Clinical Global Impressions-Severity Of Illness Scale Research Articles

Subjective assessment of brexpiprazole in patients with schizophrenia: a prospective observational study.

To investigate the subjective assessments of an antipsychotic treatment with brexpiprazole. This was a 14-week prospective observational study. Nineteen patients participated in the study between February 2019 and January 2020. Patients had a mean age of 40.6±14.2 years and a Clinical Global Impressions-Severity of Illness scale (CGI-S) score of 4.6±1.2 at the initiation of brexpiprazole treatment. The Subjective Well-being under Neuroleptic drug treatment Short form, Japanese version (SWNS-J) total score significantly improved from 68.1±22.3 in week 2 to 79.5±21.0 in week 14 (p=0.0084). The SWNS-J subscales of self-control and social integration status also significantly improved from 14.0±4.7 and 13.9±6.0 in week 2 to 17.0±4.7 and 16.0±5.1 in week 14, respectively (p=0.0053 and 0.012, respectively). No significant improvements were observed in any other SWNS-J subscales or the Drug Attitude Inventory-10 (DAI-10) in the 14-week observation period. Moreover, the SWNS-J total score did not correlate with the DAI-10 (r=0.31, p=0.19), or CGI-S (r=-0.18, p=0.47) scores. The present results suggest that brexpiprazole might improve subjective well-being, although this may not necessarily reflect psychopathological improvements. To enhance medication adherence, it is important to perform subjective assessments on patients over time.

EFFECT OF RISPERIDONE ON HEART RATE DYNAMICS OF PATIENTS HAVING SCHIZOPHRENIA

Risperidone is a first-line antipsychotic drug for treating schizophrenia. It has antiadrenergic action but vhas a negligible impact on neurocardiac regulation. However, due to the relationship between cardiac autonomic regulation and a psychotic state, risperidone induces treatment-associated changes in heart rate variability (HRV). This Prospective study was designed to assess the effect of risperidone therapy on the heart rate dynamics of schizophrenic patients. Psychiatry & Medicine Department, Nishtar Medical Hospital, conducted this study from January 2021 to January 2022. After screening, patients with psychosis causing psychosocial impairment (PANSS score 70) were included in the study. Fifteen patients were selected after the screening. All were administered risperidone. A Control group having age and gender-matched subjects was selected, and ECG was done. Data from 15 controls and 15 patients were analyzed. Clinical Global Impressions-Severity of illness scale (CGI-S) and Positive and Negative Syndrome Scale (PANSS) were used for quantifying psychiatric symptoms. Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) was used to measure drug-associated movement disorders. The mean risperidone dose was 3.2± 0.8 mg/ day. Data collected after 6 weeks of treatment showed that the mean PANSSscore, positive symptoms subscale score, negative symptoms subscale score, CGI-S score and general psychopathology score decreased significantly (p< 0.001). Comparison of HRV parameters between the control group (healthy subjects) and unmedicated patients showed a significant group effect (p<0.001). Evaluation of the association between the severity of psychotic symptoms and HRV measures shows the negative correlation between PANSS positive symptoms score changes and SDNN changes (p= .012).Risperidone treatment in acutely ill schizophrenic patients leads to an increase in cardio-vagal activity, thus causing improvement in sympathovagal imbalance.

Risperidone ISM as a New Option in the Clinical Management of Schizophrenia: A Narrative Review.

Antipsychotics are the cornerstone of schizophrenia treatment. Lack of treatment adherence encouraged the development of injectable long-acting antipsychotics. However, second-generation or atypical antipsychotics require a loading dose at the start of treatment and eventually oral supplementation to achieve therapeutic plasma levels. This review discusses the evidence emerging from studies evaluating the pharmacokinetics, efficacy and safety of the intramuscular formulation of risperidone based on in situ microparticles (ISM). ISM® technology applied to risperidone allows therapeutic levels of the active moiety to be achieved within 2 h of intramuscular administration without the need for loading doses or oral supplementation, leading to a constant release over the whole dosing period. Risperidone ISM showed significant antipsychotic efficacy versus placebo in the Positive and Negative Syndrome Scale (PANSS) total score (p < 0.0001) and on the subscales of positive symptoms after 8 days, negative symptoms in 8 weeks, and general psychopathology during the 12 weeks of treatment. The improvement was also statistically significant (p < 0.0001) against placebo in the Clinical Global Impressions-Severity of Illness scale (CGI-S) score at the end of the treatment. Risperidone ISM was generally well tolerated and the most frequently reported adverse events were similar to those observed with other risperidone formulations. There is clinical evidence that these results are maintained in the long term. In conclusion, four-weekly risperidone ISM (75 mg and 100 mg) is an adequate antipsychotic for treating schizophrenia, both in the short term when an exacerbation has recently occurred and for long-term maintenance, since it provides rapid onset of action and sustained efficacy, as well as being safe and well tolerated.

Continuation rate for asenapine and brexpiprazole treatment in patients with schizophrenia.

IntroductionThe current study sought to compare the treatment continuation rates of asenapine and brexpiprazole while specifically investigating the factors influencing this index and the clinical efficacy of brexpiprazole.MethodsRetrospective study on patients with schizophrenia who were prescribed either asenapine (n = 73) or brexpiprazole (n = 136), as part of their routine medical care.ResultsThe treatment continuation rates for asenapine and brexpiprazole were 19.0% and 38.6% at 52 weeks, with that of brexpiprazole found to be significantly higher than that of asenapine (p = .002). Moreover, age was found to be a significant factor affecting the treatment continuation rate for brexpiprazole (p = .03). Additionally, patients with a longer continuation duration had significantly lower Clinical Global Impression‐Severity of Illness (CGI‐S) scale scores compared to those who discontinued early (p = .04). The continuation rate was also significantly higher for those who began using the drug as outpatients compared to those first administered the drug as inpatients (p = .04). Furthermore, disease duration, CGI‐S scale, and continuation duration significantly affected the clinical efficacy of brexipiprazole (p < .05 for all).ConclusionsThe continuation rate for brexpiprazole increases as the age of the patient increases, as disease severity decreases, and if the patient first uses the drug as an outpatient. Shorter disease duration and longer drug administration may lead to improved clinical efficacy. These results suggest that brexpiprazole is an effective treatment option for maintenance therapy of schizophrenia.

Efficacy and safety of once-monthly Risperidone ISM\xae in schizophrenic patients with an acute exacerbation

To evaluate the efficacy and safety of Risperidone ISM® against placebo in patients with acute exacerbation of schizophrenia. A multicenter, randomized, double-blind, placebo-controlled study was conducted between June 2017 and December 2018 (NCT03160521). Eligible patients received once-monthly intramuscular injections of Risperidone ISM® (75 or 100 mg) or placebo for 12 weeks. The primary efficacy outcome was change in Positive and Negative Syndrome Scale (PANSS) total score from baseline to week 12. The key secondary efficacy outcome was change from baseline in Clinical Global Impressions-Severity of Illness scale (CGI-S) score. Altogether, 438 patients were randomized (1:1:1) and 390 included in the modified ITT efficacy set. The PANSS total score (mean difference, 95% CI) improved significantly from baseline to day 85 with Risperidone ISM® 75 and 100 mg, with placebo-adjusted differences of −13.0 (95% CI, −17.3 to −8.8); (p < 0.0001), and −13.3 (−17.6 to −8.9); (p < 0.0001), respectively. Significantly improved mean changes were also obtained for CGI-S score from baseline to day 85 for both doses of Risperidone ISM® compared with placebo −0.7 (−1.0 to −0.5); p < 0.0001, for both doses. The statistically significant improvement for both efficacy outcomes were observed as early as 8 days after first injection. The most frequently reported treatment-emergent adverse events were increased blood prolactin (7.8%), headache (7.3%), hyperprolactinemia (5%), and weight increase (4.8%). Neither new nor unexpected relevant safety information was recorded. Risperidone ISM® provided rapid and progressive reduction of symptoms in patients with acutely exacerbated schizophrenia without need of oral risperidone supplementation or loading doses. Both doses were safe and well tolerated.

Efficacy and Safety of Dasotraline in Adults With Binge-Eating Disorder: A Randomized, Placebo-Controlled, Flexible-Dose Clinical Trial.

Binge-eating disorder (BED) is the most prevalent eating disorder; however, few evidence-based treatments are available. The aim of this study was to evaluate the efficacy and safety of dasotraline, a novel dopamine and norepinephrine reuptake inhibitor, in adults with BED. Patients with a DSM-5 diagnosis of BED (intent-to-treat sample, N = 315) were randomized to 12 weeks of double-blind treatment with once-daily, flexible doses (4, 6, or 8 mg/d) of dasotraline or placebo. Primary endpoint was change in diary-based assessment of number of binge-eating days per week at week 12. Key secondary endpoints included changes from baseline in Clinical Global Impressions-Severity of Illness scale (CGI-S) and Yale-Brown Obsessive Compulsive Scale Modified for Binge-Eating (YBOCS-BE) and percentage of subjects with cessation of binge eating in the final 4 weeks. Treatment with dasotraline was associated with a significantly greater reduction in binge-eating days per week at study endpoint (vs placebo; least squares mean [SE] difference score, -0.99 [0.17]; P < .0001; effect size [ES], 0.74). Significant endpoint improvement was observed for the 3 key secondary measures, CGI-S (P < .0001; ES, 0.95), YBOCS-BE (P < .0001; ES, 0.96), and 4-week cessation of binge eating (46.5% vs 20.6%; P < .0001). The most common adverse events in the dasotraline vs placebo groups were insomnia (44.6% vs 8.1%), dry mouth (27.4% vs 5.0%), decreased appetite (19.7% vs 6.9%), and anxiety (17.8% vs 2.5%). Discontinuation due to adverse events occurred in 11.3% of patients on dasotraline vs 2.5% on placebo. The results of this placebo-controlled, double-blind study found dasotraline to be an efficacious, safe, and generally well-tolerated treatment for BED. ClinicalTrials.gov identifier: NCT02564588.

Randomized Controlled Trial of Paliperidone Extended Release Versus Risperidone for the Treatment of Methamphetamine-Associated Psychosis in Chinese Patients.

BackgroundThe efficacy or tolerability of paliperidone extended release (ER) in the treatment of methamphetamine (METH)-associated psychosis (MAP) is unknown. This study was designed to assess the tolerability and efficacy of paliperidone ER and risperidone for the treatment of MAP in China.MethodsThis 25-day randomized clinical trial involved 120 patients with acute MAP symptoms who were randomized to receive either paliperidone ER or risperidone from baseline to day 25 of an inpatient hospital stay. The primary outcome was changes in the severity of psychosis, which were assessed using the Positive and Negative Syndrome Scale (PANSS) total score changes from baseline to endpoint.ResultsOverall, 84% of the patients completed the entire study protocol. The PANSS total score, the Clinical Global Impressions-Severity of Illness scale (CGI-S) score, and a METH craving score assessed by a visual analog scale (VAS) showed statistically significant improvements from baseline for the patients in both groups (p < 0.01). The Simpson-Angus Scale (SAS) and the Barnes Akathisia Rating Scale (BARS) scores increased from baseline during treatment in both groups (p < 0.01); there were statistically significant differences between the treatment groups in the SAS scores (p < 0.01). Measures of hypermyotonia, salivation, and dizziness were significantly higher in the risperidone-treated patients than in the paliperidone ER-treated patients (all p < 0.05).ConclusionPaliperidone ER and risperidone had similar efficacy and were generally tolerable in the treatment of MAP; however, paliperidone ER had a more favorable adverse event profile than risperidone, particularly regarding extrapyramidal and prolactin-increasing effects.Clinical Trial RegistrationClinicalTrials.gov, identifier NCT01822730. Full date of first registration:03/28/2013.

Types of Adult Attention-Deficit/Hyperactivity Disorder: A Replication Analysis.

Research supports the importance of emotional symptoms in adults with attention-deficit/hyperactivity disorder (ADHD), which are not reflected in the DSM-5 or ICD-10 criteria. The Wender-Reimherr Adult Attention Deficit Disorder Scale (WRAADDS) assesses these symptoms, plus inattention, hyperactivity, and impulsivity. This scale allowed us to divide adult ADHD into 2 subtypes in a 2015 publication: ADHD inattentive presentation and ADHD emotional dysregulation presentation. The present study refines this observation using a larger, more diverse sample. Eight double-blind adult ADHD clinical trials (encompassing 1,490 subjects) were selected because they included assessment with the WRAADDS; a second, alternative ADHD measure; and the Clinical Global Impressions-Severity of Illness scale (CGI-S). These data were subjected to confirmatory factor analyses, and ADHD presentations were compared, including treatment response. The original factor structure fit poorly with these new data. However, an alternative 2-factor solution fit both the original and the new subjects. ADHD inattentive presentation (n = 774) was defined by the inattention factor, and ADHD emotional dysregulation presentation (n = 620) was defined by additional elevation of the emotional dysregulation factor. The proportion of ADHD emotional dysregulation presentation ranged from 25% to 73% across the 8 studies. The emotional dysregulation presentation was associated with both a greater severity as measured by the CGI-S (P < .001) and more manifestations of childhood ADHD as measured by the Wender Utah Rating Scale (P < .001). Factor analytic results supported the validity of 2 adult ADHD presentations based on levels of emotional dysregulation. This system offers a more clinically relevant approach to the diagnosis of ADHD in adults than does the DSM system.

Efficacy of risperidone and haloperidol in treatment of schizophrenia in tertiary care hospital

Background: Schizophrenia is a chronic debilitating disease with significant morbidity and mortality that often requires either typical or atypical antipsychotic pharmacotherapy. Atypical antipsychotic drugs are preferred over typical because of lower risk of extra pyramidal side effects. As there is paucity of data in Indian population, the present study was taken up to evaluate the efficacy of haloperidol and risperidone in the treatment of schizophrenia.Methods: It was a comparative study conducted on 60 patients of Schizophrenia for one year in a tertiary care hospital. The study subjects were randomly assigned into 2 groups of 30 patients each, where group 1 were treated with atypical antipsychotic drug risperidone and group 2 with typical antipsychotic drug Haloperidol and both groups received the treatment for one year. Efficacy was measured using positive and negative syndrome scale (PANSS), clinical global impression - severity of illness (CGI-S), clinical global impression - improvement (CGI-I) scales.Results: Both haloperidol and risperidone were associated with comparable baseline to endpoint reduction in symptom severity. However, risperidone treated subjects had significantly greater decrease in symptom severity as measured by PANSS score and total score, CGI-S scale. However, there is no significant difference between two groups in terms of CGI-S score.Conclusions: The reduction in positive, negative and general scores in risperidone treated patients were significant with that of haloperidol treated patients.

Aripiprazole and Risperidone for Treatment of Methamphetamine-Associated Psychosis in Chinese Patients

We evaluated tolerability and efficacy of aripiprazole and risperidone for treatment of methamphetamine (METH) associated psychotic symptoms in China. Patients with acute METH-associated psychotic symptoms (N=42) and with Positive and Negative Syndrome Scale (PANSS) total score between 60 and 120 were randomized to aripiprazole (initial dose 5–10mg per day followed by flexible doses 5–15mg per day) or risperidone (initial dose 2–4mg per day followed by flexible doses 4–6mg per day) from day 3 to 25 of inpatient hospital stay. Outcome measures included PANSS and Clinical Global Impressions-Severity of Illness scale (CGI-S), METH craving Visual Analogue Scale (VAS), Simpson Angus Scale (SAS), Barnes Assessments Akathasia Rating Scale (BARS), and self-reported adverse effects evaluated during treatment. Retention was evaluated using Kaplan-Meier survival analysis and the MIXED models procedure was used to compare the groups on measures of psychotic and extra-pyramidal symptoms. Patients in both aripiprazole and risperidone groups showed statistically significant reductions in psychotic symptomatology from baseline during treatment (p<0.001) with no statistically significant differences between the treatment groups (p=0.73 and p=0.15, respectively). Risperidone-treated patients reported significantly greater METH craving reductions (p<0.001). Overall, 71% of patients completed the entire study, but the aripiprazole group had a significantly lower retention than the risperidone group (p=0.007), primarily due to medication related adverse effects. Aripiprazole-treated patients also had significantly more akathisia (p=0.03) and agitation (p=0.02) than risperidone-treated patients. Patients in both groups who tolerated their medications and completed the entire study achieved comparable reductions of psychotic symptoms.

Relationship between symptomatic improvement and overall illness severity in patients with schizophrenia.

Whether improvement on ratings of global illness severity is differentially associated with improvement in specific symptom domains in patients with schizophrenia is not well understood. The present study examined the independent relationships between improvement in specific symptom clusters and change in global impressions of illness severity. This study included 589 patients with chronic schizophrenia who were assessed at baseline and after 6 months of antipsychotic treatment. Both clinicians and patients completed the Clinical Global Impressions-Severity of Illness Scale (CGI-S). Symptom severity was assessed using factor scores derived from the Positive and Negative Syndrome Scale. Change in illness severity ratings made by the clinician and those made by the patient demonstrated moderate overlap. Nearly half of the patients were evaluated as clinically improved during the 6-month period, as rated by the clinician, with less than a third of patients experiencing a reduction in illness severity as determined by both the clinician and themselves. Improvements in clinician-rated CGI-S scores were most strongly associated with reduction in positive symptom severity. In contrast, change in patient-rated CGI-S scores was not linked to reduction in positive symptoms but rather to improvement in depressive and anxiety symptoms. This latter finding remained in a subsample of patients with relatively preserved insight into illness, suggesting that lack of insight cannot account for these findings. Finally, reduction in positive symptoms beyond 2 to 3 points was found to be clinically meaningful. In conclusion, change in overall illness severity, as determined by clinicians, is not necessarily interchangeable with patients' view of improvement of their own clinical status. Moreover, changes in the 2 evaluations of illness severity are associated with changes in different symptom domains.

English

INTRODUCTION: Schizophrenia is a chronic debilitating disease with significant morbidity and mortality that often requires either typical or atypical antipsychotic pharmacotherapy. Atypical antipsychotic drugs are preferred over typical because of lower risk of extra pyramidal side effects (EPS). As there is paucity of data in Indian population, the present study was taken up. OBJECTIVE: To evaluate the efficacy of haloperidol (Typical) and olanzepine (Atypical) antipsychotic drugs in schizophrenic patients. METHODS: It was a comparative study conducted on 60 patients of Schizophrenia for one year at Department of Psychiatry, Victoria Hospital, Bangalore. The study subjects were randomly assigned into 2 groups of 30 patients each, where group 1 were treated with atypical antipsychotic drug olanzapine and group 2 with typical antipsychotic drug Haloperidol and both groups received the treatment for one year. Efficacy was measured using Positive and negative syndrome scale (PANSS), Clinical Global Impression - Severity of illness (CGI-S), Clinical Global Impression - Improvement (CGI-I) scales. RESULTS: Both typical and atypical antipsychotics were associated with comparable baseline to endpoint reduction in symptom severity. However atypical antipsychotic drug olanzapine treated subjects had significantly greater decrease in symptom severity as measured by PANSS negative score and total score, CGI-S scale and CGI-I scale.

Determinants of patient-rated and clinician-rated illness severity in schizophrenia.

The contribution of specific symptoms on ratings of global illness severity in patients with schizophrenia is not well understood. The present study examined the clinical determinants of clinician and patient ratings of overall illness severity. This study included 1,010 patients with a DSM-IV diagnosis of schizophrenia who participated in the baseline visit of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study conducted between January 2001 and December 2004 and who had available symptom severity, side effect burden, cognition, and community functioning data. Both clinicians and patients completed the 7-point Clinical Global Impressions-Severity of Illness scale (CGI-S), the primary measure of interest in the present study. Symptoms were rated using the Positive and Negative Syndrome Scale and the Calgary Depression Scale for Schizophrenia, and functional status with the Quality of Life Scale. Neurocognition, insight, and medication-related side effects were also evaluated. Clinicians rated illness severity significantly higher than patients (P < .001). There was moderate overlap between CGI-S ratings made by clinicians and patients, with almost one third of patients showing substantial (ie, greater than 1 point) discrepancies with clinician ratings. Clinician-rated CGI-S scores were most strongly associated with positive symptoms, with additional independent contributions made by negative, disorganized, and depressive symptoms, as well as functional outcome (all P values < .01). Patient-rated CGI-S scores, on the other hand, were most closely related to depressive symptoms, with additional independent contributions made by positive and anxiety symptoms, clinical insight, and neurocognition (all P values < .01). Depressive symptoms were the strongest predictor of patient-rated CGI-S scores even in patients with good clinical insight (P < .001). Patient and clinician views of overall illness severity are not necessarily interchangeable and differ in their clinical correlates. Taking these differences into account may enhance patient engagement in care and improve outcomes. ClinicalTrials.gov identifier: NCT00014001.

Augmentation with amisulpride for schizophrenic patients non-responsive to risperidone monotherapy.

The combination of antipsychotic drugs is a therapeutic resource in clinical practice. This study aimed to evaluate the efficacy and security of adding amisulpride in patients who at least partially responded to risperidone. A 3-month, open, observational study was undertaken to evaluate the effectiveness of adding amisulpride in subjects who scored at least 25 on the brief psychiatric rating scale (BPRS) after risperidone monotherapy. Patients were evaluated with BPRS, the Clinical Global Impressions Severity of Illness scale (CGI-S) and the Udvalg for Kliniske Undersøgelser Side Effect Rating Scale (UKU) at baseline, 1 and 3 months. Coadjuvant treatment with amisulpride achieves a statistically significant improvement in mental status over a period of 3 months when measured with BPRS, CGI and UKU scales. The response rate was 70 (45%) in the oral risperidone and 74 (28%) in the parenteral risperidone groups. The addition of amisulpride could lead to an improvement in schizophrenia symptoms in patients that do not, or only partially, respond to risperidone. Further research is required into alternative therapies for poor responders.

The effects of high-frequency repetitive transcranial magnetic stimulation (rTMS) on negative symptoms of schizophrenia and the follow-up study

In this double-blind, randomized controlled study, we assessed the therapeutic effects of high-frequency left dorsolateral prefrontal cortex (DLPFC) repetitive transcranial magnetic stimulation (rTMS) on negative symptoms of schizophrenia. For the study, 117 patients with prominent negative symptoms were randomized to a 20-day course of either active rTMS applied to the left DLPFC (n=78) or sham rTMS (n=39). The primary outcome measures were the Positive and Negative Symptom Scale (PANSS) and the Scale for the Assessment of Negative Symptoms (SANS). Secondary outcomes included the Clinical Global Impressions Scale (CGI) and the Udvalg for Kliniske Under sogelser (UKU) Side Effect Rating Scale. We found that treatment with high-frequency rTMS for 6weeks significantly improved negative symptoms in the active group as compared to the sham group. However, active rTMS was not correlated with significant improvement in the CGI severity of illness scale (CGI-S). The improvement of negative symptoms persisted to the 24-week follow-up assessment. These results indicate that there is a lasting beneficial effect of rTMS on negative symptoms in absence of decrease in CGI scores. We conclude that rTMS may serve as a relatively noninvasive treatment that alleviates negative symptoms in patients with schizophrenia.

Escitalopram treatment for depressive disorder following acute coronary syndrome: a 24-week double-blind, placebo-controlled trial.

Depression is common after acute coronary syndrome (ACS) and has adverse effects on prognosis. There are few evidence-based interventions for treating depression in ACS. This study investigated the efficacy and safety of escitalopram in treating depressive disorders identified 2-14 weeks after a confirmed ACS episode. A total of 217 patients with DSM-IV depressive disorders (121 major and 96 minor) and ACS were randomly assigned to receive escitalopram in flexible doses of 5-20 mg/d (n = 108) or placebo (n = 109) for 24 weeks. The study was conducted from 2007 to 2013. The primary outcome measure was the Hamilton Depression Rating Scale (HDRS). Secondary outcome measures included the Montgomery-Asberg Depression Rating Scale (MADRS), Beck Depression Inventory (BDI), Clinical Global Impressions-Severity of Illness scale (CGI-S), Social and Occupational Functioning Assessment Scale (SOFAS), and World Health Organization Disability Assessment Schedule-12. Cardiovascular safety outcomes included echocardiography, electrocardiography, laboratory test, body weight, and blood pressure results. Escitalopram was superior to placebo in reducing HDRS scores (mean difference = 2.3, P = .016, effect size = 0.38). Escitalopram was also superior to placebo in decreasing depressive symptoms evaluated by the MADRS, BDI, and CGI-S and in improving SOFAS functioning level. Escitalopram was not associated with any harmful changes in cardiovascular safety measures. Dizziness was significantly more frequently reported in the escitalopram group (P = .018), but there were no significant differences in any other adverse events. These results indicate that escitalopram has clinically meaningful antidepressant effects with no evidence of reduced cardiovascular safety in depressive disorder following ACS. ClinicalTrials.gov identifier: NCT00419471.

P.7.b.010 Symptom dimensions in the offspring of parents with bipolar disorder

We evaluated tolerability and efficacy of aripiprazole and risperidone for treatment of methamphetamine (METH) associated psychotic symptoms in China. Patients with acute METH-associated psychotic symptoms (N = 42) and with Positive and Negative Syndrome Scale (PANSS) total score between 60 and 120 were randomized to aripiprazole (initial dose 5–10 mg per day followed by flexible doses 5–15 mg per day) or risperidone (initial dose 2–4 mg per day followed by flexible doses 4–6 mg per day) from day 3 to 25 of inpatient hospital stay. Outcome measures included PANSS and Clinical Global Impressions-Severity of Illness scale (CGI-S), METH craving Visual Analogue Scale (VAS), Simpson Angus Scale (SAS), Barnes Assessments Akathasia Rating Scale (BARS), and self-reported adverse effects evaluated during treatment. Retention was evaluated using Kaplan-Meier survival analysis and the MIXED models procedure was used to compare the groups on measures of psychotic and extra-pyramidal symptoms. Patients in both aripiprazole and risperidone groups showed statistically significant reductions in psychotic symptomatology from baseline during treatment (p < 0.001) with no statistically significant differences between the treatment groups (p = 0.73 and p = 0.15, respectively). Risperidone-treated patients reported significantly greater METH craving reductions (p < 0.001). Overall, 71% of patients completed the entire study, but the aripiprazole group had a significantly lower retention than the risperidone group (p = 0.007), primarily due to medication related adverse effects. Aripiprazole-treated patients also had significantly more akathisia (p = 0.03) and agitation (p = 0.02) than risperidone-treated patients. Patients in both groups who tolerated their medications and completed the entire study achieved comparable reductions of psychotic symptoms.

Agomelatine in Generalized Anxiety Disorder

Agomelatine was efficacious in reducing symptoms in a short-term placebo-controlled trial in generalized anxiety disorder (GAD) and in preventing relapse in a longer term placebo-controlled study. An additional short-term placebo-controlled study is required by regulatory agencies to confirm the efficacy of agomelatine in GAD. This 12-week, placebo-controlled, double-blind, randomized, parallel group, international, multicenter study was designed to confirm the efficacy of agomelatine 25-50 mg/d in the treatment of patients with a primary DSM-IV-TR diagnosis of GAD. The primary outcome measure was the Hamilton Anxiety Rating Scale (HARS) total score. Assay sensitivity was evaluated by including an escitalopram (10-20 mg/d) group. The study was undertaken in 45 clinical centers in Argentina, Czech Republic, Finland, South Korea, Poland, Russia, and Slovakia from April 2010 to July 2011. One hundred thirty-nine outpatients were included in the agomelatine group, 131 in the placebo group, and 142 in the escitalopram group. Agomelatine significantly reduced mean (SD) HARS total score (agomelatine-placebo difference: 4.71 [1.03], P <.0001) and had significant effects on secondary outcome measures, including psychic and somatic HARS subscales, response rate (estimate [standard error]) (agomelatine-placebo difference: 27.4% [5.9%], P< .0001), remission on the HARS (agomelatine-placebo difference: 16.8% [5.4%], P = .002), Clinical Global Impressions-Severity of Illness scale (CGI-S) (P < .001), functional impairment (P < .0001), and sleep quality (P < .001). Findings were confirmed in the subset of more severely ill patients (HARS total score ≥ 25 with or without CGI-S ≥ 5 at baseline). Agomelatine was well tolerated by patients, with no more adverse events than placebo. Escitalopram was similarly efficacious but was accompanied by a higher incidence of adverse events compared to placebo. In clinical practice, agomelatine has at least similar efficacy to that of escitalopram for the short-term treatment of GAD and is well tolerated. Controlled-Trials.com identifier: ISRCTN03554974.

Efficacy of olanzapine monotherapy for treatment of bipolar I depression: a randomized, double-blind, placebo controlled study

Depression symptoms are now recognized to be the predominant cause of disability for bipolar disorder (BD) patients. The treatment strategies for the depressed phase of BD remain more anecdotal than data-based. Olanzapine has been investigated as an alternative to antidepressants and a mood stabilizer for acute bipolar depression. The purpose of this study was to assess the efficacy of olanzapine monotherapy for bipolar I depression. Sixty-eight patients with bipolar I depression were randomly assigned to treatment with olanzapine (mean final dose 14.4 mg/day) (n=34) or placebo (n=34) in a double-blind parallel-group study design. Planned assessments included Montgomery-Asberg Depression Rating Scale (MADRS), Young Mania Rating Scale (YMRS), Clinical Global Impressions-Severity of Illness scale (CGI-S), Clinical Global Impressions-Improvement scale (CGI-I), Hamilton Depression scale (HAMD), Hamilton Anxiety scale (HAMA), and Treatment Emergent Symptom Scale (TESS). Of the 68 patients who were randomly assigned, 57 (83.8 %) completed treatments. Improvements in MADRS total score, CGI-S, CGI-I, and HAMD in the olanzapine group were significantly greater relative to those in the placebo group during the 8-week follow-up period (p<0.001, p=0.0017, p=0.007, and p<0.001, respectively). Rates of categorical treatment response and remission in the olanzapine group (50.0 % and 35.3 %, respectively) were significantly higher than those in the placebo group (20.6 %, p=0.011 and 11.8 %, p=0.022, respectively). At the 8-week treatment, the mean weight and the total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels increased significantly in the olanzapine group (p=0.037, p=0.029, p=0.030, and p=0.028, respectively). Olanzapine is effective in the treatment of bipolar I depression but is associated with significant metabolic side effects.

The influence of switching from risperidone to paliperidone on the extrapyramidal symptoms and cognitive function in elderly patients with schizophrenia: A preliminary open-label trial

Objective. This study was to evaluate the effects on clinical symptoms and cognitive function of switching the treatment of elderly patients with schizophrenia from risperidone to paliperidone (PAL). Methods. This study was a 12-weeks, preliminary open-label trial. The subjects were 17 inpatients. Their extrapyramidal symptoms (EPS) were assessed using the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS), Abnormal Involuntary Movement Scale (AIMS), and Barnes Akathisia Scale (BAS), and their cognitive function was assessed using the Brief Assessment Cognition in Schizophrenia: Japanese language version (BACS-J), and their clinical symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression-Severity of illness scale (CGI-S) at the 0 and 12 weeks. Results. The DIEPSS and BAS significantly improved after switching from risperidone to PAL. Furthermore, improvement was found on AIMS. The mean change from baseline in z-score of the digit sequencing task was significantly increased. All items on the PANSS and CGI-S were not significant; however, changes in some cognitive function were correlated with changes in EPS. Conclusions. The results of this study suggest the possibility that switching elderly patients from risperidone to PAL may have improved pre-existing EPS, and may also have helped improve working memory.