4-week treatment period. The subcutaneous route is practical and feasible.

Mood stabilisers are the main treatment for bipolar disorder. However, it is uncertain which drugs have the best outcomes.

To investigate whether rates of suicide, self-harm and psychiatric hospital admission in individuals with bipolar disorder differ between mood stabilisers.

A cohort design was applied to people aged ≥15 years who were diagnosed with bipolar disorder and living in Denmark during 1995–2016. Treatment with lithium, valproate, other mood stabilisers and antipsychotics were compared in between- and within-individual analyses, and adjusted for sociodemographic characteristics and previous self-harm.

A total of 33 337 individuals with bipolar disorder were included (266 900 person-years). When compared with individuals not receiving treatment, those receiving lithium had a lower rate of suicide (hazard ratio 0.40, 95% CI 0.31–0.51). When comparing treatment and non-treatment periods in the same individuals, lower rates of self-harm were found for lithium (hazard ratio 0.74, 95% CI 0.61–0.91). Lower rates of psychiatric hospital admission were found for all drug categories compared with non-treatment periods in within-individual analyses (P<0.001). The low rates of self-harm and hospital admission for lithium in within-individual analyses were supported by results of between-individual analyses.

Lithium was associated with lower rates of suicide, self-harm and psychiatric hospital readmission in all analyses. With respect to suicide, lithium was superior to no treatment. Although confounding by indication cannot be excluded, lithium seems to have better outcomes in the treatment of bipolar disorder than other mood stabilisers.

Expert knowledge of cardiac malformations is essential for paediatric cardiologists. Current cardiac morphology fellowship teaching format, content, and nomenclature are left up to the discretion of the individual fellowship programmes. We aimed to assess practices and barriers in morphology education, perceived effectiveness of current curricula, and preferences for a standardised fellow morphology curriculum.

A web-based survey was developed de novo and administered anonymously via e-mail to all paediatric cardiology fellowship programme directors and associate directors in the United States of America; leaders were asked to forward the survey to fellows.

A total of 35 directors from 32 programmes (51%) and 66 fellows responded. Curriculum formats varied: 28 (88%) programmes utilised pathological specimens, 25 (78%) invited outside faculty, and 16 (50%) utilised external conferences. Director nomenclature preferences were split – 6 (19%) Andersonian, 8 (25%) Van Praaghian, and 18 (56%) mixed. Barriers to morphology education included time and inconsistent nomenclature. One-third of directors reported that <90% of recent fellow graduates had adequate abilities to apply segmental anatomy, identify associated cardiac lesions, or communicate complex CHD. More structured teaching, protected time, and specimens were suggestions to improve curricula. Almost 75% would likely adopt/utilise an online morphology curriculum.

Cardiac morphology training varies in content and format among fellowships. Inconsistent nomenclature exists, and inadequate morphology knowledge is perceived to contribute to communication failures, both have potential patient safety implications. There is an educational need for a common, online cardiac morphology curriculum that could allow for fellow assessment of competency and contribute to more standardised communication in the field of paediatric cardiology.

Not only is depression associated with increased inflammation but inflammation is a risk factor for the genesis of depression. Many of the environmental risk factors for depression are transduced through inflammatory signaling. Anti-inflammatory agents show promise for the management of depression in preclinical, epidemiological, and early clinical studies. This opens the door to the potential for anti-inflammatory agents to treat and prevent depression. There are no evidence-based pharmacotherapies for depression prevention.

ASPREE-D, aspirin in the prevention of depression in the elderly, is a sub study of ASPREE, which explores the potential of aspirin to prevent a range of inflammation related disorders in the elderly. With a sample size of 19,114, and a duration of 5 years, this placebo controlled study will be one of the largest randomized controlled trials in psychiatry and will provide definitive evidence on the ability of aspirin to prevent depression.

This paper presents the rationale for the study and presents a summary of the study design.

ASPREE-D may not only define novel therapy but will provide mechanistic proof of concept of the role of inflammation in depression.

Recent studies have proposed the existence of three distinct subgroups of bipolar 1 disorder based on age at onset (AAO). The present study aims to investigate potential clinical and functional differences between these subgroups in an Australian sample.

Participants (n = 239) were enrolled in the Bipolar Comprehensive Outcomes Study (BCOS), a 2-year longitudinal, observational, cross-sectional study. Assessment measures included the Young Mania Rating Scale (YMRS), Hamilton Depression Rating Scale (HAMD21), Clinical Global Impressions Scale (CGI-BP), SF-36, SLICE/Life Scale, and the EuroQol (EQ-5D). Participants were also asked about their age at the first major affective episode.

Three AAO groups were compared: early (AAO < 20, mean = 15.5 ± 2.72; 44.4% of the participants); intermediate (AAO 20–39, mean = 26.1 ± 4.8; 48.14% of the participants) and late (AAO > 40, mean = 50.6 ± 9.04; 7.4% of the participants). Higher rates of depression, suicidal ideation and binge drinking were reported by the early AAO group. This group also reported poorer quality of life in a number of areas. The early AAO group had a predominant depressive initial polarity and the intermediate group had a manic predominance.

Early AAO is associated with an adverse outcome.