Effects of switching from conventional antipsychotics to risperidone in Japanese patients with chronic schizophrenia

Atypical antipsychotics are rapidly evolving to become the standard pharmacotherapy in schizophrenia; however, the trend of switching to such drugs is not necessarily progressing quickly in East Asia. This might be due to the scarcity of evidence for the efficacy of switching from conventional to atypical antipsychotics, which prompted the authors to examine effects of switching from conventional antipsychotics to an atypical drug, risperidone, in Japanese patients. Fifty patients with chronic schizophrenia completed the study in which combination therapy with other antipsychotics was allowed if monotherapy with risperidone was not tolerated. Symptoms were assessed with the brief psychiatric rating scale (BPRS). Switching to monotherapy was achieved in 34 patients (68%). The number of antipsychotics prescribed to each patient was reduced (from 2.1 to 1.4 drugs; P < 0.001) and the use of antiparkinsonian drugs decreased (P < 0.001). The mean BPRS score was also reduced 6 months after initiation of the switch (P < 0.001). Failure in switching to monotherapy was associated with higher dosage of antipsychotics at baseline. Switching from conventional antipsychotics to risperidone reduced schizophrenia symptoms, antiparkinsonian medication, and polypharmacy. However, a portion of patients, particularly those who receive an excessive dosage of antipsychotics, might not tolerate such switching.     

10‐Year trends in the treatment and outcomes of patients with first‐episode schizophrenia

Nielsen J, le Quach P, Emborg C, Foldager L, Correll CU. 10‐Year trends in the treatment and outcomes of patients with first‐episode schizophrenia. Objective: The first episode of schizophrenia is a critical period for illness course and outcomes. We aimed to investigate treatments and outcomes during the first year after the diagnosis of schizophrenia. Method: Pharmacoepidemiologic inception cohort study of all newly diagnosed patients with schizophrenia in Denmark (n = 13 600) 1996–2005. Results: From 1996 to 2005, the mean age at first diagnosis decreased significantly (29.2–26.1 years), more patients received antipsychotics (67.2–80.7%, annual OR = 1.07, CI: 1.06–1.09, P < 0.001) and antipsychotic polypharmacy for >4 months (16.7–37.1%, OR = 1.14, CI: 1.12–1.57, P < 0.001). The antipsychotic defined daily dosage (DDD) doubled (150–332 DDD, P < 0.001), use of antidepressants (24.3–40.6%, P < 0.001). Bed days [89.9 days (CI: 81.8–98.8) to 71.8 days, CI: 63.7–80.8, P < 0.0001] decreased, whereas outpatient contacts [10.2 (CI: 9.5–11.0) to 21.4 (CI: 19.9–21.0), P < 0.0001] doubled. Conclusion: Between 1996 and 2005, there was an earlier recognition of schizophrenia, intensified outpatient treatment, increased use and dosing of antipsychotics and antidepressants, but also more antipsychotic polypharmacy.     

Polypharmacy in schizophrenia

In contrast to research studies that limit the use of concomitant psychotropic medications in the treatment of schizophrenia, polypharmacy is common in real-world, clinical practice. The use of psychotropic medications as an adjunct to antipsychotic agents is often necessitated by the poor response to monotherapy with one antipsychotic agent. This paper discusses the prevalence of polypharmacy in clinical settings, reviews the evidence for the adjunctive use of antipsychotics, anticonvulsants, lithium, antidepressants, benzodiazepines and other psychotropics in the treatment of schizophrenia, and offers suggestions toward use of polypharmacy in difficult and practical clinical settings.     

男性精神分裂症患者抗精神病药治疗前后血浆MicroRNA-181b表达水平

目的:研究血浆中microRNA-181b(miR-181b)在男性精神分裂症患者抗精神病药治疗过程的不同阶段表达水平的变化。方法:40例精神分裂症患者和40例正常对照,均为成年男性。以实时荧光定量PCR(RT-PCR)技术检测患者组(用药前、治疗2周和治疗4周)和对照组血浆miR-181b的表达水平。结果:和正常对照组相比,精神分裂症组在治疗前、治疗2周和治疗4周血浆miR-181b的表达水平均显著上调(P<0.001)。随着抗精神病药的治疗,病情逐渐好转,男性精神分裂症患者血浆miR-181b表达水平逐渐下降(治疗2周、治疗4周与治疗前比较,P均<0.001)。结论:血浆miR-181b可能参与精神分裂症的发病机制,其表达水平受抗精神病药影响。     

Leptin and ghrelin levels in patients with schizophrenia during different antipsychotics treatment: a review

Energy homeostasis is achieved by the integration of peripheral metabolic signals by the neural circuits involving specific hypothalamic nuclei and brain stem regions. These neural circuits mediate many of the effects of the adipocyte-derived hormone leptin and gut-derived hormone ghrelin. The former is strongly anorexigenic while the latter is the only orexigenic agent active when administered by a peripheral route. Abnormal regulation of these 2 antagonistic regulatory peptides in patients with schizophrenia could play a role in the impairment in the regulation of food intake and energy balance. This bibliographical analysis aims to compare 27 prospective and cross-sectional studies published on circulating leptin and ghrelin levels during acute and chronic administration of antipsychotics treatment, especially atypical ones. Fasting morning leptin levels of schizophrenic patients increase rapidly in the first 2 weeks after atypical antipsychotic (AAP) treatment (mostly olanzapine and clozapine) and remain somehow elevated after that period up to several months. On the contrary, conventional antipsychotics (such as haloperidol) do not interfere with leptin levels. In contrast to leptin, fasting morning ghrelin levels decrease during the first few weeks after the beginning of AAPs treatment while they increase in the longer run. Surprisingly, body weight gain and correlations between the variation of these 2 peptides and adiposity and metabolism-related parameters such as the body mass index and abdominal perimeter were not systematically considered. Finally, an objective evaluation of feeding behavior during antipsychotic treatment remains to be determined.     

Efficacy of 3-year psychiatric daycare treatment in patients with schizophrenia

The present study investigated the efficacy of a 3-year psychiatric daycare (DC) program with regard to psychiatric symptoms and difficulties with daily living experienced by patients with schizophrenia. The subjects were 28 patients who met the diagnostic criteria from the 4th edition of the Diagnostic and Statistical Manual for schizophrenia and continued DC treatment for 3 years. The present study assessed participants at two points: at the start of DC and after 3 years, by evaluating socioeconomic factors and Brief Psychiatric Rating Scale (BPRS) scores. In addition, in order to measure difficulties with daily living, the Life Assessment Scale for the Mentally Ill (LASMI) and the Etoh Daycare Assessment Scale (ETODAS) developed at the Etoh Hospital, were used. Results indicated that no significant changes in socioeconomic factors or BPRS scores occurred during the 3-year period of DC treatment. However, over this period, mean scores (+/- standard deviation [SD]) for LASMI subcategories decreased from 1.6 +/- 0.8 points to 0.9 +/- 0.7 for daily living and from 1.7 +/- 0.8 to 1.2 +/- 0.7 for interpersonal relations, indicating significant improvement (P < 0.05). In addition, mean scores (+/-SD) for the ETODAS subcategories increased from 3.4 +/- 0.8 to 4.1 +/- 0.8 for expressiveness, from 3.3 +/- 0.9 to 4.0 +/- 0.8 for communication, from 3.1 +/- 0.6 to 3.6 +/- 1.0 for initiative within a group, and from 3.4 +/- 0.5 to 3.8 +/- 0.7 for cooperation in work activities, indicating significant improvement (P < 0.05). The present study suggests that DC can enable patients with schizophrenia to maintain their condition without worsening the psychiatric symptoms, and to improve their daily living skills, social skills in human relations, and work skills.     

Prevalence of movement disorders in adolescent patients with schizophrenia and in relationship to predominantly atypical antipsychotic treatment

Objective To examine prevalence of movement disorders (MDs) such as tardive dyskinesia (TD), parkinsonism or akathisia in an adolescent population with schizophrenia and in relationship to predominantly atypical antipsychotic treatment. Method Ninety-three patients (aged 19.6±2.2 years) were ascertained in this cross-sectional/retrospective study. 76 patients (81.7%) received atypical, 10 (10.8%) typical antipsychotics and 7 (7.5%) combinations of atypical/typical antipsychotics. MD symptoms were assessed using Tardive Dyskinesia Rating Scale (TDRS), Abnormal Involuntary Movement Scale (AIMS), Extrapyramidal Symptom Scale (EPS), Barnes Akathisia Scale (BAS). Results Movement disorder symptoms were found in 37 patients (39.8%) fulfilling strict/subthreshold criteria for TD (5.4/11.8%), parkinsonism (2.2/25.8%) or akathisia (1.1/11.8%), respectively. Patients treated with typical antipsychotics displayed a significantly higher EPS-score (P=0.036) and a tendency towards a higher BAS-score (P=0.061) compared to patients with atypical antipsychotics. Treatment durations with typical/atypical antipsychotics showed trends towards advantages of atypical antipsychotics with regard to parkinsonism/akathisia symptoms (P=0.061; P=0.054), but not with regard to TD symptoms (P=0.003), possibly due to confounding effects. Conclusion Under treatment with atypical antipsychotics MD symptoms are less prevalent and less pronounced than under typical antipsychotics. We speculate that the finding of relatively high prevalence rates of subthreshold MD symptoms may be, at least partially, explained by previous or combined therapy with typical antipsychotics.     

Metabolic effects of adjunctive aripiprazole in clozapine‐treated patients with schizophrenia

Fan X, Borba CPC, Copeland P, Hayden D, Freudenreich O, Goff DC, Henderson DC. Metabolic effects of adjunctive aripiprazole in clozapine‐treated patients with schizophrenia. Objective: This study examined the effects of adjunctive aripiprazole therapy on metabolism in clozapine‐treated patients with schizophrenia. Method: In an 8‐week randomized, double‐blind, placebo‐controlled study, subjects received either aripiprazole (15 mg/day) or placebo. At baseline and week 8, metabolic parameters were assessed by the frequently sampled intravenous glucose tolerance test, nuclear magnetic resonance spectroscopy and whole‐body dual‐energy X‐ray absorptiometry (DXA). Results: Thirty subjects completed the study (16 in the aripiprazole group and 14 in the placebo group). Glucose effectiveness measured by the frequently sampled intravenous glucose tolerance test improved significantly in the aripiprazole group (0.003 ± 0.006 vs. ?0.005 ± 0.007/min, P = 0.010). The aripiprazole group showed significant reductions in both plasma low‐density lipoprotein (LDL) levels (?15.1 ± 19.8 vs. 4.4 ± 22.5 mg/dl, P = 0.019) and LDL particle numbers (?376 ± 632 vs. ?36 ± 301 nm , P = 0.035). Further, there was a significant reduction in the lean mass (?1125 ± 1620 vs. 607 ± 1578 g, P = 0.011) measured by whole‐body DXA scan in the aripiprazole group. All values were expressed as mean ± standard deviation, aripiprazole vs. placebo. Conclusion: Adjunctive therapy with aripiprazole may have some metabolic benefits in clozapine‐treated patients with schizophrenia.     

Extrapyramidal symptoms in substance abusers with and without schizophrenia and in nonabusing patients with schizophrenia

Extrapyramidal symptoms (EPS) such as parkinsonism, dystonia, dyskinesia, and akathisia are conditions of impaired motor function, which are associated with chronic antipsychotic treatment in schizophrenia. In addition, EPS is often exacerbated by psychoactive substance (PAS) abuse, which is frequently observed in this population. Few studies, however, have investigated the contribution of PAS abuse on EPS in PAS‐abusers without comorbid psychosis. This study compared the occurrence of EPS in outpatient schizophrenia patients with (DD group; n= 36) and without PAS abuse (SCZ group; n = 41) as well as in nonschizophrenia PAS abusers undergoing detoxification [substance use disorder (SUD) group; n = 38]. Psychiatric symptoms were measured using the Positive and Negative Syndrome Scale and the Calgary Depression Scale for schizophrenia. Extrapyramidal symptoms were evaluated with the Extrapyramidal Symptoms Rating Scale and the Barnes Akathisia Scale. SUD diagnoses were complemented with urine drug screenings. We found that DD patients exhibited significantly more parkinsonism than SCZ patients. Our subanalyses revealed that cocaine and alcohol abuse/dependence was responsible for the increase in parkinsonism in DD patients. Additionally, we found that SUD individuals exhibited significantly more akathisia than SCZ patients. In these latter individuals, subanalyses revealed that alcohol and cannabis abuse/dependence was responsible for the increase in akathisia. Our results suggest that PAS abuse is a contributor to EPS in individuals with and without schizophrenia. © 2010 Movement Disorder Society.     

Augmentation of clozapine with another pharmacological agent: treatment for refractory schizophrenia in the 'real world'

Pai NB, Laidlaw M, Vella S‐C. Augmentation of clozapine with another pharmacological agent: treatment for refractory schizophrenia (SZ) in the ‘real world’. Objective: Refractory schizophrenia (SZ) affects approximately 30% of people with SZ. Clozapine (CLZ) is the gold standard treatment; however, there are still patients who are non‐responsive or partially responsive to treatment. Although a lack of evidence exists in reality, these patients are treated with a combination of agents in addition to CLZ. Therefore, this article reviews the prevalence of the augmentation of CLZ with additional agents. Method: This study was cross‐sectional; physicians in a region of Australia in May 2011 were contacted to provide details of their patients on CLZ and any additional agents. The data set consists of 84 patients. Results: The majority of the patients 84.5% were taking at least one additional agent. Of those taking additional agents, they derived from the following classes’ antipsychotics (72%), antidepressants (30%), mood stabilisers (17%), antimetabolic agents (13%), benzodiazepines (7%), anticholinergics (4%) and miscellaneous agents (12.5%). Conclusion: It is apparent that CLZ is routinely augmented with other agents despite the lack of an evidence base. However, concerning was the lack of augmentation with antimetabolic agents despite the paucity of literature reporting the detrimental impact of antipsychotic treatment upon patients metabolic indices. The findings are discussed in the context of the current recommendations and empirical literature.     

Relations between movement disorders and psychopathology under predominantly atypical antipsychotic treatment in adolescent patients with schizophrenia

Objective To examine relations between movement disorders (MD) and psychopathological symptoms in an adolescent population with schizophrenia under treatment with predominantly atypical antipsychotics. Method MD symptoms and psychopathology were cross-sectionally assessed in 93 patients (aged 19.6 ± 2.2 years) using Tardive Dyskinesia Rating Scale (TDRS), Abnormal Involuntary Movement Scale (AIMS), Extrapyramidal Symptom Scale (EPS), Barnes Akathisia Scale (BAS), Brief Psychiatric Rating Scale (BPRS) and the Schedule for Assessment of Negative/Positive Symptoms (SANS/SAPS). Results All patients with MD symptoms (n = 37; 39.8 %) showed pronounced global psychpathological signs (SANS/SAPS, BPRS: p = 0.026, p = 0.033, p = 0.001) with predominant anergia symptoms (p = 0.005) and inclinations toward higher anxiety- and depression-related symptoms (p = 0.051) as well as increased thought disturbance (p = 0.066). Both negative symptoms and anergia showed trends for positive correlations with tardive dyskinesia (p = 0.068; p = 0.065) as well as significant correlations with parkinsonism symptoms (p = 0.036; p = 0.023). Akathisia symptoms correlated significantly with hostile and suspicious symptoms (p = 0.013). A superfactor-analysis revealed four factors supporting the aforementioned results. Conclusion MD symptoms and psychopathology are in some respects related to each other. Motor symptoms representing on the one hand trait characteristics of schizophrenia might additionally be triggered by antipsychotics and finally co-occur with more residual symptoms within a long-term treatment.     

精神分裂症患者治疗情况调查

目的：了解宜春市精神分裂症患者的治疗率。方法：对精神分裂症患者的治疗情况进行调查。结果：共121例,治疗率76.9%,专科门诊治疗率66.9%,专科住院治疗率32.2%,治疗依从率为14.9%,放弃治疗率65.3%,传统医学治疗率3.3%,搞迷信活动55.4%。结论：精神分裂症治疗率偏低,治疗依从率更低,应予重视。     

Maintenance antipsychotic medication patterns in outpatient schizophrenia patients: a naturalistic cohort study

OBJECTIVE: Newer antipsychotics are increasingly used in schizophrenia maintenance. The UK change has been slow with little known on switching patterns. We aimed to investigate antipsychotic prescribing patterns in schizophrenia patients. METHOD: A naturalistic six-site cohort sample of 600 patients were interviewed by researchers at 6-monthly intervals for 2 years to record their clinical and social functioning; use of services and medication for the preceding 6 months was obtained by structured extraction from clinical case notes. RESULTS: Alterations in antipsychotic medication were frequent in this group, mainly during periods of inpatient care. Atypical prescribing increased steadily, though slowly, across the period. Polypharmacy was less than anticipated. CONCLUSION: Inpatient care remains the main forum for switching of antipsychotics. The UK maintains a slow shift to atypical antipsychotics.