Treatment Of Schizophrenia In Adolescents Research Articles

Long-term safety and effectiveness of lurasidone in adolescents and young adults with schizophrenia: pooled post hoc analyses of two 12-month extension studies

Background and ObjectivesThe aim of this analysis was to evaluate the long-term safety and effectiveness of lurasidone in the treatment of schizophrenia in adolescents and young adults (13–25).MethodsThe 2 pooled studies used similar designs and outcome measures. Patients (13–25) with schizophrenia completed an initial double-blind 6-week trial of lurasidone (40 and 80 mg/day) in the adolescent trial and (80 and 160 mg/day) in the young adult trial. In open-label long-term trials, adolescent patients were treated with 20–80 mg/day lurasidone, and adults were treated with 40–160 mg/day lurasidone. Efficacy was evaluated based on the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression-Severity Scale (CGI-S).ResultsThe safety population consisted of 306 patients (mean age, 16.2 years; 208 patients (68.0%) who completed 12 months of treatment; 8.2% who discontinued treatment by 12 months due to an adverse event). The mean (SD) changes in the PANSS total score from the extension baseline to months 6 and 12 were − 11.8 (13.9) and – 15.3 (15.0), respectively (OC), and the mean (SD) changes in the CGI-S score were − 0.8 (1.0) and − 1.0 (1.1), respectively (OC). The most frequent adverse events were headache (17.6%), anxiety (11.4%), schizophrenia (9.8%), and nausea (9.8%). No clinically meaningful changes were observed in weight, metabolic parameters, or prolactin.ConclusionsIn adolescents and young adults with schizophrenia, treatment with lurasidone was generally well tolerated and effective. Long-term treatment was associated with a continued reduction in symptoms of schizophrenia. Long-term treatment was associated with minimal effects on weight, metabolic parameters, and prolactin.Clinicaltrials.gov identifiers D1050234, D1050302.

Long-Term Safety and Effectiveness of Lurasidone in Adolescents and Young Adults With Schizophrenia: Pooled Post-hoc Analyses of Two 12-month Extension Studies

AbstractIntroductionEarlier onset of schizophrenia, which occurs more commonly in males, is characterized by greater illness severity, chronicity, and functional impairment with a less favorable prognosis than later-onset schizophrenia. The aim of this pooled analysis was to evaluate the long-term safety and effectiveness of lurasidone in the treatment of schizophrenia in adolescents (13–17 years) and young adults (18–25 years).MethodsThe 2 pooled studies used similar designs and outcome measures. Patients (13–25 years) with schizophrenia completed an initial double-blind 6-week trial of lurasidone (40 and 80 mg/d), and (80 and 160 mg/d) in the young adult trial. In the open-label long-term trials, adolescent patients were treated with 20-80 mg/d of lurasidone, and adults were treated with 40–160 mg/d of lurasidone. Efficacy was evaluated based on the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression-Severity Scale (CGI-S).ResultsThe safety population consisted of 306 patients (mean age, 16.2 years; 208 patients (68.0%) who completed 12 months of treatment; 8.2% discontinued by 12 months due to an adverse event. Mean (SD) change in the PANSS total score from extension Baseline to Months 6 and 12 was -11.8 (13.9) and -15.3 (15.0), respectively (OC); and mean (SD) change in the CGI-S score was -0.8 (1.0) and -1.0 (1.1), respectively (OC). The most frequent adverse events were headache (17.6%), anxiety (11.4%), schizophrenia (9.8%), and nausea (9.8). No clinically meaningful changes were observed in weight, metabolic parameters, or prolactin.ConclusionsIn adolescents and young adults with schizophrenia, treatment with lurasidone was generally well-tolerated and effective. Long-term treatment was associated with continued reduction in symptoms of schizophrenia. Long-term treatment was associated with minimal effects on weight, metabolic parameters, and prolactin.FundingAngelini Pharma S.p.A. and Sunovion Pharmaceuticals Inc.

Cost analysis of lurasidone for the treatment of schizophrenia in adolescents and adults within the United Kingdom

BackgroundSchizophrenia is a serious mental health condition characterised by distortions in thought processes, perception, mood, sense of self, and behaviour. Lurasidone, a second-generation atypical antipsychotic, represents an additional treatment option alongside existing antipsychotics for adolescents and adults with schizophrenia. An economic model was developed to evaluate the incremental costs of lurasidone as a first-line treatment option compared to existing antipsychotics.MethodsA Markov model was developed to estimate the cost impact of lurasidone as a first-line treatment option for both adolescents and adults. The sequence-based model incorporated the following health states: stable (no relapse or discontinuation), discontinuation (due to adverse events or other reasons), and relapse. Data used to determine the movement of patients between health states were obtained from network meta-analyses (NMAs). The time horizon ranged from three to five years (depending on the patient population) and a six-weekly cycle length was used. Unit costs and resource use were reflective of the UK NHS and Personal Social Services and consisted of the following categories: outpatient, adverse events, primary and residential care. Extensive deterministic sensitivity analysis was undertaken to assess the level of uncertainty associated with the base case results.ResultsLurasidone is demonstrated to be cost-saving as a first-line treatment within the adolescent and adult populations when compared to second-line and third-line respectively. Lurasidone is more expensive in terms of treatment costs, resource use (in the stable health state) and the treatment of adverse events. However, these costs are outweighed by the savings associated with the relapse health state. Lurasidone remains cost-saving when inputs are varied in sensitivity analysis and scenario analysis.ConclusionsLurasidone is a cost-saving first-line treatment for schizophrenia for both adolescents and adults.

Med Check: Lybalvi and Weight Gain; Rexulti and Schizophrenia; and More

Back to table of contents Previous article Next article Med CheckFull AccessMed Check: Lybalvi and Weight Gain; Rexulti and Schizophrenia; and MoreTerri D’ArrigoTerri D’ArrigoSearch for more papers by this authorPublished Online:28 Feb 2022https://doi.org/10.1176/appi.pn.2022.03.3.4Lybalvi Associated With Less Weight Gain Than OlanzapinePatients in a phase 3 trial who took Lybalvi (olanzapine and samidorphan) for schizophrenia, schizophreniform disorder, or bipolar I disorder gained less weight compared with patients who took olanzapine, Alkermes announced in February. Lybalvi is approved for the treatment of adults with schizophrenia, and for the treatment of adults with bipolar I disorder.In the trial, 408 patients aged 16 to 39 were randomized to receive either Lybalvi or olanzapine for up to 12 weeks. The primary endpoint was change in body weight from baseline to week 12. At study’s end, those who took Lybalvi experienced a mean weight gain of 4.91% and those who took olanzapine had a mean weight gain of 6.77%. The proportion of patients who gained 10% or more of their baseline body weight at three months was 21.9% for Lybalvi, compared with 30.4% for olanzapine. The mean change from baseline in waist circumference at three months was 2.99 cm for patients who took Lybalvi compared with 3.90 cm for patients who took olanzapine.Rexulti Approved For Treating Adolescents With SchizophreniaIn December the U.S. Food and Drug Administration (FDA) approved the atypical antipsychotic Rexulti (brexpiprazole) for the treatment of schizophrenia in adolescents aged 13 years or older, Otsuka America Pharmaceutical Inc. announced. The approval is based on the results of a phase 3 trial of 194 adolescents aged 13 to 17 years who had schizophrenia, of which 140 took Rexulti for at least six months. Adverse events reported in this age group were generally similar to those observed in adult patients and include a rise in total cholesterol from normal to high, lowering of HDL cholesterol, and an increase in triglycerides.The recommended starting dosage for adolescents is 0.5 mg once daily on for the first four days, taken orally with or without food, 1 mg once daily on the fifth through seventh days, then 2 mg on the eighth day, after which weekly dose increases can be made in 1 mg increments. The maximum recommended daily dosage is 4 mg.FDA Approves Quviviq for Treating InsomniaIn January the FDA approved Quviviq (daridorexant) 25 mg and 50 mg for the treatment of adults with insomnia who have trouble falling or staying asleep, Idorsia Ltd. announced. Quviviq is a dual orexin receptor antagonist and does not sedate the brain. It works by interfering with the processes through which naturally occurring orexin in the body controls wakefulness.In a phase 3 clinical trial that included 1,854 adults with insomnia, patients were randomized to receive Quviviq (10 mg, 25 mg, or 50 mg) or placebo once daily in the evening for three months. Primary efficacy endpoints for both studies were the change from baseline to the end of the first month and third month in how long it took for patients to fall asleep and how long they stayed asleep as measured by polysomnography in a sleep laboratory. Patients also reported their total sleep time every morning at home using a validated sleep diary questionnaire.Patients who took either 25 mg or 50 mg of Quviviq fell asleep more quickly, stayed asleep longer, and reported more total sleep at the end of the first month and third month compared with patients who took placebo. ■ ISSUES NewArchived

Lurasidona no Manejo do Transtorno do Espectro Autista: Uma Revisão

OBJECTIVE: To demonstrate that lurasidone can be an alternative for adolescents with Autistic Spectrum Disorder (ASD), especially if the patient has a history of adverse metabolic effects and / or ineffectiveness or intolerance to the use of aripiprazole or risperidone. METHODS: Systematic review of articles from the PubMed platform, with only articles in Portuguese and English being selected, with no period limitation. Inclusion criteria for the study: studies that address the treatment of ASD; studies that address treatment focusing on the use of lurasidone; works that bring clear methodology. RESULTS: Lurasidone has shown promise, given its low profile of adverse effects, such as lower weight gain, hyperlipidemia, hyperglycemia and insulin resistance. In addition to the potential benefits of lurasidone for the treatment of irritability in children with ASD, there may also be a potential antidepressant effect, which may influence the symptom profile. It is currently approved by the Food and Drug Administration (FDA) for the treatment of schizophrenia in adolescents from the age of thirteen and on monotherapy for bipolar depression from the age of ten. However, there are studies of tolerance in children and adolescents from the age of six with doses <120 mg / day. CONCLUSION: Given the risk of long-term adverse metabolic effects of most atypical antipsychotics, lurasidone can serve as an alternative. However, to date, no evidence has been found consistent with the use of lurasidone for patients with ASD who exhibit irritability, aggressiveness and impulsivity as associated symptoms.

Psychopharmacologic Treatment of Schizophrenia in Adolescents and Children.

An increasing number of antipsychotic medications have demonstrated efficacy in randomized placebo-controlled trials in the treatment of children and adolescents with schizophrenia. This review summarizes and synthesizes relevant antipsychotic medication studies, with particular emphasis on second-generation agents, and discusses other clinical considerations that may influence medication selection. With the exception of clozapine demonstrating superior efficacy in the improvement of psychotic symptoms in treatment-resistant patients, many antipsychotic agents have been shown to be similarly efficacious, including first-generation medications. Consideration of the side-effect profile, which can differ substantially from medication to medication, is essential when choosing treatment options.

Paliperidone in Adolescents: Clinical Experience

Introduction In child and adolescent psychiatry antipsychotics are used in large and increasing quantities for a wide range of disorders and psychopathology, including psychotic, mood and disruptive behaviour disorders. The European Medicines Agency (EMA) has approved Paliperidone for the treatment of schizophrenia in adolescents from 15 years old. Objective To present our clinical experience with Paliperidone in the treatment of psychotic symptoms and other psychopathological disorders in adolescents. Aims To describe with data from clinical practice the potential usefulness of Paliperidone in adolescent disorders beyond Schizophrenia. Methods Five patients from an outpatient child and adolescent mental health service, on treatment with Paliperidone during 2014, were selected as clinical illustration. Case reports describe personal and family history, clinical presentation, management and treatment, course and outcome, with especial focus in treatment tolerance. Results We present 3 males and 2 females, age between 15 and 17 years. Diagnoses were: autism, borderline personality disorder, schizotypal personality disorder, personality disorder not otherwise specified and schizophrenia. Prescribed dose was 3-9 mg/day, and actual mean time of treatment duration is 5,8 months. In 4 cases Paliperidone was initiated as a change from other antipsychotic. There were no adverse effects that required discontinuation and in all cases symptoms improved. Conclusion Our clinical experience evidences that Paliperidone is a valuable therapeutic option on behalf of its effectiveness and tolerance. In our practice the symptoms that respond better to Paliperidone are: hallucinations, reference ideation, irritability, aggression, disorganized behaviour and stereotypies.

Efficacy and safety of extended-release quetiapine fumarate in youth with bipolar depression: an 8 week, double-blind, placebo-controlled trial.

Quetiapine is an atypical antipsychotic with demonstrated efficacy in the treatment of adolescent schizophrenia and pediatric bipolar mania. Large, placebo-controlled studies of interventions in pediatric bipolar depression are lacking. The current study investigated the efficacy and safety of quetiapine extended-release (XR) in patients 10-17 years of age, with acute bipolar depression. This multicenter, double-blind, randomized, placebo-controlled study investigated quetiapine XR (dose range, 150-300 mg/day) in pediatric outpatients with an American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision (DSM-IV-TR) diagnosis of bipolar I or bipolar II disorder (current or most recent episode depressed) treated for up to 8 weeks (ClinicalTrials.gov identifier: NCT00811473). The primary study outcome was mean change in Children's Depression Rating Scale-Revised (CDRS-R) total score. Secondary efficacy outcomes included CDRS-R-based response and remission rates. Of 193 patients randomized to treatment, 144 patients completed the study (75.3% of quetiapine XR group [n=70]; 74.0% of placebo group [n=74]). Least squares mean changes in CDRS-R total score at week 8 were: -29.6 (SE, 1.65) with quetiapine XR and -27.3 (SE, 1.60) with placebo, a between-treatment group difference of -2.29 (SE, 1.99; 95% CI, -6.22, 1.65; p=0.25; mixed-model for repeated measures analysis). Rates of response and remission did not differ significantly between treatment groups. The safety profile of quetiapine XR was broadly consistent with the profile reported previously in adult studies of quetiapine XR and pediatric studies of quetiapine immediate-release (IR). Potentially clinically significant elevations in clinical chemistry values included triglycerides (9.3%, quetiapine XR; 1.4%, placebo group) and thyroid stimulating hormone (4.7%, quetiapine XR; 0%, placebo group). An adverse event potentially related to diabetes mellitus occurred in 3.3% of the quetiapine XR versus no adverse events in the placebo group. Quetiapine XR did not demonstrate efficacy relative to placebo in this 8 week study of pediatric bipolar depression. Quetiapine XR was generally safe and well tolerated.

Ziprasidone in Adolescents with Schizophrenia: Results from a Placebo-Controlled Efficacy and Long-Term Open-Extension Study

The purpose of this study was to evaluate the short- and long-term efficacy, safety, and tolerability of ziprasidone in adolescents with schizophrenia. Subjects ages 13-17 years with schizophrenia (American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 4th ed. [DSM-IV]) were enrolled in a 6 week, randomized, double-blind, placebo-controlled multicenter trial (RCT) followed by a 26 week open-label extension study (OLE). Subjects were randomized in a 2:1 ratio to flexible-dose oral ziprasidone (40-160 mg/day, based on weight) or placebo. Primary end-point was change from baseline in Brief Psychiatric Rating Scale-Anchored (BPRS-A) total score. Safety assessments included adverse events, vital signs, laboratory measures, electrocardiograms, weight and body mass index, and movement disorder ratings. Planned interim analysis for the primary end-point in the RCT resulted in early termination of both studies because of futility. In the RCT, 283 subjects received ziprasidone (n=193) or placebo (n=90). In the intent-to-treat analysis population, the least squares mean (SE) BPRS-A score decrease from baseline at week 6 was not significantly different (p=0.15; -14.16 [0.78] for ziprasidone and -12.35 [1.05] for placebo). Per-protocol analysis was significant (p=0.02). In the OLE, 221 subjects entered the OLE and received ziprasidone for a median of 99 days. The mean (SD) change in BPRS-A score from end of RCT to end of OLE (last observation carried forward) was -6.9 (8.9). The most common treatment-emergent adverse events (≥ 10%) for all causalities during the RCT were somnolence and extrapyramidal disorders, and during OLE was somnolence only. No subjects had Fridericia's corrected QT (QTcF) ≥ 500 ms in the RCT or OLE phases. One completed suicide occurred during the OLE phase. For RCT and OLE, no clinically significant changes were reported in metabolic indices and laboratory measures. Ziprasidone failed to separate from placebo in treatment of schizophrenia in adolescents. Ziprasidone was generally well tolerated with an overall neutral weight and metabolic profile. NCT00257192 and NCT00265382 at ClinicalTrials.gov .

An Integrated Approach for Establishing Dosing Recommendations

The Food and Drug Administration recently approved Invega for the treatment of schizophrenia in adolescents 12 to 17 years. If dosing recommendations for this population would have been based only on the results of the single efficacy trial included in this program, paliperidone dosing in adolescents might have been limited to 3 mg/d in adolescents less than 51 kg and to 6 mg/d in adolescents greater than or equal to 51 kg. This article provides an illustration of a more integrated approach to arrive at dosing recommendation that included practical considerations, modeling and simulation of data from the clinical trial, and the totality of evidence for both paliperidone and the parent drug, risperidone. On the basis of this integrated approach, the agency approved a starting dose of 3 mg/d in both adolescent weight groups and subsequent dosing in a range of 3 to 6 mg/d for adolescents less than 51 kg and 3 to 12 mg/d for adolescents greater than 51 kg, although the 3-mg dose was not evaluated in the greater than or equal to 51-kg group.

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Atypical neuroleptic medication and psychosis in adolescence

Introduction: Psychopharmacologic research in patients with early onset schizophrenia has been very limited. Only two previous reports [1,2] examined the efficacy of risperidone for the treatment of schizophrenia in adolescents, one of which was retrospective [2]. These studies found significant improvements and also a range of side effects. With only two retrospective open-label studies, the situation with regard to olanzapine is not better [3,4]. No previous study has compared the efficacy and tolerability of risperidone and olanzapine with haloperidol, the three most commonly prescribed medications in adolescents with schizophrenia.

Atypical neuroleptics in child- and adolescent psychiatry

Atypical neuroleptic drugs have enriched our treatment programs, especially in childhood and adolescent schizophrenia. Reviewed here is the use of atypical neuroleptics in children and adolescents with a schizophrenic disorder. The receptor binding profile and pharmacological properties, indications, side effects, clinical application, and trials of atypical neuroleptic drugs are compared to the classical neuroleptic drug haloperidol in the treatment of adolescent schizophrenia. Special attention is paid to the most common atypical neuroleptics clozapine, olanzapine and risperidone since most studies are carried out with these compounds, most often with clozapine. More clinically controlled trials have to be conducted since only one has been performed to date. The place of atypical neuroleptic drugs is discussed and further studies are necessary in order to differentiate, and eventually broaden the spectrum of the indications tested thus far.

The loyalty bind and sacrifice of the self: Family treatment of adolescent schizophrenia and schizophreniform disorder from a psychodynamic-systemic perspective

This article reviews treatment of families with a schizophrenically functioning adolescent from a psychodynamic systemic perspective. Systemic and psychoanalytic conceptions of family binding and the sacrificial nature of schizophrenic dysfunction, both on an intrapsychic and interpersonal level, provide the theoretical foundation for a multi-dimensional approach to treatment. This treatment approach is predicated on reframing of the adolescent's behavior, a co-therapy model of reparenting and multi-family group therapy to resolve the separation-individuation impasse characteristic of such families. The case of a 16 year old boy and his family is used to illustrate the concepts discussed.

The confrontation technique as used in the treatment of adolescent schizophrenia.

The confrontation technique as used in the treatment of adolescent schizophrenia.