Arifulla Khan

Efficacy of Quetiapine Monotherapy in Bipolar I and Ii Depression: A Double-blind, Placebo-controlled Study (the Bolder Ii Study)

This study evaluated the efficacy and tolerability of quetiapine monotherapy for depressive episodes in patients with bipolar I or II disorder (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) who were randomized to 8 weeks of double-blind treatment with quetiapine (300 or 600 mg/d; once daily, evening dosing) or placebo. Patients were assessed weekly using the Montgomery-Åsberg Depression Rating Scale (MADRS) and Hamilton Depression Rating Scale (HAM-D). The primary end point was change in MADRS total score from baseline to Week 8 (analysis of covariance/last-observation-carried-forward analysis). Of 509 patients randomized, 59% completed the study. Improvements from baseline in mean MADRS total scores were significantly greater with quetiapine 300 and 600 mg/d than with placebo from first evaluation (Week 1) through Week 8 (both P ≤ 0.001 vs. placebo). Therapeutic effect sizes at Week 8 were 0.61 and 0.54 for quetiapine 300 and 600 mg/d, respectively. Improvements in mean HAM-D scores were also significantly greater with both quetiapine doses than with placebo (P < 0.001) as early as Week 1 and throughout the study. The MADRS response and remission rates were also significantly greater in both quetiapine dose groups compared with placebo. Improvements in primary and secondary outcomes were observed with both 300 and 600 mg/d quetiapine without major differences between the doses. Common adverse events included dry mouth, sedation, somnolence, dizziness, and constipation. The incidence of treatment-emergent mania or hypomania was lower with quetiapine treatment than placebo. This study demonstrates that quetiapine monotherapy is an effective and well-tolerated treatment for depressive episodes in bipolar disorder, confirming the results observed from a previous study (BipOLar DEpRession [BOLDER] I).

Bright light treatment of winter depression: morning versus evening light

In a randomized crossover design, 7 patients with winter depression were treated with 7 d of bright morning light (0600 to 0800) and 7 d of evening light (2000 to 2200). Bright lights in the morning significantly reduced the Hamilton Rating Scale for Depression (HRSD) score (18.4 to 5.0); the bright light in the evening moderately decreased the HRSD score (19.4 to 15.1). The improvement in the HRSD score was significantly greater with morning light than with evening light.

Acetaldehyde: genotoxicity and cytotoxicity in human lymphocytes

We evaluated the DNA damaging effects of ethanol and its major metabolite, acetaldehyde. Freshly isolated human lymphocytes from two healthy donors were incubated with 0, 1.56, 6.25, 25, and 100 mM of ethanol or acetaldehyde in complete medium for 1 h. We used a newly developed, sensitive, alkaline microgel electrophoresis technique to quantitate single- and double-strand DNA breaks or alkali-labile sites in individual cells. Ethanol did not induce DNA strand breaks. However, acetaldehyde induced both single-strand (even at the lowest concentration of 1.56 mM) and double-strand breaks (only at the highest concentration of 100 mM). Following exposure to acetaldehyde, cells were incubated in complete medium for 30, 60, and 120 min. During this incubation period, most cells were unable to repair DNA single- and double-strand breaks caused by acetaldehyde. We also observed a significant cell loss after exposure to acetaldehyde. To our knowledge, this is the first study demonstrating DNA single- and double-strand breaks by acetaldehyde.

A double-blind, placebo-controlled study of a flexible dose of venlafaxine ER in adult outpatients with generalized social anxiety disorder

Abstract: Venlafaxine extended release (ER) is a dual serotonin-norepinephrine reuptake inhibitor previously shown to be effective in the treatment of major depressive disorder and generalized anxiety disorder. This placebo-controlled, multicenter, randomized, double-blind trial examined the efficacy and safety of venlafaxine ER in outpatients with generalized social anxiety disorder. Two hundred seventy-two outpatients were randomly assigned to receive either a flexible dose of venlafaxine ER (75 to 225 mg/d) or placebo for 12 weeks. Venlafaxine ER was statistically significantly more effective than placebo as demonstrated by the Liebowitz Social Anxiety Scale total scores at weeks 4 to 12. Scores of both the Clinical Global Impression-Severity and Clinical Global Impression-Improvement scales showed that venlafaxine ER was significantly more effective than placebo at weeks 4 to 12. In addition, more venlafaxine ER-treated patients achieved CGI-Improvement scores of 1 or 2 than placebo-treated patients at weeks 4 to 12, demonstrating a greater percentage of responders to venlafaxine ER treatment. Assessment using the fear/anxiety and avoidance subscales of the Liebowitz Social Anxiety Scale and the Social Phobia Inventory Scale also showed venlafaxine ER to be more effective than placebo at weeks 4 to 12 and 6 to 12, respectively. The Sheehan Disability Inventory showed that patients in the venlafaxine ER-treated group had significantly better outcomes in social life at weeks 4 and 12, and in work at week 12. Adverse events were similar to those reported in studies of venlafaxine ER in depression and generalized anxiety disorder. Venlafaxine ER was safe, well tolerated, and efficacious in the short-term treatment of generalized social anxiety disorder.

The use of venlafaxine in the treatment of major depression and major depression associated with anxiety : A dose-response study

This 12-week, double-blind, placebo-controlled study evaluated the efficacy and safety of venlafaxine as first-line therapy for the treatment of major depression and major depression associated with anxiety in 384 adult outpatients. Fixed total daily dosages of 75, 150, and 200 mg of venlafaxine were administered in a twice-a-day regimen. Primary efficacy parameters were the Hamilton Rating Scale for Depression (HAM-D) total score, the HAM-D Depressed Mood Item, the Montgomery-Asberg Depression Rating Scale total score, and the Clinical Global Impressions Scale. Overall, a higher percentage of patients responded to venlafaxine than to placebo. Efficacy data indicated a dose-related response, most evident in the onset of clinical improvement; statistically significant improvements in some primary parameters were seen as early as 1 to 2 weeks after initiation of treatment, especially in the 150-and 200-mg/day groups. These dose-related clinical improvements continued through week 12. Venlafaxine-treated patients who had depression associated with anxiety showed significant dose-related improvements compared with placebo-treated patients; improvement was noted by scores on the HAM-D Anxiety-Psychic Item and Anxiety-Somatization Factor. Few clinically significant changes were observed in laboratory values, vital signs, or electrocardiogram tracings. Venlafaxine was generally well tolerated at all dosages. The most common study events included nausea, dizziness, somnolence, insomnia, dry mouth, and asthenia, which are consistent with findings of previous studies. The current study demonstrated that 75 to 200 mg/day of venlafaxine twice daily produced a dose-related improvement in the primary efficacy parameters and in the onset of significant antidepressant effects, which was noted at weeks 1 to 2 with the highest dosage tested (200 mg/day). The study also demonstrated that these dosages of venlafaxine were safe and effective as first-line therapy for major depression and depression associated with anxiety.

Morning or evening bright light treatment of winter depression ? : the significance of hypersomnia

In a randomized crossover design 19 patients with winter depression were treated with 7 days of bright morning light (6:00 to 8:00 AM) and 7 days of evening light (7:00 to 9:00 PM). Bright light in the morning reduced the Hamilton Depression Rating Scale score from 22.3 to 5.5; bright light in the evening decreased the Hamilton score from 21.0 to 12.2. Improvement in the depression as measured by the Hamilton Depression Rating scores was greater with morning light compared with evening lights. Hypersomnia was associated (p less than 0.05) with a superior response to morning light.

Ethanol-induced single-strand DNA breaks in rat brain cells

Male Sprague-Dawley rats were intubated with 4 g/kg body weight of ethanol (in a 20%, v/v, water solution). Brain cells were analyzed for single-strand DNA breaks at various post-ethanol administration time points using an alkaline microgel electrophoresis assay. Results showed a significant increase in single-strand DNA breaks in brain cells that peaked at approx. 4 h and returned to control level within 6 h after ethanol administration.

A randomized, double-blind study of once-daily extended release quetiapine fumarate (quetiapine XR) monotherapy in patients with generalized anxiety disorder.

This study evaluated once-daily, extended-release quetiapine fumarate (quetiapine XR) monotherapy in generalized anxiety disorder (GAD). This was a 10-week (8-week active treatment/2-week posttreatment drug-discontinuation/tapering phase), double-blind, randomized, placebo-controlled study (D1448C00009). Primary end point was change from randomization at week 8 in Hamilton Anxiety Rating Scale (HAM-A) total score. Overall, 951 patients with GAD were randomized (quetiapine XR: 50 mg/d, n = 234; 150 mg/d, n = 241; 300 mg/d, n = 241; placebo, n = 235). At week 8, HAM-A total scores significantly (P < 0.001) improved versus placebo (−11.10) with quetiapine XR 50 mg/d (−13.31) and 150 mg/d (−13.54), but not 300 mg/d (−11.87; P = 0.240). At week 1, HAM-A total scores significantly improved versus placebo (−5.94) with quetiapine XR 50 mg/d (−7.47; P < 0.01), 150 mg/d (−8.19; P < 0.001), and 300 mg/d (−7.23; P < 0.01). Versus placebo at week 8, quetiapine XR 50 and 150 mg/d significantly improved HAM-A psychic (P < 0.01 and P < 0.001, respectively) and somatic (P < 0.001; P < 0.01, respectively) cluster scores, HAM-A response (≥50% total score reduction; P < 0.05), and Clinical Global Impression-Improvement categorical changes (P < 0.05). For quetiapine XR 150 mg/d, significant (P < 0.05) improvements were seen for HAM-A remission (total score, ≤7) and Clinical Global Impression-Severity of Illness scores. For quetiapine XR 300 mg/d, improvements in these secondary variables were not significantly different versus placebo. Pittsburgh Sleep Quality Index global scores improved with all 3 doses (quetiapine: XR 50 mg/d, −4.07 [P < 0.05]; 150 mg/d, −4.38 [P < 0.05]; 300 mg/d, −3.97 [P < 0.05], versus −3.31 with placebo). Adverse events (>10% with quetiapine XR) were dry mouth, somnolence, sedation, dizziness, headache, and fatigue. Quetiapine XR (50/150 mg/d) monotherapy was effective at week 8 in patients with GAD; symptom improvement was seen at week 1 for all doses (50/150/300 mg/d). Safety and tolerability were consistent with the known profile of quetiapine.

Adinazolam???A New Antidepressant: Findings of a Placebo-Controlled, Double-Blind Study in Outpatients with Major Depression

Adinazolam mesylate, a new triazolobenzodiazepine with antidepressant properties, was significantly superior to placebo based on the following efficacy measures: number of subjects who completed the study; number of subjects whose total score on the 21-item Hamilton Rating Scale for Depression (HAM-D) decreased by 50% or more; and number of subjects who reported that the drug helped them. Mean scores on three HAM-D clusters (anxiety/somatization, sleep disturbance, and an endogenomorphic cluster) also showed significant differences in favor of adinazolam. Side effects were generally mild and transient; however, a seizure of moderate intensity occurred during rapid tapering of adinazolam from 90 to 40 mg/day. There were no significant anticholinergic effects, and no mania or hypomania was reported in any subject. No consistently significant differences were observed between subjects whose primary diagnosis was major depression and those with a diagnosis of bipolar II depression.

Perceptions of parental and peer attachments by women with mood disorders.

The relationship between perceptions of parental and peer attachments at various ages and adult mood disorders was examined in 156 women classified as having bipolar disorder or unipolar depression or as nonpsychiatric controls. Nonpsychiatric controls reported a decreased attachment to their parents over time, but they also reported an increased closeness to their mothers in adulthood following a distant adolescence. Never hospitalized, moderately depressed subjects showed a similar trend toward decreased relatedness, but moderately depressed subjects did not report reestablishment of a close relationship with their mothers after adolescence. Severely depressed and bipolar subjects reported little attachment to their mother at all ages. Bipolar subjects also reported little connectedness to their fathers throughout their lifespan and severely depressed women felt less attached than nonpsychiatric controls to peers during development. None of the psychiatric groups reported difficulties with parental overcontrol.