Magnitude and Correlates of Symptomatic, Global Illness, and Social Functioning Response; Out-of-Home Placement; and Length of Stay in 1,189 Consecutively Hospitalized Children and Adolescents With Mental Disorders.

Objective: To identify outcome predictors in hospitalized youth with mental disorders.Methods: This retrospective analysis of systematically recorded clinical parameters in youth hospitalized for psychiatric treatment in 2004-2015 assessed magnitude and correlates of symptom response (SR), global illness response (GIR), social functioning (SF), out-of-home placement (OOHP), and length of stay (LOS). Backward elimination regression analyses were performed to identify independent baseline correlates of each of the 5 outcomes, with R2 representing the variance explained by the independent correlates retained in the final model.Results: Across 1,189 youth (median age = 14.4 years; interquartile range = 11.6,16.1 years; range, 5-19 years; females = 61.5%), frequencies of coprimary outcomes were as follows: SR = 57.5% (statistically significant correlates = 13, R2 = 0.154), GIR = 30.0% (correlates = 5, R2 = 0.078), SF = 19.0% (correlates = 8, R2 = 0.207), OOHP recommendation = 35.2% (correlates = 13, R2 = 0.275), and mean ± SD LOS = 65.0 ± 37.5 days (correlates = 11, R2 = 0.219). In multivariable analyses, 11 factors were statistically significantly (P < .05) associated with > 1 poor outcome: 4 with 4 outcomes (disturbed social interaction, substance abuse/dependence symptoms; sole exception for both = LOS; disturbed drive/attention/impulse control, sole exception = OOHP; higher admission BMI percentile [but shorter LOS], sole exception = GIR), 3 with 3 outcomes (higher admission age [but good SF and shorter LOS], more abnormal psychosocial circumstances, more mental health diagnoses), and 4 with 2 outcomes (intelligence level [IQ] < 85, obsessive-compulsive disorder symptoms, disturbed social behavior, somatic findings). Additionally, 17 correlates were statistically significantly (P < .05) associated with 1 outcome, ie, SR = 6, OOHP = 5, LOS = 5, SF = 1.Conclusions: Higher admission BMI percentile, disturbed social interaction, disturbed drive/attention/impulse control, and substance abuse/dependence symptoms were independently associated with multiple poor outcomes in mentally ill youth requiring inpatient care. Knowledge of global and specific correlates of poor inpatient treatment outcomes may help inform treatment decisions.

Patient characteristics, validity of clinical diagnoses and Outcomes Associated with Suicidality in Inpatients with Symptoms of Depression (OASIS-D): design, procedures and outcomes.

BACKGROUND: Suicidality, ranging from passive suicidal thoughts to suicide attempt, is common in major depressive disorder (MDD). However, relatively little is known about patient, illness and treatment characteristics in those with co-occurring MDD and suicidality, including the timing of and factors associated with the offset, continuation or reemergence of suicidality. Here, we present the background, rationale, design and hypotheses of the Patient Characteristics, Validity of Clinical Diagnoses and Outcomes Associated with Suicidality in Inpatients with Symptoms of Depression (OASIS-D) study, an investigator-initiated, observational study, funded by Janssen-Cilag GmbH. METHODS/RESULTS: OASIS-D is an eight-site, six-month, cohort study of patients aged 18-75 hospitalized with MDD. Divided into three sub-studies and patient populations (PPs), OASIS-D will (i) systematically characterize approximately 4500 consecutively hospitalized patients with any form of unipolar depressive episode (PP1), (ii) evaluate the validity of the clinical diagnosis of moderate or severe unipolar depressive episode with the Mini-International Neuropsychiatric Interview (M.I.N.I.) and present suicidality (at least passive suicidal thoughts) present ≥ 48 h after admission with the Sheehan-Suicide Tracking Scale (S-STS), assessing also predictors of the diagnostic concordance/discordance of MDD in around 500 inpatients (PP2), and (iii) characterize and prospectively follow for 6 months 315 inpatients with a research-verified moderate or severe unipolar depressive episode and at least passive suicidal thoughts ≥ 48 h after admission, evaluating treatment and illness/response patterns at baseline, hospital discharge, 3 and 6 months. Exploratory objectives will describe the association between the number of days with suicidality and utilization of outpatient and inpatient care services, and structured assessments of factors influencing the risk of self-injurious behavior without suicidal intent, and of continuous, intermittent or remitted suicidality during the 6-month observation period. CONCLUSION: Despite their frequency and clinical relevance, relatively little is known about patient and treatment characteristics of individuals with MDD and suicidality, including factors moderating and mediating the outcome of both MDD and suicidality. Results of the OASIS-D study are hoped to improve the understanding of the frequency, correlates and 6-month naturalistic treatment and outcome trajectories of different levels of suicidality in hospitalized adults with MDD and suicidality. TRIAL REGISTRATION: NCT04404309 [ClinicalTrials.gov].

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.