Assessment of the effects of AZD3480 on cognitive function in patients with schizophrenia.

AZD3480 is a selective agonist of α4ß2 central neuronal nicotinic receptors (NNRs). This study investigated its effects on cognition, relative to placebo, in 440 patients with stable schizophrenia who were taking a single atypical antipsychotic medication and who were active cigarette smokers. Mean age was 41 (range 19 to 55) years and the majority of patients (88%) had a diagnosis of paranoid schizophrenia. Patients were randomized to one of 3 doses of AZD3480: 5 mg, 20 mg, and 35/100 mg (depending on CYP2D6 metabolic status), or to placebo. Treatment was given once daily for 12 weeks. The primary outcome measure was change in cognitive function from baseline to Week 12, as measured by IntegNeuro computerized test battery of cognitive function scores. Secondary outcome measures included assessment of functional capacity (University of California at San Diego Performance Based Skills Assessment [UPSA2]) and adaptive function (Social Functioning Scale [SFS]). AZD3480 failed to improve cognition relative to placebo in this population of patients or in subpopulations defined by disposition, metabolic status, antipsychotic treatment, age, age of illness onset, and sex. Likewise, no improvement relative to placebo was observed in either the SFS measure of adaptive functioning or the UPSA2 measure of functional capacity. AZD3480 was generally well tolerated in the population studied.

Efficacy and tolerability of extended release quetiapine fumarate monotherapy in the acute treatment of generalized anxiety disorder: a randomized, placebo controlled and active-controlled study.

The main objective of this study was to evaluate efficacy and tolerability of once-daily extended release quetiapine fumarate (quetiapine XR) monotherapy in generalized anxiety disorder (GAD). This was a 8 week randomized, 2-week follow-up, double-blind, placebo-controlled, and active-controlled study. Patients were randomized to quetiapine XR 150 (n=219) or 300 mg/day (n=207); escitalopram, 10 mg/day (n=213); or placebo (n=215). The primary endpoint was the change from randomization at week 8 in Hamilton Anxiety Rating (HAM-A) total score. Week 8 mean HAM-A total score was significantly reduced from randomization with quetiapine XR 150 mg/day (-13.9, P<0.001), 300 mg/day (-12.3, P<0.05) and escitalopram (-12.3, P<0.05) versus placebo (-10.7); significant improvements with quetiapine XR (150 and 300 mg/day) versus placebo (P<0.001) were also shown at day 4. At week 8, significant improvements versus placebo were observed in HAM-A psychic [quetiapine XR (both doses) and escitalopram] and somatic (quetiapine XR 150 mg/day and escitalopram) cluster scores and HAM-A response and remission rates (quetiapine XR 150 mg/day). Most common adverse events were dry mouth, somnolence and sedation (quetiapine XR), headache, and nausea (escitalopram). In patients with GAD, quetiapine XR (150 and 300 mg/day) demonstrated significant efficacy at week 8 with symptom improvement as early as day 4. We concluded that quetiapine XR safety and tolerability results were consistent with the known profile of quetiapine.

Efficacy and tolerability of extended release quetiapine fumarate (quetiapine XR) monotherapy in patients with generalised anxiety disorder: an analysis of pooled data from three 8-week placebo-controlled studies.

OBJECTIVE: Prospectively planned pooled analysis evaluating efficacy and tolerability of acute quetiapine XR monotherapy in generalised anxiety disorder. METHODS: Data from three 10-week, randomised, double-blind, placebo-controlled studies of similar design were analysed. RESULTS: At Week 8, Hamilton Anxiety Rating Scale (HAM-A) total score significantly improved with quetiapine XR: least squares means change -13.31, p < 0.001 (50 mg/day, n = 452), -14.39, p < 0.001 (150 mg/day, n = 673) and -12.50, p < 0.05 (300 mg/day, n = 444) versus -11.30 placebo; significant (p < 0.001, n = 665) improvements versus placebo were observed with each dose at Week 1. Significant improvements versus placebo at Week 8 are as follows: HAM-A psychic symptom subscale, Montgomery-Åsberg Depression Rating Scale total, Pittsburgh Sleep Quality Index global scores for all quetiapine XR doses; HAM-A response and remission rates, HAM-A somatic symptom subscale score, Clinical Global Impression-Severity of Illness total score, % patients with Clinical Global Impression-Improvement score ≤2 with quetiapine XR 50 and 150 mg/day; and Quality of Life Enjoyment and Satisfaction Questionnaire short form % maximum total score with quetiapine XR 150 mg/day. In the quetiapine XR 50, 150 and 300 mg/day and placebo groups, 13.2%, 16.5%, 24.0% and 5.4% of patients discontinued because of an adverse event, and 1.9%, 1.4%, 3.7% and 1.8% of patients experienced clinically significant changes in glucose. The most common adverse events with quetiapine XR included dry mouth, somnolence, sedation and constipation. CONCLUSION: Quetiapine XR monotherapy reduced the symptoms of generalised anxiety disorder, with improvement from Week 1. Adverse events were consistent with the known tolerability profile of quetiapine.

A double-blind, placebo-controlled study of quetiapine and paroxetine as monotherapy in adults with bipolar depression (EMBOLDEN II).

OBJECTIVE: The aim of this study was to evaluate the efficacy and tolerability of quetiapine and paroxetine monotherapy for major depression in bipolar disorder. METHOD: 740 patients (478 bipolar I, 262 bipolar II) with major depressive episodes (DSM-IV) were randomly assigned to quetiapine 300 mg/d (n = 245), quetiapine 600 mg/d (n = 247), paroxetine 20 mg/d (n = 122), or placebo (n = 126) for 8 weeks. The primary end point was the change from baseline in Montgomery-Asberg Depression Rating Scale (MADRS) total score. The study was conducted from May 2005 to May 2007. RESULTS: Mean MADRS score change from baseline at 8 weeks was -16.19 for quetiapine 300 mg, -16.31 for quetiapine 600 mg, -13.76 for paroxetine, and -12.60 for placebo (P < .001 for both quetiapine doses, P = .313 for paroxetine, vs placebo). Quetiapine-treated (both doses), but not paroxetine-treated, patients showed significantly greater improvements (P < or = .05) in most secondary outcomes measures at week 8 versus the placebo group. Paroxetine significantly improved Hamilton Anxiety Rating Scale scores versus placebo (P < .05) but not MADRS or Hamilton Depression Rating Scale (HDRS) scores. Both quetiapine doses were associated with greater improvements than paroxetine for MADRS and HDRS scores. The most common adverse events were dry mouth, somnolence, sedation, and dizziness with quetiapine (both doses) and dry mouth, sedation, headache, insomnia, and nausea with paroxetine. The incidence of treatment-emergent mania/hypomania was lower with quetiapine compared with paroxetine and placebo. CONCLUSIONS: Quetiapine (300 or 600 mg/d), but not paroxetine, was more effective than placebo for treating acute depressive episodes in bipolar I and II disorder. Quetiapine treatment was generally well tolerated. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00119652.

A single-center, double-blind, placebo-controlled evaluation of lamotrigine in the treatment of obesity in adults.

OBJECTIVE: Unlike many pharmacotherapies for mood disorders, lamotrigine has not been shown to be associated with weight gain. This study evaluated the safety and efficacy of lamotrigine, compared with placebo, as a monotherapy for weight loss in obese adult subjects. METHOD: Forty subjects were randomly assigned (1:1) to receive lamotrigine 200 mg/day or placebo for up to 26 weeks. Eligibility included a body mass index (BMI) of 30 to < 40. The primary endpoint was the change from baseline to endpoint (week 26) in subject weight. Secondary endpoints included the change from baseline to endpoint in BMI, percent body fat, serum lipid, and glycosylated hemoglobin values, subject satisfaction with treatment, and quality of life. RESULTS: Mean change in body weight from baseline to endpoint (last observation carried forward) was -6.4+/-10.26 lb and -1.2+/-7.09 lb for lamotrigine and placebo, respectively (p=.0623). Baseline body weight was slightly different between treatment groups (lamotrigine mean=207.9+/-19.88 lb, placebo mean=225.0+/-32.70 lb; p=.0588). There was a statistically significant difference (p=.0421) in mean change in BMI from baseline to endpoint (-1.5+/-2.78 and -0.1+/-1.05 for lamotrigine and placebo, respectively). Subjects were more satisfied with lamotrigine treatment compared with placebo (p=.0065). There were no significant differences between treatment groups in other secondary endpoints. The most frequently reported adverse event was mild-to-moderate headache, occurring in both treatment groups. CONCLUSION: Lamotrigine demonstrated a statistically significant difference in mean change in BMI and a trend toward a decrease in body weight and was well tolerated.