Bipolar disorder patients who have a first affective episode with psychotic symptoms and a history of mania have a semantic verbal fluency deficit that occurs in spite of generally preserved function, say UK scientists.

Bipolar disorder patients have memory, attention, and executive function deficits that persist during euthymia. While such deficits are correlated with the number of prior affective episodes, they have also been demonstrated in first-episode patients.

To examine the extent to which such deficits represent “core” bipolar disorder characteristics, Eugenia Kravariti, from King’s College London, and colleagues administered, among other tests, a neuropsychological battery to 35 bipolar disorder patients with a first affective episode showing psychotic symptoms and a positive history of mania and 274 community controls.

In addition, a subanalysis was performed between the patients and 105 controls matched for current IQ (”good” versus “poor”) and IQ trajectory (”stable,” “declined,” and “improved”).

There were no differences between patients and either groups of controls in terms of gender, education, or National Adult Reading Test IQ, whereas there were significant differences in age and ethnicity.

The results, published in the journal Bipolar Disorders, show that there was evidence of a suggested deficit in patients compared with controls on the Rey Auditory Verbal Learning Test Trial 6, and a significant deficit in patients compared with controls in semantic fluency.

Only the latter deficit was detectable in patents compared with IQ-matched controls. Compared with the overall control group, semantic fluency had a medium effect size, and a small-to-medium effect size compared with IQ-matched controls. There were no other significant deficits.

Further analysis demonstrated that antipsychotic medication had a small and nonsignificant negative correlation with semantic fluency, at average scores of 34.78 in medicated cases versus 45.00 in two non-medicated patients.

The team writes: “In summary, our results point to a moderate, isolated impairment in semantic verbal fluency in patients with a first affective episode with psychotic symptoms and a positive history of mania.

“This pattern contrasts sharply with the widespread neuropsychological dysfunction seen in the early phases of schizophrenia.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a part of Springer Science+Business Media. © Current Medicine Group Ltd; 2009

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People who develop bipolar disorder in childhood or adolescence are at greater risk for recurrence, chronicity of mood symptoms, and functional impairment than those who develop the mood disorder in adulthood, US study results confirm.

“Symptoms of bipolar disorder are increasingly recognized among children and adolescents,” explain Roy Perlis (Massachusetts General Hospital and Harvard Medical School, Boston, USA), and colleagues.

But they add: “Little is known about the course of bipolar disorder among adults who experience childhood onset of symptoms.”

To investigate, the researchers studied data on 3658 adult patients with bipolar I and II disorder who were participating the Systematic Treatment Enhancement Program for Bipolar Disorder ??” a multicenter clinical effectiveness study.

The participants were divided into three groups based on age at disease onset of less than 13 years (childhood or prepubertal onset), 13??”18 years (adolescent onset) and over 18 years (adult onset).

Baseline features and outcomes over 2 years of follow-up were compared among the three groups.

The team found that, compared with the 1187 patients with adult onset bipolar disorder, the 1068 patients with childhood or prepubertal onset of disease experienced, on average, an earlier recurrence of mood episodes after initial remission, fewer days of euthymia, and greater impairment in functioning and quality of life over follow-up.

Patients with adolescent onset bipolar disorder (n=1403) also had poorer outcomes than those with adult-onset disease, but better outcomes than those with childhood or prepubertal onset bipolar disorder.

Writing in the journal Bipolar Disorders, Perlic and team conclude: “These results… suggest that individuals with earlier onset [bipolar disorder] may be at risk for a more chronic as well as recurrent course in adulthood, with poorer functioning and quality of life.”

They add that the findings “underscore the need to develop better strategies for early identification and early interventions which achieve and maintain symptomatic remission and enhance functioning over the course of development.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a part of Springer Science+Business Media. © Current Medicine Group Ltd; 2009

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Results presented today at the 162nd American Psychiatric Association (APA) congress in San Francisco, CA, demonstrated the efficacy and tolerability of SEROQUEL® (quetiapine fumarate) for treating depressive episodes in bipolar disorder, including the difficult-to-treat bipolar II patient population.1,2 The data are from combined analyses of four large-scale clinical trials to examine SEROQUEL as a treatment for depressive episodes associated with bipolar I and II disorders. SEROQUEL and SEROQUEL XR™, a once-daily, extended-release formulation of SEROQUEL, is one of the most widely studied atypical antipsychotic in bipolar depression and the only agent approved as monotherapy to treat the spectrum of mood episodes associated with bipolar disorder.

“Bipolar disorder is a chronic illness with patients experiencing severe debilitating mood swings. Patients spend a majority of their time ill in the depressed phase of the illness. These important findings confirm that SEROQUEL is an effective agent for the treatment of bipolar depression, and particularly encouraging are the results in bipolar II patients who historically have not responded well to treatment,” said Professor Alan Young of the Department of Psychiatry, University of British Columbia, Vancouver, Canada.

Results from a combined analysis of all patients with bipolar I or II disorder (n=2593) demonstrated that SEROQUEL monotherapy was significantly more effective than placebo for treating depressive episodes associated with bipolar disorder as measured by improvements in the Montgomery-?sberg Depression Rating Scale (MADRS) total score (P<0.001 for both doses of SEROQUEL). Similar results were observed in a combined analysis of patients with bipolar II disorder (n=819). In both analyses, improvements were evident as early as week 1 and continued through week 8. The four studies, BOLDER (BipOLar DEpRession) I and II and EMBOLDEN (Efficacy of quetiapine Monotherapy in BipOLar DEpressioN) I and II, had a similarly designed 8-week, randomised, double-blind, placebo-controlled phase to evaluate the efficacy and safety of SEROQUEL monotherapy (fixed dose 300 mg or 600 mg daily) compared with placebo in adult patients with bipolar I or II disorder. The EMBOLDEN studies also included an active comparator arm, lithium in EMBOLDEN I and paroxetine in EMBOLDEN II.

The EMBOLDEN studies also included a 26- to 52-week continuation phase, where patients who achieved remission continued on the same dose of SEROQUEL or were switched to placebo. In the combined analysis of this phase, both doses of SEROQUEL significantly increased the time to recurrence of any mood event (hazard ratio 0.59 [95% CI, 0.41-0.84; P=0.004] for 300 mg/day and 0.45 [95% CI, 0.30-0.67; P<0.001] for 600 mg/day). In the subpopulation of patients with bipolar II disorder, both doses of SEROQUEL significantly reduced the risk of recurrence of any mood event compared with placebo (hazard ratio 0.47 [95% CI, 0.25-0.92; P<0.05] for 300 mg/day and 0.18 [95% CI, 0.07-0.51; P<0.001] for 600 mg/day).

The combined data indicate that SEROQUEL was generally well-tolerated and adverse events were consistent with the known safety profile of quetiapine. The most common adverse events in patients with bipolar disorder were dry mouth, somnolence, sedation, and dizziness. In the subpopulation of patients with bipolar II disorder, the most common adverse events were dry mouth, somnolence, sedation, dizziness, and headache. In the continuation phase of the EMBOLDEN studies, the most common treatment-emergent adverse events with SEROQUEL were headache, somnolence, nasopharyngitis, nausea, diarrhoea, and dry mouth and in the subpopulation of patients with bipolar II disorder were headache, dry mouth, somnolence, nasopharyngitis, dizziness, and nausea.

Similar findings have been observed for SEROQUEL XR, which was approved in the U.S. and Europe in 2008 for the acute treatment of depressive episodes associated with bipolar disorder. In an 8-week study (D144CC00002), SEROQUEL XR 300 mg/day demonstrated significant improvements in MADRS total scores from week 1 though week 8 (both P<0.001) compared with placebo.3

The mechanism of action of SEROQUEL, which involves both antipsychotic and antidepressant activities, may help explain its unique efficacy across the spectrum of mood episodes associated with bipolar disorder. The efficacy of quetiapine in depressive episodes may be partly explained by norepinephrine reuptake inhibition by norquetiapine, the active metabolite of quetiapine.

About SEROQUEL and SEROQUEL XR

Launched in 1997, it is estimated that SEROQUEL has been prescribed to more than 22 million patients worldwide. SEROQUEL has been approved in 94 countries for schizophrenia, 92 countries for bipolar mania, in 41 countries for bipolar depression and in 6 countries for bipolar maintenance.

SEROQUEL XR has been approved in 53 countries for schizophrenia, 19 countries for bipolar mania, in 20 countries for bipolar depression, in 9 markets for bipolar maintenance, in 1 market for Major Depressive Disorder (MDD), and in 1 market for Generalised Anxiety Disorder (GAD).

References

1. Calabrese JR, et al. The efficacy of quetiapine monotherapy in bipolar depression: combined data from the BOLDER and EMBOLDEN studies. Presented at the American Psychiatric Association, San Francisco, CA, USA, 16-21 May, 2009.

2. Young AH, et al. The efficacy of quetiapine monotherapy in bipolar II depression: combined data from the BOLDER and EMBOLDEN studies. Presented at the American Psychiatric Association, San Francisco, CA, USA, 16-21 May, 2009.

3. Suppes T, et al. Effectiveness of the new extended release formulation of quetiapine as monotherapy for the treatment of acute bipolar depression (trial D144CC00002). Presented at the Eighth International Review of Bipolar Disorder Conference, Copenhagen, Denmark, 14-16 April, 2008.

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