Therapeutics targeting frontotemporal dementia (FTD) are entering clinical trials. There are challenges to conducting these studies, including the relative rarity of the disease. Remote assessment tools could increase access to clinical research and pave the way for decentralized clinical trials. We developed the ALLFTD Mobile App, a smartphone application that includes assessments of cognition, speech/language, and motor functioning. The objectives were to determine the feasibility and acceptability of collecting remote smartphone data in a multicenter FTD research study and evaluate the reliability and validity of the smartphone cognitive and motor measures.

A diagnostically mixed sample of 207 participants with FTD or from familial FTD kindreds (CDR®+NACC-FTLD=0 [n=91]; CDR®+NACC-FTLD=0.5 [n=39]; CDR®+NACC-FTLD>1 [n=39]; unknown [n=38]) were asked to remotely complete a battery of tests on their smartphones three times over two weeks. Measures included five executive functioning (EF) tests, an adaptive memory test, and participant experience surveys. A subset completed smartphone tests of balance at home (n=31) and a finger tapping test (FTT) in the clinic (n=11). We analyzed adherence (percentage of available measures that were completed) and user experience. We evaluated Spearman-Brown split-half reliability (100 iterations) using the first available assessment for each participant. We assessed test-retest reliability across all available assessments by estimating intraclass correlation coefficients (ICC). To investigate construct validity, we fit regression models testing the association of the smartphone measures with gold-standard neuropsychological outcomes (UDS3-EF composite [Staffaroni et al., 2021], CVLT3-Brief Form [CVLT3-BF] Immediate Recall, mechanical FTT), measures of disease severity (CDR®+NACC-FTLD Box Score & Progressive Supranuclear Palsy Rating Scale [PSPRS]), and regional gray matter volumes (cognitive tests only).

Participants completed 70% of tasks. Most reported that the instructions were understandable (93%), considered the time commitment acceptable (97%), and were willing to complete additional assessments (98%). Split-half reliability was excellent for the executive functioning (r’s=0.93-0.99) and good for the memory test (r=0.78). Test-retest reliabilities ranged from acceptable to excellent for cognitive tasks (ICC: 0.70-0.96) and were excellent for the balance (ICC=0.97) and good for FTT (ICC=0.89). Smartphone EF measures were strongly associated with the UDS3-EF composite (ß's=0.6-0.8, all p<.001), and the memory test was strongly correlated with total immediate recall on the CVLT3-BF (ß=0.7, p<.001). Smartphone FTT was associated with mechanical FTT (ß=0.9, p=.02), and greater acceleration on the balance test was associated with more motor features (ß=0.6, p=0.02). Worse performance on all cognitive tests was associated with greater disease severity (ß's=0.5-0.7, all p<.001). Poorer performance on the smartphone EF tasks was associated with smaller frontoparietal/subcortical volume (ß's=0.4-0.6, all p<.015) and worse memory scores with smaller hippocampal volume (ß=0.5, p<.001).

These results suggest remote digital data collection of cognitive and motor functioning in FTD research is feasible and acceptable. These findings also support the reliability and validity of unsupervised ALLFTD Mobile App cognitive tests and provide preliminary support for the motor measures, although further study in larger samples is required.

We examined demographic, clinical, and psychological characteristics of a large cohort (n = 368) of adults with dissociative seizures (DS) recruited to the CODES randomised controlled trial (RCT) and explored differences associated with age at onset of DS, gender, and DS semiology.

Prior to randomisation within the CODES RCT, we collected demographic and clinical data on 368 participants. We assessed psychiatric comorbidity using the Mini-International Neuropsychiatric Interview (M.I.N.I.) and a screening measure of personality disorder and measured anxiety, depression, psychological distress, somatic symptom burden, emotional expression, functional impact of DS, avoidance behaviour, and quality of life. We undertook comparisons based on reported age at DS onset (<40 v. ⩾40), gender (male v. female), and DS semiology (predominantly hyperkinetic v. hypokinetic).

Our cohort was predominantly female (72%) and characterised by high levels of socio-economic deprivation. Two-thirds had predominantly hyperkinetic DS. Of the total, 69% had ⩾1 comorbid M.I.N.I. diagnosis (median number = 2), with agoraphobia being the most common concurrent diagnosis. Clinical levels of distress were reported by 86% and characteristics associated with maladaptive personality traits by 60%. Moderate-to-severe functional impairment, high levels of somatic symptoms, and impaired quality of life were also reported. Women had a younger age at DS onset than men.

Our study highlights the burden of psychopathology and socio-economic deprivation in a large, heterogeneous cohort of patients with DS. The lack of clear differences based on gender, DS semiology and age at onset suggests these factors do not add substantially to the heterogeneity of the cohort.

Available data suggest that sex hormone levels during puberty may affect symptom onset and expression, treatment responsiveness and outcomes in schizophrenia, whereas post-pubertal adolescents may have a similar clinical presentation and treatment response compared to adults with schizophrenia.

Post-hoc analyses were conducted to assess the similarity of short- and long-term efficacy between post-pubertal adolescents and adults with schizophrenia treated with aripiprazole.

Based on available European epidemiologic data, a cut-off age of 15 years was used to isolate a subgroup of mostly post-pubertal adolescents with schizophrenia in aripiprazole clinical studies. Outcome measures from this subgroup (ages 15-17; n=147) were then compared to outcomes from one adult study (n=853) on short and long-term measures of efficacy, including PANSS scores, response rates, and remission rates.

Comparable short and long-term treatment effects were observed on the PANSS total and subscale scores, demonstrated by overlapping 95% confidence intervals (mean change from baseline in PANSS total score (OC dataset): at week 6 in adults: -27,7; in adolescents 15-17 yr: -29,6; at week 30 in adults: -39,2; in adolescents 15-17 yr: -36). Percent of adolescents achieving response (defined as ≥ 30% decrease in PANSS total score from baseline) at 32 weeks (80,2%) on open label treatment was similar to that in adult studies at week 34 (80%) on double blind treatment (OC dataset).

Adolescents with schizophrenia (ages 15-17, mostly post-pubertal) demonstrate a positive treatment response in short-term and long-term studies which is similar to that observed in the adult patient population.

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.

Brexpiprazole is a serotonin-noradrenaline-dopamine agent that binds with high affinity to multiple serotonin, norepinephrine and dopamine receptors. In particular, Brexpiprazole is a partial agonist at dopamine D2/D3 and 5-HT1A receptors and an antagonist at 5-HT2A and norepinephrine alpha1B receptors.

We assessed the efficacy and safety of brexpiprazole versus placebo as adjunctive therapy to anti-depressant therapy (ADT) in subjects with MDD who demonstrated inadequate response to ADT.

This trial had 3 phases: a screening phase (7-28 days); a prospective phase (Phase A): 8-week, single-blind placebo plus an investigator-determined, open-label ADT; a randomized phase (Phase B): 6-week, double-blind, adjunctive brexpiprazole (2 mg/day) vs. placebo in patients with an inadequate response to ADT.

The primary efficacy endpoint was the change from the end of Phase A (Week 8) to the end of Phase B (Week 14) in MADRS Total Score. The key secondary endpoint was the change in mean SDS score. Other secondary endpoints were mean change in CGI-S, IDS-R, HAMD and HAMA.

Of 379 randomized patients, completion rates at Week 14 were high (92.9%). Statistically significant improvements in mean MADRS Total score were observed for subjects receiving adjunctive brexpiprazole 2mg/day compared with placebo (p=0.0001) at endpoint. In addition, on all secondary endpoints Brexpiprazole showed a statistically significant advantage over placebo.

Commonly reported adverse events in the brexpiprazole group (>5% and more than twice placebo) were weight gain (8.0%), akathisia (7.4%).

Brexpiprazole was effective and well tolerated as adjunctive treatment for MDD patients with an inadequate response to ADT.

Animal assisted therapy (AAT) is becoming increasingly utilized for psychiatric patients with suboptimal response to traditional therapies. Larger animals, such as horses, may be especially effective therapy enhancers for some patients.

We have introduced AAT at a 500 bed psychiatric hospital in New Jersey. We previously conducted a randomized control trial (n=103) of ten weekly AAT group therapy sessions, comparing canine assisted therapy, equine facilitated therapy (EFT), enhanced psychosocial therapy, and standard treatment in highly regressed and/or violent patients. Initial analyses indicated that the EFT group had fewer violence-related incidents during the 3 months following the intervention compared with the other groups (p< 0.05).

We have initiated a second randomized controlled study comparing EFT with standard hospital treatment in a similar sample.

Based on observations that patients with trauma/abuse histories may find AAT beneficial, this partial replication study is assessing whether trauma history and perceptions relate to symptomatic and functional outcome with EFT.

Preliminary post-session interviews over several weeks for a subgroup of four patients with reported trauma histories (rates comparable to persons with PTSD on the Traumatic Life Events Questionnaire) elicited explicit trauma-related themes (e.g., recollection of past abuse) as well as putative indirect references such as identifying with the horses as understanding their pain and representing “hope.”

The presentation reviews the evolution and refinement of the intervention at our hospital, challenges to implementation, therapeutic course, preliminary outcome assessments, quantitative and qualitative, comparing EFT with standard treatment in the studies.