To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure email@example.com
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
What does it take for women to win political office? This book uncovers a gendered qualifications gap, showing that women need to be significantly more qualified than men to win elections. Applying insights from psychology and political science and drawing on experiments, public opinion data, and content analysis, Nichole M. Bauer presents new evidence of how voter biases and informational asymmetries combine to disadvantage female candidates. The book shows that voters conflate masculinity and political leadership, receive less information about the political experiences of female candidates, and hold female candidates to a higher qualifications standard. This higher standard is especially problematic for Republican female candidates. The demand for masculinity in political leaders means these women must “look like men” but also be better than men to win elections.
As the unemployment rate continues to shrink, organizations are increasingly in competition for the best talent. For this reason, the ability to effectively source, recruit, and hire qualified employees has become a cornerstone of effective human resource management, and a critical function in creating value through human capital. However, in order to capitalize on effective recruitment and hiring, organizations need to be able to retain and motivate new employees throughout their first year, during which studies estimate the risk of newcomer turnover ranges from 10 percent to as much as 50 percent and above for some jobs (Maurer, 2017). Thus the organizational entry period comes on the heels of substantial investment on the part of employers with the potential for both significant payoff and significant risk (Kammeyer-Mueller & Wanberg, 2003; Wanberg, 2012).
Our research group demonstrated that vitamin A restriction affected meat quality of Angus cross and Simmental steers. Therefore, the aim of this study is to highlight the genotype variations in response to dietary vitamin A levels. Commercial Angus and Simmental steers (n = 32 per breed; initial BW = 337.2 ± 5.9 kg; ~8 months of age) were fed a low-vitamin A (LVA) (1017 IU/kg DM) backgrounding diet for 95 days to reduce hepatic vitamin A stores. During finishing, steers were randomly assigned to treatments in a 2 × 2 factorial arrangement of genotype × dietary vitamin A concentration. The LVA treatment was a finishing diet with no supplemental vitamin A (723 IU vitamin A/kg DM); the control (CON) was the LVA diet plus supplementation with 2200 IU vitamin A/kg DM. Blood samples were collected at three time points throughout the study to analyze serum retinol concentration. At the completion of finishing, steers were slaughtered at a commercial abattoir. Meat characteristics assessed were intramuscular fat concentration, color, Warner-Bratzler shear force, cook loss and pH. Camera image analysis was used for determination of marbling, 12th rib back fat and longissimus muscle area (LMA). The LVA steers had lower (P < 0.001) serum retinol concentration than CON steers. The LVA treatment resulted in greater (P = 0.03) average daily gain than the CON treatment, 1.52 and 1.44 ± 0.03 kg/day, respectively; however, there was no effect of treatment on final BW, DM intake or feed efficiency. Cooking loss and yield grade were greater and LMA was smaller in LVA steers (P < 0.05). There was an interaction between breed and treatment for marbling score (P = 0.01) and percentage of carcasses grading United States Department of Agriculture (USDA) Prime (P = 0.02). For Angus steers, LVA treatment resulted in a 16% greater marbling score than CON (683 and 570 ± 40, respectively) and 27% of LVA Angus steers graded USDA Prime compared with 0% for CON. Conversely, there was no difference in marbling score or USDA Quality Grades between LVA and CON for Simmental steers. In conclusion, feeding a LVA diet during finishing increased marbling in Angus but not in Simmental steers. Reducing the vitamin A level of finishing diets fed to cattle with a high propensity to marble, such as Angus, has the potential to increase economically important traits such as marbling and quality grade without negatively impacting gain : feed or yield grade.
Compare quetiapine+antidepressant (AD) with lithium+AD, and quetiapine monotherapy with lithium+AD in open, rater-blinded treatment.
Patients with treatment resistant depression (Thase et al 1997 stage 1 and 2) with severity of MADRS ≥25 received: quetiapine XR 300mg/day plus AD (SSRIs or venlafaxine) (n=229), lithium (monitored to between 0.6 to 1.0 meq/l) plus AD (n=221) or quetiapine XR alone (300mg/day) (n=225) for 6 weeks. Primary efficacy measure was change from baseline in MADRS total score. The pre-specified non-inferiority limit was 3 points on the MADRS.
Fewer patients discontinued on quetiapine+AD (15.2%) than lithium+AD (20.5%) and quetiapine monotherapy (21.5%). Quetiapine+AD and quetiapine monotherapy, were not inferior to lithium+AD in the primary (per protocol) analysis with a mean difference (97.5%CI) on the MADRS of -2.32 (-4.6 to -0.05) favouring add-on quetiapine and -0.97 (-3.24 to 1.31) favouring quetiapine monotherapy. This mandated superiority testing on the modified ITT population showing no significant difference at endpoint.
In a post hoc analysis discounting multiplicity, quetiapine+AD was significantly more effective than lithium+AD on the MADRS change from baseline, p=0.046. The advantage was observed at day 4 (p=0.007) and persisted throughout. Efficacy was supported by CGI-I (p=0.07). Quetiapine+AD showed a numerically greater advantage over lithium+AD in those with two failed treatments (Stage 2) rather than one (Stage 1).
Quetiapine+AD and quetiapine monotherapy, were non-inferior to lithium+AD in treatment resistant depression. There was an early significant and persistent efficacy advantage on MADRS for quetiapine augmentation compared with lithium augmentation of SSRI or venlafaxine treatment.
Evaluate the effects of once-daily extended release quetiapine fumarate (quetiapine XR) monotherapy in patients with major depressive disorder (MDD) according to disease severity.
Pooled data (quetiapine XR 50, 150 and 300mg/day doses combined) from four 6- or 8-week placebo-controlled quetiapine XR monotherapy studies (D1448C00001, D1448C00002, D1448C00003, D1448C00004) were analysed. Key inclusion criterion for all 4 studies: HAM-D total score ≥22. Primary endpoint: change from randomisation in Montgomery-Åsberg Depression Rating Scale (MADRS) total score. A post-hoc analysis assessed change from randomisation in MADRS total score and MADRS response (≥ 50% reduction in MADRS total score) at endpoint (Week 6 or Week 8) in 6 severity cohorts (defined by a MADRS total score at randomisation ≥24, ≥26, ≥28, ≥30, ≥32 or ≥34).
1752 patients (comprising the l’ all patients’ group) were evaluated (MADRS score ≥24 at randomisation, n=1601; ≥26, n=1467; ≥28, n=1269; ≥30, n=1038; ≥32, n=745; ≥34, n=500). Quetiapine XR significantly reduced mean MADRS total score at endpoint in lrsquo;all patients’ (p< 0.001 vs placebo) and in all 6 severity cohorts (≥24, ≥26, ≥28, ≥30 and ≥32, p< 0.001 vs placebo; ≥34, p< 0.01 vs placebo). MADRS response rates were significantly higher in the quetiapine XR group vs placebo in the ‘all patients’ group (p< 0.001 vs placebo) and in all 6 severity cohorts (≥24, ≥26, ≥28, ≥30 and ≥32, p< 0.001 vs placebo; ≥34, p=0.001 vs placebo).
Quetiapine XR monotherapy significantly improved depressive symptoms in patients with MDD irrespective of disease severity, including the most severe levels of depression.
(I) Profound alterations of the hypothalamic-pituitary-adrenocortical (HPA) axis regulation were repeatedly shown in depressed patients. The most sensitive challenge test of the HPA axis, the combined dexamethasone/CRH test (DEX/CRH test), shows an overstimulation of ACTH and cortisol in depressed patients. Under tricyclic antidepressant treatment, a normalization of the HPA axis overdrive was found to precede the clinical improvement.
(II) Lithium is a well established drug for the treatment of affective disorders. Yet, its exact mode of action and its effects on the HPA axis are still unknown.
Design and methods
Three 4-week studies with each 30 acutely depressed patients (unipolar, SCID I confirmed) were conducted. In study 1, patients refractory to a treatment trial with an antidepressant of at least four weeks were treated with lithium augmentation. In study 2 and 3, drug free patients were treated with lithium monotherapy or citalopram monotherapy respectively. Weekly HAM-D ratings were performed. In each study, the DEX/CRH test was conducted right before and four weeks after initiation of the pharmacotherapy.
All three pharmacological strategies showed good antidepressive efficacy. Both lithium monotherapy and lithium augmentation led to a (for most parameters significant) increase in the HPA axis activity. In contrast, citalopram monotherapy resulted in a decrease of the hormone response to the DEX/CRH test.
The aim of this study was to examine the long-term efficacy and safety of a monotherapy with quetiapine or sodium valproate (VPA) in patients with rapid cycling bipolar disorder.
This open-label trial was conducted at three German centers. A sample of 38 remitted or partly remitted bipolar patients with rapid cycling (quetiapine n = 22; VPA n = 16) were treated with quetiapine or VPA (flexible-dose design) up to 12 months. Analyses were based on the ITT-LOCF principle.
41 % of the patients with quetiapine and 50 % with VPA completed the trial. According to the Clinical Global Impression Scale responder rates tended to be higher for quetiapine than for VPA: i.e. 43 % vs. 25 % (depression), 48 % vs. 36 % (mania), and 43 % vs. 19 % (improvement in both mania and depression). There were no differences found between the treatment groups evaluating the HRSD, MADRS and YMRS. In contrast, Life Chart Method data showed that patients being treated with quetiapine had significantly less depressive days than patients on VPA whilst they did not differ in the number of days with manic symptoms. The incidence of adverse events, especially of orthostatic dysregulation and sedation was higher in the quetiapine group.
Quetiapine may be more effective than VPA regarding depressive symptoms and as effective as VPA in the treatment of manic symptoms in the long-term treatment of rapid cycling bipolar disorder. The side effect profile of quetiapine tends to be less favorable than the one of VPA.
Depression is a common psychiatric disorder, with the prevalence for major depression in Europe of around 5%. Depression is the fourth leading cause of disease burden worldwide. The high disease burden is reflected in the morbidity and mortality associated with the condition, in reduced functioning and well-being and in impaired quality of life. Although the efficacy of antidepressant medications are well established, their effectiveness in improving a broad range of outcomes is less clear.
Because European countries differ in their healthcare systems and practice settings for treating depression, a multinational study was initiated to examine the influence of patient and non-patient factors on quality of life outcomes in depression.
Factors Influencing Depression Endpoints Research (FINDER) is a large prospective 6-month observational study conducted in 12 European countries that investigates health-related quality of life (HRQOL) in depressed outpatients in routine primary and specialist care settings receiving standard antidepressant pharmacological treatment, and aims to assess the association of different factors such as patient demographics or reporting of previous psychiatric disorders with the patients' HRQOL.
Data from 3468 patients enrolled by 437 investigators were eligible for analysis. The objectives of this presentation are to describe the background and study design of FINDER.
FINDER Study Team
Michael Bauer (Germany), Nicolas Dantchev (France), Koen Demytteneare (Belgium), Ana Garcia-Cebrian (UK), Luigi Grassi (Italy), Angel Luis Montejo (Spain), Brigitta Monz (Germany), David Perahia (UK), Deborah Quail (UK), Catherine Reed (UK), Andre Tylee (UK).
Eli Lilly and Company Limited & Boehringer Ingelheim GmbH
Understanding factors that affect treatment adherence may help to prevent non-adherence and increase the quality of care as well as cost-effectiveness.
Objectives & aims
To measure the level of adherence to clinical guidelines and to examine the correlates of adherence among outpatients with mood, anxiety and somatoform disorders in a routine clinical setting.
We developed quality measures and assessed adherence during up to 3 years of follow-up in a randomly selected sample of 300 outpatients who started routine psychiatric treatment. Patients were treated with pharmacotherapy, psychotherapy or a combination. At baseline, a standardized diagnostic interview (MINI-PLUS), the brief symptom inventory (BSI), general health status (SF-36) and demographics were assessed, as part of the usual intake procedure. Using multivariable regression analysis we identified independent predictors associated with guideline adherence.
Most indicators were highly positive, indicating that most treatment was delivered according to guidelines. The combined treatment group as compared to the two other groups had lower scores on indicators “correct treatment module” and “stepped care” (p < 0.005). Patients receiving psychotherapy scored best on the separate indicators. Only a minority was treated in complete accordance with guidelines. Low-adherence was independently predicted by a low score on the SF-36 vitality-subscale. No significant differences were found within socio-demographic variables, comorbidity and BSI-scores between the adherence groups.
Assessment of guideline adherence is feasible with this cross-diagnostic set of process indicators. Patients with low scores on the vitality-subscale of the SF-36 were at the highest risk to receive low guideline-concordant care.
This prospective, longitudinal study compared the frequency and pattern of mood changes between outpatients receiving usual care for bipolar disorder who were either taking or not taking antidepressants. One hundred and eighty-two patients with bipolar disorder self-reported mood and psychiatric medications for 4 months using a computerized system (ChronoRecord) and returned 22,626 days of data. One hundred and four patients took antidepressants, 78 did not. Of the antidepressants taken, 95% were selective serotonin or norepinephrine reuptake inhibitors, or second-generation antidepressants. Of the patients taking an antidepressant, 91.3% were concurrently taking a mood stabilizer. The use of antidepressants did not influence the daily rate of switching from depression to mania or the rate of rapid cycling, independent of diagnosis of bipolar I or II. The primary difference in mood pattern was the time spent normal or depressed. Patients taking antidepressants frequently remained in a subsyndromal depression. In this naturalistic study using self-reported data, patients with bipolar disorder who were taking antidepressants—overwhelmingly not tricyclics and with a concurrent mood stabilizer—did not experience an increase in the rate of switches to mania or rapid cycling compared to those not taking antidepressants. Antidepressants had little impact on the mood patterns of bipolar patients taking mood stabilizers.
To describe the pattern of antidepressant (AD) therapy in routine care over a 6-month period and to explore associations with health-related quality of life (HRQoL).
FINDER was a 6-month prospective, observational study to investigate the HRQoL of 3,468 depressed outpatients receiving AD treatment. Type and dose of AD(s) prescribed at baseline and throughout the follow-up period was recorded and grouped into SSRIs, SNRIs, TCAs, others and combinations (ADs from >1 group). ‘Switching’ groups were defined when medication taken changed between period 1 (baseline-3 months) and period 2 (3-6 months). HRQoL measures included the EQ-5D Visual Analogue Scale (VAS), from ‘best imaginable health’ (100) to ‘worst imaginable health’ (0).
Complete information to assess switching patterns was available for 2,672 (77%) patients. Of those, 8.0% discontinued their AD, 5.6% decreased dose, 60.5% remained on stable dose, 9.6% increased dose; 5.1% and 8.6 % switched within and between AD groups, respectively. In addition, 2.7% re-started treatment or remained untreated. The mean(sd) EQ-5D VAS changes from baseline to 3-months were: 20(22), 20(22), 18(21), 17(21), 12(21), 12(24), and 13(22), respectively and from baseline to 6-months were: 24(24), 28(25), 26(24), 24(24), 16(23), 21(26) and 15(24), respectively. Those patients switching within classes and those without treatment in period 1 had worst HRQoL outcomes.
The majority of patients treated for depression remained on the same medication at a stable dose. HRQoL may have contributed to the decision to change AD therapy.
FINDER was supported by Eli Lilly and Company Limited & Boehringer Ingelheim GmbH
To evaluate the efficacy and tolerability of once-daily quetiapine XR adjunctive to antidepressant therapy versus antidepressant alone in patients with MDD showing an inadequate response to antidepressant treatment (mainly SSRIs/SNRIs).
6-week, multicentre, double-blind, parallel-group study (D1448C00007). Patients were randomised to receive quetiapine XR 150mg/day (n=167), 300mg/day (n=163) or placebo (n=163) as add-on to maintained antidepressant treatment. Primary endpoint: baseline to Week 6 change in MADRS total score. Secondary variables included: baseline to Week 1 change in MADRS total score; baseline to Week 6 change in HAM-A total and psychic anxiety subscale scores. Safety assessments included AE reporting.
Mean change in MADRS total score (overall baseline mean, 28.4) from baseline to Week 6 was significant (p<0.01) for quetiapine XR 150mg/day (-15.26) and 300mg/day (-14.94) versus placebo (-12.21). Separation from placebo in MADRS total score was apparent from Week 1 for both quetiapine doses (p<0.001).
At Week 6, mean change from baseline in HAM-A total score (overall baseline mean, 20.8) was significant for quetiapine XR 150mg/day (-10.27, p<0.01) and 300mg/day (-9.70, p<0.05) versus placebo (-7.92). Mean change from baseline in HAM-A psychic anxiety subscale score (overall baseline mean, 12.83) was significant with quetiapine XR 150mg/day (-6.82, p<0.001) and 300mg/day (-6.47, p<0.01) versus placebo (-5.11).
Most common AEs (>10%) were dry mouth, somnolence, fatigue, sedation, constipation and dizziness with quetiapine XR.
In patients with MDD with an inadequate response to antidepressant treatment, adjunctive quetiapine XR 150mg/day and 300mg/day was well tolerated and effective at reducing depressive and anxiety symptoms.
Investigate effects of adjunct extended release quetiapine fumarate (QTP-XR) on sleep disturbance and quality in patients with MDD and inadequate response to antidepressant (AD) therapy.
Data were pooled from two (D1448C00006/D1448C00007) 6-week, double-blind, randomised, placebo (placebo+AD)-controlled studies of adjunct QTP-XR (15 0 mg/day and 300 mg/day). Primary endpoint: MADRS total score change versus placebo+AD. Secondary endpoints (post hoc): change from randomisation in MADRS item 4 (reduced sleep), HAM-D items 4, 5 and 6 (early-, middle- and late-insomnia), sleep disturbance factor (HAM-D items 4+5+6) and sleep quality (PSQI global score). MADRS total score change in patients with baseline HAM-D sleep disturbance factor score > = 4 or < 4 (high and low sleep disturbance, respectively) was evaluated.
919 patients received adjunct QTP-XR: 150 mg/day (n = 309), 300 mg/day (n = 307), placebo+AD (n = 303). At Week 6, adjunct QTP-XR (both doses) reduced MADRS item 4, HAM-D sleep disturbance factor, HAM-D items 4, 5 and 6 and PSQI global scores from baseline versus placebo+AD (p < 0.001). In patients with baseline HAM-D>=4 (n = 226, 215 and 210, respectively) adjunct QTP-XR (both doses) improved (p< 0.01) MADRS total score versus placebo+AD from Week 1 onward. In patients with baseline HAM-D< 4 (n = 83, 92, 93, respectively) adjunct QTP-XR (both doses) improved (not statistically significantly) MADRS total score versus placebo+AD at Week 6.
Adjunct QTP-XR significantly restored sleep and improved sleep quality in patients with MDD and inadequate response to AD. Significant improvement in depressive symptoms was demonstrated with adjunct QTP-XR in patients with MDD and high baseline sleep disturbance. AstraZeneca funded.
Based on evidences in molecular neuroimaging, postmortem and genetic studies, impaired serotonergic neurotransmission has been implicated with affective disorders. Moreover, a growing number of evidences showed strong interrelations within the serotonergic system suggesting a common mechanism in the modulation of receptor and transporter densities.
Here we directly investigated the regional expression of the 5-HT1A, 5-HT2A and 5-HTT using PET and the three highly selective and specific radioligands [carbonyl-11C]WAY-100635, [18F]Altanserin and [11C]DASB in healthy subjects.
A total of 55 healthy subjects (5-HT1A: 36 subjects, 18 males, age = 26.0 ± 4.9; 5-HT2A: 19 subjects, 11 males, age = 28.2 ± 5.9; 5-HTT: 8 males, age = 28.12 ± 3.6) were included in this study. Binding potential (BPND) values were quantified according to the AAL parcellation scheme.
BPND values averaged over both hemispheres ranged from 0.40–6.35 for the 5-HT1A receptor; 0.01–2.01 for the 5-HT2A receptor and 0.09–2.05 for the 5-HTT, respectively. There was a specific topological pattern according to the ratio between the 5-HT1A, 5-HT2A receptors and 5-HTT (“fingerprints”).
Such information can be essential for detecting potential local alterations in the ratio between different binding proteins on a network level in pathological conditions.
Moreover, these data might provide further insight in area-specific effects of frequently prescribed selective serotonin re-uptake inhibitors (SSRI):
1) due to the distinct local receptor and transporter availability;
2) SSRI application alters the postsynaptic receptor expression and thus;
3) leads to a modified interaction of inhibitory and exhibitory receptors.
To evaluate quetiapine XR as adjunct to ongoing antidepressant therapy in patients with MDD showing inadequate response to antidepressant treatment.
Data were analysed from two 6-week, multicentre, double-blind, randomised, placebo-controlled studies (D1448C00006; D1448C00007), prospectively designed to be pooled. Outpatients received adjunctive quetiapine XR 150mg/day (n=309), 300mg/day (n=307), placebo (n=303). Primary endpoint: change at Week 6 in MADRS total score. Other assessments included: MADRS individual item scores, HAM-A total scores, MADRS response and remission; AE reporting.
Quetiapine XR 150mg/day and 300mg/day (p< 0.001) reduced MADRS total scores versus placebo at Week 6 (-14.5, -14.8, -12.0) and Week 1 (-7.8, -7.3, -5.1). Subgroup analyses showed the therapeutic effect of quetiapine XR was neither limited to nor driven by factors such as gender or antidepressant class (SSRI/SNRI). Quetiapine XR demonstrated consistent improvements in individual MADRS items: 150mg/day and 300mg/day significantly improved 4/10 and 7/10 items at Week 6 versus placebo. At Week 6, MADRS response (≥50% decrease in total score) was 53.7% (p=0.063), 58.3% (p< 0.01) versus 46.2%; MADRS remission (total score ≤8) was 35.6% (p< 0.01), 36.5% (p< 0.001) versus 24.1% for quetiapine XR 150mg/day and 300mg/day and placebo, respectively. Quetiapine XR 150mg/day and 300mg/day improved HAM-A total scores versus placebo at Week 1 (-4.8 [p< 0.001], -4.2 [p< 0.01], -3.0) and Week 6 (-8.9 [p< 0.01], -9.1 [p< 0.001], -7.3). AEs (≥10%) were dry mouth, somnolence, sedation, dizziness, fatigue, constipation and headache with quetiapine XR.
In patients with MDD and an inadequate response to antidepressant therapy adjunctive quetiapine XR is effective and generally well tolerated.
The objective is to describe the prevalence and nature of painful symptoms among depressive outpatients and how are they related with depressive symptoms and somatic non painful symptoms at baseline.
The FINDER study, conducted in 12 European countries in depressed outpatients in routine primary and specialist care settings provides a unique opportunity to answer these questions.
Painful symptoms were evaluated among 3468 patients enrolled by 437 investigators, using the 28-item Somatic Symptom Inventory (SSI-28) and 6 Visual Analogue Scales (1 item on overall pain and 5 items on pain characteristics: headaches, back pain, shoulder pain, interferences with daily activities and pain while awake). There was a strong correlation between the VAS overall pain score and the pain sub score of the SSI-28. The threshold score of 30 mm on the overall pain severity in combination with selected comorbidities was used to divide patients in three pain cohorts: (1) those with no/mild pain; (2) those with moderate/severe œmedically explained pain and (3) those with moderate/severe medically unexplained pain.
Results showed that 1447 (43.7%) patients had no/mild pain, 550 (16,6%) had moderate/severe medically explained pain, and 1311 (39,6%) had moderate/severe medically unexplained pain. Of the different locations of pain symptoms (from the SSI-28), headaches were the most common, followed by muscle soreness and lower back pain. The mean depression score (HADS-D) was higher in patients with pain-related symptoms.
We studied the correlations between the measures of pain and depression. These results and their implications will be discussed.
This pooled analysis evaluated efficacy of adjunct quetiapine XR (QTP-XR) in subgroups of patients with anxious depression and lower levels of anxiety.
Pooled data from two 6-week, double-blind, randomised, placebo-controlled trials (D1448C00006/D1448C00007) in patients with inadequate response to antidepressants were analysed. Patients received adjunct QTP-XR (150 or 300 mg/day) or placebo+antidepressant (SSRI or SNRI). Using criteria defined in the STAR*D study, analyses conducted in patients with anxious depression or lower baseline anxiety levels (HAM-D anxiety/somatic factor score >/ = 7 and < 7, respectively) included LSM change at Week 6 in: MADRS total (primary endpoint), HAM-A and CGI-S total scores.
For patients with anxious depression (n = 697; 76% patients), adjunct QTP-XR 150mg/day (-14.44, p < 0.01) and 300 mg/day (-15.09, p < 0.001) significantly improved MADRS total scores versus placebo+antidepressant (-11.78) at Week 6, with significant improvement demonstrated from Week 1 onwards. Significant improvements were seen in HAM-A (QTP-XR 150 mg/day: -9.05, p < 0.01; 300 mg/day -9.43, p < 0.01) and CGI-S total scores (QTP-XR 150 mg/day: -1.60, p< 0.001; 300 mg/day -1.63, p < 0.001) versus placebo+antidepressant (-7.40, -1.22, respectively) at Week 6.
A smaller subgroup (n = 222; 24% patients) had lower baseline anxiety levels. At Week 1, adjunct QTP-XR (150 mg/day -9.09; p < 0.01; 300 mg/day -8.60; p < 0.05) significantly improved MADRS total score versus placebo+antidepressant (-5.93). At Week 6 there were no significant changes (QTP-XR 150 mg/day -14.49; p = 0.243; 300 mg/day -14.01; p = 0.388) versus placebo+antidepressant (-12.78).
For patients with anxious depression, adjunct QTP-XR (150 and 300 mg/day) was effective at reducing symptoms of anxiety and depression, with symptom improvement observed from Week 1 onwards. AstraZeneca funded.
Bipolar disorder is for most patients a life-long illness, associated with a recurrent, chronic course, and functional disability. Primary treatment goals are to stabilize the patient and prevent recurrence of episodes and suicide.
Although bipolar disorder has traditionally been regarded as an illness with good prognosis and most patients returning to normal functioning when a mood episode is over, several longitudinal studies suggest that the long-term outcome is less favorable than previously thought. Combinations of drugs are frequently used in clinical practice for mood stabilization, especially for those who have not responded to monotherapy. Although combination treatments are commonly administered, full interepisode recovery is not achieved in all patients, and as a consequence, bipolar disorder is one of the leading causes of disability.
Among clinicians and in international guidelines, lithium is widely considered as the ‘gold standard’ for long-term treatment. The choice of treatments is undergoing considerable change as new treatments are available, anticonvulsants and atypical antipsychotics are taking a more prominent position. However, the evidence available for the newer treatment options including the various combination treatments varies greatly.
The episodic nature of bipolar disorder requires prophylactic long-term treatment. Many previous worthwhile treatment effects of available mood stabilizing agents and psychotherapeutic interventions on major outcomes in bipolar disorder are only of moderate size and therefore require large-scale studies. Such trials to investigate longer-term outcomes are logistically challenging and expensive, and therefore only feasible within a multisite and multinational approach based on a common documentation system of the illness course.