Comparative efficacy of risperidone versus haloperidol on behavioural and psychological symptoms of dementia

BACKGROUND: Behavioural and psychological symptoms of dementia (BPSD) cannot be regarded as a single clinical syndrome, but rather as a heterogeneous group of symptoms, each of which can be considered as possible targets for therapy. OBJECTIVE: To compare the efficacy of risperidone and haloperidol on specific manifestations of BPSD. METHODS: A post-hoc analysis was conducted using data from an 18-week, randomized, double-blind, crossover head-to-head trial of risperidone vs haloperidol in treating 114 nursing-home residents with BPSD. Dependent variables were item scores of the Korean versions of the Behavioural Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD-K) and Cohen-Mansfield Agitation Inventory (CMAI-K). RESULTS: On the BEHAVE-AD-K, risperidone was significantly more effective than haloperidol in treating wandering (p = 0.0496), agitation (p = 0.0091), diurnal rhythm disturbances (p = 0.0137), anxiety regarding upcoming events (p = 0.0002), and other anxieties (p = 0.0088). On the CMAI-K, risperidone was significantly more effective in treating physical sexual advances (p = 0.0202), pacing and aimless wandering (p = 0.0123), intentional falling (p = 0.0398), hoarding things (p = 0.0499), performing repetitious mannerisms (p = 0.0048), repetitive sentence or questions (p = 0.0025), complaining (p = 0.0101), and negativism (p = 0.0027). Haloperidol was not significantly superior to risperidone on any individual item in either scale. CONCLUSIONS: When comparing treatment effects on individual symptoms frequently occurring in patients with dementia, risperidone significantly improved symptoms of agitation, wandering, diurnal rhythm disturbance and anxieties, among other symptoms, compared with haloperidol.     

A double-blind randomised comparison of risperidone and haloperidol in the treatment of behavioural and psychological symptoms in Chinese dementia patients.

BACKGROUND: Behavioural and psychological symptoms (BPSD) are common during the course of dementia and present severe problems to patients and their caregivers. OBJECTIVES: To assess the therapeutic efficacy and safety of haloperidol and risperidone in treating BPSD in Chinese dementia patients. METHODS: A 12-week double-blind randomised comparison of haloperidol and risperidone treatments was conducted in 58 patients with DSM-IV diagnosis of dementia of Alzheimer's type or vascular dementia. They were randomly assigned to receive flexible doses (0.5 to 2 mg/day) of haloperidol or risperidone. Clinical response was evaluated using the Cohen-Mansfield Agitation Inventory (CMAI), the Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD), Simpson-Angus Scale, Functional Assessment Staging and Cantonese version of the Mini-Mental State Examination. RESULTS: The mean doses at the last week were 0.90 mg/day of haloperidol and 0.85 mg/day of risperidone. Both haloperidol and risperidone significantly reduced the severity of BPSD (scores on CMAI and BEHAVE-AD), with no significant between-group differences. Haloperidol-treated patients showed a worsening on Simpson-Angus scale while there was no significant change in this measure in risperidone-treated patients. CONCLUSIONS: Low-dose haloperidol and risperidone were well tolerated and associated with reductions in the severity and frequency of behavioural symptoms in subjects with dementia. Risperidone may have a more favourable risk-benefit profile in view of its lower propensity to induce extrapyramidal symptoms.     

A randomized trial of risperidone, placebo, and haloperidol for behavioral symptoms of dementia.

OBJECTIVE: To compare effects of risperidone with placebo (efficacy and tolerability) and haloperidol (tolerability) for treating demented patients with aggression and other behavioral symptoms. METHODS: A 13-week double-blind study involving 344 patients with dementia randomly assigned to receive placebo or flexible doses (0.5 to 4 mg/d) of risperidone or haloperidol. Behavioral symptoms were assessed by the Behavior Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD), the Cohen-Mansfield Agitation Inventory (CMAI), and the Clinical Global Impression (CGI) scale. Tolerability assessments included the Extrapyramidal Symptom Rating Scale, sedation levels, Functional Assessment Staging, Mini-Mental State Examination, and incidence of adverse events. RESULTS: The mean dose at endpoint was 1.1 mg/d of risperidone and 1.2 mg/d of haloperidol. Although not significant, a higher percentage of patients receiving risperidone than those receiving placebo showed clinical improvement (> or =30% reduction from baseline to endpoint in BEHAVE-AD total score) at endpoint and week 12. Reductions in the BEHAVE-AD total score were significantly greater with risperidone than with placebo at week 12. In a further analysis of aggression, the most dominant symptom in these patients, BEHAVE-AD and CMAI aggression cluster scores were significantly reduced compared with placebo at endpoint and week 12. CGI scores were also significantly reduced at endpoint and week 12. Severity of extrapyramidal symptoms with risperidone did not differ significantly from that of placebo and was less than that of haloperidol. A post hoc analysis showed significantly greater reductions in the BEHAVE-AD aggressiveness score with risperidone than haloperidol at week 12. CONCLUSION: Low-dose risperidone (mean 1.1 mg/d) was well tolerated and associated with reductions in the severity and frequency of behavioral symptoms, particularly aggression, in elderly patients with dementia.     

Antipsychotic treatment of behavioral and psychological symptoms of dementia in geropsychiatric inpatients.

Behavioral/psychological symptoms of dementia (BPSD) affect caregiver burden and transition from home to hospital or long-term care. The authors examined change in BPSD for dementia patients (from hospital admission to discharge) who were prescribed haloperidol (n= 289), olanzapine (n=209), or risperidone (n=500). Olanzapine was associated with significantly greater overall improvement in BPSD (based on the Psychogeriatric Dependency Rating Scale total score) than risperidone or haloperidol. Olanzapine was significantly superior on measures of active-, verbal-, and passive-aggression and delusions/hallucinations to risperidone or haloperidol, and, on manipulative behavior and noisiness, to risperidone. Results support the effectiveness of olanzapine in improving several BPSD in hospitalized dementia patients.     

Effect of antipsychotics on mortality in elderly patients with dementia: a 1-year prospective study in a nursing home

BACKGROUND AND OBJECTIVES: The use of risperidone or olanzapine to treat behavioral problems associated with dementia is no longer recommended in the U.K. because of the increased risk of cerebrovascular adverse effects (CVAEs) and/or mortality. To evaluate the risks and benefits of antipsychotics, we measured the rate of mortality in patients with dementia, Alzheimer's disease (AD) and vascular/mixed dementia and compared mortality rates between those who had received antipsychotics and those who had not received antipsychotics. METHODS: A total of 273 subjects were assessed at baseline, 6 months and 12 months using a 1-year prospective follow-up design. Mortality rates between groups were compared using a Kaplan-Meier curve and log-rank statistics. Relative risks (RRs) were examined by the Cox proportional-hazards model. RESULTS: The overall 1-year mortality rate in dementia was 23.8%. The mortality rate in those who had not received antipsychotics (26.8%) was higher than that in those who had received antipsychotics (20.6%). RR and 95% confidence interval (CI) of mortality, when we compared those who had not received antipsychotics with those who had received antipsychotics, was 1.277 (95% CI 1.134-1.437) after controlling for age, severity of dementia, medical comorbidities, cognitive impairment (measured by the Korean version of the Mini-mental State Examination (MMSE)) and behavioral and psychological symptoms of dementia (BPSD), measured by the Behavioral Pathology in Alzheimer's Disease Rating Scale, Korean version (BEHAVE-AD-K). When those who had not received antipsychotics were compared with those who had received both risperidone and haloperidol, RR (95% CI) was 1.225 (1.101-1.364). CONCLUSION: This study does not support reports that antipsychotics increase mortality in dementia.     

Risperidone for psychosis of Alzheimer's disease and mixed dementia: results of a double-blind, placebo-controlled trial

OBJECTIVE: To evaluate the efficacy and safety of low-dose risperidone in treating psychosis of Alzheimer's disease (AD) and mixed dementia (MD) in a subset of nursing-home residents who had dementia and aggression and who were participating in a randomized placebo-controlled trial of risperidone for aggression. METHOD: This post-hoc analysis included only patients diagnosed with AD or MD with psychosis, defined by a score of >or= 2 on any item of the Behavioral Pathology of Alzheimer's Disease (BEHAVE-AD) psychosis subscale at both screening and baseline. Co-primary efficacy endpoints were changes in scores on BEHAVE-AD psychosis subscale and Clinical Global Impression of Change (CGI-C). RESULTS: Overall, 93 patients (46 risperidone and 47 placebo) fulfilled the psychosis of AD criteria. Mean change at endpoint in BEHAVE-AD psychosis subscale with risperidone was superior to placebo (-5.2 vs -3.3; p = 0.039). Distribution of CGI-C at endpoint also favoured risperidone (p < 0.001). The superior improvement with risperidone compared with placebo occurred as early as the first two weeks and persisted to the end of the treatment period. At endpoint, 59% of risperidone-treated patients were responders (i.e. were 'very much' or 'much' improved) compared with 26% of patients receiving placebo. The mean risperidone dose was 1.03 +/- 0.61 mg/day. Twelve weeks of treatment were completed by 37 patients treated with risperidone (80%) and 35 with placebo (74%). A total of 46 (98%) placebo- and 44 (96%) risperidone-treated patients experienced at least one adverse event, with only somnolence occurring more frequently in the risperidone group. CONCLUSION: Risperidone effectively reduces psychosis and improves global functioning in elderly patients with moderate-to-severe psychosis of AD and MD.     

Quetiapine treatment for behavioural and psychological symptoms of dementia in Alzheimer's disease patients: a 6-week, double-blind, placebo-controlled study

SETTING: Treating elderly patients with Alzheimer's disease (AD) and behavioral and psychological symptoms of dementia (BPSD) is challenging due to the increased risk of iatrogenic movement disorders with old neuroleptics and the seemingly increasing risk of cardiovascular events with newer atypical agents. Quetiapine is an atypical antipsychotic agent that warrants further investigation. OBJECTIVES: To assess tolerability, safety, and clinical benefit of quetiapine in AD patients with BPSD. PARTICIPANTS AND DESIGN: AD patients with BPSD participated in a 6-week randomized, double-blind, placebo-controlled trial. Quetiapine was increased on the basis of clinical response and tolerability. Primary efficacy assessments included the Neuropsychiatric Inventory (NPI) and Clinical Global Impression of Change (CGI-C). Secondary efficacy measures included the Mini-Mental State Examination (MMSE), the Simpson-Angus Scale (SAS) and the Abnormal Involuntary Movement Scale (AIMS). RESULTS: Forty patients (26 women), mean age 82.2 (SD 6.4) years were enrolled, 27 completed treatment. Median dose of quetiapine was 200 mg/day. Significant NPI total scores reductions (79% for placebo and 68.5% for quetiapine) were observed. The CGI-C score decreased significantly in the quetiapine group (p = 0.009 at 6 weeks) and did not change significantly in the placebo group (p = 0.48). The MMSE, AIMS, SAS scores and adverse events did not differ significantly between the two arms. CONCLUSIONS: Quetiapine did not significantly improve psychosis scores. It did not cause cognitive and motor deterioration. These results might possibly be due to small sample size.     

Risperidone in the treatment of psychosis of Alzheimer disease: results from a prospective clinical trial.

OBJECTIVE: The objective of this study was to evaluate efficacy and safety of low-dose risperidone for treating psychosis of Alzheimer disease (AD). METHOD: The authors conducted a randomized, eight-week, double-blind, placebo-controlled, multicenter trial involving nursing home residents diagnosed with AD and psychosis. Four hundred seventy-three patients were randomly assigned to placebo (N = 238) or 1.0 to 1.5 mg risperidone per day (N = 235). Coprimary efficacy end points were: changes in scores on the Behavioral pathology in Alzheimer's Disease (BEHAVE-AD) Psychosis subscale and Clinical Global Impression of Change (CGI-C). Protocol-specified subgroup analyses were performed by demographics and dementia severity. RESULTS: Efficacy analysis included 416 patients. Both groups improved significantly on the BEHAVE-AD Psychosis subscale and CGI-C with no significant difference between groups. In the subgroups analyses, a statistically significant treatment by Mini-Mental Status Examination (MMSE) interaction on the CGI-C (F([2,381]) = 3.90, p = 0.021) was observed with patients with more severe dementia (MMSE <10) showing significant differences at end point favoring risperidone treatment (chi(2) ([1]) = 5.11, p = 0.024). Mean risperidone dose was 1.03 +/- 0.24 mg per day. All-cause discontinuation rates were 25% for both risperidone and placebo. Treatment-emergent adverse events occurred in 74% risperidone versus 64% placebo patients, with somnolence occurring significantly more frequently with risperidone (16.2% versus 4.6%). Nine (3.8%) risperidone- and six (2.5%) placebo patients died during or within 30 days after treatment. CONCLUSION: This trial did not confirm earlier findings in this population.     

氟哌啶醇与利培酮改善痴呆患者行为症状和精神状态的临床实效性探讨

目的观察并探讨氟哌啶醇与利培酮改善痴呆患者行为症状和精神状态(behavioural and psychological symptoms of dementia,BPSD)的临床实效性。方法选择2011-08-2013-10我院接诊的痴呆患者80例,随机分为观察组和对照组,观察组40例使用利培酮(risperidone,RPD)治疗,对照组使用氟哌啶醇(haloperidol,HPL)治疗。以PANSS-EC和PANSS评定量表作为主要疗效评价指标。结果 2组给药6周PANSS总分和PANSS-EC分比较差异无统计学意义(P0.05)。而给药6周后与治疗前2组比较差异均具有统计学意义(P0.05)。用药后观察组、对照组锥体外系不良反应发生率分别为42.5%、67.5%,差异有统计学意义(P0.05)。观察组有效率为87.5%,对照组为65.0%,2组比较差异有统计学意义(P0.05)。结论RPD口服对改善BPSD与HPL疗效相当,但RPD的临床实效性更好,锥体外系不良反应发生率低,值得临床推广应用。     

Efficacy and safety of risperidone oral solution in agitation associated with dementia in the elderly.

BACKGROUND: Behavioral and psychological symptoms in dementia (BPSD) contribute to caregiver burden and institutionalization of elderly. Neuroleptics are prescribed to control agitation. Side effects of typical neuroleptics are harmful, making atypical neuroleptics an indication. OBJECTIVES: To evaluate efficacy and tolerability of risperidone oral solution (ROS) given once daily to demented elderly outpatients with BPSD (agitation). METHOD: Patients (n=26), 76.35+/-8.63 years, Diagnostic and Statistical Manual of Mental Disorders 4th ed. (DSM-IV) criteria for dementia. RSO was given, starting dose of 0.25 mg and increments of 0.25 mg every week. Mini-Mental State Examination (MMSE) assessed cognitive status, Behavioral and Emotional Activities Manifested in Dementia (BEAM-D) and Clinical Global Impression (CGI) measured BPSD, Extrapiramidal Symptom Rating Scale (ESRS) evaluated extrapyramidal symptoms. Cardiovascular side effects were evaluated clinically. RESULTS: There was a 26% reduction in agitation and no cardiovascular side effects in the range from 1.0 to 1.25 mg. Side effects were more prevalent above 2.5 mg. CONCLUSION: Risperidone oral solution improved agitation with good tolerability from 0.5 to 1.25 mg. A single dose with increments of 0.25 mg may be more acceptable to patients and caregivers.     

A comparative study of behavioral and psychological symptoms of dementia in patients with Alzheimer's disease and vascular dementia referred to psychogeriatric services in Korea and the U.K

BACKGROUND: There is a paucity of cross-cultural studies of behavioral and psychological symptoms of dementia (BPSD). METHOD: BPSD were examined in consecutive series of referrals to a psychogeriatric service in Korea and the U.K. using the Behavioral Pathology in Alzheimer's Disease (BEHAVE-AD) rating scale and the Cornell Scale for Depression in Dementia (CSDD). Results were analyzed separately for Alzheimer's disease and vascular dementia. RESULTS: Koreans in both diagnostic groups had lower Mini-mental State Examination (MMSE) scores and higher BEHAVE-AD total and subscale scores for most subscales. In both countries, for both diagnostic groups, the total BEHAVE-AD score and several subscale scores were negatively correlated with the MMSE scores. Logistic regression analysis for Alzheimer's disease revealed that BEHAVE-AD total and most subscale scores independently predicted the country of origin in addition to the MMSE scores predicting the same. CONCLUSIONS: These differences in BPSD are most likely explained by the lower MMSE scores in the Korean sample. However, genuine differences in BPSD between the two countries can only be critically examined in a cross-cultural population-based epidemiological study for both diagnostic categories using validated instruments to measure BPSD and controlling for the influence of MMSE score.     

Risperidone in the treatment of schizophrenia: results of a study of patients from Germany, Austria, and Switzerland

Results of a subanalysis of data from the multinational risperidone trial (RIS-INT-2) are reported. Patients with chronic schizophrenia were treated with risperidone at 1 mg/day (n = 25), 4 mg/day (n = 27), 8 mg/day (n = 29), 12 mg/day (n = 31), or 16 mg/day (n = 29), or 10 mg/day of haloperidol for 8 weeks. According to the Positive and Negative Syndrome Scale (PANSS) total and subscale scores, improvements were noted in each treatment group from baseline to treatment endpoint. On each scale the magnitude of improvement was greater in the risperidone patients than in the haloperidol patients. The onset of action of risperidone was faster than haloperidol. By treatment week 2, over half of the patients receiving ≥ 4 mg/day of risperidone were clinically improved (≥ 20% reduction in total PANSS scores). This rate of improvement was not seen until week 6 in the haloperidol patients. Severity of extrapyramidal symptoms (scores on the Extrapyramidal Symptom Scale) was significantly lower in patients receiving 1 or 4 mg/day of risperidone than in patients receiving higher risperidone doses and in haloperidol patients. The optimal dose of risperidone, in terms of both efficacy and safety, was 4 mg/day. These results confirm the findings of the controlled trials of risperidone conducted in North America and the multinational trial.     

Risperidone versus haloperidol in children and adolescents with AD

Objective The aim of the study was to compare safety, efficacy and tolerability of risperidone with haloperidol in the treatment of Autistic Disorder (AD). Method This study was designed as a double-blind, prospective, for a 12-week period. A total of 30 subjects, between the ages of 8 and 18 with AD based on DSM IV criteria, were included in the study. Behavioral Rating Scales were performed by the investigators and the parents. Safety assessment included vital signs, electrocardiogram, electroencephalogram, adverse events, laboratory tests, extrapyramidal symptoms and the side effects. Both treatments were applied in a once daily dosage regimen of 0.01–0.08 mg/kg/day. Results The reduction from baseline in Ritvo–Freeman Real Life Rating Scale (RF-RLRS), sensory motor (subscale I) and language (subscale V) scores were significant in risperidone group (P < 0.05). Compared to haloperidol, risperidone led to a significantly greater reduction in the Aberrant Behavior Checklist (ABC) and Turgay DSM-IV Pervasive Developmental Disorder (PDD) scale scores (P < 0.05 and P < 0.01). There was a greater increase of prolactin in the risperidone group, while alanine amino transferase (ALT) had further increased in the haloperidol group. Sensory motor behaviors (subscale I) and language at the end of the 12th week, RF-RLRS sensory motor and language subscale scores decreased in the risperidone group further than the other group (P < 0.05). Conclusions Risperidone was found to be more effective than haloperidol in the treatment of behavioral symptoms, impulsivity, language skills, and impaired social relations in children with AD. These results demonstrated that both drugs were safe and well tolerated in the treatment of AD.     

The efficacy and safety of risperidone in the treatment of psychosis of Alzheimer's disease and mixed dementia: a meta-analysis of 4 placebo-controlled clinical trials

BACKGROUND: Dementia typically includes behavioral and psychological symptoms of dementia (BPSD) as well as cognitive decline. Psychosis of Alzheimer's disease (AD) is a specific component of AD, characterized by delusions, misidentifications, and hallucinations. METHODS: This study is a meta-analysis of patients with psychosis of AD from four large placebo-controlled clinical trials of risperidone in dementia. Three trials included patients diagnosed with heterogeneous symptoms of BPSD (those with psychosis of AD were included in this analysis), while one trial included only those diagnosed with psychosis of AD. Efficacy was measured using the Behavioral Pathology in Alzheimer's Disease (BEHAVE-AD) Psychosis subscale and Clinical Global Impression (CGI). RESULTS: Primary analyses in the psychosis of AD population demonstrated that risperidone significantly improved scores on the BEHAVE-AD Psychosis subscale and CGI scale compared with placebo. Secondary analyses demonstrated that patients with more severe symptoms showed a more pronounced response to treatment with risperidone compared with placebo than those patients with less severe symptoms. Extrapyramidal symptoms and somnolence were more frequent with risperidone than placebo (p=0.04). Cerebrovascular adverse events and all-cause mortality were observed more frequently, although not statistically significantly, with risperidone versus placebo. CONCLUSIONS: This meta-analysis of psychosis of AD showed improvement in psychotic symptoms and general clinical improvement in patients with psychosis of AD treated with risperidone compared with placebo. The benefits of treatment were most significant in patients with severe symptoms. The safety profile of risperidone in this psychosis of AD population was similar to the more general BPSD population.     

A randomized placebo-controlled trial of risperidone for the treatment of aggression,agitation, and psychosis of dementia

BACKGROUND: This randomized, double-blind, placebo-controlled trial examined the efficacy and safety of risperidone in the treatment of aggression, agitation, and psychosis in elderly nursing-home patients with dementia. METHOD: Elderly patients with a DSM-IV diagnosis of dementia of the Alzheimer's type, vascular dementia, or a combination of the 2 (i.e., mixed dementia) and significant aggressive behaviors were randomized to receive, for a period of 12 weeks, a flexible dose of either placebo or risperidone solution up to a maximum of 2 mg/day. Outcome measures were the Cohen-Mansfield Agitation Inventory (CMAI), the Behavioral Pathology in Alzheimer's Disease (BEHAVE-AD) rating scale, and the Clinical Global Impression of Severity (CGI-S) and of Change (CGI-C) scales. RESULTS: A total of 345 patients were randomized to treatment with risperidone or placebo, and 337 patients received at least one dose of study drug. The trial was completed by 67% of patients in the placebo group and 73% of patients in the risperidone group. The mean +/- SE dose of risperidone was 0.95 +/- 0.03 mg/day. The primary endpoint of the study, the difference from baseline to endpoint in CMAI total aggression score, showed a significant reduction in aggressive behavior for risperidone versus placebo (p <.001). A similar improvement was also seen for the CMAI total non-aggression subscale (p <.002) and for the BEHAVE-AD total (p <.001) and psychotic symptoms subscale (p =.004). At endpoint, the CGI-S and the CGI-C scores indicated a significantly greater improvement with risperidone compared with placebo (p <.001). Overall, 94% and 92% of the risperidone and placebo groups, respectively, reported at least 1 adverse event. Somnolence and urinary tract infection were more common with risperidone treatment, whereas agitation was more common with placebo. There was no significant difference in the number of patients who reported extrapyramidal symptoms between the risperidone (23%) and placebo (16%) groups. CONCLUSION: Treatment with low-dose (mean = 0.95 mg/day) risperidone resulted in significant improvement in aggression, agitation, and psychosis associated with dementia.     

Rapid antimanic effect of risperidone monotherapy: a 3-week multicenter, double-blind, placebo-controlled trial

OBJECTIVE: This study evaluated the efficacy and safety of risperidone monotherapy in the treatment of acute bipolar mania. METHOD: Patients with DSM-IV bipolar I disorder experiencing an acute manic episode (baseline Young Mania Rating Scale score >/==" BORDER="0">20) were randomly assigned to 3 weeks of treatment with risperidone (flexible dose: 1-6 mg/day) or placebo. The primary efficacy measure was the mean baseline-to-endpoint change in total score on the Young Mania Rating Scale. Secondary efficacy measures included the Clinical Global Impression (CGI) severity rating and scores on the Montgomery-Asberg Depression Rating Scale, Positive and Negative Syndrome Scale, and Global Assessment Scale (GAS). Safety assessments consisted of monitoring adverse events, vital signs, electrocardiogram and laboratory results, and scores on the Extrapyramidal Symptom Rating Scale. RESULTS: Subjects (N=259) received treatment with either risperidone (N=134) or placebo (N=125). The mean modal dose of risperidone was 4.1 mg/day. Improvement in mean Young Mania Rating Scale total score (adjusted for covariates) was significantly greater in the risperidone than in the placebo group at endpoint (mean change=-10.6 [SD=9.5] versus -4.8 [SD=9.5], respectively), with significant between-group differences seen as early as 3 days after start of treatment (change with risperidone: mean=-6.8 [SD=5.8]; change with placebo: mean=-4.0 [SD=5.8]) and continuing throughout all time points. Improvements in CGI severity ratings and scores on the Montgomery-Asberg Depression Rating Scale, Positive and Negative Syndrome Scale, and GAS were also significantly greater among patients receiving risperidone than those given placebo. The most common adverse event reported among risperidone patients was somnolence. While Extrapyramidal Symptom Rating Scale scores were significantly greater in patients receiving risperidone, mean total and subscale scores were low. CONCLUSIONS: Risperidone monotherapy was significantly more efficacious than placebo in the treatment of acute mania and demonstrated a rapid onset of action. Risperidone was well tolerated by patients in this study.     

Combination of a mood stabilizer with risperidone or haloperidol for treatment of acute mania: a double-blind,placebo-controlled comparison of efficacy and safety

OBJECTIVE: The study assessed the efficacy and safety of risperidone as an adjunctive agent to mood stabilizers in the treatment of acute mania. METHOD: This 3-week randomized, double-blind, placebo-controlled study included 156 bipolar disorder patients with a current manic or mixed episode who received a mood stabilizer (lithium or divalproex) and placebo, risperidone, or haloperidol. The primary efficacy measure was the Young Mania Rating Scale. Other assessments used the Brief Psychiatric Rating Scale, the Clinical Global Impression scale, and safety measures. RESULTS: The trial was discontinued by 25 (49%) of the 51 placebo group patients, 18 (35%) of the 52 risperidone group patients, and 28 (53%) of the 53 haloperidol group patients. Mean modal doses were 3.8 mg/day (SD=1.8) of risperidone and 6.2 mg/day (SD=2.9) of haloperidol. Significantly greater reductions in Young Mania Rating Scale scores at endpoint and over time were seen in the risperidone group and in the haloperidol group, compared with the placebo group. Young Mania Rating Scale total scores improved with risperidone and with haloperidol both in patients with psychotic features and in those without psychotic features at baseline. Extrapyramidal Symptom Rating Scale total scores at endpoint were significantly higher in the haloperidol patients than in the placebo patients. Antiparkinsonian medications were received by 8%, 17%, and 38% of patients in the placebo, risperidone, and haloperidol groups, respectively. CONCLUSIONS: Risperidone plus a mood stabilizer was more efficacious than a mood stabilizer alone, and as efficacious as haloperidol plus a mood stabilizer, for the rapid control of manic symptoms and was well tolerated.     

Suicide and undetermined death by drowning

INTRODUCTION : To compare the efficacy and safety of olanzapine and haloperidol in partial-responder paranoid schizophrenic patients. METHOD : In this multi-centre, double-blind study, 28 patients with DSM-IV paranoid schizophrenia were randomized to receive 14 weeks treatment with either olanzapine or haloperidol at flexible doses. The pre- and post-treatment assessment included the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Negative Symptoms (SANS), the CGI, the Simpson-Angus Rating Scale, and the Barnes Akathisia Rating Scale. RESULTS : The two treatment groups showed similar improvement on the BPRS positive symptoms subscale, while the improvement of BPRS negative symptoms subscale was significant only in the olanzapine group (ANOVA with repeated measures, group effect: F=5.89, P =0.023). Only the olanzapine-treated patients experienced a significant improvement of negative symptoms as rated by the SANS (ANOVA with repeated measures, group effect: F=6.81, P =0.016). No significant differences were found between the two groups on the Simpson and Angus Rating Scale scores, but a significant difference was found in the Barnes Akathisia Rating Scale scores: no patient in the olanzapine-treated group experienced akathisia, while a few patients in the haloperidol-treated group showed this side-effect, thus resulting in a significant group effect detected by the ANOVA (F=4.23, P =0.05). CONCLUSIONS : These preliminary results suggest that olanzapine is superior to haloperidol in the treatment of partial-responder paranoid schizophrenic patients, and also shows a better tolerability profile. Further investigations, including different diagnostic subgroups, are still needed to further clarify the clinical profile of olanzapine. (Int J Psych Clin Pract 2002; 6: 107-111)     

Adverse effects of risperidone and haloperidol treatment in schizophrenia

PURPOSE: Side effects of pharmacological treatment in schizophrenia continue to be a major issue in spite of the development of new antipsychotics. The aim of this study is to explore the adverse effects of conventional and atypical antipsychotic drugs and their associated factors. METHODS: Over 3 months, 41 patients with schizophrenia were randomized to treatment with risperidone 1-12 mg (n=21) or haloperidol 2-20 mg (n=20) daily. Efficacy was assessed by improvement of psychotic symptoms, measured on the Positive and Negative Syndrome Scale (PANSS). The safety and tolerability were assessed with the Extrapyramidal Symptom Rating Scale, the UKU Side-Effect Rating Scale and clinical laboratory assessments. RESULTS: Each treatment reduced psychotic symptoms. PANSS total scores, positive scores, and general psychopathology scores declined as trial went on without significant differences between the two groups. While PANSS negative scores improved better in the risperidone group than in the haloperidol group. The tolerability of antipsychotics was statistical significantly better in the risperidone than in the haloperidol-treated patients. The most frequent adverse effects for both groups were tremor and rigidity. Antipsychotics, their doses, and hyperprolactinemia predict short-term extrapyramidal side effects. Serum prolactin levels could predict parkinsonism and dyskinesia severity. However, dyskinesia was best predicted by the doses of neuroleptics. The predictive factor of dystonia was the antipsychotic drug itself. After adjusting drug doses and concomitant medications, side effects could be markedly improved. CONCLUSIONS: This study suggested that risperidone was superior to haloperidol in improving negative symptoms and better tolerated during the 12 weeks' treatment of schizophrenia. Serum prolactin levels could predict the severity of parkinsonism and dyskinesia.     

喹硫平与利培酮治疗阿尔茨海默病精神行为异常的临床疗效及安全性分析

目的 对喹硫平和利培酮治疗阿尔茨海默病（AD） 患者的精神行为症状（BPSD）的疗效和安全性进行比较和评价.方法 选取70例伴精神行为症状的AD患者,随机分为2组,分别给予喹硫平和利培酮治疗,疗程均为6周.采用痴呆病理行为评定量表（BEHAVE-AD）和简易智力状态检查（MMSE） 评定疗效;采用副反应量表（TESS） 评定不良反应.结果 喹硫平治疗组总有效率82.9%,利培酮治疗组80%,2组疗效比较差异无统计学意义（P〉0.05）;治疗2周后,2组BEHAVE-AD评分均较治疗前均显著下降（P〈0.05）;治疗6周后,2组MMSE评分较治疗前均显著提高（P〈0.05）;不良反应比较差异无统计学意义（P〉0.05）,但喹硫平治疗组锥体外系反应发生率明显低于利培酮治疗组（P〈0.05）.结论 喹硫平与利培酮均能显著改善AD患者BPSD,喹硫平安全性略高,值得临床推广应用.