Assessing impact of treatment from the patient perspective provides additional information about treatment efficacy in major depressive disorder (MDD) trials.

Pooled data from three identically designed clinical trials showed aripiprazole adjunctive to antidepressant therapy (ADT) was effective in treating MDD.1

Patients who completed an 8-week prospective ADT phase with inadequate response were randomized double-blind to 6-weeks adjunctive treatment with aripiprazole or placebo. The Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) is a 16-item, self-report measure to evaluate daily functioning, with higher scores indicating better satisfaction. Comparisons of mean change from baseline (Week 8) to Week 14 in Q-LES-Q-SF items and general subscores were performed using ANCOVA (LOCF).

There was significant improvement in the Q-LES-Q-SF Overall-General subscore (total of items 1-14 expressed as a percentage of the maximum possible score) in the aripiprazole-treatment group (9.49% [n=507]) vs placebo (5.71% [n=492] p< 0.001). Placebo was significantly higher than aripiprazole in Physical Ability (placebo 0.13 vs aripiprazole 0.02, p=0.020). Aripiprazole was significantly higher than placebo in all other items except Physical Health and Vision. Aripiprazole also produced significant increases in both the Satisfaction with Medication (Item 15) (aripiprazole 0.36 vs placebo 0.20, p< 0.01) and Overall Satisfaction (Item 16) (aripiprazole 0.61 vs placebo 0.35, p< 0.001) scores.

Results emphasize that assessment of patient functioning and quality of life may have utility both in clinical trials and clinical practice.2

To evaluate the efficacy of aripiprazole adjunctive antidepressant therapy (ADT) with regard to functioning in patients with major depressive disorder (MDD) who did not achieve an adequate response with standard ADT.

Pooled data were analyzed from three nearly identically designed randomized, double-blind, placebo-controlled trials: CN138-139, CN138-163 and CN138-165. These included patients with MDD, without psychotic features, who had failed at least one ADT treatment in the present episode. Patients completing an 8-week prospective ADT phase with inadequate response were randomized to 6-weeks’ treatment with adjunctive aripiprazole (n=508) or placebo (n=494). Functioning was assessed using the Sheehan Disability Scale (SDS). Comparisons of mean change from baseline in total SDS score, and domains of family life, social life and work/school were performed using ANCOVA.

Adjunctive aripiprazole produced significant improvements in total SDS (-1.2 on an adjusted scale of 1-10, with 10=worst level of functioning/1=best) vs adjunctive placebo (-0.7, p< 0.001). Adjunctive aripiprazole produced significant changes in the family life domain (-1.4 for adjunctive aripiprazole vs -0.7 for adjunctive placebo, p< 0.001) and the social life domain (-1.4 for adjunctive aripiprazole vs -0.7 for adjunctive placebo, p< 0.001). No difference between groups was observed on the work/school domain (-0.8 for adjunctive aripiprazole and -0.6 for adjunctive placebo, p=0.34).

Adjunctive aripiprazole showed significant improvements in overall SDS scores, and family and social life domains. Less change was observed in the work/school domain. The results emphasize that assessment of patient functioning may have utility both in clinical trials and clinical practice.

Aripiprazole has demonstrated efficacy for the treatment of paediatric patients (10–17 years) with a manic or mixed episode associated with bipolar I disorder in a clinical trial that utilised the Young Mania Rating Scale (YMRS) Total score as the primary outcome measure.

This analysis evaluated the profile of discrete symptom response using the YMRS and other measures.

Post-hoc analysis of individual items of the YMRS and the parent or subject version of the General Behaviour Inventory (GBI) Mania and Depression scales using data from a 4-week, double-blind, randomised trial that compared aripiprazole (10 or 30 mg/day, n = 197) with placebo (n = 99).

In total, 296 patients were randomised; 80% completed the study. Significant decreases at Week 4 (p < 0.05) were seen in eight YMRS items: elevated mood, increased motor activity/energy, need for sleep, irritability, speech (rate and amount), language/thought disorder, abnormal thought content and disruptive/aggressive behaviour. For the GBI, effect sizes for parent-reported mania items were medium to large (for example, 0.41 for ‘depressed but high energy’ to 0.78 for ‘rage combined with unusually happy’) but were consistently small on subject self-reported items of mania and depression and, for the overall scale, had the poorest agreement with clinician ratings.

Aripiprazole demonstrated improvements in some of the more troublesome symptoms of paediatric patients with bipolar I disorder experiencing an acute manic or mixed episode. Of note, irritability and aggression showed large treatment effects on both clinician and parent-reported measures, but less so for subject-reported measures.

Optimal management of schizophrenia in adolescents is limited by the lack of available therapies. The efficacy and tolerability of aripiprazole was investigated in this patient population.

This 6-week, randomized, double-blind, placebo controlled trial was conducted at 101 international centers, with a safety monitoring board. 13-17 year-olds with a DSM-IV diagnosis of schizophrenia were randomized to placebo, or a fixed dose of aripiprazole 10 mg or 30 mg reached after a 5 or 11 day titration, respectively. The primary endpoint was mean change from baseline on the PANSS Total score at week 6. Secondary endpoints included the PANSS Positive and Negative subscales, and CGI Improvement score. Tolerabilility assessements included frequency and severity of adverse events, as well as blood chemistries, metabolic parameters and weight gain.

Over 85% of 302 patients completed this study. Both 10 mg and 30 mg doses were superior to placebo on the primary endpoint (PANSS total), with significant differences observed as early as Week 1 (30mg). Both doses showed significant improvement on the PANSS Positive and CGI-I scales; and the 10 mg dose group was superior on PANSS Negative score. Approximately 5% of aripiprazole patients discontinued due to AEs. Weight gain and changes in prolactin were minimal.

10mg and 30mg doses of aripiprazole were superior to placebo in the treatment of adolescents with schizophrenia. Aripiprazole was well tolerated, in general, with few discontinuations due to AEs. EPS was the most common AE. Change in body weight was similar to placebo.

There is limited published data from long-term pediatric bipolar clinical trials with which to guide appropriate treatment decisions. Long-term efficacy and safety of aripiprazole was investigated in this patient population.

296 youths, ages 10-17 year-old with a DSM-IV diagnosis of bipolar I disorder were randomized to receive either placebo or aripiprazole (10mg or 30mg) in a 4-week double-blind trial. Completers continued assigned treatments for an additional 26 weeks (double-blind). Efficacy endpoints included mean change from baseline to week 4 and week 30 on the Young Mania Rating Scale; Children's Global Assessment Scale, Clinical Global Impressions-Bipolar version severity scale, General Behavior Inventory, Attention Deficit Hyperactivity Disorders Rating Scale, and time to discontinuation. Tolerability/safety assessments included incidence and severity of AEs, blood chemistries and metabolic parameters.

Over the 30-week course of double-blind treatment, aripiprazole (10 mg and 30 mg) was superior to placebo as early as week 1 (p< 0.002) and at all scheduled visits from week 2 through week 30 on mean change from baseline in the Y-MRS total score (p<.0001; all visits). Significant improvements were observed on multiple endpoints including the CGAS, GBI, CGI-BP, ADHD-RS-IV total score, time to discontinuation, and response and remission rates. The 3 most common AEs were somnolence, extrapyramidal disorder, and fatigue. Mean change in body weight z-scores over 30 weeks was not clinically significant.

Over 30-weeks of treatment, both doses of aripiprazole were superior to placebo in the long term treatment of pediatric bipolar patients. Aripiprazole was generally well tolerated.

Acute pulmonary embolism is a life-threatening condition and rarely occurs in children. In adults, catheter-directed therapy emerges as a potentially safer and effective therapeutic option. However, there is a paucity of data on the safety and efficacy of catheter-directed therapy for pulmonary embolism in children. We report a single-centred experience of catheter-directed therapy for acute pulmonary embolism in children.

This is a retrospective study of children who had no CHD and underwent catheter-directed therapy at Detroit Medical Center during a 12-year period from 2005 to 2017. Demographic and clinical data associated with pulmonary embolism were collected along with the outcome.

A total of nine patients of median age 16 years with the range from 12 to 20 received catheter-directed therapy for sub-massive (n = 6) and massive pulmonary embolism (n = 3). Among nine patients, one patient received Angiojet thrombectomy and balloon angioplasty, whereas eight patients received catheter-directed thrombolysis using tissue plasminogen activator through infusion catheters (n = 3) or EkoSonic ultrasound-accelerated thrombolysis system (n = 5). In four out of five patients treated with EkoSonic, significant clinical improvement was noticed within 24 hours. Among seven patients who survived, two patients had minor gastrointestinal bleeding with median hospital stay of 8 days with the range from 5 to 24 days, and two patients with massive pulmonary embolism died possibly due to delayed institution of catheter-directed therapy.

Catheter-directed therapy with/without EkoSonic is an emerging alternative therapy for sub-massive and massive pulmonary embolism in children. A timely institution of catheter-directed therapy appeared important to improve the outcome.

To determine the patterns and predictors of treatment response trajectories for veterans with post-traumatic stress disorder (PTSD).

Conditional latent growth mixture modelling was used to identify classes and predictors of class membership. In total, 2686 veterans treated for PTSD between 2002 and 2015 across 14 hospitals in Australia completed the PTSD Checklist at intake, discharge, and 3 and 9 months follow-up. Predictor variables included co-morbid mental health problems, relationship functioning, employment and compensation status.

Five distinct classes were found: those with the most severe PTSD at intake separated into a relatively large class (32.5%) with small change, and a small class (3%) with a large change. Those with slightly less severe PTSD separated into one class comprising 49.9% of the total sample with large change effects, and a second class comprising 7.9% with extremely large treatment effects. The final class (6.7%) with least severe PTSD at intake also showed a large treatment effect. Of the multiple predictor variables, depression and guilt were the only two found to predict differences in response trajectories.

These findings highlight the importance of assessing guilt and depression prior to treatment for PTSD, and for severe cases with co-morbid guilt and depression, considering an approach to trauma-focused therapy that specifically targets guilt and depression-related cognitions.

Parents may experience anxiety and stress when their children undergo cardiac catheterisation. The goal of this study was to assess the level of anxiety in parents of children undergoing cardiac catheterisation and to identify factors that were associated with level of anxiety.

This was a cross-sectional survey of parents of children who underwent cardiac catheterisation. Anxiety levels were measured using a validated self-report questionnaire – State-Trait Anxiety Inventory, which generates state anxiety scores on the current state of anxiety and trait anxiety scores on the stable aspects of anxiety proneness. One sample t-test was used to compare the data with normative data. Multiple linear regression was used to assess the factors associated with the state score.

A total of 113 parents completed the survey. The mean age of parents was 34.0±7.7 years and the mean age of children undergoing catheterisation was 6.7±5.7 years. Compared with normative data, mean state score was significantly higher in our cohort (p<0.05) despite no difference in the trait score. Final multivariate model showed that the state score was significantly associated with child age group (<1 year [coefficient β 7.2] and 10–18 years [6.3], compared to 1 to <10 years of age [reference]) and history of previous catheterisation (−5.2) (p<0.05).

Concurrent state anxiety level was high among parents of children undergoing cardiac catheterisation, whereas trait anxiety level was not. Higher anxiety was experienced by parents of infants and adolescents without a history of previous catheterisation.

Identifying youth who may engage in future substance use could facilitate early identification of substance use disorder vulnerability. We aimed to identify biomarkers that predicted future substance use in psychiatrically un-well youth.

LASSO regression for variable selection was used to predict substance use 24.3 months after neuroimaging assessment in 73 behaviorally and emotionally dysregulated youth aged 13.9 (s.d. = 2.0) years, 30 female, from three clinical sites in the Longitudinal Assessment of Manic Symptoms (LAMS) study. Predictor variables included neural activity during a reward task, cortical thickness, and clinical and demographic variables.

Future substance use was associated with higher left middle prefrontal cortex activity, lower left ventral anterior insula activity, thicker caudal anterior cingulate cortex, higher depression and lower mania scores, not using antipsychotic medication, more parental stress, older age. This combination of variables explained 60.4% of the variance in future substance use, and accurately classified 83.6%.

These variables explained a large proportion of the variance, were useful classifiers of future substance use, and showed the value of combining multiple domains to provide a comprehensive understanding of substance use development. This may be a step toward identifying neural measures that can identify future substance use disorder risk, and act as targets for therapeutic interventions.

The effect of Hybrid stage 1 palliation for hypoplastic left heart syndrome on right ventricular function is unknown. We sought to compare right ventricular function in normal neonates and those with hypoplastic left heart syndrome before Hybrid palliation and to assess the effect of Hybrid palliation on right ventricular function, using the right ventricular myocardial performance index and the ratio of systolic and diastolic durations.

We carried out a retrospective review of echocardiographic data on 23 infants with hypoplastic left heart syndrome who underwent Hybrid palliation and 35 normal controls. Data were acquired before Hybrid and after Hybrid palliation – post 1, 0–4 days; post 2, 1 week; post 3, 2–3 weeks; post 4, 1–1.5 months following Hybrid palliation.

Myocardial performance index and ratio of systolic and diastolic durations were higher in the pre-Hybrid hypoplastic left heart syndrome group (n=23) – 0.47±0.16 versus 0.25±0.07, p<0.001; 1.59±0.44 versus 1.09±0.14, p<0.0001 – compared with controls (n=35). There was no significant change in the myocardial performance index at any of the post-Hybrid time points. Ratio of systolic and diastolic durations increased significantly 2 weeks after Hybrid – post 3: 2.08±0.62 and post 4: 2.21±0.45 versus pre: 1.59±0.44, p=0.043 and 0.003. There were no significant differences in parameters between sub-groups of infants who died (n=10) and survivors (n=13).

Right ventricular myocardial performance index and ratio of systolic and diastolic durations were significantly higher in infants with hypoplastic left heart syndrome before intervention compared with controls. The ratio of systolic and diastolic durations increased significantly 2 weeks after Hybrid palliation. Our data suggest that infants with hypoplastic left heart syndrome have right ventricular dysfunction before intervention, which worsens over 2 weeks after Hybrid palliation.

Both maternal obesity and disordered mood have adverse effects on pregnancy outcome. We hypothesized that maternal very severe obesity (SO) is associated with increased anxiety and depression (A&D) symptoms during pregnancy, with adverse effects on gestational weight gain (GWG), postpartum mood and postpartum weight retention (PPWR) and explored any mediation by circulating glucocorticoids.

We measured A&D symptoms with validated questionnaires at weeks 17 and 28 of pregnancy and 3 months postpartum in 135 lean [body mass index (BMI) ⩽25 kg/m2] and 222 SO (BMI ⩾40 kg/m2) pregnant women. Fasting serum cortisol was measured by radioimmunoassay; GWG and PPWR were recorded.

A&D symptoms were higher in the SO group during pregnancy and postpartum despite adjusting for multiple confounders including previous mental health diagnosis (p < 0.05), and were non-linearly correlated with total GWG (anxiety R2 = 0.06, p = 0.037; depression R2 = 0.09, p = 0.001). In the SO group only, increased maternal anxiety (β = 0.33, p = 0.03) and depression (β = 0.19, p = 0.04) symptoms at week 17 of pregnancy were associated with increased PPWR, independent of total GWG and breastfeeding. Anxiety symptoms at week 28 of pregnancy, but not depression, were non-linearly correlated with serum cortisol level at week 36 of pregnancy (R2 = 0.06, p = 0.02). Cortisol did not mediate the link between A&D symptoms and GWG.

Maternal SO was associated with increased A&D symptoms, and with adverse effects on GWG and PPWR independent of circulating glucocorticoids. Strategies to optimize GWG and postpartum weight management in SO women should include assessment and management of maternal mood in early pregnancy.

Although post-traumatic stress disorder (PTSD) has been a focus of attention in 1990/1991 Gulf War veterans, the excess risk of depression has not been clearly identified. We investigated this through a systematic review and meta-analysis of studies comparing depression in Gulf War veterans to depression in a comparison group of non-deployed military personnel.

Multiple electronic databases and grey literature were searched from 1990 to 2012. Studies were assessed for eligibility and risk of bias according to established criteria.

Of 14 098 titles and abstracts assessed, 14 studies met the inclusion criteria. Gulf War veterans had over twice the odds of experiencing depression [odds ratio (OR) 2.28, 95% confidence interval (CI) 1.88–2.76] and dysthymia or chronic dysphoria (OR 2.39, 95% CI 2.0–2.86) compared to non-deployed military personnel. This finding was robust in sensitivity analyses, and to differences in overall risk of bias and psychological measures used.

Despite divergent methodologies between studies, depression and dysthymia were twice as common in Gulf War veterans and are important medical conditions for clinicians and policymakers to be aware of in managing Gulf War veterans’ health.