Clinical Global Impression Of Change Scale Research Articles

Medication Preference, Satisfaction, and Clinical Improvement Among Adults Receiving Long-Term Treatment With Rimegepant for Migraine (P10-12.011)

Medication Preference, Satisfaction, and Clinical Improvement Among Adults Receiving Long-Term Treatment With Rimegepant for Migraine (P10-12.011)

A Comparison of Pediatric- and Adult-Onset Aquaporin-4 Immunoglobulin G–Positive Neuromyelitis Optica Spectrum Disorder: A Review of Clinical and Radiographic Characteristics

The identification of immunoglobulin G antibodies against the aquaporin-4 channel (AQP-IgG) in the majority of adult patients differentiates neuromyelitis optica as a distinct disease entity. The high specificity of AQP4-IgG for neuromyelitis optica has allowed the identification of seropositive patients with atypical presentations of this disease. Neuromyelitis optica spectrum disorder has been increasingly recognized in children who demonstrate patterns of clinical involvement beyond the traditional boundaries of the optic pathways and spinal cord. This is a single-center, retrospective review comparing demographic, clinical/paraclinical, and laboratory features of children and adults with a serologically confirmed diagnosis of AQP4-IgG-positive neuromyelitis optica spectrum disorder. Of 151 reviewed patient charts, 12 pediatric-onset and 31 adult-onset patients had AQP4-IgG-positive neuromyelitis optica spectrum disorder. The mean age of pediatric-onset neuromyelitis optica spectrum disorder was 12 ± 3.58 years with a female predilection (3:1). Pediatric patients showed more frequent involvement of the brainstem (6/12 [50%]); P = .008) and diencephalon (3/12 [25%]; P = .018). A preceding infection was identifiable in only 3 of 12 (25%) pediatric-onset patients. Moreover, disability as calculated on the expanded disability status scale was less severe in pediatric-onset cases compared to adult-onset cases in their most recent assessment (0 [0-9]) vs 6.5 [0-10]; P = .005). Pediatric-onset patients were also more likely to respond to treatment of acute episodes with corticosteroids ± intravenous immunoglobulin and/or plasmapheresis (Clinical Global Impression-Change scale: 2.5 [1-4] vs 4 [1-6], P = .009). This retrospective study was able to compare and contrast pediatric- and adult-onset neuromyelitis optica spectrum disorder. Relative to their adult counterparts, pediatric-onset neuromyelitis optica spectrum disorder patients were more likely to respond to treatment and less likely to be disabled from their disease at follow-up. Therefore, pediatric-onset disease may represent a less virulent form of neuromyelitis optica spectrum disorder.

A Novel Dual-Frequency Deep Brain Stimulation Paradigm for Parkinson's Disease.

IntroductionDeep brain stimulation (DBS) of the subthalamic nucleus (STN) using high-frequency (130–185 Hz) stimulation (HFS) is more effective for appendicular than for axial symptoms. Low-frequency stimulation (LFS) of the STN may reduce gait/balance and speech impairment but can result in worsened appendicular symptoms, limiting its clinical usefulness. A novel dual-frequency paradigm (interleave–interlink, IL–IL) was created in order to reduce gait/balance and speech impairment while maintaining appendicular symptom control in Parkinson’s disease (PD) patients chronically stimulated with DBS.MethodsTwo overlapping LFS programs are applied to each DBS lead, with the overlapping area focused around the optimal electrode contact. As a result, this area receives HFS, controlling appendicular symptoms. The non-overlapping area receives LFS, potentially reducing gait/balance and speech impairment. Patients were separated into three categories based on their chief complaint(s): gait/balance impairment, speech impairment, and/or incomplete PD symptom control. The Clinical- Global Impression of Change scale (CGI-C) was completed retrospectively based on patient/caregiver feedback in patients who remained on IL–IL (at 3 months and at the last follow-up).ResultsSeventy-six patients were switched from optimized HFS to IL–IL. Fifty-five (72%) patients remained on IL–IL after 22 ± 8.7 months. The median (range) CGI-C for gait was 2 (1–5) at 3 months and 3 (1–4) at last follow-up, for dysarthria it was 4 (1–4) at 3 months and 4 (1–5) at last follow-up, and for PD motor it was 2 (1–3) at 3 months and 2 (1–3) at last follow-up.ConclusionA substantial number of patients remained on IL–IL because of subjective improvements in gait/balance, speech, or PD symptoms. A prospective, double-blind, crossover study with objective/quantitative outcome measures is underway.

A randomized controlled pilot trial of vilazodone for adult separation anxiety disorder.

Separation anxiety disorder was recently recognized by fifth edition of the Diagnostic and Statistical Manual of Mental Disorders as a diagnosis in adults, but no publications to date have characterized a sample of patients seeking treatment for adult separation anxiety disorder (ASAD) or assessed treatment efficacy. We hypothesized that vilazodone, a selective serotonin reuptake inhibitor (SSRI) and serotonin 1a (5HT1a ) receptor partial agonist, would have efficacy in ASAD, because SSRIs have appeared efficacious in children with mixed diagnoses including separation anxiety disorder and in animal models of separation anxiety. In this pilot study, 24 adults (ages 18-60) with a principal diagnosis of ASAD were randomized to 12weeks of double-blind treatment with vilazodone (n=13) or placebo (n=11). Outcome was assessed by an independent evaluator and self-ratings, and analyzed with mixed effect models. This sample was predominantly female (67%), with comorbid psychiatric disorders (58%), and adult onset of separation anxiety disorder (62%). Response rates at week 12 did not differ significantly between groups. Across all time points, the vilazodone group evidenced greater improvement on the Structured Clinical Interview for Separation Anxiety Symptoms (P=.026) and the Quality of Life Enjoyment and Satisfaction Questionnaire (P=.011), and trends toward greater improvement on the Adult Separation Anxiety Questionnaire (P=.054) and the Clinical Global Impression-Change Scale (P=.086), all with large between-group effect sizes. Findings demonstrate feasibility of a clinical trial in ASAD, and they suggest that vilazodone may have efficacy in the treatment of ASAD and warrants further study.

Factors Related to Early Clinical Effects of Quetiapine Extended-Release: A Multinational, Prospective, Observational Study.

The first weeks of treatment with antipsychotics are important for the development of their long-term efficacy. The objective of this study was to identify factors related to early clinical effects and quality of life (QoL) improvements with quetiapine extended-release (XR). Six hundred and sixty-five patients starting with quetiapine XR were followed up for 8weeks (schizophrenia=153, major depression=200, bipolar depression=252, other psychiatric conditions=60). Clinical effects were assessed by the Clinical Global Impression of Change scale (CGI-C), QoL by the visual analog scale (VAS) of the EQ-5D (QoL-VAS), and adherence by the Moriksy scale. Adverse events were explored: movement disorders by the UKU and Simpson-Angus scales, weight gain by calibrated balances, and diurnal somnolence by the Epworth Somnolence Scale (ESS). The mean dose of quetiapine XR during follow-up was 195.6±154.8mg/day. CGI and QoL-VAS scores improved significantly at week 8 by 2.7±0.1 points and 25.1±0.9 points. Adverse events were observed in 34 and 26% of patients at weeks 4 and 8, respectively. A significant reduction in ESS score was also observed at week 8. Factors independently associated with change in QoL-VAS≥20 points (n=292, 43%) were female gender, more severe disease at baseline, higher antipsychotic dose during follow-up, and improvements in somnolence. Factors independently associated with clinically significant improvement (CGI-C≥5, n=610, 93%) were greater change in QoL-VAS, less frequent movement disorders at baseline, and lack of adverse events during follow-up, especially somnolence. Results from this real-setting, large observational study in Central America suggest that disease severity at baseline, gender, antipsychotic dose, and occurrence of adverse reactions has a significant impact on the early clinical effects of quetiapine XR. Clinicaltrials.gov registration number NCT02409823.

EPA-1547 - Once monthly paliperidone palmitate – tolerability and treatment response in recently diagnosed versus chronic non-acute schizophrenia patients switched from previously unsuccessful treatment with oral antipsychotics

To explore tolerability and treatment response of flexibly dosed once-monthly paliperidone palmitate (PP) in recently diagnosed versus chronic adult non-acute schizophrenia patients previously unsuccessfully treated with oral antipsychotics. International prospective 6-month open-label study. Patients were stratified by years since diagnosis [≤3 versus >3 years]. Outcomes were changes from baseline to endpoint in Positive and Negative Syndrome Scale (PANSS) total score, Clinical Global Impression- Change Scale (CGI-C), Extrapyramidal Symptom Rating Scale (ESRS) and treatment-emergent adverse events (TEAEs). N=233 recently diagnosed (63.9% male, mean age 32.2±10.3 years, mean time since diagnosis 1.2±0.9 years) and n=360 chronic patients (62.5% male, mean age 42.4±11.0, mean time since diagnosis 13.9±9.3 years) were included. 71% of recently diagnosed and 59% of chronic patients showed a ≥20% improvement in PANSS total score at endpoint. Mean changes in PANSS total score at endpoint were - 15.1±15.6 and -9.6±15.7, respectively (between-group difference p<0.0001). Changes in PANSS positive, negative and general subscores were consistently higher in recently diagnosed patients (all p≤0.001). At endpoint, 52.4% of recently diagnosed patients were rated much or very much improved on CGI-C compared to 38.1% in the chronic group (p=0.0008). TEAEs ≥5% in both subgroups (recently diagnosed and chronic) were injection site pain (12.9% vs. 11.9%), insomnia (9.9% vs. 7.8%), anxiety (6.4% vs. 6.9%), and headache (6.0% vs.5.3%). These data suggest that both recently diagnosed and chronic patients previously unsuccessfully treated with oral antipsychotics benefit from paliperidone palmitate, with recently diagnosed patients showing consistently higher treatment response and lower disease severity at endpoint.

Changes in Nursing Burden Following Memantine for Agitation and Aggression in Long-Term Care Residents with Moderate to Severe Alzheimerʼs Disease

Agitation and aggression are common neuropsychiatric symptoms of Alzheimer's disease (AD) with a negative impact on caregivers. The aim of the study was to determine whether changes in agitation and aggression would follow memantine treatment and, if so, be associated with changes in nursing burden in institutionalized patients with moderate to severe AD. This was a 3-month open-label trial of memantine. The setting was two long-term care facilities. Thirty-one institutionalized patients with moderate to severe AD and significant behavioural and psychiatric symptoms were included in the study. Memantine was titrated to a target dose of 10 mg twice daily. Effectiveness was assessed by the change in the Neuropsychiatric Inventory-Nursing Home (NPI-NH) agitation/aggression subscale and Clinical Global Impression of Change (CGI-C) scale using the intent-to-treat population. To establish caregiver impact, the effect on nursing burden was measured by the Modified Nursing Care Assessment Scale (primary outcome). As a secondary analysis, the caregiver distress subscale of the NPI-NH was examined, as well as changes in as required (pro re nata [prn]) psychotropic medication use. Twenty-four patients completed the study. A significant decrease in agitation and aggression (F-test with 3 and 90 degrees of freedom [F(3,90)] = 3.721, p = 0.014) was demonstrated following memantine, with 48% of patients improving (either much improved or minimally improved) on the CGI-C scale. In addition, nursing burden (t-test with 30 degrees of freedom [t(30)] = 3.02, p = 0.005), caregiver distress (F(3,90) = 4.125, p = 0.009) and the use of prn psychotropics decreased following memantine treatment (Z = -1.99, p = 0.046). Fourteen patients experienced at least one adverse event during memantine treatment. The most common adverse event associated with treatment was somnolence (n = 5). The results of this study suggest that the decreased agitated and aggressive behaviour in institutionalized patients with moderate to severe AD following treatment with memantine was accompanied by improvements in nursing burden and decreased psychotropic use. These findings should be confirmed in a larger, controlled trial.

Clinical relevance of findings in trials of antipsychotics: systematic review

There is concern over the methods used to evaluate antipsychotic drugs. To assess the clinical relevance of findings in the literature. A systematic review identified studies of antipsychotics that used the Brief Psychiatric Rating Scale (BPRS) and Positive and Negative Syndrome Scale (PANSS). A published method of translating these into Clinical Global Impression - Change scale (CGI-C) scores was used to measure clinical relevance. In total 98 data-sets were included in the BPRS analysis and 202 data-sets in the PANSS analysis. When aggregated scores were translated into notional CGI-C scores, most drugs reached 'minimal improvement' on the BPRS, but few reached that level for PANSS. This was true of both first- and second-generation drugs, including clozapine. Amisulpride and olanzapine had better than average CGI-C scores. Our findings show improvements of limited clinical relevance. The CGI-C scores were better for the BPRS than for the PANSS.

Atomoxetine for the treatment of executive dysfunction in Parkinson's disease: A pilot open‐label study

Executive dysfunction (ED) is a prominent and often disabling feature of cognitive impairment in Parkinson's disease (PD). Few studies have examined treatments. Given the role of noradrenergic pathology in ED, atomoxetine, a norepinephrine reuptake inhibitor indicated for attention deficit hyperactivity disorder (ADHD), may be a potential treatment for PD-related ED. Twelve patients with PD and disabling ED completed an 8-week pilot open-label, flexible dose (25-100 mg/day) trial of atomoxetine. On primary outcome measures, atomoxetine was associated with improved ED based on the Clinical Global Impression-Change Scale (75% positive response rate; 95% CI: 43-95%, P < 05) and behavioral measures of ED [Frontal Systems Behavior Scale (FrSBE) Executive Dysfunction and Connors Adult ADHD Rating Scale (CAARS) inattention/memory subscales]. Adverse effects included sleep and gastrointestinal disturbances and hypomania. Atomoxetine is tolerable in PD and may benefit clinical manifestations of ED, warranting further study in controlled trials.

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Sodium Oxybate Improves Excessive Daytime Sleepiness in Narcolepsy

To assess the effectiveness of sodium oxybate therapy, modafinil therapy and the combination of the two for excessive daytime sleepiness in narcolepsy patients previously taking modafinil. Double-blind, placebo-controlled, multicenter study. Forty-four sites in the United States, Canada, the Czech Republic, France, Germany, the Netherlands, Switzerland, and the United Kingdom. Two hundred seventy- adult patients with narcolepsy taking 200 to 600 mg of modafinil daily for the treatment of excessive daytime sleepiness. Patients received unchanged doses of modafinil (with sodium-oxybate placebo) during a 2-week baseline phase. Following a baseline polysomnogram and Maintenance of Wakefulness Test, they were randomly assigned to 1 of 4 treatment groups: sodium-oxybate placebo plus modafinil placebo, sodium oxybate plus modafinil placebo, modafinil plus sodium-oxybate placebo, or sodium oxybate plus modafinil. Sodium oxybate was administered as 6 g nightly for 4 weeks and was then increased to 9 g nightly for 4 additional weeks. The primary efficacy measure was the Maintenance of Wakefulness Test; secondary measures included the Epworth Sleepiness Scale, diary recordings, and the Clinical Global Impression-change scale. Following the switch from modafinil to placebo, the mean average daytime sleep latency on the Maintenance of Wakefulness Test decreased from 9.74 minutes at baseline to 6.87 minutes after 8 weeks (p < .001). In the sodium-oxybate group, there was no decrease in sleep latency, suggesting that this drug was as efficacious in treating the excessive daytime sleepiness as the previously administered modafinil. In contrast, the sodium-oxybate/modafinil group demonstrated an increase in daytime sleep latency from 10.43 minutes to 13.15 minutes (p < .001), suggesting that this combination of drugs produced an additive effect. The sodium-oxybate group also demonstrated a decrease in median average Epworth Sleepiness Scale scores, from 15 to 12.0, whereas the sodium-oxybate/modafinil group decreased from 15.0 to 11.0 (for both, p < .001). The Clinical Global Impression-Change scale demonstrated similar results. Sodium oxybate and modafinil are both effective for treating excessive daytime sleepiness in narcolepsy, producing additive effects when used together. Sodium oxybate is beneficial as both monotherapy and as adjunctive therapy for the treatment of excessive daytime sleepiness in narcolepsy.

An Open Pilot Study of Interpersonal Psychotherapy for Panic Disorder (IPT-PD)

Interpersonal psychotherapy (IPT) is a time-limited psychotherapy initially developed to treat depression. It has yet to be studied systematically for treatment of panic disorder. We modified IPT for the treatment of panic disorder and tested this treatment in an open clinical trial with 12 patients seeking treatment of DSM-IV panic disorder. Patients were assessed before during and after treatment. At completion of treatment, nine patients (75%) were independently categorized as responders (i.e., rated as much improved or very much improved on the Clinical Global Impression-Change Scale). Substantial improvement was found for panic symptoms, associated anxiety and depressive symptoms, and physical and emotional well-being. Degree of change in this sample approximated that obtained in studies using established treatments such as cognitive behavioral therapy. Results, though preliminary, suggest that IPT may have efficacy as a primary treatment of panic disorder. Further study is warranted.

Serotonin transporter gene promoter polymorphism predicts SSRI response in generalized social anxiety disorder

To determine whether variation in the serotonin transporter gene promoter (5HTTLPR) influences the efficacy of selective serotonin reuptake inhibitors (SSRIs) in generalized social anxiety disorder (GSAD). Consecutive series of N=32 patients with DSM-IV GSAD for whom DNA and standardized outcome data from a 12-week SSRI trial were available. After ensuring that neither clinical response [clinical global impression of change scale (CGI-C)] nor 5HTTLPR genotype was confounded by ethnicity or sex, we determined whether the number of copies (0, 1, or 2) of hi-risk alleles using either the diallelic L-S system or the triallelic La-Lg-S system, predicted response and change in Liebowitz social anxiety scale (LSAS) and brief social phobia scale (BSPS) scores during SSRI treatment. Twenty-one patients (66%) were responders to SSRI (i.e., CGI-C much or very much improved). A trend was seen for a linear association between 5HTTLPR genotype and likelihood of response to SSRI: diallelic classification L/L 7/8 (88%), L/S 12/18 (67%), S/S 2/6 (33%), p=0.051; triallelic classification L'/L' 4/5 (80%), L'/S' 14/19 (74%), S'/S' 3/8 (38%), p=0.093. Reduction in LSAS (and BSPS) scores during SSRI treatment was significantly (p<0.02) associated with 5HTTLPR genotype using either the diallelic or triallelic classification. Variation in a functional polymorphism known to influence serotonin reuptake is associated with SSRI response in patients with GSAD. Independent replication in larger samples is required before the predictive utility of this information can be confirmed and generalized to clinical settings.

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Back to table of contents Previous article Next article Med CheckFull AccessMed CheckJim RosackJim RosackSearch for more papers by this authorPublished Online:1 Jul 2005https://doi.org/10.1176/pn.40.13.00400025Memantine consistently benefits memory in patients with mild to severe Alzheimer's disease and improves language function in those with moderate to severe Alzheimer's, reported Elaine Peskind, M.D., of the University of Washington and colleagues in the Memantine Study Group. The group presented an exploratory analysis of the efficacy of memantine for cognitive deficits from one trial in patients with mild to moderate disease and a second trial in patients with moderate to severe disease. The two trials, involving a total of nearly 800 patients, were 24 weeks long, double blind, and placebo controlled. The mild to moderate trial compared memantine with placebo, while the moderate to severe trial involved patients who were already taking donepezil and then had either memantine or placebo added. The findings suggest that memantine's effects in patients with mild to moderate disease are less robust than in patients with more severe disease and that the drug may provide cognitive benefit through effects on both memory and language.APA 2005: NR 741; Funding: Forest LabsSwitching patients on donepezil to rivastigmine may significantly improve treatment outcomes, reported Gary Figiel, M.D., of Southeastern Geriatric Healthcare Group in Snellville, Ga., and colleagues. A 26-week switch study involving 270 patients assessed the safety and efficacy of rivastigmine in patients with mild to moderate Alzheimer's who were not responding to donepezil therapy. Seventy percent of patients experienced improvement, or no further decline, in scores on the Clinical Global Impression–Change scale at week 26. Adverse events reported included those already known to be associated with rivastigmine, including nausea, vomiting, anorexia, weight loss, and dizziness.APA 2005: NR 887; Funding: NovartisAripiprazole appears to be qualitatively similar in safety compared with other antipsychotics used to treat psychosis associated with Alzheimer's, reported William Carson, M.D., and colleagues at Bristol-Myers Squibb (BMS) and Otsuka America Pharmaceuticals. A company meta-analysis of three placebo-controlled trials involved pooled safety data from 938 patients. Overall, 15.8 percent of those treated with aripiprazole discontinued the study due to an adverse event, compared with 10.2 percent of those on placebo. The most frequent adverse events seen with aripiprazole were accidental injury, urinary-tract infection, somnolence, asthenia, vomiting, pain in extremities, peripheral edema, diarrhea, and urinary incontinence. Only somnolence occurred statistically significantly more often in those on aripiprazole. Similar to other second-generation antipsychotics used in this population, aripiprazole was associated with increased mortality overall (3.9 percent) compared with placebo (1.7 percent) and an increase in cerebrovascular events (1.3 percent) compared with placebo (0.6 percent).A separate analysis, led by BMS researcher Dusan Kostic, Ph.D., pooled efficacy data from two trials in institutionalized patients with Alzheimer's-related psychosis. In this analysis, which included 246 patients, aripiprazole was particularly effective at reducing agitation, compared with placebo. Significant reductions were also seen in measures of tension, hostility, uncooperativeness, and excitement.APA 2005: NR 268 and NR 742; Funding: BMS/OtsukaRisperidone is significantly superior to placebo in reducing psychotic symptoms in patients with psychosis related to Alzheimer's, reported Jacobo Mintzer, M.D., of the Medical University of South Carolina and colleagues. In a meta-analysis of four controlled trials involving 895 patients, risperidone statistically significantly reduced psychotic symptoms as early as the second week of treatment, and beneficial effects were sustained throughout the 16-week trials. The most commonly reported adverse events associated with risperidone were injury, somnolence, urinary-tract infection, rash, cough, and peripheral edema. In these trials, incidence of mortality was 3.1 percent for those on risperidone compared with 1.8 percent for those taking placebo. Cerebrovascular adverse events occurred in 1.6 percent of those taking risperidone compared with 0.8 percent of those taking placebo.APA 2005: NR 738; Funding: JanssenOlanzapine and quetiapine show concentration-dependent anticholinergic activity at doses commonly prescribed to elderly patients for control of psychosis associated with Alzheimer's, reported Benoit Mulsant, M.D., of the University of Pittsburgh School of Medicine and colleagues. However, aripiprazole, risperidone, and haloperidol showed no detectable anticholinergic activity at therapeutic doses. Anticholinergic activity is thought to be of concern in elderly patients due to its linear association with cognitive decline. It is particularly important in patients with dementia who already have a cholinergic deficit. Differences in assayed anticholinergic activity may be associated with some of the differences in adverse-effect profiles of the drugs studied, including decreased cognitive function, increased risk of falls, and gastrointestinal adverse effects.APA 2005: NR 730; Funding: Janssen ▪ ISSUES NewArchived

Gradations of clinical severity and sensitivity to change assessed with the Beck Depression Inventory-II in Japanese patients with depression

Knowledge of what constitutes a minimal clinically important difference and change on a psychiatric rating scale is essential in interpreting its scores. The present study examines the Beck Depression Inventory-II (BDI-II), a recently revised successor to the world's most popular self-rating instrument for depression. BDI-II was administered to 85 patients with major depression, diagnosed with DSM-IV along with its severity specifiers. It was again administered to 40 first-visit patients from the original sample when they returned 14 or more days later. The Clinical Global Impression-Change Scale was rated at the same time. All the ratings were done independent of each other. The BDI-II was able to distinguish between all grades of depression severity. An approximate 10-point difference existed between each severity specifier. The BDI-II was also sensitive to change in depression: a 5-point difference corresponded to a minimally important clinical difference, 10–19 points to a moderate difference, and 20 or more points to a large difference. Given the already established high reliability, content validity, construct validity and factorial validity, and the high sensitivity to between-subject differences and within-subject changes demonstrated in the present study, the BDI-II promises to continue to be a leading self-rating instrument to assess depression severity worldwide.

A Randomized, Double-Blind, Crossover Comparison of Risperidone and Haloperidol in Korean Dementia Patients With Behavioral Disturbances

Objective Behavioral disturbances in dementia are extremely prominent and distressful, and often result in serious physical, social, and economic consequences. The authors compared the efficacy and tolerability of risperidone and haloperidol in the treatment of behavioral and psychological symptoms of dementia (BPSD) in institutionalized elderly Korean patients with Alzheimer disease, vascular dementia, or mixed dementia. Methods This was an 18-week double-blind, crossover study involving 120 patients who were randomly assigned to receive flexible doses (0.5–1.5 mg/day) of risperidone or haloperidol. BPSD were assessed using the Korean version of the Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD-K), the Korean version of the Cohen-Mansfield Agitation Inventory (CMAI-K), and the Clinical Global Impression of Change scale (CGI-C). Safety and tolerability assessments included the Extrapyramidal Symptom Rating Scale and the incidence of adverse events. Results Both risperidone and haloperidol were efficacious in alleviating BPSD. However, when receiving risperidone, patients showed significantly greater improvement than when receiving haloperidol in the total and subscale scores of the BEHAVE-AD-K, the total and subscale scores of the CMAI-K, and the scores on the CGI-C scale. Also, risperidone had an additional benefit on aggressiveness and anxieties/phobias. The risk of antipsychotic-induced parkinsonism throughout this study was significantly lower with risperidone than with haloperidol. Conclusion Risperidone had a favorable efficacy and tolerability profile compared with haloperidol in the treatment of BPSD in this patient population.

Long-term treatment of chronic schizophrenia with risperidone: an open-label, multicenter study of 386 patients.

An open-label, multicentre study was conducted to assess the long-term efficacy and safety of risperidone in patients with chronic schizophrenia. Three hundred and eighty-six patients at 70 centres in 11 countries received risperidone (2-16 mg/day) for up to 57 weeks; 247 patients were treated for at least 1 year. All but 48 patients had been treated with antipsychotic agents before entering the trial. The mean (+/- SD) daily risperidone dose at endpoint was 8.6 +/- 4.4 mg. The mean total Positive and Negative Syndrome Scale (PANSS) scores were reduced significantly from 76.7 at baseline to 67.4 at endpoint (p < 0.001). Even though no patients had acutely exacerbated symptoms at the start of the trial, mean scores on each of the PANSS positive, negative, and general psychopathology subscales were significantly reduced during the first month of open treatment, and these mean scores continued to improve over the course of the trial. At endpoint, 64% of patients were rated as improved on the Clinical Global Impression change scale. Extrapyramidal symptoms (scores on the Extrapyramidal Symptom Rating Scale) tended to decrease in severity or remained unchanged over the course of risperidone treatment; 27.7% of patients required antiparkinsonian medication during the study. The results demonstrate that risperidone's efficacy against the positive and negative symptoms of chronic schizophrenia can be maintained in long-term treatment with a low incidence of adverse experiences; moreover, the drug reduces preexisting extrapyramidal symptoms over time.

Clinical evaluation of global change in Alzheimer's disease: identifying consensus.

It is important that clinicians who rate global change as part of Alzheimer's disease (AD) clinical drug trials agree on a relevant set of behaviors and information to be considered in formulating their rating. Yet, consensus among raters has been difficult to establish, and inter-rater reliability of clinical global impression of change (CGIC) ratings has been low. In preparation for the development of a new CGIC scale to be used in AD clinical trials, the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC), we surveyed clinicians at sites comprising the National Institute on Aging-sponsored ADCS participating centers to identify whether or not consensus regarding CGICs exists. Overall, respondents reported that a CGIC should include an assessment of the patient's function and mental status, a care giver interview, and a standardized set of questions, and it should take approximately 20 minutes per interview. Depending on a patient's level of impairment, raters consider different areas of behavior in formulating a CGIC rating. These findings demonstrate the considerable consensus regarding the CGIC rating process, and were integrated into the design of the ADCS-CGIC, currently in use.