Effects of typical antipsychotic drugs and risperidone on the quality of sleep in patients with schizophrenia: a pilot study.

OBJECTIVE: To investigate the effects of a newer antipsychotic drug, risperidone (a potent serotonin 5-HT2A/2C and dopamine D2-receptor blocker), on the quantity and quality of sleep in patients with schizophrenia. DESIGN: Prospective pilot study. SETTING: Outpatient treatment at a mental health hospital. PATIENTS: Two groups of age- and sex-matched patients with schizophrenia receiving either risperidone (n = 8) or a typical antipsychotic drug (n = 8), and a group of age- and sex-matched controls (n = 8). OUTCOME MEASURES: Sleep quality, measured by a visual analogue scale, and sleep continuity, measured using a movement index calculated from actigraph data. RESULTS: Patients with schizophrenia had more disturbed sleep than controls. Compared with patients treated with typical antipsychotic drugs, patients treated with risperidone reported significantly better sleep quantity and quality as well as general functioning. CONCLUSION: Improvement by risperidone may be related to 5-HT2A/2C receptor blockade; however, further controlled studies are required to confirm these results.     

Influence of aging on the improvement of subjective sleep quality by atypical antipsychotic drugs in patients with schizophrenia: comparison of middle-aged and older adults.

OBJECTIVE: The authors investigated the influence of aging on the improvement of subjective sleep quality by atypical antipsychotic drugs in patients with schizophrenia. METHODS: Subjects were 86 inpatients (mean age: 61.4 years) who had been receiving treatment with conventional antipsychotic drugs and who met DSM-IV criteria for schizophrenia. Their antipsychotic medication was changed from conventional antipsychotics to one of four atypical antipsychotic drugs (olanzapine, perospirone, quetiapine, or risperidone). Patients were grouped by age (older or younger than 65 years). Subjective sleep quality and psychopathology were assessed twice: 1) at baseline, and 2) 8 weeks after switching to the atypical antipsychotic drugs. Subjective sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI), and the Positive and Negative Syndrome Scale (PANSS) was used to measure psychopathology. RESULTS: The proportion of the patients who experienced improved subjective sleep quality was significantly higher in the elderly than in the middle-aged group. Logistic-regression analysis revealed that the improvement in subjective sleep quality through administration of atypical antipsychotic drugs was predicted by increased age, daytime dysfunction, and longer sleep latency at baseline. CONCLUSION: These results demonstrate that atypical antipsychotic drugs are beneficial to the quality of sleep in elderly patients with schizophrenia.     

Effects of typical, atypical, and no antipsychotic drugs on visual contrast detection in schizophrenia

OBJECTIVE: Visual contrast detection has been reported in some studies to be normal in schizophrenia patients, but in other studies impairments have been reported. Because contrast detection in the visual processing system is mediated by dopamine, and because the pharmacotherapy of schizophrenia involves blocking dopamine postsynaptic receptor sites, the authors investigated the effects of dopamine-blocking antipsychotic drugs on visual contrast detection in schizophrenia. METHOD: Visual contrast detection thresholds were measured in healthy subjects and schizophrenia patients receiving typical and atypical antipsychotic drugs; a two-alternative, forced-choice psychophysical method was used. Also included were six patients receiving no antipsychotic treatment as well as clinically unaffected first-degree relatives of the schizophrenia patients. RESULTS: Patients receiving atypical antipsychotic drugs showed unimpaired visual contrast detection, those given typical antipsychotic drugs exhibited higher visual contrast detection thresholds, and the unmedicated schizophrenic patients showed visual contrast detection thresholds significantly below those of healthy subjects. CONCLUSIONS: Dopamine modulation via D(2) receptor blockade affects sensory processes in schizophrenia, shifting visual contrast detection from hypersensitivity in the unmedicated state to normal and even to hyposensitive levels. Thus, antipsychotic drug treatment may account for the inconsistent reports concerning visual contrast detection in schizophrenia.     

非典型抗精神病药对精神分裂症患者血清甲状腺激素水平的影响

目的探讨非典型抗精神病药利培酮、奥氮平对精神分裂症患者甲状腺功能的影响。方法将符合《中国精神障碍分类与诊断标准(第3版)》(CCMD-3)的54例精神分裂症患者,采用随机数字表法分成服用利培酮和奥氮平两组,其中利培酮组29例,给药初始剂量为4 mg/d,2周内逐渐加至6 mg/d,观察至8周末;奥氮平组25例,给药初始剂量为10 mg/d,2周内逐渐加至15mg/d,观察至8周末。分别在治疗前、治疗第8周末测血清总三碘甲状腺原氨酸(TT3)、血清总甲状腺素(TT4)、游离三碘甲状腺原氨酸(FT3)、血清游离甲状腺素(FT4)及促甲状腺激素(TSH)水平。结果利培酮组治疗前后血清TT3、TT4、FT3、FT4、TSH水平差异均无统计学意义(P0.05),奥氮平组治疗前后血清TT3、TT4、TSH水平差异无统计学意义(P0.05),治疗前后FT3、FT4差异有统计学意义[(3.01±0.28)pg/mlvs.(2.81±0.26)pg/ml,(0.91±0.2)pg/mlvs.(0.77±0.14)pg/ml,P0.05]。利培酮组治疗后血清TT3、FT3水平升高,较奥氮平组差异有统计学意义(P0.05)。结论利培酮对精神分裂症患者甲状腺功能无实质影响,奥氮平能影响精神分裂症患者血清FT3、FT4的水平,在治疗中应注意监测服用奥氮平的精神分裂症患者的甲状腺激素水平。     

Effects of typical and atypical antipsychotic drugs on gene expression profiles in the liver of schizophrenia subjects

Background

To develop and psychometrically assess a multiple choice question (MCQ) instrument to test knowledge of depression and its treatments in patients suffering from depression.

Methods

A total of 63 depressed patients and twelve psychiatric experts participated. Based on empirical evidence from an extensive review, theoretical knowledge and in consultations with experts, 27-item MCQ knowledge of depression and its treatment test was constructed. Data collected from the psychiatry experts were used to assess evidence of content validity for the instrument.

Results

Cronbach's alpha of the instrument was 0.68, and there was an overall 87.8% agreement (items are highly relevant) between experts about the relevance of the MCQs to test patient knowledge on depression and its treatments. There was an overall satisfactory patients' performance on the MCQs with 78.7% correct answers. Results of an item analysis indicated that most items had adequate difficulties and discriminations.

Conclusion

There was adequate reliability and evidence for content and convergent validity for the instrument. Future research should employ a lager and more heterogeneous sample from both psychiatrist and community samples, than did the present study. Meanwhile, the present study has resulted in psychometrically tested instruments for measuring knowledge of depression and its treatment of depressed patients.     

A longitudinal study on the effects of typical versus atypical antipsychotic drugs on hippocampal volume in schizophrenia

BACKGROUND: Previous studies have reported that hippocampal volumes correlate with symptom severity in schizophrenia. This longitudinal study measured changes in symptoms and hippocampal volume in patients switched from typical antipsychotics to olanzapine. METHODS: MRI scans were acquired from patients with chronic schizophrenia (n=10) and healthy volunteers (n=20). At baseline, patients were treated with typical antipsychotics for at least one year, then switched to olanzapine, and rescanned approximately one year later. RESULTS: Olanzapine treatment resulted in no significant change in right or left hippocampal volume. Individual changes in right hippocampal volume correlated significantly with changes in symptoms. CONCLUSIONS: Hippocampal volume change may serve as a marker of symptom change in patients on olanzapine.     

Effects of typical and atypical antipsychotic drugs on maternal behavior in postpartum female rats

Understanding the effects of antipsychotic drugs (APDs) on social behaviors such as maternal behavior is valuable for understanding the complete spectrum of therapeutic and side-effects of antipsychotics. Although previous studies have suggested that typical antipsychotics impair maternal behavior, the effects of the atypical antipsychotics have not been systematically explored. The purpose of the present report was to examine the effects of typical (haloperidol, HAL) and several atypical (clozapine, CLZ; risperidone, RIS; quetiapine, QUE) antipsychotics on maternal behavior in female rats. Maternal behaviors were examined repeatedly over a period of 24 h after a single injection of a range of doses of HAL, CLZ, RIS or QUE on Day 6 postpartum. All antipsychotic drugs, typical or atypical, elicited a qualitatively similar disruptive effect on the active components of maternal behavior such as pup approach, pup retrieval and nest building at clinically relevant doses. However, HAL caused a prolonged disruption, whereas CLZ, RIS and QUE induced an early onset but shorter duration disruption. In addition, only the atypical antipsychotics showed some inhibitory effects on nursing behavior, possibly due to sedative side-effects shared by all atypical antipsychotics. The current generation of atypical antipsychotics shows a disruptive influence on maternal behavior similar to that of the typical antipsychotics. This effect may be intrinsic to antipsychotic activity or may be reflective of a side-effect. Since the latter is more likely, this may be an effect to avoid in the design of future antipsychotics.     

Treatment with olanzapine, risperidone or typical antipsychotic drugs in Asian patients with schizophrenia

OBJECTIVE: To examine clinical outcomes in Asian patients with schizophrenia receiving monotherapy with olanzapine, risperidone or typical antipsychotics in naturalistic settings. METHOD: In this report, data from the first 12 months of the prospective, observational, 3-year Intercontinental Schizophrenia Outpatient Health Outcomes study are presented for patients from participating Asian countries (Korea, Taiwan and Malaysia) who were started on, or switched to, monotherapy with olanzapine (n = 484), risperidone (n = 287) or a typical antipsychotic drug (n = 127) at baseline. RESULTS: At 12 months, overall reduction in the score of Clinical Global Impressions-Severity of Illness rating scale was greatest with olanzapine (p < 0.001 vs typical agents), followed by risperidone (p = 0.007 vs typical agents) treatment. Olanzapine treatment was found to have significantly better effects than typical agents on negative and depressive symptom scores, and significantly greater improvements than risperidone on negative and cognitive symptoms. The occurrence of extrapyramidal symptoms was least likely with olanzapine (p < 0.001 vs typical agents, and p = 0.012 vs risperidone), while the estimated odds of tardive dyskinesia were greatest in the typical treatment group (p = 0.046 vs olanzapine, and p = 0.082 vs risperidone). Mean weight increase was greater for olanzapine-treated patients compared with the other agents (p = 0.030 vs typical agents and p < 0.001 vs risperidone). The risk of menstrual disturbance was relatively high with risperidone when compared with olanzapine treatment (p < 0.001). CONCLUSIONS: The results of this observational study indicate that, in Asian patients with schizophrenia, olanzapine may offer benefits when compared with typical agents or risperidone. However, the significantly greater odds of weight gain should be considered in the clinical management of olanzapine-treated patients.     

Switching from depot antipsychotic drugs to olanzapine in patients with chronic schizophrenia

BACKGROUND: Patients with chronic schizophrenia (DSM-IV criteria) often receive depot antipsychotic medications to assure longer administration and better compliance with their treatment regimen. This study evaluated whether patients stabilized on depot antipsychotic medication could be successfully transitioned to oral olanzapine. METHOD: In a 3-month open-label study, 26 clinically stable patients with schizophrenia taking depot antipsychotics for over 3 years were randomly assigned to continue on their current depot dose or to switch to oral olanzapine. Clinical ratings (Positive and Negative Syndrome Scale [PANSS], Global Assessment of Functioning [GAF] scale, and Clinical Global Impressions [CGI] scale) and side effect parameters (Abnormal Involuntary Movement Scale [AIMS], Barnes Akathisia Scale, AMDP-5 scale, vital signs, and weight) were obtained monthly. RESULTS: Oral olanzapine patients (N = 13) demonstrated significant clinical improvement over the depot control group (N = 13) from baseline to 3-month endpoint (PANSS total, p =.012; PANSS general, p =.068; PANSS negative, p =.098; CGI-Improvement, p =.007; CGI-Severity, p =.026; GAF, p =.015). Side effect rating scales showed no statistical differences between the 2 groups (AIMS, Barnes Akathisia Scale, AMDP-5, vital signs). The depot control group showed no statistical superiority in any measure except weight change (p =.0005). After 3 months, all olanzapine patients preferred olanzapine to their previous depot medications and chose to continue on olanzapine treatment. CONCLUSION: Clinicians may expect clinical improvement when switching chronically psychotic patients from traditional depot antipsychotic drugs to oral olanzapine. Switching may be completed within a 4-week period with relative compliance being maintained and patients preferring oral olanzapine to their previous depot medications.     

Prevalence of hyperprolactinemia in schizophrenia: association with typical and atypical antipsychotic treatment

OBJECTIVE: To evaluate the prevalence and severity of hyperprolactinemia among a large sample of patients with schizophrenia and related psychotic disorders treated with typical and atypical antipsychotic medications. METHOD: Three electronic databases (general medical, psychiatric, and pharmacologic) containing the census data from November 2002 through March 2003 for a state-funded, inpatient hospital serving the chronically mentally ill were merged (N = 470). This database was purged of patient names, while the unique hospital identification number and demographic variables in each record were retained. These records were then screened to exclude patients with medications (except neuroleptics) or medical conditions known to elevate or suppress prolactin, leaving an overall sample (N = 422) in which to evaluate the prevalence of hyperprolactinemia. The sample was composed of patients with DSM-IV schizophrenia (N = 213), other related psychotic disorders (N = 131), mood disorders (N = 44), and other disorders (N = 34). RESULTS: For the overall sample (N = 422), which combined men and women, the mean serum prolactin level was 41.5 ng/mL; 290 of 422 patients were above the normal range. For women (N = 133), the mean serum prolactin level was 57.9 ng/mL, and 67% had levels above normal. For men (N = 289), the mean level was 33.9 ng/mL, with a 70% prevalence of hyperprolactinemia. While age did not influence the prevalence of elevated prolactin among men, age (reflecting reproductive status) was a significant variable in women; older age was associated with lower prolactin levels. For the study sample, a highly significant correlation was observed between neuroleptic dose (chlorpromazine equivalent) and serum prolactin level; however, this relationship was not determined on a medication-by-medication basis. Medications known to elevate prolactin were associated with higher prevalence rates of hyperprolactinemia, and "prolactin-sparing" medications had lower prevalence rates. However, when they were used in combination, the prolactin-elevating medication overwhelmed the effects of prolactin-sparing medication. CONCLUSIONS: This study suggested that neuroleptic treatment of schizophrenia is strongly associated with hyperprolactinemia and showed important differences between prolactin-sparing and prolactin-elevating medications.     

The impact of prolactin elevation with antipsychotic medications on subjective quality of life in patients with schizophrenia

In this cross-sectional study, the author tested the hypothesis that prolactin elevation with antipsychotic medications was associated with low subjective quality-of-life scores in patients with schizophrenia. The subjects were 42 male inpatients meeting Diagnostic and Statistical Manual of Mental Disorders, 4th edition, criteria for schizophrenia on typical antipsychotics. No correlations were found between prolactin or testosterone and the 3 subscales in the Japanese version of the Schizophrenia Quality of Life Scale. Multiple regression analyses showed total variance in the ratings of 3 subscales in the Japanese version of the Schizophrenia Quality of Life Scale as follows: Brief Psychiatric Rating Scale (BPRS) anxiety/depression factor, dosage of antipsychotics and BPRS hostile/suspiciousness factor in the psychosocial subscale (adjusted R2 = 0.394), BPRS anxiety/depression factor and dose of antipsychotics in the motivation/energy subscale (adjusted R2 = 0.475), and dose of antipsychotics and BPRS anergia factor in the symptoms/side effects subscale (adjusted R2 = 0.206). The results did not support the hypothesis.     

Effects of clozapine and typical antipsychotic drugs on plasma 5-HT turnover and impulsivity in patients with schizophrenia: a cross-sectional study

OBJECTIVE: To compare the efficacy of clozapine with typical antipsychotic drugs in controlling impulsivity and to explore the possible correlation of impulsivity with plasma 5-hydroxytryptamine (5-HT) levels, plasma 5-hydroxyindoleacetic acid (5-HIAA) levels and plasma 5-HT turnover. DESIGN: Prospective, cross-sectional study open to medication and blinded to biochemical analyses. PARTICIPANTS: Healthy control subjects (n = 24) and 46 inpatients and outpatients meeting the DSM-IV criteria for schizophrenia; 20 were being treated with clozapine and 26 were taking typical antipsychotic drugs. INTERVENTIONS: All psychotropic drugs other than clozapine or typical antipsychotic drugs were discontinued for at least 5 days and subjects fasted overnight before they were assessed. OUTCOME MEASURES: Coccaro Impulsivity Scale scores, plasma 5-HT levels, 5-HIAA levels and 5-HT turnover. RESULTS: Patients treated with clozapine and those treated with typical antipsychotics had significantly higher impulsivity scores than the control group, and the mean impulsivity score of the typical antipsychotic group was significantly higher than that of patients treated with clozapine. The mean concentration of 5-HT of the typical antipsychotic group was significantly lower than that of the control group and patients treated with clozapine; however, mean plasma levels of 5-HIAA were significantly higher for the clozapine group than the other 2 groups. 5-HT turnover was significantly higher for the 2 drug-treatment groups than for the control group. CONCLUSIONS: These results suggest that treatment with clozapine should be considered for patients with schizophrenia who are impulsive and aggressive.     

Weight change and atypical antipsychotic treatment in patients with schizophrenia

Schizophrenic patients who have been prescribed atypical antipsychotics have a potential risk of gaining weight. The implications of weight gain for clinical care may differ depending on whether a patient is underweight or overweight at baseline. The exact mechanism for weight gain is not known, but several factors have been identified that can help predict which patients are at risk for gaining weight. These factors include better clinical outcome, increased appetite, and low baseline body mass index. In patients treated with olanzapine for up to 3 years, weight gain trended toward a plateau at approximately 36 weeks. Weight gain interventions, including behavioral modifications, show promise in controlling or reducing weight in patients treated with antipsychotics.     

Comparison of withdrawal of typical and atypical antipsychotic drugs: a case study

Haloperidol and clozapine were rapidly withdrawn from a schizophrenic patient on separate occasions several months apart. Mental status changes and fluctuations in involuntary movements were carefully observed under both conditions. Although little change in either mental status or involuntary movements was observed within the 3 weeks following the withdrawal of haloperidol, marked deterioration in mental status and involuntary movements occurred within 1 week of withdrawal of clozapine. Implications of this differential response to withdrawal of antipsychotic medications are discussed.     

Reduced thalamic volume in patients with chronic schizophrenia after switching from typical antipsychotic medications to olanzapine

OBJECTIVE: The authors performed a longitudinal study of the effects on thalamic volume of switching from typical to atypical antipsychotic medications. METHOD: Magnetic resonance imaging scans were acquired from 10 subjects with chronic schizophrenia taking typical antipsychotics and 20 healthy volunteers. Subjects with schizophrenia were switched to olanzapine; both groups were rescanned. RESULTS: At baseline, thalamic volumes in subjects with chronic schizophrenia were 5.8% greater than those of healthy volunteers. At follow-up, there was no significant difference between groups. Additional analysis revealed a significant positive correlation between baseline thalamic volume and dosage of typical antipsychotic medication. Higher dosages at baseline were correlated with larger reductions in volume after the switch to olanzapine. CONCLUSIONS: Antipsychotic medication effects may be a factor in the wide range of thalamic volume differences reported between subjects with schizophrenia and healthy volunteers.     

四种非典型抗精神病药对血清催乳素和血脂的影响

目的探讨四种非典型抗精神病药对精神分裂症患者血脂和血清催乳素（PRL）的影响,以及血清PRL水平与药物疗效的关系。方法118例精神分裂症患者分为4组,分别予以喹硫平（29例）、氯氮平（30例）、奥氮平（30例）和利培酮（29例）治疗12周。于治疗前及治疗4、8及12周末予以阳性与阴性症状量表（PANSS）评定,测定血总胆固醇（TC）、甘油三脂（TG）高密度脂蛋白（HDL）、低密度脂蛋白（LDL）、阿朴脂蛋白A—I（ApoA-1）、阿朴脂蛋白-B（Apo—B）及血清PRL浓度。结果（1）喹硫平组TG、HDL在12周末有显著升高（P〈0．05）,氯氮平组Apo—B在4、12周末有显著升高（P〈0．05）、LDL在8、12周末有显著升高（P〈0．05）,利培酮组除TG外其余血脂指标在8、12周末有显著升高（P〈0．05）,奥氮平组TG、HDL、LDL、ApoA-1、Apo—B在12周末有显著升高（P〈0．05）,TC在8与12周有显著升高（P〈0．05）。（2）利培酮组治疗8、12周后血清PRL明显升高（P〈0．01）。（3）氯氮平组和利培酮组PANSS一般病理分的减分率分别与PRL、LDL有显著相关;氯氮平组PRL与LDL有显著相关。结论利培酮、奥氮平、喹硫平和氯氮平均影响血脂代谢;氯氮平疗效与血清催乳素及LDL有关,利培酮疗效与LDL有关。     

Amoxapine shows atypical antipsychotic effects in patients with schizophrenia: results from a prospective open-label study

OBJECTIVE: Amoxapine is marketed as an antidepressant. However, its receptor occupancy, in vitro and in vivo, and its effects in pre-clinical models are very similar to atypical antipsychotics. To examine if this leads to an atypical antipsychotic effect in the clinical context, the authors examined the antipsychotic and side-effect profile of amoxapine in acutely psychotic patients with schizophrenia. METHODS: Seventeen patients were enrolled and 15 completed a prospective open-label 6-week study of amoxapine starting with a fixed-starting dose (150 mg/h) with standardized titration up to 250 mg/h, if required. Positive, negative, affective symptoms and side-effects were monitored using standardized weekly assessments. RESULTS: Amoxapine (median final dose 210 mg/h) was well-tolerated and showed significant improvement in positive and negative symptoms (both p<0.001), with a trend towards improvement in mood symptoms and no treatment-emergent extrapyramidal side-effects, akathisia or weight gain. Prolactin elevation was observed. CONCLUSION: These clinical data lend support to the pre-clinical suggestions that amoxapine may be an atypical antipsychotic. Given its lack of weight gain and that it is considerably less expensive than current options, amoxapine could be a valuable alternative for some patients. These considerations strongly call for more systematic, double-blind studies of amoxapine as an atypical antipsychotic.     

抗精神病药对老年精神分裂症患者血清催乳素的影响

目的：探讨几种抗精神病药对老年精神分裂症患者血清催乳素（PRL）的影响。方法：随机选取抗精神病药治疗老年精神分裂症患者121例,分别在治疗前后测定血清PRL水平。结果：患者经舒必利、奋乃静、氟哌啶醇和利培酮治疗后血清PRL明显升高,各药物之间以及治疗前后比较差异均有显著性（F=15．95,P〈0．01）。PRL水平的升高与药物剂量呈正相关。氯氮平对PRL水平影响不明显。结论：典型和非典型抗精神病药对老年精神分裂症患者血清PRL水平的影响同样明显,强弱的顺序依次是舒必利、奋乃静、氟哌啶醇和利培酮。