Specialized inpatient treatment for young people with early psychosis: acute-treatment and 12-month results.

The objective of the study was to investigate the development of clinical outcomes of young people with early psychosis in a specialized inpatient treatment and assess the feasibility of such an intervention in an inpatient setting. The study was a prospective cohort study of patients with early psychosis treated at the specialized inpatient treatment "Fühinterventions-und Therapiezentrum, FRITZ" (early intervention and therapy center) in Berlin, Germany. The primary outcomes were attitudes towards psychiatric medication and patient satisfaction with treatment after 6 weeks. Secondary outcomes were clinical symptoms, functioning, remission, recovery, all-cause treatment discontinuation, and rehospitalisation at 6 and 12 months after inpatient treatment. We recruited 95 inpatients with early psychosis. Attitudes towards psychiatric medication (Δ6weeks = 3.00, d6weeks = 0.55; Δ6mo = 2.15, d6mo = 0.35; Δ12mo = 3.03, d12mo = 0.52) and patient satisfaction (Δ6weeks = 0.21, d6weeks = 0.40; Δ6mo = 0.32, d6mo = 0.43; Δ12mo = 0.13, d12mo = 0.17) changed with medium effect sizes at six weeks up to a 6- and 12-month follow-up. Clinical outcomes changed significantly with medium-to-large-effect sizes over 12 months CGIΔ12mo = 1.64, d12mo = -1.12; PANSS totalΔ12mo = 20.10, d12mo = -0.76; GAFΔ12mo = 19.58, d12mo = 1.25). The all-cause treatment discontinuation rate was 13.69% (n = 13) at a 6-month and 35.79% (n = 34) at a 12-month follow-up. The rehospitalization rate was 30.53% (n = 29) at a 6-month and 43.16% (n = 41) at a 12-month follow-up. Patients with specialized inpatient treatment for early psychosis showed improvements in attitude towards psychiatric medication, patient satisfaction, symptoms, and functioning for up to 12 months.Trial registration: DRKS00024351, 2021/02/11 retrospectively registered.

Long-Acting Injections in Schizophrenia: a 3-Year Update on Randomized Controlled Trials Published January 2016-March 2019.

PURPOSE OF REVIEW: This study was conducted in order to review randomized controlled trial (RCT) data published January 2016-March 2019 on long-acting injectable antipsychotics (LAIs) for schizophrenia. RECENT FINDINGS: Thirty-one RCTs (primary studies = 7; post hoc analyses = 24; n = 4738) compared LAIs vs. placebo (studies = 11, n = 1875), LAIs vs. oral antipsychotics (OAPs) (studies = 7, n = 658), and LAI vs. LAI (studies = 13, n = 2205). LAIs included two new formulations, aripiprazole lauroxil nanocrystal dispersion and subcutaneously injectable risperidone Perseris, as well as aripiprazole lauroxil, aripiprazole once-monthly, paliperidone once-monthly, paliperidone 3-monthly, and risperidone-LAI. Regarding prevention of relapse and hospitalization, LAIs consistently outperformed placebo, being partly superior to OAPs, without relevant LAI-LAI differences. LAIs were comparable to OAPs regarding all-cause discontinuation, functioning, quality of life, and tolerability, being associated with higher patient satisfaction and service engagement. Recent meta-analyses yielded mixed results, but never favoring OAPs over LAIs. In RCTs, LAIs are superior to placebo, but only in some aspects, superior to OAPs. Comparative effectiveness of LAIs vs. OAPs requires further study, ideally in generalizable/real-world samples.

Keeping up with the therapeutic advances in schizophrenia: a review of novel and emerging pharmacological entities.

Schizophrenia remains one of the most severe medical diseases. Current dopamine modulating first-generation and second-generation antipsychotics target mainly positive symptoms, but not/inadequately negative and cognitive symptoms. Additional challenges include non-adherence and adverse effects, especially cardiometabolic dysregulation. This review evaluates new/emerging pharmacological treatments for schizophrenia. Therapies targeting total symptoms include cannabidiol, D3 antagonist/5-HT1A partial agonist F17464, lumateperone (ITI-007), phosphodiesterase 10A (PDE10A) inhibitors MK-8189 and TAK-063, sodium nitroprusside, and trace amine-associated receptor-1 (TAAR1) agonist RO5263397 and SEP-363856. Treatments targeting negative symptoms include the PDE10A inhibitor LuAF-11167, 5-HT2A inverse agonist pimavanserin, sigma-2/5-HT2A antagonist roluperidone (MIN-101), and d-amino acid oxidase (DAAO) inhibitor TAK-831. Agents targeting primarily cognitive dysfunction are the glycine transporter-1 inhibitor BI-425809 and cannabidiol. Therapies targeting residual positive symptoms/treatment-resistant schizophrenia include pimavanserin, dopamine D1/D2 antagonist LuAF-35700, and DAAO inhibitor sodium benzoate. Two new long-acting injectable antipsychotic formulations, Aripiprazole Lauroxil NanoCrystal® and the first subcutaneous injectable LAI Perseris (RBP-7000), were recently approved by U.S. Food and Drug Administration, and positive results were announced for Risperidone ISM®, each achieving therapeutic levels within 24 hours, without need for initial oral cotreatment/loading injection-strategies. Paliperidone palmitate 6-monthly intramuscularly injectable and Risperidone subcutaneously injectable TV46000 are currently under investigation. Finally, the samidorphan+olanzapine combination targets reduced weight gain liability, while maintaining olanzapine's efficacy. Most of these trial programs are still ongoing or have yielded mixed or even negative results. Thus, additional mechanisms of action and agents require study to improve schizophrenia outcomes for total/positive symptoms with reduced adverse effects, but also cognitive symptoms, negative symptoms, and treatment resistance, the areas of greatest need in schizophrenia currently.

soulspace: Integrated youth mental health care in Berlin, Germany-An introduction to the program and a description of its users.

AIM: A substantial gap between young people's need for mental health care services and their actual access to such services led worldwide organizations (e.g., the WHO) to recommend the implementation of early intervention programs and youth mental health services. Some countries around the world have established structures to meet this recommendation. In this paper, we describe soulspace as the first integrated youth mental health service for young people aged between 15 and 35 years in Berlin, Germany. METHODS: We introduce soulspace as easily accessible mental health care for young people, and we characterize soulspace along the lines of the internationally established eight key principles of integrated youth mental health services (Killackey, et al., 2020, World Economic Forum). Soulspace is a cooperation between clinical outpatient units of psychiatric clinics for adolescents and young adults as well as a community-based counselling service. It provides initial contact, counselling, diagnostics, and treatment. RESULTS: Our analyses of the pathways to soulspace and the characteristics of the soulspace users suggest that the low threshold is a facilitator to help finding for young people in comparison to more conventional early intervention models. That is, having transferred the early intervention center in a youth-facing counselling service as was done in soulspace seems to have reduced the threshold to seek help for families and for young people in need for support. CONCLUSIONS: In summary, with soulspace, an easily accessible mental health care service was established that integrates counselling and specialized psychiatric treatment if needed.

Feasibility and efficacy of an acceptance and mindfulness-based group intervention for young people with early psychosis (Feel-Good group).

Background: Over the last decade, researchers have sought for alternative interventions that have better treatment effects than Cognitive Behavioral Therapy (CBT) when treating psychotic symptoms. Mindfulness-based interventions have been a proposed alternative to CBT, yet research regarding its feasibility, acceptance and effectiveness is lacking when treating individuals with early psychosis in inpatient settings. Objective: Before conducting a large-scale randomized-controlled trial (RCT), this pilot study evaluated the feasibility and the potential efficacy of a mindfulness-based inpatient group intervention that targets emotion regulation in patients with early psychosis, and thus indirectly improving psychotic symptoms. Methods: A pre-post study was performed. Thirty-six patients with early psychosis treated at the specialized inpatient treatment "Frühinterventions- und Therapiezentrum; FRITZ" (early intervention and therapy center) received eight group therapy sessions. Assessments were performed at baseline, after 8 weeks post treatment and at follow-up after 16 weeks. Results: Rates of patients who participated in the study suggests that a mindfulness-based group therapy is highly accepted and feasible for patients with early psychosis being treated in an inpatient ward. Friedman analyses revealed significant changes in the primary outcomes of emotional goal attainment (Goal 1: W = 0.79; Goal 2: W = 0.71) and psychotic symptoms (PANSS-T: W = 0.74). Significant, albeit small, effect sizes were found in patients' self-perception of emotion regulation skills (ERSQ: W = 0.23). Discussion: We found favorable findings regarding the feasibility and acceptance of the Feel-Good mindfulness-based intervention. Results of the study provide a basis for an estimation of an adequate sample size for a fully powered RCT that needs to be conducted to test whether Feel-Good is effective in the inpatient treatment of psychotic symptoms for individuals with early psychosis. Clinical trial registration: [https://clinicaltrials.gov/ct2/show/NCT04592042], identifier [NCT04592042].

Early Antipsychotic Nonresponse as a Predictor of Nonresponse and Nonremission in Adolescents With Psychosis Treated With Aripiprazole or Quetiapine: Results From the TEA Trial.

OBJECTIVE: To evaluate 1) whether early nonresponse to antipsychotics predicts nonresponse and nonremission, 2) patient and illness characteristics as outcome predictors, and 3) response prediction of 30-item Positive and Negative Syndrome Scale (PANSS-30) compared with 6-item PANSS (PANSS-6) and Clinical Global Impressions-Improvement Scale (CGI-I) in youths with first-episode psychosis. METHOD: Post hoc analysis from a 12-week, double-blinded, randomized trial of aripiprazole vs extended-release quetiapine in adolescents (age 12-17 years) with first-episode psychosis was performed. Early nonresponse (week 2 or week 4) was defined as <20% symptom reduction (PANSS-30) (or <20% symptom reduction [PANSS-6] or CGI-I score 4-7 [less than "minimally improved"]). Nonresponse (week 12) was defined as <50% symptom reduction (PANSS-30). Nonremission (week 12) was defined as a score of >3 on 8 selected PANSS-items. Positive/negative predictive values (PPV/NPV) and receiver operating characteristics, binary logistic regression models, and PPV/NPV using PANSS-6 and CGI-I were analyzed. RESULTS: Of 113 randomized patients, 84 were included in post hoc analysis (mean [SD] age = 15.7 [1.3] years; 28.6% male). The 12-week symptom decrease was 31.9% [27.9%], most pronounced within the first 2 weeks (61.1% of total PANSS reduction). Response (27.4%) and remission (22.6%) rates were low. Results indicated that early nonresponse reliably predicted 12-week nonresponse (PPV: week 2, 82.2%; week 4, 90.0%) and nonremission (PPV: week 2, 80.0%; week 4, 90.0%); early nonresponse at week 4 was a statistically significant baseline predictor for 12-week nonresponse; and PANSS-6 had similar predictive significance as PANSS-30. However, outcomes were heterogeneous using CGI-I. CONCLUSION: In youths with first-episode psychosis showing early nonresponse to aripiprazole or extended-release quetiapine, switching antipsychotic drug should be considered. PANSS-6 is a feasible and clinically relevant alternative to PANSS-30 to predict 12-week nonresponse/nonremission. CLINICAL TRIAL REGISTRATION INFORMATION: Tolerance and Effect of Antipsychotics in Children and Adolescents With Psychosis; https://www. CLINICALTRIALS: gov/; NCT01119014.