CGI-S) And Improvement Research Articles

Autologous umbilical cord blood infusion for the treatment of autism in young children: A within-subjects open label study on safety (assessed via caregiver report) and efficacy.

This study aimed to document the safety and efficacy of a single infusion of autologous umbilical cord blood (UCB) in 20 autistic children aged 24-72 months. A pre-post treatment within-subjects open label design was used. At T = 0, 6, 12, and 18 months, participants underwent detailed and structured safety evaluations (via caregiver report), Vineland Adaptive Behavior Scale (Vineland-3), Stanford Binet Intelligence Scale (SB-5), Expressive One-Word Picture Vocabulary Test, Brief Observation of Social Communication Change (BOSCC), Pervasive Developmental Disorder-Behavior Inventory, Repetitive Behavior Scale-Revised, Sensory Experience Questionnaire (SEQ-2.1), Child Behavior Checklist, Clinical Global Impression-Severity and Improvement (CGI-I) Scales, and eye-gaze tracking. UCB infusion was conducted at T = 6 months, hence, 0-6 months was the control period, and 6-18 months the follow-up period. Of 20 children recruited, 19 completed the study and 1 was withdrawn due to UCB not meeting quality control criteria for infusion. There were 15 males and 4 females with an overall mean (SD) age of 4.15 (0.62) years. Mean (SD) cell dose administered was 38.16 (9.82) million cells/kg. None suffered serious adverse events although there were mild behavioral side effects and one unit grew coagulase negative staphylococcus from a post-thaw sample. There were no significant differences in Vineland-3, SB-5, BOSCC, and SEQ-2.1 scores at T = 12 and T = 18 months. Twelve participants had T = 18 CGI-I scores of 2-3 (minimally to much improved), seven participants had scores of 4 (no change). Autologous UCB infusion in autistic children is generally safe but not without risks, including that of infection. In this within-subjects study, some children showed global symptom improvements while others showed no change. Stem cell therapies for autism should only be conducted under strict clinical trial conditions with clear risk discussions.

Safety and Efficacy of Paliperidone Palmitate in Pediatric Patients with Autism and Intellectual Disability.

This retrospective chart review examines the safety, tolerability and effectiveness of long acting injectable paliperidone palmitate (P-LAI) targeting irritability in twenty-six youth and transition-aged individuals with autism spectrum disorder (ASD) and/or intellectual disability (ID) over a 3-year window. Clinical response was evaluated via prospectively assigned Clinical Global Impressions Severity (CGI-S) and Improvement (CGI-I) scales as well as number of hospital presentations. P-LAI was well tolerated with only 3 patients stopping P-LAI due to side effects. The average duration of P-LAI treatment was 21.1months. Difficulty with medication compliance was the most common reason for initiating P-LAI. There was a statistically significant improvement in CGI-I, CGI-S and hospital visits and no change in BMI noted. Given the potential difficulty of medication administration in this population, this evidence of safety, tolerability as well as preliminary data supporting effectiveness is an important addition to the literature regarding psychopharmacologic management of irritability in youth with ASD and ID.

Oxcarbazepine for the treatment of bipolar and depressive disorders in the outpatient setting: A retrospective chart review

Oxcarbazepine is often utilized off-label for bipolar and depressive disorders in outpatient settings despite limited evidence. We performed a retrospective chart review on 38 adult outpatients diagnosed with bipolar and depressive disorders (ICD-10 codes F30-39), treated with oxcarbazepine by psychiatrists and psychiatric nurse practitioners between 2015 and 2021. Primary outcomes were Clinical Global Impression Severity (CGI-S) and Improvement (CGI-I) scores, assigned retrospectively from clinical documentation. Patients were predominantly female (70%), aged 20–76 (mean 36), with a mean of 1.8 DSM diagnoses (range 1–4) and 1.7 (range 0–5) concurrent psychotropic medications. A starting mean oxcarbazepine dose of 489 mg/day, titrated to a mean final dose of 663 mg/day, was associated with a CGI-I of 2.5 [2.25, 2.75] and a pre-to-post treatment decrease in CGI-S from 3.4 to 2.4. Overall response and remission rates were 52% and 29%, respectively. Limitations of this study include potential sample bias, documentation bias and rater bias among other limitations inherent to retrospective study designs.

Safety profile of pimavanserin therapy in elderly patients with neurodegenerative disease‐related neuropsychiatric symptoms: a Phase 3b study

AbstractBackgroundPatients with neurodegenerative diseases including Parkinson’s disease often experience neuropsychiatric symptoms, including hallucinations and delusions, apathy, and agitation.1,2 These symptoms can greatly impair daily function and lead to reduced quality of life and significant caregiver burden. These patients are generally elderly and often frail. Treatment options are limited, representing a substantial unmet need. Pimavanserin, a 5‐HT2A receptor inverse agonist/antagonist, is FDA‐approved to treat hallucinations and delusions associated with Parkinson’s disease psychosis.3 MethodThis Phase 3b, multicenter, randomized, double‐blind, placebo‐controlled, parallel‐group study evaluated the safety of pimavanserin (34 mg) versus placebo in frail adults and elderly patients with neuropsychiatric symptoms related to neurodegenerative disease. The primary endpoint was safety and tolerability as measured by treatment‐emergent adverse events. Secondary safety endpoints included change from baseline in motor (Extrapyramidal Symptom Rating Scale‐Abbreviated [ESRS‐A]) and cognitive function (Mini‐Mental State Examination [MMSE]) at Week 8. Suicidality was assessed using the Columbia‐Suicide Severity Rating Scale (C‐SSRS) or Global Clinician Assessment of Suicidality (GCAS). Exploratory efficacy endpoints included Clinical Global Impression‐Severity (CGI‐S) and ‐Improvement (CGI‐I), 5‐level version of EQ‐5D (EQ‐5D‐5L), and Sleep Disorders Inventory (SDI).ResultOverall, incidence of TEAEs were similar between pimavanserin (n = 392) and placebo (n = 392); 29.8% reported ≥1 TEAE (pimavanserin: 30.4%; placebo: 29.3%) and 1.8% reported serious TEAEs (pimavanserin: 2.0%; placebo: 1.5%) (Table 1). TEAEs leading to discontinuation or study termination were reported in 2.6% and 2.3% of patients on pimavanserin and placebo, respectively. The most frequently reported TEAEs included urinary tract infection (pimavanserin: 6.4%; placebo: 4.1%) and headache (pimavanserin: 2.0%; placebo: 3.8%). Mortality due to TEAEs was similar between groups (0.5% each). Pimavanserin did not impact motor‐ or cognition‐related function (ESRS‐A and MMSE, respectively); an improvement was seen in CGI‐I (MMRM LSM [SE]: ‐0.2 [0.07], p = 0.0140] and sleep function (SDI) at Week 8 (MMRM LSM [SE]: ‐0.3 [0.06], p<0.0001] compared to placebo (Figures 1, 2); no differences were observed across other measures.ConclusionPimavanserin was well tolerated in patients with neuropsychiatric symptoms related to neurodegenerative disease, consistent with the known safety profile of pimavanserin, informing its use in Parkinson’s disease psychosis. Pimavanserin was not associated with cognitive decline or motor dysfunction.

Single trajectory treatment response for predominant negative symptoms: Post-hoc analysis of a clinical trial with cariprazine and risperidone.

Examining the heterogeneity of negative symptoms of schizophrenia contributes to the identification of available treatment targets. Generally, prior evidence classified three to four symptom treatment response trajectory groups over the course of positive symptoms, yet, no evidence exists regarding the heterogeneity of medium-term response to predominant negative symptoms. The current post-hoc analysis aims to identify the heterogeneity in negative symptom treatment response trajectories among patients with predominant negative symptoms who received either cariprazine or risperidone for 26weeks. Treatment response was analyzed based on the: the Positive and Negative Syndrome Scale Factor Score for Negative Symptoms (PANSS-FSNS), and the Clinical Global Impression Severity (CGIS) and Improvement (CGII) scales. To identify subgroups of patients with a similar course of treatment response, group-based trajectory modelling was utilized. Results demonstrated that in comparison with competing models, a single trajectory best described the treatment response of patients with predominant negative symptoms. The results indicate that patients with predominant negative symptoms with over ten years of schizophrenia respond rapidly to adequate treatment and follow a course of steady improvement.

The safety and efficacy of sequential intramuscular/oral ziprasidone treatment of acute episode in patients with schizophrenia: a multicenter, open-labeled study

BackgroundZiprasidone mesylate injection is an atypical antipsychotic drug which is recently approved in China. In combination with its oral formulation, sequential therapy with ziprasidone brings new interventions to patients with agitation in the acute phase of schizophrenia. The purpose of this 7-day multicenter study conducted in China was to evaluate the efficacy and safety of ziprasidone sequential treatment through intramuscular/oral routes in agitated patients with schizophrenia.MethodsA total of 95 patients were enrolled from three centers in this study. The study duration was 7 days. In the first 3 days, subjects were administered an intramuscular injection of ziprasidone 10–40 mg daily and started sequentially with oral ziprasidone 40–80 mg at dinner (or lunch) from the day of the last intramuscular injection. In the following 4 days, according to the severity of the symptoms and the drug response, 120–160 mg of ziprasidone was orally administered daily. In total, six visits were scheduled to assess the Positive and Negative Syndrome Scale (PANSS), the Behavioral Activity Rating Scale (BARS), the Clinical Global Impression of Severity (CGI-S), and Improvement (CGI-I) scores throughout the procedure. Lastly, adverse events were recorded during treatment.ResultsOut of the 95 patients that were enrolled, 83 cases were effectively completed. Visits 3, 4, 6, PANSS, and PANSS-excited component (PANSS-EC) subscale points, and Visit 2–Visit 6 viewpoints, BARS scale points, and baseline scores denote a progressive downward trend (P < 0.001). In this study, 62 adverse events were reported. The most common adverse events were extrapyramidal symptoms (EPS) (23 cases) and excessive sedation(10 cases), and 13 cases of prolonged QTc interval were reported.ConclusionsZiprasidone IM demonstrated significant and rapid reduction in agitation, and sequential oral formulation keep stability and continuation of the treatment can further ensure efficacy. Ziprasidone sequential therapy may provide a new approach to acute agitation in schizophrenic patients.Trial registrationThe Chinese Clinical Trials Registry; URL: https://www.chictr.org.cn: ChiCTR-OIC-16007970.

Pharmacogenetic markers to predict safety of antipsychotics in adolescents experiencing acute psychotic episodes

Introduction There are relatively fewer pharmacogenetic studies of antipsychotics in adolescents than in adult patients. The development of personalized pharmacotherapy is promising.ObjectivesIdentify the most significant pharmacogenetic predictors of antipsychotic safety in adolescents experiencing acute psychotic episodesMethods The study included 101 adolescents diagnosed with acute polymorphic psychotic disorder at the time of admission (F23.0-9 according to ICD-10). All patients were taking an antipsychotic as their main treatment for 14 days. Children’s Global Assessment Scale (CGAS), Positive and Negative Symptoms Scale (PANSS), Clinical Global Impression Severity (CGI-S) and Improvement (CGI-I), UKU Side Effects Rating Scale (UKU SERS), Sympson-Angus Scale (SAS), Barnes Akathisia rating scale (BARS) were used. All study participants underwent pharmacogenetic testing of pharmacokinetic and pharmacodynamic factors.Results CYP2D6 “intermediate” metabolism increased the risk of developing an adverse reaction by a trend of significance (OR=2.616 (95% CI 0.950-7.203); p=0.063). Carriage of HTR2A rs6313 was associated with a lower score on the UKU SERS “Other Symptoms” subscale (Beta=(-0.289); p=0.003) and an objective score on the BARS akathisia severity scale (Beta=(-0.217); p=0.029). DRD3 rs324026 carriers had a lower BARS akathisia scale score (Beta=(-0.349); p=0.004); DRD3 rs6280 carriers had a lower SAS extrapyramidal symptom severity scale score (Beta=(-0.351); p=0.003). Carriers of ANKS1B rs7968606 were associated with a higher SAS scale score (Beta=0.237; p=0.017).ConclusionsWe proposed that genotyping of CYP2D6*4, *10, DRD3 rs324026 (C allele), DRD3 rs6280 (C allele), HTR2A rs6313 (TT genotype) and ANKS1B rs7968606 (T allele) will predict the high risk of intolerance to antipsychotics in adolescents with acute psychotic episodes.DisclosureNo significant relationships.

Findings from a pilot open-label trial of N-acetylcysteine for the treatment of pediatric mania and hypomania

BackgroundPediatric bipolar disorder is a highly prevalent and morbid disorder and is considered a prevalent public health concern. Currently approved treatments often pose the risk of serious side effects. Therefore, this study assessed the efficacy and tolerability of N-acetylcysteine (NAC), in children and adolescents with bipolar spectrum disorder.MethodsWe conducted a 12-week open-label trial of NAC for treatment of mania and hypomania in children and adolescents ages 5–17 with bipolar spectrum disorder including participants with full and subthreshold manic symptoms, accepting those with and without mixed states with co-occurring depression, and Young Mania Rating Scale scores ≥ 20 and < 40. Symptoms of mania and depression were assessed using the Young Mania Rating Scale (YMRS), Hamilton Depression Rating Scale (HDRS), Children’s Depression Rating Scale (CDRS), and Clinical Global Impression (CGI) Severity (CGI-S) and Improvement (CGI-I) scales for mania and depression.ResultsThis study had a high drop-out rate with only 53% completing all 12 weeks. There was a significant reduction in YMRS, HDRS, and CDRS mean scores from baseline to endpoint. Of the 24 exposed participants, 54% had an anti-manic response measured by a reduction in YMRS ≥ 30% and 46% had a CGI-I mania score ≤ 2 at endpoint. Additionally, 62% of participants had an anti-depressive response measured by a reduction in HDRS ≥ 30%, 31% had an anti-depressive response measured by a reduction in CDRS ≥ 30%, and 38% had a CGI-I depression score ≤ 2 at endpoint.ConclusionsThese pilot open-label findings in a small sample provide preliminary data supporting the tolerability and safety of NAC in a pediatric population. The findings of this pilot scale study indicating improvement in mania and depression are promising, but require replication with a monotherapy randomized placebo controlled clinical trial and larger sample.Trial RegistrationClinicalTrials.gov Identifier: NCT02357290. First Registration 06/02/2015.

Associations of CYP2D6, ABCB1 2677G&gt;T/A and 3435C&gt;T with effectiveness and safety of pharmacotherapy for acute psychotic episodes in adolescents over 28 days

Introduction. Pharmacokinetic genetic factors are prognostically relevant when prescribing antipsychotics to adult patients. Currently, there is a dearth of research on adolescents with an acute psychotic episode. Aim. To identify possible associations of CYP2D6, CYP3A4/5 and ABCB1 gene polymorphic variants with the efficacy and safety of pharmacotherapy in adolescents with an acute psychotic episode within 28 days. Materials and methods. The study included 68 adolescents with an established diagnosis of acute polymorphic psychotic disorder at the time of admission (F23.0-9 according to ICD- 10). All patients received an antipsychotic as their main therapy. Patients were monitored for 28 days. The effectiveness of antipsychotics was assessed using the Children’s Global Assessment Scale (CGAS), Positive and Negative Symptoms Scale (PANSS), Clinical Global Impression Severity (CGI-S) and Improvement (CGI-I). The safety of pharmacotherapy was assessed using the UKU Side Effects Rating Scale (UKU SERS), Sympson-Angus Scale (SAS), Barnes Akathisia rating scale (BARS). From each patient we obtained a buccal scraped epithelium, extracted DNA from it by sorbent method and detected carriage of genetic polymorphisms CYP3A4*22 (rs2740574), CYP3A5*3 (6986A&gt;G, rs776746), CYP2D6*4, *9, *10 (rs3892097, rs4986774, rs1065852), ABCB1 1236C&gt;T (rs1128503), 2677G&gt;T/A (rs2032582), 3435C&gt;T (rs1045642) by real-time PCR. Results. Carriers of ABCB1 2677G&gt;T/A significantly less frequently demonstrated response to pharmacotherapy according to PANSS scale on day 14 compared to GG homozygotes (64.6 % vs. 94.7 %; p=0.014). Carriers of the ABCB1 3435C&gt;T differed by a higher total UKU SERS score on day 14 compared to CC genotype carriers (9.21±5.95 vs. 5.1±4.48; p=0.037). Patients with «intermediate» CYP2D6 metabolism were more likely to have reduced sleep duration (13.6 % vs. 0 %; p=0.031). ABCB1 2677G&gt;T/A (51 % vs. 15.8 %; p=0.012) and 3435C&gt;T (46.6 % vs. 10 %; p=0.039) were more frequently associated with dry mouth. ABCB1 3435C&gt;T carriers were also more likely to have orthostatic vertigo (34.5 % vs. 0 %; p=0.028). Conclusion. Carriage of the ABCB1 3435C&gt;T was associated with greater efficacy of pharmacotherapy for acute psychotic episode in adolescents after 28 days, but also increases the risk of adverse reactions in the first 2 weeks of treatment. The ABCB1 2677G&gt;T/A was associated with an increased risk of adverse reactions as well as less reduction of psychotic symptoms on day 14 of pharmacotherapy.

Analysis of associations between pharmacodynamic genetic factors and antipsychotics’ effectiveness and safety in adolescents with acute psychotic episodes taking antipsychotics during a 28-day follow-up

Introduction. Antipsychotics are the main drugs for treatment of schizophrenia spectrum disorders. Pharmacodynamic genetic factors are being actively studied to improve the accuracy of antipsychotic selection based on pharmacogenetic testing.Purpose of this study: to establish associations of genetic polymorphisms of the DRD2, DRD3, DRD4, HTR2A, COMT, ZNF804A, and ANKS1B genes with the efficacy and safety of antipsychotics in adolescents with an acute psychotic episode during a 28-day follow-up.Materials and methods. The study included 68 adolescents with an established diagnosis of acute polymorphic psychotic disorder at the time of admission (F23.0-9 according to ICD-10). All patients received an antipsychotic as their main therapy. Patients were monitored for 28 days. The effectiveness of antipsychotics was assessed using the Children’s Global Assessment Scale (CGAS), Positive and Negative Symptoms Scale (PANSS), Clinical Global Impression Severity (CGI-S) and Improvement (CGI-I). The safety of pharmacotherapy was assessed using the UKU Side Effects Rating Scale (UKU SERS), Sympson-Angus Scale (SAS), Barnes Akathisia rating scale (BARS). From each patient we obtained a buccal scraped epithelium, extracted DNA from it by sorbent method and detected carriage of genetic polymorphisms DRD2 rs1800497 (C&gt;T), DRD3 rs6280 (C&gt;T), DRD3 rs324026 (C&gt;T), DRD4 rs1800955 (C&gt;T), HTR2A rs6313 (T&gt;C), COMT rs4680 (Val158Met, G&gt;A), ZNF804A rs1344706 (A&gt;C), ANKS1B rs7968606 (C&gt;T) by real-time PCR.Results. DRD2 rs1800497 T allele carriers had a stronger reduction in the PANSS subscore «Productive Symptomatics» on day 14 (Me=-7.0 [-9.0;-5.0] vs Me=-7.0 [-8.0;-2.0]; p=0.018) and day 28 of follow-up (Me=-11.0 [-9.0;-5.5] vs Me=-8.0 [-8.0;-2.0]; p=0.019). Also, greater improvement on the CGAS scale on day 14 of follow-up was seen in TC+CC HTR2A rs6313 carriers (Me=2.0 [1.0;3.0] vs. Me=2.0 [1.0;2.0]; p=0.029). DRD3 rs324026 homozygous carriers (TT) had a significantly lower SAS score (Me=0.5 [0.0; 1.0] vs. Me=1.0 [0.0; 5.0]; p=0.016) and UKU subscore «Neurological Disorders» on 28 days of antipsychotic therapy (Me=0.0 [0.0; 0.0] vs. Me=1.0 [0.0; 3.8]; p=0.005). DRD3 rs324026 TT carriers also had lower severity of akathisia according to the BARS scale. Carriers of the T DRD4 rs1800955 allele had a higher SAS scale score on day 28 of therapy compared with CC homozygotes (Me=1.0 [0.0;4.0] vs Me=0.0 [0.0;1.0]; p=0.036).Conclusion. The DRD2 rs1800497 was a predictor of better reduction of productive symptoms; HTR2A rs6313 demonstrated a similar association. The DRD2 rs1800497 polymorphic variant was a predictor of better reduction of productive symptomatology; HTR2A rs6313 demonstrated a similar association. DRD3 rs324026 and HTR2A rs6313 were associated with a lower frequency of neurological adverse reactions and akathisia. In contrast, carriers of the DRD4 rs1800955 were more prone to adverse reactions on pharmacotherapy.

INVESTIGATION OF RISPERIDONE; CASE OF SELECTED PATIENTS FROM KENYA

Risperidone is considered as an atypical antipsychotic. It is considered as an effective treatment of psychotic disorders in adults. However, our understanding of its usage among young individuals is limited. In this study, the objective was to identify the safety profile of Risperidone among young children. Methodology wise, the study was conducted among children of less than 5 years old who were treating behavioral problems associated with various childhood disorders. The study was conducted in a hospital in Nairobi, Kenya. Common childhood disorders were diagnosed using the Diagnostic and Statistical Manual (DSM IV) and those associated with disruptive behavioral problems. We used Clinical Global Impression- Severity (CGI-S) and Improvement (CGI-I) scales for symptoms severity and improvement respectively. We took informed consents from parents of the children and initiated Risperidone. The total of 12 patients were included in the study consist of PDD (n=4), PDD plus ADHD (n=2), PDD plus ADHD plus Intellectual disability (n=2), Cerebral Palsy with Epilepsy (n=2) and Global developmental delay (n=2). Baseline and end point CGI scores were 5-6 and 1-2 respectively. Baseline investigations such as lipid profile, fasting blood sugar levels, Electro cardiogram (ECG) were recorded and compared before and after initiation of risperidone. Dose range of risperidone was 0.5-2mg per day. Common side effects were sedation and weight gain in a few patients only. No life-threatening side effects were noted. Our conclusion is that risperidone is well tolerated even in children below 5 years of age over a period of 1 year with improvement in target symptoms.

The Effects of a Traditional Chinese Medication on Children with Attention-Deficit/Hyperactivity Disorder.

Objective: This feasibility study examined the effects of a particular Traditional Chinese Medicine (TCM) herbal formula on attention-deficit/hyperactivity disorder (ADHD) and related problem behaviors. Design: A total of 79 participants aging 6-12 years consumed a granulated TCM herbal formula twice daily over a period of 3 months and underwent assessments at months 0, 3, and 6. Changes in ADHD symptoms and related behaviors were measured using the ADHD rating scale-IV (ADHD-RS-IV), child behavior checklist (CBCL), children's global sssessment scale (CGAS), as well as the clinical global impressions-severity (CGI-S) and improvement (CGI-I) scales. Results: Repeated measures mixed model analyses revealed significant differences in scores across time on all ADHD-RS-IV and CBCL subscales as well as on the CGAS, CGI-S, and CGI-I scales. Pairwise comparisons between months 0 and 3 as well as months 0 and 6 indicated significant improvements in scores. Scores also did not differ significantly between months 3 and 6. The results may suggest that this particular TCM formula possesses potential therapeutic qualities in the treatment of ADHD. Furthermore, changes in ADHD symptoms generally appear to be stable 3 months after discontinuation. However, these findings could also be attributed to placebo effects as well as reporting biases. Conclusion: This particular TCM formula may prove to be a useful adjunctive treatment for children with ADHD, and randomized controlled trials need to be conducted to evaluate its efficacy.

Integrating evidence-based assessment into clinical practice for pediatric anxiety disorders.

Although evidence-based assessments are the cornerstone of evidence-based treatments, it remains unknown whether incorporating evidence-based assessments into clinical practice enhances therapists' judgment of therapeutic improvement. This study examined whether the inclusion of youth- and parent-reported anxiety rating scales improved therapists' judgment of treatment response and remission compared to the judgment of treatment-masked independent evaluators (IEs) after (a) weekly/biweekly acute treatment and (b) monthly follow-up care. Four hundred thirty six youth received cognitive-behavioral therapy (CBT), medication, CBT with medication, or pill placebo through the Child/Adolescent Anxiety Multimodal Study. Participants and parents completed the following anxiety scales at pretreatment, posttreatment, and follow-up: Screen for Childhood Anxiety and Related Disorders (SCARED) and Multidimensional Anxiety Scale for Children (MASC). IEs rated anxiety on the Clinical Global Impression of Severity (CGI-S) and Improvement (CGI-I) at posttreatment and follow-up. Therapists rated anxiety severity and improvement using scales that paralleled IE measures. Fair-to-moderate agreement was found between therapists and IEs after acute treatment (κ = 0.38-0.48), with only slight-to-fair agreement found after follow-up care (κ = 0.07-0.33). Optimal algorithms for determining treatment response and remission included the combination of therapists' ratings and the parent-reported SCARED after acute (κ = 0.52-0.54) and follow-up care (κ = 0.43-0.48), with significant improvement in the precision of judgments after follow-up care (p < .02-.001). Therapists are good at detecting treatment response and remission, but the inclusion of the parent-report SCARED optimized agreement with IE rating-especially when contact was less frequent. Findings suggest that utilizing parent-report measures of anxiety in clinical practice improves the precision of therapists' judgment.

O7.5. LONG-TERM SAFETY AND TOLERABILITY OF BREXPIPRAZOLE IN PATIENTS WITH SCHIZOPHRENIA

BackgroundLong-term maintenance treatment is recommended to control the symptoms of schizophrenia1,2; therefore, safety monitoring for longer than the period required to treat an acute exacerbation is warranted. The aim of the present study (Lighthouse extension; NCT01810783) was to assess the long-term safety and tolerability of open-label treatment with brexpiprazole (flexible dose 1–4 mg/day) in adult patients with schizophrenia. Brexpiprazole is a serotonin-dopamine activity modulator that acts as a partial agonist at the serotonin 5-HT1A and dopamine D2 receptors, and as an antagonist at the 5-HT2A and noradrenaline α1B/2C receptors, all with subnanomolar potency. Brexpiprazole is approved in the US as adjunctive therapy to antidepressants for the treatment of major depressive disorder (MDD) and in the US, Australia and Canada as monotherapy for treatment of schizophrenia.MethodsPatients rolled over into this 52-week open-label study from a randomized, double-blind, placebo-controlled, active referenced, Phase 3 study (Lighthouse3; NCT01810380). The primary endpoint was safety and tolerability. Efficacy was assessed as an exploratory endpoint using the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impressions – Severity of illness (CGI-S) and Improvement (CGI-I) scales, and the Personal and Social Performance (PSP) scale. Changes from baseline were analyzed using a mixed model repeated measurements (MMRM) approach.Results210 patients were enrolled, and 101 (48.3%) completed the study. The mean and mean modal doses of brexpiprazole were 3.07mg/day and 3.18mg/day, respectively; at last visit, 50% of the patients received 4mg/day. Among patients who took ≥1 dose of brexpiprazole, the incidence of discontinuation due to treatment-emergent adverse events (TEAEs) was 17.2%. TEAEs with an incidence of ≥5.0% were schizophrenia (worsening of the underlying disease; 11.5%), weight increase (10.5%), headache (8.6%), and insomnia (8.1%). Most TEAEs were mild or moderate in severity. The mean increase in body weight from baseline to Week 52 was 2.6kg (observed cases [OC]) and 19.6% of patients had a weight increase ≥7% at any time during the study. There were no clinically relevant findings for either metabolic parameters (lipids and glucose), or for events related to ECGs, vital signs, extrapyramidal symptoms, or prolactin. Patients’ symptoms and functioning showed continual improvement; at Week 52, mean change from baseline in PANSS was -6.8 (95% confidence interval [CI]: -9.3, -4.2); CGI-S: -0.4 (95%CI: -0.5, -0.2); and PSP: 4.2 (95%CI: 2.2, 6.1). The CGI-I score at Week 52 was 2.8 (95%CI: 2.6, 3.1). The percentage of responders (reduction of ≥30% from baseline in PANSS total score or a CGI-I score of 1 [very much improved] or 2 [much improved]) increased throughout the study, from 16% (OC and last observation carried forward [LOCF]) at Week 1 to 48% (OC) and 35% (LOCF) at Week 52.DiscussionTreatment with open-label brexpiprazole 1–4 mg/day was generally well tolerated for up to 52 weeks in patients with schizophrenia. Further, long-term treatment with brexpiprazole was associated with continued improvement in efficacy measures and functional outcomes.

Efficacy and Safety Profile of Risperidone Long-acting Injection in Adolescents in a Real-life Setting.

ObjectiveRisperidone long-acting injection (RLAI) was shown to be an alternative option in adult patients, but there is not available data in child and adolescents about this medication. The aim of this study is to evaluate the safety and efficiency profile of RLAI in a group of adolescents.MethodsEleven cases with conduct disorder and severe aggressive behaviors were initiated treatment with risperidone oral form. All cases were then shifted to RLAI 25 mg injection in each 15 days due to poor compliance to oral risperidone treatment. Efficiency of treatment included indicators of clinical severity and improvement, which were evaluated by Clinical Global Impression-Severity (CGI-S) and Improvement (CGI-I). Safety evaluation was performed by using Extrapyramidal Symptoms Rating Scale, and by monitoring body weight. Follow-up visits were done at the treatment initiation, and 8th, 16th, and 24th weeks of first injection.ResultsStudy included 9 girls, and 2 boys, with a mean age of 14.9±1.0 years. The CGI-S scores decreased from 6.6±0.5 at the beginning to 2.2±1.1 at the last visit (p<0.001), which is a very significant decrease through better clinical level. The CGI-I scores were also improved significantly from 2.4±0.5 to 1.9±0.5 at 24th week (p=0.001). Safety parameters were also showed favorable results, which there was no significant weight gain (p=0.076), and well-tolerated extrapyramidal adverse effects.ConclusionOur results showed that RLAI is an efficient and safe medication option in the treatment of psychiatric disorders and severe behavioral problems in adolescents with low-compliance to oral treatment in our cases.

Evaluating clonidine response in children and adolescents with attention-deficit/hyperactivity disorder

Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder in childhood, which is generally treated with stimulant and non-stimulant medications. However, 10–30% of patients in clinical setting do not present with adequate response to initial stimulant treatment. Thereby, clonidine may be considered for those patients who have failed to respond to psychostimulant/atomoxetine monotherapy or as an augmentation for inadequate response/comorbidity. This observational study evaluated its effectiveness as a single drug in ADHD cases unresponsive to previous treatment trials. Seventeen ADHD cases that were non-responders to stimulant, non-stimulant and combination therapy for the primary symptoms of ADHD were included in the study. Four cases dropped out before follow up, leaving thirteen cases who were administered immediate release clonidine treatment alone with a mean dose of 0.2 ± 0.05 mg/day at baseline. The trial lasted for 12 weeks, and treatment outcomes were evaluated by the Turgay DSM-IV Based Child and Adolescent Behavior Disorders Screening and Rating Scale (T-DSM-IV-S) and the Clinical Global Impressions-Severity (CGI-S) and Improvement (CGI-I) scales. Mean age of the sample was 12.5 years (SD = 3.0) and eleven of the subjects had another comorbid psychopathology. Only two cases were evaluated as “very much improved”, while another patient was judged to be “minimally improved” after 12 weeks of clonidine treatment. Attrition during follow-up was associated with higher median scores on the hyperactivity and impulsivity subscales (Mann-Whitney U test, p = 0.02). According to the T-DSM-IV-S, CGI-S, and CGI-I scales, clonidine treatment by itself had minimal benefits in this sample of treatment of refractory cases with ADHD evaluated at the study center. Clonidine is not available in Turkey pharmaceutical marketing system and patients’ access to drug is limited. Our results provide first data regarding the use of clonidine in Turkish ADHD patients.

A descriptive study of pattern of psychiatric referrals and effect of psychiatric intervention in consultation-liaison set up in a tertiary care center

Background: There is paucity of published data pertaining to consultation psychiatric services (CLP) in India. The data available reflect the under developed status of this subspecialty and need for strengthening the same. Research assessing the effectiveness of CLP services is the need of the hour. Objectives: Current study was taken up with the aim to study the pattern of psychiatric referrals in a teaching hospital, and to study the effect of intervention in CLP at the end of 4 weeks. Materials and Method: Sample was drawn from Indoor patients referred to department of psychiatry. Psychiatric diagnosis was made using International classification of diseases (CD-10 DCR). Clinical Global Impression severity (CGI-S) and Improvement (CGI-I) ware used to assess the effect of psychiatric intervention after 4 weeks. Results: about half of patients were referred from Internal Medicine, followed by Neurological sciences and surgical branches. About 30% of patients had no diagnosable psychiatric disorder. Common reasons for referral were evaluation of medical patient having co- morbid psychiatric symptoms, followed by assessment for intentional self-harm, past history of psychiatric illness, and substance use. There was a statistically significant reduction in the mean CGI-S scores after four weeks (t=16.356; p <0.001). Mean CGI-I score after 4 weeks was 1.89(±0.993). suggesting much improvement. Conclusion: Majority of patients are referred to Psychiatry from internal medicine and neurology. About one-third of the patient did not receive any Psychiatric diagnosis. Psychiatric intervention was found to be significantly beneficial.

The Effectiveness of Telepsychiatry-Based Culturally Sensitive Collaborative Treatment for Depressed Chinese American Immigrants

This study evaluates the effectiveness of a telepsychiatry-based culturally sensitive collaborative treatment (T-CSCT) intervention to improve treatment outcomes for depressed Chinese American immigrants. Participants were Chinese Americans recruited from primary care settings from February 1, 2009, to July 31, 2012, with DSM-IV major depressive disorder (MDD) identified by the Mini-International Neuropsychiatric Interview. Eligible patients were randomized to receive either T-CSCT or treatment as usual (TAU) for 6 months. T-CSCT involves (1) cultural consultation via videoconference and (2) care management. The primary outcome measure was the 17-item Hamilton Depression Rating Scale (HDRS₁₇); positive response was defined as a ≥ 50% decrease in HDRS₁₇ score, and remission was defined as HDRS₁₇ score ≤ 7. Secondary outcome measures were the Clinical Global Impressions-Severity of Illness (CGI-S) and Improvement (CGI-I) scales and the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q). Outcomes were compared using multivariate logistic regression and mixed-model for repeated measures methods. Among participants (N = 190), 63% were female, and the mean (SD) age was 50 (14.5) years. They were randomized to T-CSCT (n = 97; 51%) or TAU (n = 93; 49%). Using multivariate logistic regression analyses, the odds of achieving response and remission were significantly greater for the T-CSCT group compared to the control group (odds ratio [OR] = 3.9 [95% CI, 1.9 to 7.8] and 4.4 [95% CI, 1.9 to 9.9], respectively). Multivariate general linear model analyses showed that patients in the T-CSCT group had significantly greater improvement over time in HDRS₁₇ (F4,95 = 4.59, P = .002), CGI-S (F4,95 = 4.22, P = .003), and CGI-I (F4,95 = 2.95, P = .02) scores. T-CSCT is effective in improving treatment outcomes of Chinese immigrants with MDD. ClincialTrials.gov identifier: NCT00854542.

Effects of milnacipran on neurocognition, pain, and fatigue in fibromyalgia: a 13-week, randomized, placebo-controlled, crossover trial.

To investigate whether milnacipran is safe and effective in improving cognitive function in patients with fibromyalgia. Patients were randomly assigned to receive milnacipran or placebo for 6 weeks, followed by a 1-week washout and then crossover to the other arm for another 6 weeks. The overall trial lasted 13 weeks and was conducted between July 2011 and May 2013. Assessments were performed at each visit. Neurocognition was measured by the Brief Assessment of Cognition (BAC) and MATRICS. Pain was assessed by the visual analog scale (VAS) for pain. Global assessment of fibromyalgia symptoms was measured by the Fibromyalgia Impact Questionnaire (FIQ) and tender point examination. Depression was assessed by the Beck Depression Inventory (BDI). Fatigue was assessed by the Fatigue Severity Scale. Functional outcome was evaluated by the Health Assessment Questionnaire. The Clinical Global Impressions-Severity of Illness (CGI-S) and Improvement (CGI-I) scales and the Patients Clinical Global Impression of Change were used to measure the global impression of severity and improvement. 26 subjects were screened, and 20 subjects completed the trial. The change in verbal memory (P = .001) and the composite T score (P = .044) of the BAC and the change in the attention-vigilance domain T score (P = .042) were significantly improved, but there were no differences between the drug and placebo groups. The changes in the CGI-S scores were not significant, but the changes in the Clinical Impression-Improvement (CGI-I) scores showed worsening in the placebo group at week 1 (P = .032), week 2 (P = .024), week 4 (P = .024), and week 6 (P = .60) compared to baseline. The change in FIQ scores was not significant. Milnacipran may have a potential role in the improvement of pain, disability, and mood. The effect of milnacipran on cognition in fibromyalgia needs further research. ClinicalTrials.gov identifier: NCT01829243.

Efficacy and Safety of Levomilnacipran Sustained Release 40 mg, 80 mg, or 120 mg in Major Depressive Disorder

This phase 3, randomized, double-blind, placebo-controlled study evaluated the efficacy and tolerability of fixed-dose levomilnacipran sustained release (SR) compared with placebo in patients with major depressive disorder (MDD); the study was conducted from September 2009-May 2011. Outpatients met DSM-IV-TR criteria for MDD with an ongoing major depressive episode ≥ 8 weeks' duration. After a 1-week placebo lead-in, patients were randomly assigned to receive placebo (n = 179) or levomilnacipran SR 40 mg (n = 181), 80 mg (n = 181), or 120 mg (n = 183) once daily for 8 weeks of double-blind treatment, followed by a 2-week double-blind down-taper. The primary efficacy parameter was change from baseline on the clinician-rated Montgomery-Asberg Depression Rating Scale (MADRS) total score. The prespecified secondary efficacy parameter was change from baseline in Sheehan Disability Scale (SDS) total score. Additional efficacy measures included the 17-item Hamilton Depression Rating Scale (HDRS(17)) and Clinical Global Impressions-Severity of Illness (CGI-S) and -Improvement (CGI-I). Safety and tolerability were also evaluated. The least squares mean difference (LSMD) for change from baseline in MADRS total score was significantly superior to placebo for all dose groups: -3.23 (P = .0186), -3.99 (P = .0038), and -4.86 (P = .0005) for levomilnacipran SR 40, 80, and 120 mg, respectively. The LSMD was significantly different for levomilnacipran SR 80 mg and 120 mg versus placebo on the SDS (-2.51 and -2.57, respectively, P < .05 for both doses), HDRS(17) (-2.09 and -2.34, respectively, P < .05 for both doses), CGI-S (-0.43 [P < .01] and -0.35 [P < .05], respectively), and CGI-I (-0.34 and -0.32, respectively, P < .05 for both doses) assessments. The most common treatment-emergent adverse events (≥ 10% of any treatment group) were headache, nausea, constipation, dry mouth, increased heart rate, and hyperhidrosis. Levomilnacipran SR demonstrated significant improvement in depressive symptoms and functioning relative to placebo. In this study, levomilnacipran SR was generally well tolerated. ClinicalTrials.gov identifier: NCT00969709.