There is some initial evidence that attachment security priming may be useful for promoting engagement in therapy and improving clinical outcomes.

This study sought to assess whether outcomes for behavioural activation delivered in routine care could be enhanced via the addition of attachment security priming.

This was a pragmatic two-arm feasibility and pilot additive randomised control trial. Participants were recruited with depression deemed suitable for a behavioural activation intervention at Step 2 of a Talking Therapies for Anxiety and Depression service. Ten psychological wellbeing practitioners were trained in implementing attachment security priming. Study participants were randomised to either behavioural activation (BA) or BA plus an attachment prime. The diagrammatic prime was integrated into the depression workbook. Feasibility outcomes were training satisfaction, recruitment, willingness to participate and study attrition rates. Pilot outcomes were comparisons of clinical outcomes, attendance, drop-out and stepping-up rates.

All practitioners recruited to the study, and training satisfaction was high. Of the 39 patients that were assessed for eligibility, 24 were randomised (61.53%) and there were no study drop-outs. No significant differences were found between the arms with regards to drop-out, attendance, stepping-up or clinical outcomes.

Further controlled research regarding the utility of attachment security priming is warranted in larger studies that utilise manipulation checks and monitor intervention adherence.

Adolescent major depressive disorder (MDD) is associated with disrupted processing of emotional stimuli and difficulties in cognitive reappraisal. Little is known however about how current pharmacotherapies act to modulate the neural mechanisms underlying these key processes. The current study therefore investigated the neural effects of fluoxetine on emotional reactivity and cognitive reappraisal in adolescent depression.

Thirty-one adolescents with MDD were randomised to acute fluoxetine (10 mg) or placebo. Seventeen healthy adolescents were also recruited but did not receive any treatment for ethical reasons. During functional magnetic resonance imaging (fMRI), participants viewed aversive images and were asked to either experience naturally the emotional state elicited (‘Maintain’) or to reinterpret the content of the pictures to reduce negative affect (‘Reappraise’). Significant activations were identified using whole-brain analysis.

No significant group differences were seen when comparing Reappraise and Maintain conditions. However, when compared to healthy controls, depressed adolescents on placebo showed reduced visual activation to aversive pictures irrespective of the condition. The depressed adolescent group on fluoxetine showed the opposite pattern, i.e. increased visuo-cerebellar activity in response to aversive pictures, when compared to depressed adolescents on placebo.

These data suggest that depression in adolescence may be associated with reduced visual processing of aversive imagery and that fluoxetine may act to reduce avoidance of such cues. This could reflect a key mechanism whereby depressed adolescents engage with negative cues previously avoided. Future research combining fMRI with eye-tracking is nonetheless needed to further clarify these effects.

Looked-after children are at risk of suboptimal attachment patterns and reactive attachment disorder (RAD). However, access to interventions varies widely, and there are no evidence-based interventions for RAD.

To modify an existing parenting intervention for children with RAD in the UK foster care setting, and test the feasibility of conducting a randomised controlled trial (RCT) of the modified intervention.

The intervention was modified with expert input and tested on a case series. A feasibility and pilot RCT compared the new intervention with usual care. Foster carers and children in their care aged ≤6 years were recruited across nine local authorities, with 1:1 allocation and blind post-treatment assessments. The modified intervention was delivered in-home by trained mental health professionals over 4–6 months. Children were assessed for RAD symptoms, attachment quality and emotional/behavioural difficulties, and foster carers were assessed for sensitivity and stress.

Minimal changes to the intervention programme were necessary, and focused on improving its suitability for the UK foster care context. Recruitment was challenging, and remained below target despite modifications to the protocol and the inclusion of additional sites. Thirty families were recruited to the RCT; 15 were allocated to each group. Most other feasibility outcomes were favourable, particularly high numbers of data and treatment completeness. The revised intervention was positively received by practitioners and foster carers.

A large-scale trial may be feasible, but only if recruitment barriers can be overcome. Dedicated resources to support recruitment within local authorities and wider inclusion criteria are recommended.

The opioid epidemic in the United States is getting worse: in 2020 opioid overdose deaths hit an all-time high of 92,183. This underscored the need for more effective and readily available treatments for patients with opioid use disorder (OUD). Prescription digital therapeutics (PDTs) are FDA-authorized treatments delivered via mobile devices (eg, smartphones). A real-world pilot study was conducted in an outpatient addiction treatment program to evaluate patient engagement and use of a PDT for patients with OUD. The objective was to assess the ability of the PDT to improve engagement and care for patients receiving buprenorphine medication for opioid use disorder (MOUD).

Patients with OUD treated at an ambulatory addiction treatment clinic were invited to participate in the pilot. The reSET-O PDT is comprised of 31 core therapy lessons plus 36 supplementary lessons, plus contingency management rewards. Patients were asked to complete at least 4 lessons per week, for 12-weeks. Engagement and use data were collected via the PDT and rates of emergency room data were obtained from patient medical records. Data were compared to a similar group of 158 OUD patients treated at the same clinic who did not use the PDT. Abstinence data were obtained from deidentified medical records.

Pilot participants (N = 40) completed a median of 24 lessons: 73.2% completed at least 8 lessons and 42.5% completed all 31 core lessons. Pilot participants had significantly higher rates of abstinence from opioids in the 30 days prior to discharge from the program than the comparison group: 77.5% vs 51.9% (P < .01). Clinician-reported treatment retention for pilot participants vs the comparison group was 100% vs 70.9% 30 days after treatment initiation (P < .01), 87.5% vs 55.1% at 90 days post-initiation (P < .01), and 45.0% vs 38.6% at 180 days post-initiation (P = .46). Emergency room visits within 90 days of discharge from the addiction program were significantly reduced in pilot participants compared to the comparison group (17.3% vs 31.7%, P < .01).

These results demonstrate substantial engagement with a PDT in a real-world population of patients with OUD being treated with buprenorphine. Abstinence and retention outcomes were high compared to patients not using the PDT. These results demonstrate the potential value of PDTs to improve outcomes among patients with OUD, a population for which a significant need for improved treatments exists.

Trinity Health Innovation and Pear Therapeutics Inc.

Depression is characterised by negative views of the self. Antidepressant treatment may remediate negative self-schema through increasing processing of positive information about the self. Changes in affective processing during social interactions may increase expression of prosocial behaviours, improving interpersonal communications.

To examine whether acute administration of citalopram is associated with an increase in positive affective learning biases about the self and prosocial behaviour.

Healthy volunteers (n = 41) were randomised to either an acute 20 mg dose of citalopram or matched placebo in a between-subjects double-blind design. Participants completed computer-based cognitive tasks designed to measure referential affective processing, social cognition and expression of prosocial behaviours.

Participants administered citalopram made more cooperative choices than those administered placebo in a prisoner's dilemma task (β = 20%, 95% CI: 2%, 37%). Exploratory analyses indicated that participants administered citalopram showed a positive bias when learning social evaluations about a friend (β = 4.06, 95% CI: 0.88, 7.24), but not about the self or a stranger. Similarly, exploratory analyses found evidence of increased recall of positive words and reduced recall of negative words about others (β = 2.41, 95% CI: 0.89, 3.93), but not the self, in the citalopram group.

Participants administered citalopram showed greater prosocial behaviours, increased positive recall and increased positive learning of social evaluations towards others. The increase in positive affective bias and prosocial behaviours towards others may, at least partially, be a mechanism of antidepressant effect. However, we found no evidence that citalopram influenced self-referential processing.

The pan-Canadian Oncology Drug Review (pCODR) evaluates new cancer drugs for public funding recommendations. While pCODR's deliberative framework evaluates overall clinical benefit and includes considerations for exceptional circumstances, rarity of indication is not explicitly addressed. Given the high unmet need that typically accompanies these indications, we explored the impact of rarity on oncology HTA recommendations and funding decisions.

We examined pCODR submissions with final recommendations from 2012 to 2017. Incidence rates were calculated using pCODR recommendation reports and statistics from the Canadian Cancer Society. Indications were classified as rare if the incidence rate was lower than 1/100,000 diagnoses, a definition referenced by the Canadian Agency for Drugs and Technologies in Health. Each pCODR final report was examined for the funding recommendation/justification, level of supporting evidence (presence of a randomized control trial [RCT]), and time to funding (if applicable).

Of the ninety-six pCODR reviews examined, 16.6 percent were classified as rare indications per above criteria. While the frequency of positive funding recommendations were similar between rare and nonrare indication (78.6 vs. 75 percent), rare indications were less likely to be presented with evidence from RCT (50 vs. 90 percent). The average time to funding did not differ significantly across provinces.

Rare indications appear to be associated with weaker clinical evidence. There appears to be no association between rarity, positive funding recommendations, and time to funding. Further work will evaluate factors associated with positive recommendations and the real-world utilization of funded treatments for rare indications.

It is not clear to what extent associations between schizophrenia, cannabis use and cigarette use are due to a shared genetic etiology. We, therefore, examined whether schizophrenia genetic risk associates with longitudinal patterns of cigarette and cannabis use in adolescence and mediating pathways for any association to inform potential reduction strategies.

Associations between schizophrenia polygenic scores and longitudinal latent classes of cigarette and cannabis use from ages 14 to 19 years were investigated in up to 3925 individuals in the Avon Longitudinal Study of Parents and Children. Mediation models were estimated to assess the potential mediating effects of a range of cognitive, emotional, and behavioral phenotypes.

The schizophrenia polygenic score, based on single nucleotide polymorphisms meeting a training-set p threshold of 0.05, was associated with late-onset cannabis use (OR = 1.23; 95% CI = 1.08,1.41), but not with cigarette or early-onset cannabis use classes. This association was not mediated through lower IQ, victimization, emotional difficulties, antisocial behavior, impulsivity, or poorer social relationships during childhood. Sensitivity analyses adjusting for genetic liability to cannabis or cigarette use, using polygenic scores excluding the CHRNA5-A3-B4 gene cluster, or basing scores on a 0.5 training-set p threshold, provided results consistent with our main analyses.

Our study provides evidence that genetic risk for schizophrenia is associated with patterns of cannabis use during adolescence. Investigation of pathways other than the cognitive, emotional, and behavioral phenotypes examined here is required to identify modifiable targets to reduce the public health burden of cannabis use in the population.