Long-term safety,tolerability, and clinical efficacy of quetiapine in adolescents: an open-label extension trial

Quetiapine is a novel, atypical antipsychotic agent that has been shown to provide long-term efficacy without serious adverse effects in adults. This is the first study of the extended use of quetiapine in adolescents. Five boys and 5 girls, ages 12.3 to 15.9 years, with diagnoses of schizoaffective disorder (n = 7) or bipolar disorder with psychotic features (n = 3) were eligible for entry into this single-site, 88-week, open-label trial. Subjects had completed a pharmacokinetic study over 23 days, during which the dosage of quetiapine was increased sequentially from 25 mg bid to a maximum of 400 mg bid (800 mg/day) (McConville et al. 2000). In the open-label extension of this trial, which followed directly after this trial, a physician's choice design allowed for flexible dose titration of quetiapine by the study physician to an optimal dose for each patient, with ending doses ranging from 300 mg/day to 800 mg/day. Concomitant medications, especially for anxiety and/or manic symptoms, were allowed as deemed necessary. Tolerability and safety were assessed using clinical laboratory tests, physical examinations, measurements of vital signs, interviews for selective symptomatology, and electrocardiograms. Psychiatric measurements included the 18-item Brief Psychiatric Rating Scale (BPRS), the Clinical Global Impression (CGI) scale, and the modified Scale for the Assessment of Negative Symptoms (SANS). Neurologic symptom ratings included the Simpson-Angus Scale and the Abnormal Involuntary Movement Scale. Mean BPRS, CGI, and SANS scores improved significantly during the trial (p < 0.05). No extrapyramidal symptoms or evidence of tardive dyskinesia was seen. Clinically, there was a nonsignificant increase in mean weight and body mass index at week 64. This long-term study suggests that quetiapine is a well-tolerated antipsychotic agent that is efficacious for the treatment of symptoms of selected psychotic disorders in adolescents.     

3-year study of donepezil therapy in Alzheimer's disease: effects of early and continuous therapy

Delays in the diagnosis of Alzheimer's disease, and, therefore, delays in treatment, may have a detrimental effect on a patient's long-term well-being. This study assessed the effects of postponing donepezil treatment for 1 year by comparing patients treated continuously for 3 years with those who received placebo for 1 year followed by open-label donepezil for 2 years. Patients (n = 286) with possible or probable Alzheimer's disease (according to DSM-IV, NINCDS-ADRDA, and Mini-Mental State Examination criteria; see text) were randomized to receive donepezil (5 mg/day for 4 weeks, 10 mg/day thereafter) or placebo (delayed-start group) for 1 year. Of the 192 completers, 157 began a 2-year, open-label phase of donepezil treatment. Outcome measures were the Gottfries-Br?ne-Steen scale, the Mini-Mental State Examination, the Global Deterioration Scale, the Progressive Deterioration Scale, the Neuropsychiatric Inventory, and safety (adverse events). Mixed regression analysis was used to compare changes between the groups over 3 years on the efficacy measures. There was a trend for patients receiving continuous therapy to have less global deterioration (Gottfries-Br?ne-Steen scale) than those who had delayed treatment (p = 0.056). Small but statistically significant differences between the groups were observed for the secondary measures of cognitive function (Mini-Mental State Examination; p = 0.004) and cognitive and functional abilities (Global Deterioration Scale; p = 0.0231) in favor of continuous donepezil therapy. Over 90% of the patients in both cohorts experienced one treatment-emergent adverse event; most were considered mild or moderate. In conclusion, patients in whom the start of treatment is delayed may demonstrate slightly reduced benefits as compared with those seen in patients starting donepezil therapy early in the course of Alzheimer's disease. These data support the long-term efficacy and safety of donepezil.     

Quetiapine, a novel antipsychotic: experience in elderly patients with psychotic disorders. Seroquel Trial 48 Study Group.

BACKGROUND: This uncontrolled trial examines the safety and effects of quetiapine, a new atypical antipsychotic, in elderly patients with psychotic disorders. METHOD: This is an ongoing, multicenter, open-label, 52-week trial of quetiapine in men and women at least 65 years old with DSM-IV psychotic disorders. Patients received quetiapine, 25 to 800 mg/day. Assessments included the 18-item Brief Psychiatric Rating Scale (BPRS), the Clinical Global Impressions scale (CGI), the Simpson-Angus Neurologic Rating Scale, and the Abnormal Involuntary Movement Scale (AIMS). RESULTS: An interim analysis was performed at 12 weeks with results from 151 patients. The median total daily dose was 100 mg/day. The most common adverse events were somnolence (32%), dizziness (14%), postural hypotension (13%), and agitation (11%). Extrapyramidal symptom adverse events occurred in 6% of patients. Mean Simpson-Angus Scale total score showed significant (p<.0001) improvement at endpoint; there were no changes in AIMS scores. BPRS total and CGI-Severity of Illness scores showed significant (p<.0001 and p<.01, respectively) improvement at endpoint. No clinically important effects were reported for hematologic or liver function test variables; small changes in mean free levorotatory thyroxine (T4) levels were not associated with substantial changes in mean thyroid-stimulating hormone concentration. Mean corrected QT interval (QTc) was unchanged, but a slight increase in mean heart rate was noted. CONCLUSION: Quetiapine was well tolerated in a nonrandomized study of elderly patients and was associated with improvement in symptoms.     

Treatment of tardive dyskinesia with donepezil: a pilot study

BACKGROUND: Tardive dyskinesia (TD) remains a significant clinical problem for which there is no uniformly effective treatment. Earlier trials with acetylcholine precursors may have been disappointing because of underlying damage to striatal cholinergic neurons in patients with TD. In contrast, new cholinesterase inhibitors, developed for the treatment of dementia, may improve TD by directly increasing cholinergic synaptic transmission. METHOD: We conducted an 8-week open-label trial of donepezil in the treatment of TD. Ten patients with schizophrenia or schizoaffective disorder who received stable doses of antipsychotics and met DSM-IV criteria for TD were treated with donepezil, 5 to 10 mg/day, for 6 weeks after a 2-week baseline period. Changes in total Abnormal Involuntary Movement Scale (AIMS) scores measured every 2 weeks were assessed for significance. Patients were also assessed using the Brief Psychiatric Rating Scale, the Mini-Mental State Examination, the Barnes Akathisia Scale, and the Simpson-Angus Scale. RESULTS: Total AIMS scores decreased significantly (p = .0009), with no changes in other measures. Nine patients showed a positive response. Improvement was greatest in orofacial and upper extremity movements. No significant interactions were noted between the total AIMS scores and age (p > .29), duration of TD (p > .38), or duration of antipsychotic treatment (p > .14). CONCLUSION: Donepezil appeared to be effective in suppressing TD in this pilot study. However, placebo-controlled, double-blind studies are necessary before donepezil can be recommended as a treatment for TD.     

Olanzapine in Chinese treatment-resistant patients with schizophrenia: an open-label,prospective trial

The role of olanzapine in treatment-resistant schizophrenia has still not been clearly resolved. In addressing this issue, the current report presents an open-label, prospective, 13 week trial with olanzapine use in Chinese schizophrenic patients who were resistant to more than two different classes of antipsychotics during a minimal 4 week treatment period for each antipsychotic drug at adequate dosage. Fifty-one inpatients were recruited after a cross-titration period and given 10-25 mg of olanzapine daily, without any concomitant antipsychotic medication. Patients were evaluated with the Brief Psychotic Rating Scale (BPRS), the Positive and Negative Symptoms Scale, the Clinical Global Impression Scale (CGI), the Abnormal Involuntary Movement Scale, the Simpson-Angus scale, and the Barnes Akathisia Scale. The olanzapine-treated patients showed significant improvement in both the positive and negative symptoms of schizophrenia by the end of the study. Overall, 20 of 51 (39.2%) responded to 10-25 mg of olanzapine per day as measured by the BPRS and CGI scores. Five patients dropped out due to the worsening of their psychotic symptoms, two patients discontinued owing to poor drug compliance, and the remaining patient complained of a lack of efficacy. Extrapyramidal side-effects were mild, and anticholinergic medications required has decreased. The present open study suggests that olanzapine may be effective and well-tolerated in Chinese treatment-resistant schizophrenic patients. Further double-blinded trials are needed to confirm this result.     

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.     

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

OBJECTIVE: The goal of this study was to assess the effectiveness and tolerability of olanzapine in the treatment of acute mania in children and adolescents. METHODS: This was an 8-week, open-label, prospective study of olanzapine monotherapy (dose range 2.5-20 mg/day) involving 23 bipolar youths (manic, mixed, or hypomanic; 5-14 years old). Weekly assessments were made using the Young Mania Rating Scale (YMRS), Clinical Global Impressions Severity Scale (CGI-S), Brief Psychiatric Rating Scale, and Children's Depression Rating Scale. Adverse events were assessed through self-reports, vital sign and weight monitoring, laboratory analytes, and extrapyramidal symptom rating scales (Barnes Akathisia Scale, Simpson-Angus Scale, and Abnormal Involuntary Movement Scale). RESULTS: Twenty-two of the 23 youths (96%) completed the study. Olanzapine treatment was associated with significant improvement in mean YMRS score (-19.0 +/- 9.2, p < 0.001). Using predefined criteria for improvement of > or = 30% decline in the YMRS and a CGI-S Mania score of < or = 3 at endpoint, the overall response rate was 61%. Overall, olanzapine was well tolerated, and extrapyramidal symptom measures were not significantly different from baseline. Body weight increased significantly over the study (5.0 +/- 2.3 kg, p < 0.001). CONCLUSIONS: Open-label olanzapine treatment was efficacious and well tolerated in the treatment of acute mania in youths with bipolar disorder. Future placebo-controlled, double-blind studies are warranted.     

The influence of switching from risperidone to paliperidone on the extrapyramidal symptoms and cognitive function in elderly patients with schizophrenia: A preliminary open-label trial

Objective. This study was to evaluate the effects on clinical symptoms and cognitive function of switching the treatment of elderly patients with schizophrenia from risperidone to paliperidone (PAL). Methods. This study was a 12-weeks, preliminary open-label trial. The subjects were 17 inpatients. Their extrapyramidal symptoms (EPS) were assessed using the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS), Abnormal Involuntary Movement Scale (AIMS), and Barnes Akathisia Scale (BAS), and their cognitive function was assessed using the Brief Assessment Cognition in Schizophrenia: Japanese language version (BACS-J), and their clinical symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression-Severity of illness scale (CGI-S) at the 0 and 12 weeks. Results. The DIEPSS and BAS significantly improved after switching from risperidone to PAL. Furthermore, improvement was found on AIMS. The mean change from baseline in z-score of the digit sequencing task was significantly increased. All items on the PANSS and CGI-S were not significant; however, changes in some cognitive function were correlated with changes in EPS. Conclusions. The results of this study suggest the possibility that switching elderly patients from risperidone to PAL may have improved pre-existing EPS, and may also have helped improve working memory.     

Olanzapine versus flupenthixol in the treatment of inpatients with schizophrenia: a randomized double-blind trial

OBJECTIVE: The atypical antipsychotic olanzapine has extensively been compared with haloperidol, whereas studies vs. other (conventional) neuroleptics are scarce. This exploratory double-blind 4-week study was designed to compare the efficacy and the safety of olanzapine (OLA) and flupenthixol (FLU) which have recently been considered as a "partially atypical" antipsychotics. METHODS: Twenty-eight inpatients with schizophrenia (DSM-IV) were randomly assigned for treatment with OLA (N = 15, 5-20 mg/d) or FLU (N = 13, 5-20 mg/d). The Brief Psychiatric Rating Scale (BPRS) and the Negative Symptoms Rating Scale (NSRS), plus the Patient Global Impression (PGI) and Clinical Global Impression (CGI) scales, were used to assess the efficacy of both compounds; safety was determined by using the Simpson Angus Scale (SAS) and the Abnormal Involuntary Movement Scale (AIMS) and by assessing treatment-emergent adverse events. Non-parametric statistics were applied. RESULTS: BPRS and NSRS scores improved in both groups (exploratory tests; all p < or = 0.02). Similar results were observed for CGI-Severity, CGI- and PGI-Improvement. There were no significant group differences. Responder rates (at least 40 % decrease in BPRS total) were 9/13 OLA patients (69 %) and 9/12 FLU patients (75 %). EPS events were reported only in the FLU group (p < 0.01); FLU patients needed significantly more anticholinergic medication. Weight gain was higher in OLA patients (p < 0.01). Overall, fewer patients with adverse events were observed in the OLA group (p = 0.04). No significant changes were noted on SAS and AIMS scores. CONCLUSION: Findings from this study suggest that overall and negative symptomatology improved in both treatment groups, while the safety and tolerability profiles differed for both substances.     

A prospective,open-label trial of olanzapine in adolescents with schizophrenia

BACKGROUND: Olanzapine is an atypical antipsychotic that has efficacy in adults with psychotic disorders. This preliminary study examined the effectiveness of olanzapine in adolescents with schizophrenia or its related conditions. METHOD: Adolescents aged 12-17 years (inclusive) with a diagnosis of schizophrenia, schizoaffective, or schizophreniform disorder were enrolled in this 8-week, open-label, outpatient study. The Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impressions Scale (CGI), and the Children's Global Assessment Scale (CGAS) were administered as outcome measures. Extrapyramidal side effects were assessed at each visit. Olanzapine was initiated at a dose of 2.5 mg/day and could be increased to a maximum total daily dose of 20 mg. RESULTS: Sixteen participants with a mean age of 13.8 (SD = 1.5) years were treated. Significant improvements were found in the PANSS, CGI severity, and CGAS scores. Reductions in both positive and negative symptoms were found. Increased appetite and sedation were the most frequently reported side effects. Two subjects required treatment for extrapyramidal side effects. CONCLUSIONS: Psychotic symptoms significantly improved during study. Overall, olanzapine was well tolerated. Future studies are needed to confirm these findings, to assess long-term treatment outcomes, and to compare the effectiveness of olanzapine with that of other antipsychotics.     

Effects of donepezil on emotional/behavioral symptoms in Alzheimer's disease patients

BACKGROUND: This open-label study examined the effects of the reversible cholinesterase inhibitor donepezil on emotional/behavioral symptoms in Alzheimer's disease (AD) patients. METHOD: Patients were diagnosed as having probable/possible AD by National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS/ADRDA) criteria. This study used the CERAD Behavior Rating Scale for Dementia (CBRSD) and its subscales to evaluate a group of 25 AD patients treated with donepezil. Dosage was increased at 4 months for most patients from 5 to 10 mg q.h.s. Analysis of variance was used to compare scores over a period of 12 months. These patients were also compared, using t tests, to a reference group that had received no donepezil or other anticholinesterase. RESULTS: Donepezil administration was associated with improvement in Mini-Mental State Examination (MMSE) and CBRSD total scores at 3-month evaluation (p< or =.05). CBRSD depression and behavioral dysregulation scores improved transiently at 4 months (p< or =.05). MMSE, CBRSD total, CBRSD depression, and CBRSD behavioral dysregulation scores returned to baseline levels at 12 months, in contrast to the reference group, whose MMSE and CBRSD total scores worsened minimally over the 12 months. CONCLUSION: Donepezil has a mildly positive effect on emotional/behavioral symptoms in AD in addition to its effect on cognitive function.     

Clozapine in the treatment of refractory psychotic mania

OBJECTIVE: The efficacy of clozapine was examined in a group of patients with treatment-refractory bipolar disorder, manic type with psychotic features.METHOD: Twenty-two subjects with treatment-refractory bipolar disorder with active manic and psychotic symptoms participated in a 12-week open-label trial of clozapine. After a 2-10-day drug washout period, patients began treatment with clozapine at 25 mg/day; the dose was increased 25 mg/day (as tolerated) to a maximum level of 550 mg/day. Patients were evaluated longitudinally over the course of the study with the Brief Psychiatric Rating Scale (BPRS), the Young Mania Rating Scale, and the Clinical Global Impressions (CGI) scale.RESULTS: Fourteen of the 22 subjects in the study continued taking clozapine for at least 10 of the 12 weeks. Among the entire group, mean improvements of 56. 7%, 56.6%, and 39.1% were seen on the BPRS, Young Mania Rating Scale, and CGI, respectively. Seventeen of the 22 subjects (77.3%) experienced at least a 20% improvement in scores on all three scales. CONCLUSIONS: The findings from this open-label study, which are consistent with previous retrospective studies, case reports, and one other open-label prospective study, suggest that clozapine is an effective agent for patients with treatment-refractory psychotic mania.     

Comparison of functional and cognitive donepezil effects in Alzheimer's disease

Donepezil has been shown to improve aspects of cognitive functioning in persons with Alzheimer's disease (AD), but its impact on instrumental activities of daily living has received little attention. In a within-subject design, 24 community-dwelling persons with AD were treated with open-label donepezil over a 12-month period. To assess functional abilities, a brief, objective measure of instrumental activities of daily living skills was used (Texas Functional Living Scale; TFLS). Global cognitive abilities were assessed with the Mini-Mental State Examination (MMSE). Changes in TFLS and MMSE scores were much the same. Improvements on the TFLS and MMSE were seen over a 3-month period. At 12 months, both TFLS and MMSE scores declined slightly below baseline. These results support an effect of donepezil on cognitive measures and day-to-day function and also suggest that the MMSE reflects well the actual functional ability of persons with moderate AD.     

Effectiveness, safety, and tolerability of risperidone in adolescents with schizophrenia: an open-label study

Data on risperidone's efficacy and tolerability in adolescents with schizophrenia are scarce. We found only one prospective, open-label study in this population. The aim of this open-label, prospective study was to estimate the effectiveness, safety, and tolerability of risperidone treatment in adolescents with first-episode schizophrenia. Subjects were adolescent inpatients diagnosed with Diagnostic and Statistical Manual of Mental Disorders (fourth edition) first-episode schizophrenia by the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present Episode version. Most of the patients (10/11) were drug na?ve. Improvement was assessed during the first 6 weeks of treatment using the Positive and Negative Syndrome Scale (PANSS), the Brief Psychiatric Rating Scale (BPRS), and the Clinical Global Impression (CGI) scale. Side effects were monitored using the Abnormal Involuntary Movement Scale, the Simpson-Angus Scale, the Barnes Akathisia Rating Scale, and the Udvalg for Kliniske Undersogelser Side Effect Rating Scale. Eleven adolescents between 15.5 and 20 years of age (mean = 17.27, SD = 1.27 years) were included in this study. Risperidone in an average dose of 3.14 mg/day (SD = 1.60 mg/day) produced a significant improvement on the total PANSS score (28%, p < 0.01), BPRS score (30.11%, p < 0.01), and CGI-Severity score (31.36%, p < 0.01). Risperidone was ineffective in the treatment of negative signs as assessed by the PANSS. The major side effects were extrapyramidal side effects, somnolence, depression, and weight gain. In conclusion risperidone appears to be a safe, acceptably tolerated, and effective antipsychotic medication for the treatment of adolescent-onset schizophrenia.     

Long-term olanzapine therapy in the treatment of bipolar I disorder: an open-label continuation phase study

BACKGROUND: Olanzapine has demonstrated efficacy in the treatment of acute mania in 2 double-blind, placebo-controlled trials. We describe the results of the open-label extension from one of these trials. METHOD: In a 3-week, double-blind study of patients with DSM-IV bipolar I disorder, olanzapine was superior to placebo for the treatment of acute manic symptoms. Of the 139 patients who entered the double-blind phase of the 3-week study, 113 patients continued into the 49-week open-label extension. Efficacy measurements including the Young Mania Rating Scale (YMRS), the 21-item Hamilton Rating Scale for Depression (HAM-D-21), the Clinical Global Impressions scale-Bipolar Version, and the Positive and Negative Syndrome Scale and safety measurements including the Simpson-Angus scale, the Barnes Akathisia Scale, and the Abnormal Involuntary Movement Scale were completed throughout. The analysis considered all treatment results, starting with the first olanzapine dose. Adjunctive lithium and fluoxetine were allowed during the open-label extension. RESULTS: The mean length of olanzapine treatment was 6.6 months, with a mean modal dose of 13.9 mg/day. A significant mean improvement in the YMRS total score, baseline to endpoint (-18.01, p < .001), was observed. During treatment, 88.3% of patients experienced a remission of manic symptoms (YMRS total score < or =12), and only 25.5% subsequently relapsed (YMRS total score > or = 15). Significant improvement in HAM-D-21 scores was observed (p < .001). Forty-one percent of patients were maintained on olanzapine monotherapy. The most common treatment-emergent adverse events reported were somnolence (46.0%), depression (38.9%), and weight gain (36.3%). CONCLUSION: During up to 1 year of olanzapine therapy, either as monotherapy or in combination with lithium and/or fluoxetine, patients with bipolar disorder demonstrated significant improvement in mania and depression symptoms with a favorable safety profile. Further double-blind, controlled studies are needed to confirm these results.     

Sertindole is associated with a low level of extrapyramidal symptoms in schizophrenic patients: Results of a phase III trial

OBJECT: The objective of this double-blind, multicentre study was to evaluate four doses of sertindole and haloperidol 10 mg. METHOD: The 617 schizophrenic patients were randomized to receive sertindole 8, 16, 20 or 24 mg/day or haloperidol 10 mg/day. Patients were assessed for extrapyramidal symptoms (EPS) using the Simpson-Angus Scale (SAS) and Barnes Akathisia Scale (BAS), and for movement disorders using the Abnormal Involuntary Movement Scale (AIMS). RESULTS: Patients receiving haloperidol experienced significantly more EPS than patients receiving sertindole, supporting observations made in previous studies. The incidence of adverse events was similar for all doses of sertindole. SAS and BAS scores were significantly worse in the haloperidol group than in the sertindole groups. There were significantly greater increases in mean QT c interval in the sertindole groups than in the haloperidol group. Sertindole did not cause sedation. CONCLUSIONS: Sertindole is well tolerated and does not cause the debilitating EPS associated with traditional antipsychotic drugs. (Int J Psych Clin Pract 2000; 4:47-54)     

Acute antipyschotic efficacy and side effects in schizophrenia: association with serotonin transporter promoter genotypes

BACKGROUND: The serotonin transporter (5-HTT) plays an important role in serotonergic neurotransmission. In the present study, we investigated the effects of the 44 bp insertion/deletion polymorphism in the promoter region of 5-HTT gene (5-HTTLPR) on symptomatology of psychosis and clinical response to antipsychotic drugs. METHODS: In total 56 patients acutely treated with haloperidol or risperidone either for the first episode of schizophrenia, schizophreniform or schizoaffective disorders, or for the relapse of these psychotic disorders after tapering their maintenance treatment, were genotyped for the 5-HTTLPR L and S alleles and for the new A/G functional variant within the L alelle (La/g). Psychopathological symptoms were assessed with the Brief Psychiatric Rating Scale (BPRS) and with Clinical Global Impression (CGI) twice: at 8-12 days after the first dose of antipsychotic and after 4 weeks. Extrapyramidal side effects were assessed with the Simpson-Angus Extrapyramidal Side Effects Scale (EPS), the Barnes Akathisia Scale (BARS) and the Abnormal Involuntary Movement Scale (AIMS). RESULTS: Age, body mass index (BMI), illness duration, drug type and dosage were considered as covariates when analysing association with genetic variants as they were associated with baseline or final BPRS and CGI scores and/or extrapyramidal side effects. 5-HTTLPR was not associated with baseline and final BPRS and CGI scores or with the CGI% reduction. However, the 5-HTTLPR S allele was associated with a lower improvement in BPRS scores (P=0.022) and this effect was even stronger after pooling subjects with S or Lg containing alleles (P=0.006). We did not observe any effect of 5-HTTLPR on acute antipsychotics side effects. CONCLUSION: Present result supports a contribution of serotonin system to neuroleptics efficacy for the treatment of schizophrenia. The analysis of the La/g functional variant may significantly improve the predictive power of 5-HTTLPR genotyping and represent a step further towards the development of the personalized antipsychotic treatment.     

An observational clinical study of the efficacy and tolerability of donepezil in the treatment of Alzheimer's disease

An open-label, observational Post-Marketing Surveillance (PMS) study was undertaken in Germany to examine the efficacy and tolerability of donepezil in routine clinical practice. Alzheimer's disease (AD) patients were treated with donepezil (5 or 10 mg once daily) and observed for a period of approximately 3 months. Study assessments included the Mini-Mental State Examination (MMSE), the Nurses' Observation Scale for Geriatric Patients (NOSGER), and adverse events (AEs). A total of 2,092 patients (mean age 73.0 years; mean +/- SD MMSE score 17.8 +/- 5.8) were included in the efficacy assessments. MMSE and NOSGER scores showed statistically significant improvements in the total patient population and in the subpopulations with severe AD or AD with concomitant Parkinsonian symptoms (ADPS cohort). AEs were reported in a total of 12% of patients and were mostly due to peripheral cholinergic effects. In this observational PMS study, donepezil was shown to be an effective and well-tolerated therapy in the overall patient population, in patients with severe AD, and in the ADPS cohort.     

Comparison of older patients with bipolar disorder and schizophrenia/schizoaffective disorder.

OBJECTIVE: The aim of this cross-sectional study was to explore differences in measures of symptoms and cognition, side effects, and functional impairment between older patients with schizophrenia and bipolar disorder. METHODS: Representative samples (N = 132) of older patients (age >54 years) with either bipolar disorder or schizophrenia and schizoaffective disorder were compared on several clinical and psychosocial variables. The measures used included the Brief Psychiatric Rating Scale, The Scale for the Assessment of Negative Symptoms, the Geriatric Depression Scale, the Abnormal Involuntary Movement Scale, the Clinical Global Impression, and the Mini-Mental Status Examination. RESULTS: Despite being similar in age (mean age: 68 years), patients with schizophrenia/schizoaffective disorder had significantly greater negative symptoms (Cohen's d = 1.2), a higher clinical global impression of impairment (Cohen's d = 1.16), were less likely to drive (Cohen's d = 0.79), were less likely to be married (Cohen's d = 0.55), and less likely to live independently (Cohen's d = 0.45). CONCLUSION: Although the absolute ratings suggested both diagnostic samples had significant disability, those with schizophrenia and schizoaffective disorder had a greater degree of impairment.     

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.