No significant QTc interval changes with high-dose ziprasidone: a case series

This study examined the effects of high-dose ziprasidone on the electrocardiograms (ECGs) of adult inpatients. This was done in an effort to assess the incremental risk of QTc interval prolongation when using ziprasidone in doses above the maximum dose of 160 mg/day approved by the Food and Drug Administration. We retrospectively examined pre- and post-treatment QTc intervals in 15 subjects at the James A. Haley Veterans Affairs Medical Center who had received high doses of ziprasidone, ranging from 240 to 320 mg/day, due to intractable psychotic symptoms. Pure baseline ECGs were not always attainable, since the majority of the subjects were taking concomitant medications at the time that ziprasidone was initiated. Analysis yielded an average increase of 3.4 msec from pre- to post-treatment, with a maximum post-treatment interval of 452 msec and no cases having a pre- to post- treatment QTc interval increase > 20 msec. These findings are statistically insignificant and do not approach the 500 msec threshold of concern. This study suggests that high-dose ziprasidone does not have a significant incremental effect on QTc interval prolongation in certain subsets of patients. However, it does not rule out the possibility that ziprasidone could have deleterious effects in higher risk populations or that ziprasidone could have rare, idiosyncratic cardiogenic effects. Limitations of the study are identified and recommendations for future research are presented.     

Cardiovascular safety of aripiprazole and pimozide in young patients with Tourette syndrome

The pharmacotherapy for tic management in Tourette syndrome (TS) relies on neuroleptics, which have been associated with electrocardiographic abnormalities, including QTc interval prolongation. This study assessed the cardiovascular safety of the newer antipsychotic aripiprazole in comparison with the neuroleptic pimozide among young patients affected by TS. Fifty patients aged 6–18 years were assigned to either pimozide (n = 25; mean daily dose 4.4 mg/die) or aripiprazole (n = 25; 5.3 mg/die) treatment for up to 24 months. All patients underwent five serial cardiovascular assessments (baseline, 6, 12, 18 and 24 months). The group treated with pimozide showed significant changes in blood pressure (decreased), QT and QTc (both prolonged). The aripiprazole group showed changes from baseline to peak values in blood pressure (increased), whilst modifications in QT and QTc were not statistically significant. At equivalent doses, aripiprazole is characterised by a safer cardiovascular profile than pimozide, being associated with a lower frequency of QTc prolongation.     

A retrospective study of the safety of intramuscular ziprasidone in agitated elderly patients

OBJECTIVE: Authors evaluated the safety of intramuscular ziprasidone for use in acute agitation in an elderly population. METHOD: Medical records were reviewed retrospectively to identify consecutive patients who were admitted to our neuropsychiatry service with the presenting complaint of dementia (DSM-IV) with agitation and who were given intramuscular ziprasidone and then administered an electrocardiogram (ECG) (N = 23). Some patients also had a baseline ECG (N = 14). QTc intervals were recorded, and significance was defined as a QTc of > or =450 ms or a 10% prolongation from baseline. A paired-samples t test was performed to compare the baseline and postmedication QTc intervals. Confounding factors were examined, and cardiac events (torsades de pointes, cardiac arrest) were recorded. RESULTS: There was no significant difference in the QTc interval between the baseline and the post-ziprasidone values. One patient had a QTc greater than 500 ms and 25% over baseline, and therefore the medication was discontinued. The mean prolongation of the QTc interval was only 0.5 ms. There were no episodes of torsades de pointes. Other medications that the patients were taking did not appear to affect the QTc interval in an expected manner. CONCLUSION: Larger studies need to be done to evaluate the safety of intramuscular ziprasidone in agitated elderly patients, a population with an increased risk of QT prolongation and torsades de pointes because of their age, comorbid conditions, and concomitant use of multiple medications.     

Incidence of tardive dyskinesia in first-episode psychosis patients treated with low-dose haloperidol

BACKGROUND: Previous studies suggest that the risk of tardive dyskinesia is increased with higher doses of conventional antipsychotics. This study evaluates the 12-month incidence of tardive dyskinesia in subjects with first-episode psychosis who were treated with very low doses of haloperidol. METHOD: Fifty-seven subjects with first-episode psychosis and a DSM-IV diagnosis of schizophreniform disorder, schizophrenia, or schizoaffective disorder were treated according to a fixed protocol with a mean dose of haloperidol of 1.68 mg/day and prospectively studied for 12 months. Subjects were assessed for extrapyramidal symptoms and psychiatric symptoms at 3-month intervals. Data were gathered from 1999 to 2001. RESULTS: Twelve-month incidence of probable or persistent tardive dyskinesia according to Schooler and Kane criteria was 12.3% (N = 7). Subjects with tardive dyskinesia did not differ from the rest of the sample regarding gender, race, duration of untreated psychosis, or baseline clinical characteristics. Subjects with tardive dyskinesia were older compared with subjects without tardive dyskinesia (37.14 +/- 9.23 vs. 27.30 +/- 8.09 years, respectively; t = -2.77, df = 30, p = .01) and received higher mean doses of haloperidol at 12 months (2.80 +/- 1.64 vs. 1.39 +/- 0.69 mg/day, respectively; t = -3.13, df = 25, p = .004). Cox regression analysis revealed that age at inclusion (p = .031), percentage change in negative symptoms (p = .028), and dose of haloperidol at 12 months (p = .016) were significant predictors of risk for tardive dyskinesia. CONCLUSION: Incidence of tardive dyskinesia was at least as high as in other samples treated with standard doses of conventional antipsychotics. Subjects at risk for tardive dyskinesia could not be identified on the basis of initial clinical features or acute treatment response. Risk of tardive dyskinesia was related to age, antipsychotic dose, and worsening of negative, depressive, and parkinsonian symptoms.     

Effect of initial ziprasidone dose on length of therapy in schizophrenia

OBJECTIVE: To examine the effects of initial ziprasidone dose on discontinuation rates, using retrospective integrated medical and pharmacy claims data. METHODS: Patients > or = 18 years with a diagnosis of schizophrenia or schizoaffective disorder and a ziprasidone claim between March 2001 and February 2003 who were continuously enrolled for at least six months before and three months after initiation of ziprasidone were included. They were stratified by initial daily dose (> or = 40 and < 80 mg [low] vs. > or = 80 and < 120 mg [medium] vs. 120-160 mg [high]). The six-month risk of discontinuation was examined using Cox proportional hazards models controlling for gender, psychiatric comorbidities, and pre-ziprasidone utilization of antipsychotics (atypical, conventional, none). RESULTS: The mean age of the sample (n=1058) was 38 years; 42% were male. The six-month risk of discontinuation was significantly lower in patients in the high-dose group as compared to the low-dose group (HR=0.737 for high-dose vs. low-dose, 95% CI=0.581, 0.935; P=0.012) and trended towards significance when comparing high-dose and medium-dose groups (HR=0.857 for high-dose vs. medium-dose, 95% CI=0.694, 1.059; P=0.153). CONCLUSIONS: Patients initiating ziprasidone therapy with an initial dose of at least 120 mg/day had better medication adherence compared to those initiating at lower doses. These findings confirm results seen in clinical trials suggesting improved efficacy and tolerability at higher ziprasidone doses.     

Functional polymorphisms of the cytochrome P450 1A2 (CYP1A2) gene and prolonged QTc interval in schizophrenia

CYP1A2 is an important inducible enzyme involved in the metabolism of antipsychotics. This study examined two functional polymorphisms in the gene as potential markers in predicting prolongation of QTc interval in patients treated with antipsychotics. QT intervals were measured by 12-lead electrocardiography (ECG) for patients with a DSM-IV diagnosis of schizophrenia. Genomic DNA extracted from venous blood were genotyped for the two polymorphisms by PCR-RFLP. Statistically significant result for CYP1A2(*)1F was noted for all patients receiving chlorpromazine equivalent doses of above 300 mg and also for a further subgroup on antipsychotics known to be CYP1A2 substrates (p=0.007, mean QTc in ms for A/A: 395.5+/-15.1, A/C: 425.7+/-25.1, C/C: 427.3+/-20.7). For CYP1A2(*)1C, there was no statistically significant association between genotypes and mean QTc interval. Overall, there was a trend of those with the C allele of the CYP1A2(*)1F polymorphism having longer QTc intervals. The results of this study suggest that the CYP1A2(*)1F polymorphism may contribute to the risk of developing prolonged QT-interval in patients who are treated with higher doses of antipsychotics.     

A prospective open-label treatment trial of ziprasidone monotherapy in children and adolescents with bipolar disorder

OBJECTIVE: To assess the effectiveness and tolerability of ziprasidone for treating pediatric mania. METHODS: This was an eight-week, open-label, prospective study of ziprasidone monotherapy (57.3 +/- 33.9 mg/day) in 21 bipolar youth [manic, mixed, or bipolar not otherwise specified (NOS); 6-17 years old]. Assessments included the Young Mania Rating Scale (YMRS), Clinical Global Impressions-Improvement scale (CGI-I), and Brief Psychiatric Rating Scale (BPRS). Adverse events were assessed through spontaneous self-reports, vital signs, weight monitoring, and laboratory analysis. RESULTS: Fourteen of the 21 youth (67%) completed the study. Ziprasidone treatment was associated with clinically and statistically significant improvement in mean YMRS scores (-10.8 +/- 8.4, p < 0.0001) and 57% had a CGI-I 相似文献   

Ziprasidone in adolescents with autism: an open-label pilot study

INTRODUCTION: The antipsychotic drugs are the best-studied agents shown to reduce symptoms in autism, including hyperactivity, aggression, self-abusive behavior, temper tantrums, lability, irritability, social withdrawal, and stereotypical behaviors. However, significant weight gain has been associated with use of many atypical agents. Ziprasidone has been weight neutral in adult populations, but data from adolescents and patients with autism are sparse. However, ziprasidone administration has been associated with increases in the QTc. The purpose of this study was to collect pilot data on the efficacy and safety of ziprasidone in adolescents with autism, focusing on safety issues of weight gain and QTc. METHODS: Twelve adolescents with autism (mean age 14.5 +/- 1.8 years) were treated in a 6-week open pilot study. Ziprasidone dosage ranged from 20 to 160 mg/day (mean, 98.3 +/- 40.4 mg/day). The primary efficacy measure was the Clinical Global Impressions-Improvement item (CGI-I); other efficacy measures included the Aberrant Behavior Checklist and the Children's Psychiatric Rating Scale. RESULTS: Based on the CGI-I, 9 of 12 (75%) patients were treatment responders. Ziprasidone was weight neutral, and the QTc increased by a mean of 14.7 msec. Two subjects had acute dystonic reactions. Cholesterol decreased and prolactin remained the same. CONCLUSIONS: Ziprasidone shows promise as a treatment for adolescents with autism. More definitive trials are needed.     

A PET study of dopamine D2 and serotonin 5-HT2 receptor occupancy in patients with schizophrenia treated with therapeutic doses of ziprasidone

OBJECTIVE: Ziprasidone is an atypical antipsychotic drug that shows a higher affinity for serotonin 5-HT(2) receptors compared with dopamine D(2) receptors in vitro. The affinity of ziprasidone for these receptors in vivo in patients was examined in a positron emission tomography (PET) study. METHOD: The authors conducted a PET study to evaluate D(2) occupancy (using [(11)C]raclopride) and 5-HT(2) occupancy (using [(18)F]setoperone) in brain regions of interest in 16 patients with schizophrenia or schizoaffective disorder randomly assigned to receive 40, 80, 120, or 160 mg/day of ziprasidone, which reflected the recommended dose range. PET scanning was done after 3 weeks of administration and at trough plasma levels, i.e., 12-16 hours after the last dose. RESULTS: The mean 5-HT(2) receptor occupancy was significantly higher than the mean D(2) receptor occupancy (mean=76%, SD=15%, and mean=56%, SD=18%, respectively). The estimated plasma ziprasidone concentration associated with 50% maximal 5-HT(2) receptor occupancy was almost four times lower than that for D(2) receptor occupancy. CONCLUSIONS: These data affirm that ziprasidone is similar to other novel antipsychotics in having greater 5-HT(2) than D(2) receptor occupancy at therapeutic doses and suggest that the optimal effective dose of ziprasidone is closer to 120 mg/day than to the lower doses suggested by previous PET studies. The relatively high D(2) receptor occupancy, even at trough plasma levels, suggests that ziprasidone is more similar to risperidone and olanzapine in receptor occupancy profile than to clozapine and quetiapine. Since ziprasidone plasma levels show significant (more than twofold) variation within a single dose cycle, studies that are aimed at peak plasma levels (6 hours after the last dose) and that examine extrastriatal regions are required to fully characterize the in vivo occupancy profile of ziprasidone.     

Effectiveness, tolerability, and safety of ziprasidone in patients with schizophrenia or schizoaffective disorder: results of a multi-centre observational trial.

PURPOSE: The ZEISIG study (Ziprasidone Experience in Schizophrenia in Germany/Austria) investigated the effectiveness of ziprasidone as measured by discontinuation rates and mean changes of the BPRS total. Secondary objectives included quality of life, subjective well-being, tolerability, and safety. SUBJECTS AND METHODS: Two hundred and seventy-six subjects with schizophrenia and schizoaffective disorder were treated within an open-label, 12-week, prospective, flexible-dose observational trial of ziprasidone (40-160 mg/day). Baseline and outcome assessments mainly included Brief Psychiatric Rating Scale (BPRS), Clinical Global Impressions Scale (CGI), Short-Form 12 (SF-12), and Subjective Well-being under Neuroleptic treatment (SWN-K). RESULTS: Study discontinuation due to any cause was evident in 58% of subjects, most of them within the first 4 weeks after study initiation. In study completers, ziprasidone was associated with improvements in BPRS total (44.8 to 33.6; p<0.001), CGI, SF-12, and SWN-K total scores (80.5 to 89.5). Ziprasidone was related to reduction of weight, fasting glucose, and serum lipids. No cardiovascular adverse event or significant increase of the QTc interval was observed. DISCUSSION AND CONCLUSION: Approximately 60% of subjects discontinued ziprasidone prematurely, probably related to an initial and overall underdose. The present study confirmed previous tolerability and safety data of ziprasidone as well as results of its effectiveness. Independent from reason to switch, previous antipsychotic class, and severity of illness at baseline, the recommended starting dose of 80 mg/day as well as the maximum treatment dose of 160 mg/day may not be sufficient for a selected subgroup of patients.     

Rapid-acting IM ziprasidone in a psychiatric emergency service: a naturalistic study

Atypical antipsychotics have gained acceptance as first-line treatment for psychotic disorders. Rapid-acting intramuscular (IM) atypicals may supplant benzodiazepine and/or neuroleptic alternatives. IM atypical ziprasidone studies excluded severe psychiatric agitation (PSYCH), or that due to the abuse of alcohol (ETOH) or other substances (SUBS). We report Behavioral Activity Rating Scale agitation scores (range, 1-7) and duration of physical restraints in a naturalistic study in a psychiatric emergency service using IM ziprasidone 20 mg and various doses for conventional antipsychotics. Baseline scores were high for PSYCH, ETOH and SUBS patients (mean, 6.5, 6.9 and 6.6, respectively). Agitation decreased rapidly from baseline with ziprasidone [mean, 5.6, 5.3 and 5.8, respectively, at 15 min (P<.05 for all), and 4.2, 4.1 and 4.1, respectively, at 30 min (P<.01 for all)]. At 2 h, scores were 2.6, 2.1 and 2.3 (P<.01 for all versus baseline). For 9 patients receiving conventional IM antipsychotics, scores were 6.6 (baseline), 5.7 (15 min), 4.2 (30 min) and 2.9 (2 h) (P<.02 versus ziprasidone). Compared with restraint durations from 80 patients receiving conventional IM agents 1 month prior to this study, restraint duration decreased from 91+/-4 to 54+/-3 min with ziprasidone (n=77; P<.01) and varied with conventional IM agents (mean, 60+/-12 min; n=4; P=NS). None of the 19 ziprasidone patients who received electrocardiograms showed prolonged QTc; one had a dystonic reaction. IM ziprasidone appears effective for severe agitation, including agitation associated with alcohol or substance intoxication, and may reduce time in restraints.     

Striatal dopaminergic D2 receptor occupancy and clinical efficacy in psychosis exacerbation: a 123I-IBZM study with ziprasidone and haloperidol

OBJECTIVE: The aim of this study was to compare striatal dopaminergic D2 receptor occupancy (D2 RO) induced by ziprasidone and haloperidol and its relationship with clinical response and extrapyramidal side effects (EPS) in patients with acute psychosis exacerbation. METHOD: Twenty patients hospitalized with an acute psychosis exacerbation were randomised in a single-blind study to receive either ziprasidone (80-120 mg/day) or haloperidol (5-20 mg/day) for more than 2 weeks. When stable doses were achieved, data on 123I-IBZM single-photon emission computed tomography (SPECT), as well as data on clinical efficacy (positive and negative symptoms scale [PANSS]) and EPS (Simpson Angus scale [SAS]), were compared between the two groups of patients. Clinical response was defined as a percentage of change of >30% in PANSS. Striatal D2 RO and clinical data were also compared between responders and nonresponders on each treatment group. RESULTS: All patients on haloperidol and four patients on ziprasidone showed EPS. Mean D2 RO was significantly higher in the haloperidol (74.7+/-3.5) than in the ziprasidone (60.2+/-14.4) group (Mann Whitney U-test [M-W U-test] 8.50; p=0.002). Five patients were responders, and five were nonresponders on each group of treatment. Haloperidol responders and nonresponders did not differ in D2 RO, duration of treatment, doses or EPS. Ziprasidone responders were on higher doses than nonresponders and showed higher D2 RO although below 74%. A positive correlation of ziprasidone D2 RO was found with dose (r Spearman 0.87; p=0.001) and with SAS scores (r Spearman 0.88; p=0.001). CONCLUSIONS: Ziprasidone induces lower D2 RO and EPS than haloperidol, which is consistent with an atypical antipsychotic profile. A direct relationship of ziprasidone D2 RO with dose, clinical efficacy and EPS has been found in this study. These data suggest that high ziprasidone doses might be more beneficial in patients with psychosis exacerbation and claim for caution regarding EPS appearance with such high dosages.     

Ziprasidone treatment of children and adolescents with Tourette's syndrome: a pilot study

OBJECTIVE: To evaluate the efficacy and tolerability of ziprasidone in children and adolescents with Tourette's syndrome and chronic tic disorders. METHOD: Twenty-eight patients aged 7 to 17 years were randomly assigned to ziprasidone or placebo for 56 days. Ziprasidone was initiated at a dose of 5 mg/day and flexibly titrated to a maximum of 40 mg/day. RESULTS: Ziprasidone was significantly more effective than placebo in reducing the Global Severity (p = .016) and Total Tic (p = .008) scores on the Yale Global Tic Severity Scale. Compared with placebo, ziprasidone significantly reduced tic frequencies as determined by blind videotape tic counts (p = .039). The mean (+/- SD) daily dose of ziprasidone during the last 4 weeks of the trial was 28.2 +/- 9.6 mg. Mild transient somnolence was the most common adverse event. No clinically significant effects were observed on specific ratings of extrapyramidal symptoms, akathisia, or tardive dyskinesia. CONCLUSIONS: In this limited sample, ziprasidone (5-40 mg/day) appears to be effective and well tolerated in the treatment of Tourette's syndrome. Ziprasidone may be associated with a lower risk of extrapyramidal side effects in children. However, additional studies are necessary to evaluate more fully its safety and efficacy in children with tic disorders.     

Intramuscular ziprasidone compared with intramuscular haloperidol in the treatment of acute psychosis. Ziprasidone I.M. Study Group

BACKGROUND: This 7-day, randomized, open-label, multicenter, international study compared the efficacy and tolerability of intramuscular (i.m.) ziprasidone with haloperidol i.m. and the transition from i.m. to oral treatment in hospitalized patients with acute psychotic agitation (related to DSM-III-R diagnoses). METHOD: Patients received up to 3 days of flexible-dose ziprasidone i.m. (N = 90) or haloperidol i.m. (N = 42) followed by oral treatment to day 7. After an initial ziprasidone i.m. dose of 10 mg, subsequent i.m. doses of 5 to 20 mg could be given every 4 to 6 hours (maximum daily dose = 80 mg) if needed, followed by oral ziprasidone, 80-200 mg/day. Haloperidol i.m. doses of 2.5 to 10 mg were given on entry, followed by 2.5 to 10 mg i.m. every 4 to 6 hours (maximum daily dose = 40 mg) if needed, then by oral haloperidol, 10-80 mg/day. RESULTS: The mean reductions in Brief Psychiatric Rating Scale (BPRS) total, BPRS agitation items, and Clinical Global Impressions-Severity scale scores were statistically significantly greater (p < .05, p < .01, and p < .01, respectively) after ziprasidone i.m. treatment compared with haloperidol i.m. treatment. Further reductions in these scores also occurred in both groups following transition to oral treatment. Ziprasidone was associated with a lower incidence of movement disorders and a reduced requirement for anticholinergic medication during both i.m. and oral treatment compared with haloperidol. Movement disorder scale scores improved with ziprasidone i.m. and oral treatment, but deteriorated with haloperidol. Other adverse events were rare with both treatments. CONCLUSION: Ziprasidone i.m. was significantly more effective in reducing the symptoms of acute psychosis and was better tolerated than haloperidol i.m., particularly in movement disorders. The transition from ziprasidone i.m. to oral ziprasidone was effective and well tolerated.     

Efficacy and Tolerability of Switching to Ziprasidone in Italian Patients with Acute Exacerbation of Schizophrenia: An Open-Label Trial

The long-term maintenance of a stable condition is an important aim of schizophrenia therapy, which frequently requires the switch between 2 antipsychotic agents. This 8-week multicenter study, conducted in Italy, evaluates the switch from a previous antipsychotic to ziprasidone.Adult acute schizophrenic patients requiring a change in antipsychotic for lack of efficacy or tolerability issues took ziprasidone 20?-?80?mg/bid. Dosages could be adjusted during the study. The primary efficacy outcomes were the differences in positive and negative syndrome scale (PANSS) and clinical global impression severity (CGI-S) scores from baseline to study end. Other efficacy variables were clinical global impression improvement, global assessment of functioning, patient preference scale and drug attitude inventory.189 patients were evaluated; the mean (±SD) ziprasidone dose was 95.9±34.5?mg/day. PANSS and CGI-S scores significantly decreased throughout the study. All secondary outcomes significantly improved at the end of the study vs. baseline values. Ziprasidone was well tolerated; 13 patients reported a QTc prolongation (mild in 12 patients).Notwithstanding the limitations of any non-comparative study, these results suggest that ziprasidone may be an effective and well-tolerated option in acute schizophrenia patients who discontinued a previous antipsychotic agent.     

Electrocardiographic changes in patients receiving neuroleptic medication

Warner JP, Barnes TRE, Henry JA. Electrocardiographic changes in patients receiving neuroleptic medication. Acta Psychiatr Scand 1996: 93: 311–313. © Munksgaard 1996. The precise aetiology of sudden death in patients receiving neuroleptic medication is uncertain, but cardiac arrhythmias are a possible cause. We investigated the link between neuroleptic medication and electrocardiographic changes predictive of malignant cardiac arrhythmias. Electrocardiographs were performed on 111 patients receiving neuroleptic medication and on 42 unmedicated controls. Prolonged QTc intervals were more common in the patient sample, but QTc dispersion was not significantly increased. QTc interval prolongation was more likely in patients on doses above 2000 mg chlorpromazine equivalents daily (odds ratio 4.28, P<0.02). Neuroleptic medication, especially at high doses, is associated with ECG changes that may herald more serious cardiac problems.     

齐拉西酮注射剂与氟哌啶醇注射剂治疗精神分裂症急性期患者的对照研究

目的比较齐拉西酮注射剂与氟哌啶醇注射剂治疗精神分裂症急性期的疗效与副作用。方法选用齐拉西酮注射剂与氟哌啶醇注射剂,将75例患者分至齐拉西酮组（n=38）和氟哌啶醇组（n=37）,进行为期5天的治疗。两组分别完成34例和33例。在治疗前及治疗后采用阳性与阴性综合征量表（PANSS）、修改版外显攻击行为量表（MOAS）、临床总体印度量表（CG I）、不良反应量表（TESS）评定疗效及药物不良反应。治疗前进行基线心电图测定,与治疗后QTc间期比较。结果齐拉西酮组和氟哌啶醇组治疗前后PANSS阳性症状量表因子分、MOAS加权总分减分率相当;CG I评分达到好转与以上者分别为25例（73.5%）、26例（78.8%）;齐拉西酮组不良反应主要为失眠10例（29.4%）,QTc间期延长3例（7.9%）,心律失常2例（5.3%）。氟哌啶醇组不良反应主要为锥体外系反应16例（48.5%）,无QTc间期延长者。结论齐拉西酮注射剂与氟哌啶醇注射剂对治疗精神分裂症急性期患者的疗效相当,但应高度重视齐拉西酮对心脏不良反应,特别是心律失常及QTc间期的延长。     

The effect of a switch to ziprasidone in an adult population with autistic disorder: chart review of naturalistic, open-label treatment

BACKGROUND: The present investigation retrospectively assessed the effect of an open-label switch to ziprasidone from other atypical antipsychotics on behavior, weight, and lipid levels in an adult population with autistic disorder. METHOD: We conducted a chart review of 10 adults (mean +/- SD age = 43.8 +/- 6.0 years) with DSM-IV autistic disorder who were switched from other atypical antipsychotics to ziprasidone, primarily due to weight gain, but other reasons included hypercholesterolemia, maladaptive behaviors, drowsiness, and depression. They had been treated with ziprasidone for at least 6 months. Our review focused on frequency of maladaptive behaviors, weight, and lipid levels. RESULTS: The mean +/- SD daily dose of ziprasidone was 128 +/- 41 mg, and all 10 patients continued with this same treatment after completion of the 6-month trial. Seven patients were found to have an improvement or no change in their maladaptive behavior. Eight patients (80%) lost weight (mean change = -13.1 +/- 7.0 lb [-5.9 +/- 3.2 kg]), 4 (80%) of 5 patients had a decrease in total cholesterol level, and 3 (60%) of 5 had a decrease in triglyceride levels. Data on lipid levels were available for 5 of the 10 patients. Behavioral activation was not noted in this population. There were no significant adverse effects associated with ziprasidone. CONCLUSION: In adults with autism, a switch to ziprasidone from other atypical antipsychotics appears to have the potential for maintaining beneficial effect on behavior while improving major health indices including weight and lipid levels.