BackgroundDysfunction of neuroplasticity due to N-methyl-d-aspartate (NMDA) receptor hypofunction may be a causal factor for memory and executive dysfunctioning in schizophrenia. Deregulation of NMDA transmission in the prefrontal cortex may also explain negative and positive symptoms. Clozapine augmentation with memantine targets altered NMDA receptor-mediated neurotransmission in schizophrenia and showed substantial beneficial effects on several symptom domains in a small proof-of-concept study. We evaluate effects of memantine add-on treatment to clozapine for memory and executive function, and negative and positive symptoms in schizophrenia.MethodClozapine-treated patients with refractory schizophrenia were randomly assigned to 12 weeks of double-blind adjunctive treatment with memantine (n = 26) or placebo (n = 26). Crossover occurred after a 2-week placebo wash-out period. Primary endpoints were change from baseline to 12 weeks treatment and 14 weeks to 26 weeks treatment on memory and executive function using the Cambridge Neuropsychological Test Automated Battery (CANTAB), Positive and Negative Syndrome Scale (PANSS), and Clinical Global Impression Severity Scale (CGI-S). Side effects were assessed using the Liverpool University Neuroleptic Side-Effect Rating Scale.ResultsWhen compared with placebo, memantine improved a composite memory score comprising verbal recognition memory and paired associates learning task scores on the CANTAB (effect size = 0.30) and PANSS negative subscale score (effect size = 0.29). Side effects were mild and transient.ConclusionsIn patients with clozapine-treated refractory schizophrenia, memantine addition significantly improved verbal and visual memory and negative symptoms without serious adverse effects. These results justify further investigations on long-term memantine augmentation to clozapine in treatment-resistant schizophrenia.

Background Evidence for the effectiveness of treatments in early-onset psychosis is sparse. Current guidance for the treatment of early-onset psychosis is mostly extrapolated from trials in adult populations. The UK National Institute for Health and Care Excellence has recommended evaluation of the clinical effectiveness and cost-effectiveness of antipsychotic drugs versus psychological intervention (cognitive behavioural therapy [CBT] and family intervention) versus the combination of these treatments for early-onset psychosis. The aim of this study was to establish the feasibility of a randomised controlled trial of antipsychotic monotherapy, psychological intervention monotherapy, and antipsychotics plus psychological intervention in adolescents with first-episode psychosis.Methods We did a multicentre pilot and feasibility trial according to a randomised, single-blind, three-arm, controlled design. We recruited participants from seven UK National Health Service Trust sites. Participants were aged 14-18 years; help-seeking; had presented with first-episode psychosis in the past year; were under the care of a psychiatrist; were showing current psychotic symptoms; and met ICD-10 criteria for schizophrenia, schizoaffective disorder, or delusional disorder, or met the entry criteria for an early intervention for psychosis service. Participants were assigned (1:1:1) to antipsychotics, psychological intervention (CBT with optional family intervention), or antipsychotics plus psychological intervention. Randomisation was via a web-based randomisation system, with permuted blocks of random size, stratified by centre and family contact. CBT incorporated up to 26 sessions over 6 months plus up to four booster sessions, and family intervention incorporated up to six sessions over 6 months. Choice and dose of antipsychotic were at the discretion of the treating consultant psychiatrist. Participants were followed up for a maximum of 12 months. The primary outcome was feasibility (ie, data on trial referral and recruitment, session attendance or medication adherence, retention, and treatment acceptability) and the proposed primary efficacy outcome was total score on the Positive and Negative Syndrome Scale (PANSS) at 6 months. Primary outcomes were analysed by intention to treat. Safety outcomes were reported according to as-treated status, for all patients who had received at least one session of CBT or family intervention, or at least one dose of antipsychotics. The study was prospectively registered with ISRCTN, ISRCTN80567433. Findings Of 101 patients referred to the study, 61 patients (mean age 16•3 years [SD 1•3]) were recruited fromApril 10, 2017, to Oct 31, 2018, 18 of whom were randomly assigned to psychological intervention, 22 to antipsychotics, and 21 to antipsychotics plus psychological intervention. The trial recruitment rate was 68% of our target sample size of 90 participants. The study had a low referral to recruitment ratio (around 2:1), a high rate of retention (51 [84%] participants retained at the 6-mon...

Background This article provides a generalizable method, rooted in co-design and stakeholder engagement, to identify, specify, and prioritize implementation strategies. To illustrate this method, we present a case example focused on identifying strategies to promote pediatric hypertension (pHTN) Clinical Practice Guideline (CPG) implementation in community health center-based primary care practices that involved meaningful engagement of pediatric clinicians, clinic staff, and patients/caregivers. This example was chosen based on the difficulty clinicians and organizations experience in implementing the pHTN CPG, as evidenced by low rates of guideline-adherent pHTN diagnosis and treatment. Methods We convened a Stakeholder Advisory Panel (SAP), comprising 6 pediatricians and 5 academic partners, for 8 meetings (~12 h total) to rigorously identify determinants of pHTN CPG adherence and to ultimately develop a testable multilevel, multicomponent implementation strategy. Our approach expanded upon the Expert Recommendations for Implementation Change (ERIC) protocol by incorporating a modified Delphi approach, user-centered design methods, and the Implementation Research Logic Model (IRLM). At the recommendation of our SAP, we gathered further input from youth with or at-risk for pHTN and their caregivers, as well as clinic staff who would be responsible for carrying out facets of the implementation strategy. Results First, the SAP identified 17 determinants, and 18 discrete strategies were prioritized for inclusion. The strategies primarily targeted determinants in the domains of intervention characteristics, inner setting, and characteristics of the implementers. Based on SAP ratings of strategy effectiveness, feasibility, and priority, three tiers of strategies emerged, with 7 strategies comprising the top tier implementation strategy package. Next, input from caregivers and clinic staff confirmed the feasibility and acceptability of the implementation strategies and provided further detail in the definition and specification of those strategies. Conclusions This method—an adaptation of the ERIC protocol—provided a pragmatic structure to work with stakeholders to efficiently identify implementation strategies, particularly when supplemented with user-centered design activities and the intuitive organizing framework of the IRLM. This generalizable method can help researchers identify and prioritize strategies that align with the implementation context with an increased likelihood of adoption and sustained use.

The cumulative effect of repeated traumatic experiences in early childhood incrementally increases the risk of adjustment problems later in life. Surviving traumatic environments can lead to the development of an interrelated constellation of emotional and interpersonal symptoms termed complex posttraumatic stress disorder (CPTSD). Effective treatment of trauma begins with a multimethod psychological assessment and requires the use of several evidence-based therapeutic processes, including establishing a safe therapeutic environment, reprocessing the trauma, constructing a new narrative, and managing emotional dysregulation. Therapeutic Assessment (TA) is a semistructured, brief intervention that uses psychological testing to promote positive change. The case study of Kelly, a middle-aged woman with a history of repeated interpersonal trauma, illustrates delivery of the TA model for CPTSD. Results of this single-case time-series experiment indicate statistically significant symptom improvement as a result of participating in TA. We discuss the implications of these findings for assessing and treating trauma-related concerns, such as CPTSD.

No abstract