quetiapine-fumarate and Fatigue

Combining antipsychotics is common practice in the treatment of schizophrenia. This study investigated aripiprazole adjunctive to risperidone or quetiapine for treating schizophrenia and schizoaffective disorder.. In this multicenter, double-blind, 16-week, placebo-controlled study conducted at 43 American sites from July 2006 to October 2007, patients with chronic, stable schizophrenia or schizoaffective disorder diagnosed with DSM-IV-TR were randomly assigned to receive aripiprazole (2-15 mg/d) or placebo in addition to a stable regimen of quetiapine (400-800 mg/d) or risperidone (4-8 mg/d). The primary outcome measure was the mean change from baseline to endpoint (week 16, last observation carried forward) in the Positive and Negative Syndrome Scale (PANSS) total score.. 323 subjects being treated with either risperidone (n = 177) or quetiapine (n = 146) were randomly assigned to receive adjunctive aripiprazole (n = 168) or placebo (n = 155). Baseline characteristics were similar (mean PANSS total score: aripiprazole, 74.5; placebo, 75.9) except for history of suicide attempts (aripiprazole, 27%; placebo, 40%). Nearly 70% of subjects in each arm completed the trial. Adjunctive aripiprazole and placebo groups were similar in the mean change from baseline to endpoint in the PANSS total score (aripiprazole, -8.8; placebo, -8.9; P = .942). The incidence of treatment-emergent adverse events was similar between groups. Mean changes in Simpson-Angus Scale, Abnormal Involuntary Movement Scale, and Barnes Akathisia Rating Scale scores were not statistically significantly different. Adjunctive aripiprazole was associated with statistically significantly greater decreases in mean serum prolactin levels from baseline than was adjunctive placebo (-12.6 ng/mL for aripiprazole vs -2.2 ng/mL for placebo; P < .001), an effect that was seen in the risperidone subgroup (-18.7 ng/mL vs -1.9 ng/mL; P < .001) but not in the quetiapine subgroup (-3.01 ng/mL vs +0.15 ng/mL; P = .104).. The addition of aripiprazole to risperidone or quetiapine was not associated with improvement in psychiatric symptoms but was generally safe and well tolerated. Further research is warranted to explore whether antipsychotic combination therapy offers benefits to particular patient populations-for example, in cases of hyperprolactinemia.. clinicaltrials.gov Identifier: NCT00325689.

Topics: Adult; Ambulatory Care; Antipsychotic Agents; Aripiprazole; Diagnostic and Statistical Manual of Mental Disorders; Dibenzothiazepines; Double-Blind Method; Drug Therapy, Combination; Fatigue; Female; Headache; Humans; Male; Piperazines; Placebos; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Risperidone; Schizophrenia; Severity of Illness Index; Sleep Initiation and Maintenance Disorders; Treatment Outcome

The aim of the study was to assess the efficacy, tolerability and safety of the own developed generic quetiapine, Ketilept (EGIS Pharmaceutical Ltd, Budapest) in patients with an acute episode of schizophrenia and schizoaffective disorder.. These was a multicenter, non comparative, open label, 12-week trial on oral generic quetiapine conducted in 110 patients with DSM-IV acute schizophrenia or schizoaffective disorder. Patients received Ketilept 50 mg on day 1, 100 mg on day 2, 200 mg on day 3, 300 mg on day 4. The flexible dosing (150-750 mg/day) started on day 5. Patients were evaluated at baseline, at day 7, 14, 28 and 84. Baseline and outcome assessment included Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression Severity of Illness Subscale (CGI-S) and Global Improvement Subscale (CGI-I), Subjective Well-being on Neuroleptics Scale (SWN), Simpson-Angus Extrapyramidal Rating Scale (SAS), Barnes Akathisia Rating Scale (BARS) and UKU Side Effects Rating Scale (UKU). Changes in overall body weight, body mass index (BMI) and abdominal circumference were also evaluated.. After 12 weeks on Ketilept therapy, significant improvements were observed on all major symptoms measures and subscales. 44 (44%) of patients were rated much or very much improved on CGI-I at week 12. The mean SAS and BARS score significantly reduced during the generic quetiapine treatment period (p = 0.0001, p = 0.001). No change was found in the body weight, BMI and abdominal circumference during treatment with Ketilept for 12 weeks. The most common side effects were sedation, and dizziness. 14 adverse events occurred in 6 subjects (5%), of whom 3 patients (2.7%) encountered 3 serious adverse events. The adverse events were mainly mild and moderate. 103 patients (93.6)% completed the study, 2 patients (1.8%) were discontinued from the study due to serious adverse events (insufficient clinical response, sedation).. Despite the limitations of the design, our results suggest that the generic quetiapine, Ketilept in patients with acute schizophrenia and schizoaffective disorder is therapeutic equivalent to the innovator drug in terms of efficacy, tolerability and safety.

Topics: Acute Disease; Aged; Body Mass Index; Body Weight; Dibenzothiazepines; Drug Therapy, Combination; Drugs, Generic; Fatigue; Female; Humans; Male; Middle Aged; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Sleep; Time Factors; Treatment Outcome; Waist Circumference

The prevalence of and morbidity associated with treatment-resistant depression has motivated the exploration of treatment alternatives. In this study, quetiapine was compared with lithium in the augmentation of treatment-resistant depression.. Open-label, comparative study in 20 patients with major depression who had failed to respond after 4 weeks of treatment with an antidepressant at the maximal recommended dose. Patients were randomised to either lithium or quetiapine in addition to the maximally dosed antidepressant and any other concurrent medications. Lithium was initiated at 600 mg/day; quetiapine was titrated to 400 mg by day 7.. Depression, measured by the Hamilton Depression Rating Scale (HAM-D), significantly improved from baseline in both quetiapine (F(1,90) = 25.11, p < 0.0001) and lithium (F(1,90) = 34.54, p < 0.0001). The difference in improvement between the two groups began at day 14 and was seen at all timepoints thereafter (p < 0.05), with the quetiapine group showing greater improvement than the lithium group. In the Montgomery-Asberg Depression Rating Scale (MADRS) analysis, the difference between the quetiapine and lithium group was significant from day 28 onwards (p < 0.05), with subjects improving more in the quetiapine group than the lithium group. The treatment by week interaction showed a significant difference overall between the two groups (p < 0.0001). The severity of psychomotor retardation showed a significant decrease in the Widlocher Psychomotor Retardation Scale scores in the quetiapine (p < 0.0001) and lithium (p < 0.0001) groups.. In this pilot study, quetiapine was an effective augmenting agent in treatment-resistant depression.

Topics: Adult; Aged; Antidepressive Agents; Depressive Disorder; Dibenzothiazepines; Drug Resistance; Drug Synergism; Drug Therapy, Combination; Fatigue; Female; Humans; Lithium Compounds; Male; Middle Aged; Nausea; Pilot Projects; Psychomotor Performance; Quetiapine Fumarate; Serotonin Receptor Agonists; Severity of Illness Index; Treatment Outcome; Tremor

The aim of this study was to investigate the effectiveness, tolerability, and safety of quetiapine in adolescents with schizophrenia, schizophreniform, and schizoaffective disorders in a prospective open-label study.. A total of 56 subjects (all-subjects-treated, AST), ages 12-17, received 200-800 mg of quetiapine per day (forced titration to 400 mg within week 1; median study dose 600 mg/day at week 6) in Germany, 2002 through 2004. Primary outcome measure was the change of Positive and Negative Syndrome Scale (PANSS) total score (based on the intent-to-treat (ITT) population, n = 52), secondary outcome measures were changes of PANSS subscales, severity of illness, subjective wellbeing, and safety/tolerability (the latter based on the AST population). Correlates of PANSS response (=50% reduction in PANSS total score) and discontinuation due to lack of effectiveness were analyzed by Cox regression analyses.. Twenty-seven subjects (48%) completed the study; 17 subjects (30%) were discontinued due to lack of effectiveness. A significant reduction of PANSS total score (last observation carried forward, LOCF; p < 0.0001; effect size = 0.92) and of secondary effectiveness outcomes were detected. In all, 34.6% fulfilled the PANSS response criterion, correlated with the degree of PANSS total change within week 1. Somnolence (21.4%) and fatigue (17.9%) were the most frequent adverse events. A significant mean weight gain (6.2 kg) and mean decrease in total serum thyroxine (2.5 ng/dl) were detected.. In this sample of mostly drug-naïve patients with early-onset schizophrenia spectrum disorders, significant reductions in PANSS total and positive scores were detected. Controlled studies are needed to confirm these findings. The significant weight gain with its potentially severe medical consequences must be weighed against quetiapine's effectiveness.

Topics: Adolescent; Antipsychotic Agents; Child; Dibenzothiazepines; Dose-Response Relationship, Drug; Fatigue; Female; Humans; Male; Prospective Studies; Psychiatric Status Rating Scales; Quetiapine Fumarate; Regression Analysis; Schizophrenia; Schizophrenic Psychology; Severity of Illness Index; Sleep Stages; Thyroxine; Treatment Failure; Weight Gain

Major depressive disorder (MDD) is a debilitating psychiatric illness with a high cost burden. This analysis evaluates the cost-effectiveness of adjunctive brexpiprazole versus comparator branded adjunctive treatment for MDD and background antidepressant therapy (ADT) alone from a US payer perspective.. An economic model was developed to assess the cost-effectiveness of brexpiprazole versus comparator adjunctive treatment and ADT alone on total direct medical costs using a 6-week cycle time frame for a total of 48 weeks, with treatment response and remission as primary outcomes. The model consisted of 3 parts, 1 to represent the acute treatment phase and 2 to represent the maintenance stage.. In the base-case analysis, brexpiprazole as reference treatment resulted in cost per additional responder ranging from $19,442-$48,745 and cost per additional remitter ranging from $27,196-$71,839 versus comparator treatments over 48 weeks. Sensitivity analyses showed treatment with brexpiprazole was more costly, but more clinically effective in all probabilistic simulations.. This representation of disease natural history over 48 weeks may not account for all possible health states. Resource utilization on treatment was estimated using the resource use data from previous trials, and may overestimate medical costs compared to the real-world setting. Treatment comparators were limited to branded therapies, and head-to-head studies were not available to obtain data inputs.. Compared to other branded adjunctive therapies, brexpiprazole increases response and remission at 6 weeks; medical care cost savings were observed with the use of brexpiprazole. These findings may assist clinicians and formulary decision makers when selecting treatment for MDD.

Topics: Adolescent; Adult; Aged; Akathisia, Drug-Induced; Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Cost-Benefit Analysis; Depressive Disorder, Major; Disorders of Excessive Somnolence; Drug Costs; Drug Therapy, Combination; Fatigue; Female; Health Care Costs; Humans; Male; Middle Aged; Models, Economic; Olanzapine; Patient Selection; Quetiapine Fumarate; Quinolones; Serotonin Agents; Thiophenes; Weight Gain; Young Adult