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During the 2017 to 2019 growing seasons, samples of waterhemp and Palmer amaranth that had reportedly survived field-rate applications of protoporphyrinogen oxidase (PPO)–inhibiting herbicides were collected from the American Midwest and tested for target-site mutations known at the time to confer resistance. Target-site resistance was identified in nearly all (135 of 145) tested common waterhemp populations but in only 8 of 13 Palmer amaranth populations. Follow-up research on one population of Palmer amaranth (W-8), which tested negative for all such mutations, confirmed it was resistant to lactofen, with a magnitude of resistance comparable to that conferred by the ΔG210 PPO2 mutation. Gene sequences from both isoforms of PPO (PPO1 and PPO2) were compared between W-8 and known PPO inhibitor–sensitive sequence. A glycine-to-alanine substitution at the 399th amino acid position (G399A) of PPO2, recently identified to reduce target-site herbicide sensitivity, was observed in a subset of resistant W-8 plants. Because no missense mutation completely delimited resistant and sensitive sequences, we initially suspected the presence of a secondary, non-target-site resistance mechanism in this population. To isolate G399A, a segregating F2 population was produced and screened with a delimiting rate of lactofen. χ2 goodness-of-fit analysis of dead/alive ratings indicated single-locus inheritance of resistance in the F2 population, and molecular markers for the W-8 parental PPO2 coding region co-segregated tightly, but not perfectly, with resistance. More research is needed to fully characterize Palmer amaranth PPO inhibitor–resistance mechanisms, which appear to be more diverse than those found in common waterhemp.
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.
To evaluate once-daily extended release quetiapine fumarate (quetiapine XR) as monotherapy (50, 150 and 300mg/day) (acute and maintenance treatment) or adjunct treatment (150 and 300mg/day) in patients with MDD.
Eight (7 acute, 1 maintenance) placebo-controlled studies were analysed. Primary endpoints: change from randomisation in Montgomery-Åsberg Depression Rating Scale (MADRS) scores (acute); time from randomisation to depressed event (maintenance). Statistical analyses: ANCOVA for difference between quetiapine XR and placebo in LSM change in MADRS total score from randomisation to study end (LOCF; acute); hazard ratio (HR) for time to recurrence of a depressed event (maintenance).
Figure 1 shows treatment differences (95% CIs) for primary efficacy variable for the seven acute studies. Four monotherapy studies (D1448C00001, D1448C00002, D1448C00003, D1448C00014) were significant in favour of quetiapine XR; Study D1448C00004 (monotherapy) was not. Studies D1448C00006 and D1448C00007 were significant in favour of adjunct quetiapine XR. Time from randomisation to depressed event (Study D1448C00005) significantly increased with quetiapine XR; HR (95% CI): 0.34(0.25, 0.46); p< 0.001; number of depressed events: 55, quetiapine XR; 132, placebo. Safety findings were consistent with the known tolerability profile of quetiapine.
Quetiapine XR consistently demonstrated antidepressant efficacy, with 6/7 acute studies positive in favour of quetiapine XR (monotherapy or adjunct). Quetiapine XR maintenance therapy significantly reduced risk of a depressed event, demonstrating relapse prevention. AstraZeneca funded
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.
To evaluate risperidone long-acting injectable (RLAI) versus placebo in prevention of mood episodes in adults with bipolar I disorder.
A 12-week open-label period with RLAI (N=585) was followed by an 18-month randomized, double-blind period with RLAI (25, 37.5 or 50 mg/2 weeks; N=137) or placebo (N=140); a third group (N=138) was randomized to olanzapine for reference and exploratory comparisons. Primary efficacy endpoint: time to relapse of any mood episode for risperidone LAI vs. placebo in the double-blind period (Kaplan-Meier analysis). Relapse was defined by criteria including DSM diagnosis, further treatment, hospitalisation, or Clinical Global Impression score ≥4 combined with YMRS or MADRS >12.
Dosing was fixed during the double-blind period at patients’ final open-label dose (25 mg, 66%; 37.5 mg, 31%; 50 mg, 4%). Time to recurrence (any mood episode) was longer with RLAI versus placebo (log-rank test stratified by region and patient type, p=0.062; stratified by region only, p=0.032); the difference was significant for time to recurrence of elevated mood episodes (p=0.005) but not depressive episodes (p=0.587). Discontinuations due to adverse events (AEs) occurred in 2% of patients in the open-label period, and 4% and 1% in the RLAI and placebo groups, respectively, in the double-blind period. The most frequently reported AE in the open-label period was insomnia (15%). During double-blind treatment, the most frequently reported AEs with RLAI were weight increased (24%; placebo, 9%) and insomnia (16%; placebo, 17%).
Type of recurrence
Type of episode, n (%)
Risperidone LAI (N=135)
All mood episodes
Elevated mood episode
RLAI significantly delayed time to relapse of elevated mood episodes and was well tolerated.
To evaluate the efficacy and tolerability of once-daily quetiapine XR (extended release) monotherapy in patients with MDD (unipolar depression) compared with placebo.
8-week (6-week active treatment, randomised phase; 2-week post-treatment drug-discontinuation/tapering phase), multicentre, double-blind, parallel-group, placebo- and active-controlled study (D1448C00002). 612 patients were randomised to quetiapine XR 150mg/day (n=152), 300mg/day (n=152), duloxetine 60mg/day (n=151) and placebo (n=157). Primary endpoint: baseline to Week 6 change in MADRS total score. Secondary variables included: baseline to Week 6 change in HAM-D total and Item 1 (depressed mood) scores. Safety assessments included AE reporting.
Mean MADRS total score (overall baseline mean, 30.15) was significantly reduced at Week 6 by quetiapine XR 150mg/day, 300mg/day and duloxetine versus placebo (−14.81, −15.29, −14.64, −11.18, respectively; p≤0.001).
At Week 6, mean HAM-D total scores (overall baseline mean, 25.25) were significantly reduced versus placebo (−10.26) by quetiapine XR 150mg/day, 300mg/day (−13.12, −14.02, respectively, p≤0.001) and duloxetine (−12.37, p<0.05). Mean HAM-D item 1 scores (overall baseline mean, 3.03) were significantly reduced versus placebo (−1.07) by quetiapine XR 150mg/day, 300mg/day (−1.49, −1.56, respectively, p≤0.001) and duloxetine (−1.53, p<0.001).
Incidence of serious AEs were low (≤2%) in all groups. Most common AEs (>10%) were dry mouth, sedation, somnolence, dizziness, headache and nausea with quetiapine; dizziness and headache with placebo; and dry mouth, sedation, somnolence, dizziness, headache, constipation, nausea, diarrhoea and insomnia with duloxetine. Most AEs were mild-to-moderate in intensity.
Quetiapine XR monotherapy at 150 and 300mg/day was effective and well tolerated in the treatment of patients with MDD.
Few studies have been conducted looking at clinical features associated to treatment resistant depression (TRD) defined as failure to at least two consecutive antidepressant trials. The objective of this study was to identify clinical and demographic factors associated to TRD in a large sample of depressed patients who failed to reach response or remission after at least two consecutive adequate treatments.
A total of 702 patients with unipolar major depression were included in the analysis. 346 patients were considered as non resistant. The remaining 356 patients were considered as resistant with a HAM-D-17 score remaining ≥ 17 after 2 consecutive adequate trials. Cox regression models were used to examine the association between individual clinical variables and TRD.
Eleven variables were found to be associated with TRD. Anxiety comorbidity (p<0.001, OR=2.6), comorbid panic disorder (p<0.001, OR=2.6) and social phobia (p<0.008, OR=2.1), personality disorder (p<0.049, OR=1.7), suicidal risk (p<0.001, OR=2.2), severity (p<0.001, OR=1.7), melancholia (p<0.018, OR=1.5), a number of hospitalizations > 1 (p<0.003, OR=1.6), recurrent episodes (p<0.009, OR=1.5), early age of onset (p<0.009, OR=2.0) and non response to the first antidepressant received lifetime (p<0.019, OR=1.6).
Our findings provide a set of eleven relevant clinical variables associated to TRD which can be explored at the clinical level. The statistical model used in this analysis allowed for a hierarchy of these variables (based on the OR) showing that comorbid anxiety disorder is the most powerful clinical factor associated to TRD.
Suicidal behaviour runs in families and the existence of genetic vulnerability to suicidality is well-established. Mental disorders, especially depression, are present in more of 90% of suicides. The incidence of treatment emergent suicidal ideation in major depression (MDD) varies from 4% to 20%, depending on the definition of suicidal ideation and sample characteristics.
In the present study, we further elucidated the impact of depression candidate genes in treatment emergent suicidal ideation in MDD. One hundred-seventy MDD patients were collected in the context of a resistant depression study and treated with antidepressants at adequate doses for at least 4 weeks. MDD subjects were genotyped for SNPs within the COMT gene, BDNF, DTNBP1, 5HT1A, 5HT2A, GNB3, GRIK4, PTGS1, PTGS2, CREB, and cytochrome P450 CYP1A2, CYP2C9, CYP2C19 and CYP2D6 gene. Response, remission and treatment resistance, as well as suicidality information derived from Mini International Neuropsychiatric Interview (MINI) and Hamilton Rating Scale for Depression (HAM-D) were recorded.
A quantitative and measure of suicidal behaviour was defined using the Hamilton rating scale (score 0 to 4) and the MINI-item (yes/no) on suicidality in a large cohort of depression cases. In addition, we tested for association with ‘serious suicidal attempts’ corresponding to a HAMD score of 4 (discrete trait analyses). Results of this candidate gene approach in treatment emergent suicidal ideation in MDD will be presented and discussed.
Those with psychiatric disorders have long suffered from prejudice, their illnesses and suffering often trivialised by journalists in their columns and by government agencies. Tougher regulations appear to be imposed on the licensing of new treatments in psychiatry and harsher criteria for their reimbursement by government agencies compared with other therapeutic areas despite clear evidence that these disorders are associated with the highest levels of suffering and disability according to the WHO.
For a new treatment for a psychiatric disorder to be licensed in the EU more studies meeting stricter conditions are required than is the case with equivalent licensing authorities such as the FDA. For example, in the EU a comparator arm is required in clinical trials in addition to the more scientific placebo control. There is no adequate justification for this demand which appears to confound the demonstration of efficacy and safety versus placebo with pricing issues. A further hurdle in the EU is the requirement that long term efficacy compared to placebo is established before a treatment can be licensed which causes delay in bringing the drug to the market and adds to the cost of development. The process might be eased if access to specialist advice by the licensing agencies, strictly limited in the CHMP in contrast to other agencies, were improved.
Difficulties in the licensing process and delays following the granting of a licence inevitably have a negative effect on the viability of developing new treatments. Even when a licence is granted transparency/pricing commissions are the source of serious delays before clinicians are allowed to prescribe the treatment. Delays in allowing access to treatment by EU citizens can be so long that medications become available only after they have come off patent. These issues have led some pharmaceutical companies to withdraw from the development of treatments in psychiatry for the EU market and to close their neuroscience laboratories. The resulting loss of expertise in neuroscience will not be easily reversed. Psychiatric patients in the EU will find that the options for new treatments of their serious disorders are declining compared with other countries.
To evaluate the safety and efficacy of pregabalin in relieving the symptoms of GAD in patients ≥65 years of age.
This was a multicenter, randomized, flexible-dose, placebo-controlled, double-blind, parallel-group trial of pregabalin in the treatment of GAD. Randomization was 2:1, pregabalin:placebo. Patients underwent an 8-week double-blind, flexible-dosage (150-600 mg/d) treatment phase, including a 1-week dose-escalation period (50 mg/d to 150 mg/d). The primary efficacy assessment was change from baseline to endpoint-LOCF in HAM-A total score. Additionally, change from baseline to week 8 (observed cases) in HAM-A psychic and somatic factors was evaluated.
Mean age at GAD onset was 56 years; 77% of patients were women; mean age at enrollment was 72 years; mean duration of GAD was 17 years. Mean change from baseline in HAM-A total score was –12.84 (n=177) for the pregabalin group and –10.7 (n=96) for the placebo group (P=.0437). At week 8, patients treated with pregabalin had significant improvement in both the HAM-A psychic (–7.8 vs –6.3, P=.0111) and somatic (–6.6 vs –5.4, P=.0248) factors. The most common adverse events (AEs) among pregabalin-treated patients were dizziness (20.3%), somnolence (13.0%), headache (10.2%), and nausea (9.0%). Most AEs were mild-to-moderate and self-limiting. Discontinuation rates due to AEs were 10.7% and 9.4% in the pregabalin and placebo groups, respectively.
Pregabalin was effective in reducing the symptoms of GAD in patients aged 65 years and older, and it was safe and well tolerated in this population.
To evaluate efficacy and tolerability of quetiapine XR monotherapy in patients with MDD.
Data were analysed from two 6-week, multicentre, double-blind, placebo-controlled studies (D1448C00001, D1448C00002), prospectively designed to be pooled. Outpatients received quetiapine XR 150mg/day (n=315), 300mg/day (n=323), placebo (n=330). Primary outcome: change at Week 6 in MADRS total scores. Other assessments: MADRS individual item scores, HAM-A total scores, MADRS response and remission; AE reporting.
Quetiapine XR 150mg/day and 300mg/day reduced MADRS total scores at Week 6 (-14.7 and -14.7; p< 0.001) versus placebo (-11.1); significant reductions were also seen at Week 1 (p< 0.001).
Subgroup analyses showed the therapeutic effect of quetiapine XR was neither limited to nor driven by factors such as gender, age or depression severity.
Quetiapine XR demonstrated consistent improvements in MADRS items: both doses significantly improved 8/10 items at Week 6 versus placebo. At Week 6, MADRS response (≥50% decrease in total score) was 52.7% (p< 0.001), 49.5% (p< 0.001) versus 33.0%; MADRS remission (total score ≤10) was 33.7% (p< 0.01), 34.7% (p< 0.01) versus 24.2% 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 (-4.6 [p< 0.01], -4.7 [p< 0.01], -3.6) and Week 6 (-8.1 [p< 0.001], -7.9 [p< 0.001], -6.2). Common AEs (≥10%) were dry mouth, sedation, somnolence, dizziness, headache and nausea with quetiapine XR.
In patients with MDD, quetiapine XR monotherapy improved a broad range of depressive symptoms, with improvements seen from Week 1. Quetiapine XR was generally well tolerated.
We evaluated the efficacy of eszopiclone (ESZ) and concurrent escitalopram oxalate (EO) in patients with insomnia and co-morbid GAD.
Patients meeting DSM-IV-TR criteria for GAD and insomnia received 10 weeks of EO 10mg and co-therapy with ESZ 3mg or placebo (PBO) for 8 weeks. For the last 2 weeks, ESZ was replaced with single-blind PBO to evaluate discontinuation effects. Sleep, daytime functioning and anxiety measures were captured during the study.
ESZ+EO improved sleep and daytime functioning at each week and the double-blind period average (p<0.05). At Week 8, significantly more ESZ+EO patients had no clinically meaningful insomnia based on ISI</=7. Significant improvements with ESZ+EO (relative to PBO+EO) were observed in HAM-A total scores each week, and Weeks 4-10 excluding the insomnia item. ESZ+EO was significantly better at every timepoint on CGI-I (p<0.02); CGI-S was not different between treatments after Week 1. Median time to anxiolytic response was reduced with ESZ+EO based on HAM-A and CGI-I. HAM-A response and remission rates at Week 8 were higher with ESZ+EO, and HAM-D17 scores were improved at all timepoints (p<0.004). After eszopiclone discontinuation, there was no evidence of rebound insomnia, and no treatment differences in sleep or daytime function. Significant treatment differences in anxiety and mood were maintained after discontinuation.
In this study, ESZ+EO was well tolerated and associated with improved sleep and daytime function without evidence of tolerance. Improvements in anxiety and mood were observed with ESZ+EO.
Support for this study provided by Sepracor Inc., Marlborough, MA.
Major Depressive Disorder (MDD) and generalized anxiety disorder (GAD) can coexist and patients may have insomnia marked by difficulty falling and/or staying asleep and potentially reduced quality of life (QoL). Eszopiclone has been shown to improve sleep in patients with insomnia comorbid with MDD or GAD. This analysis examined the effects of eszopiclone co-therapy on the HAM-D17 in these two patient populations.
Patients with insomnia comorbid with MDD and baseline HAM-D17>14 (excluding insomnia items; n=545) received morning fluoxetine and were randomized to nightly eszopiclone 3mg or placebo for 8 weeks. Patients with insomnia comorbid with GAD and screening MADRS≤20 (n=593) received daily escitalopram oxalate and were randomized to nightly eszopiclone 3mg or placebo for 8 weeks. Clinician-administered HAM-D17 was evaluated at baseline and Weeks 4 and 8 in both studies.
Baseline HAM-D17 median scores were 22 and 15 in the MDD and GAD populations, respectively. Change from baseline HAM-D17 scores were significantly improved (p<0.02) with eszopiclone co-therapy at Weeks 4 (−10.0±7.6) and 8 (−13.6±7.7) relative to fluoxetine monotherapy (−8.4±6.8 and –11.5±7.1) in the MDD population. Similarly, change from baseline HAM-D17 scores in the GAD population were significantly improved (p<0.002) with eszopiclone co-therapy at Weeks 4 and 8 (−5.8±4.9 and –6.7±5.4) relative to escitalopram monotherapy (−4.3±5.1 and –5.4±5.6).
Treatment of insomnia with eszopiclone was associated with significant improvements in HAM-D17 scores relative to fluoxetine or escitalopram monotherapy in patients with insomnia comorbid with MDD or GAD, even after removal of insomnia items from the scale.
Short-term clinical trials have demonstrated the efficacy and safety of pregabalin for the treatment of generalized anxiety disorder (GAD).
Objectives and aims
This study examines the long-term safety and efficacy of pregabalin (150–600 mg/day) in patients diagnosed with GAD.
Patients completing two short-term, double-blind efficacy trials of pregabalin for the treatment of GAD (n = 329) were enrolled in this 1-year, non-randomized, open-label safety extension study. Disease severity was assessed at baseline, week 27, and week 52 using the Clinical Global Impression of Severity (CGI-S) score (7-point scale). Patients were characterized as “responders” or “non-responders” based on CGI-S scores of ≤2 an >2, respectively. Safety and tolerability were also assessed.
Patients were predominately white (98.5%), female, (67.8%) and had a mean (SD) age of 55 (17) years. Mean (SD) CGI-S scores at baseline (n = 329) and endpoint (n = 319) were 3.55 (1.07) and 2.58 (1.18), respectively, for all patients. One hundred fifty-four (46.8%) patients were characterized as CGI-S responders at endpoint compared to 50 (15.2%) patients at baseline. The number of patients shifting from a non-responder to a responder was 122 (37.1%). Conversely, the number of patients shifting from a responder to a non-responder was 14 (4.3%).
Pregabalin's anxiolytic efficacy was maintained over the 1 year study period. The severity of anxiety symptoms decreased with extended pregabalin treatment, evident by decreased CGI-S score and an increased number of CGI-S responders at endpoint compared to baseline.This study was funded by Pfizer Inc.
Many association studies have reported associations between the brain-derived neurotrophic factor (BDNF) gene and psychiatric disorders including major depression (MDD). the BDNF gene has further been associated with suicidal behaviour, as well as with treatment response, although with conflicting results. in the present study, we further elucidate the impact of BDNF in MDD patients with suicide risk and/or a personal history of suicide attempts.
Two hundred fifty MDD patients were collected in the context of a European multicentre resistant depression study and treated with antidepressants at adequate doses for at least 4 weeks. Suicidality was assessed using Mini International Neuropsychiatric Interview (MINI) and Hamilton Rating Scale for Depression (HAM-D). Treatment response was defined as HAM-D ≤ 17 and remission as HAM-D ≤ 7 after 4 weeks of treatment with antidepressants at adequate dose. Genotyping was performed for eight SNPs within the BDNF gene.
With regard to suicide risk and personal history of suicide attempts, neither single marker nor haplotypic association was found with any SNP after multiple testing correction. However, in gender-specific analyses, we found haplotypic association with suicide risk in males, but not in females (rs925946-rs10501087-rs6265, rs10501087-rs6265-rs122733). the only single-marker association with suicide risk in males (rs908867) did not resist multiple testing correction. No significant associations were found in gender-specific analyses with regard to a personal history of suicide attempts.
In conclusion, we found two BDNF haplotypes significantly associated with suicide risk in male MDD patients. However, replication in larger well-defined cohorts is required to dissect this further.
The multicenter, cross-sectional survey summarizes the current prescription patterns of psychopharmacological medications in patients with major depressive disorder (MDD) treated in European university psychiatric centers.
The study included a total of 1181 MDD patients who were recruited in 9 academic sites across 8 European countries. Socio-demographic, clinical, and psychopharmacological characteristics were collected within a detailed clinical interview and the current depressive symptom severity was measured by the Montgomery and Åsberg Depression Rating Scale (MADRS). Symptom reduction during the present MDD episode was analyzed by calculating retrospective MADRS scores. Descriptive statistics, analyses of variance (ANOVAs), and Spearman correlation analyses were performed to examine the impact of various features on the applied pharmacological strategies.
Regarding first-line antidepressant medication, the most frequently prescribed drug classes were selective serotonin reuptake inhibitors (SSRIs) (53.4%), serotonin-norepinephrine reuptake inhibitors (SNRIs) (23.6%), noradrenergic and specific serotonergic antidepressants (NaSSAs) (8.2%), tricyclic antidepressants (TCA) (5.1%), and the melatonergic antidepressant agomelatine (5.0%). The most commonly used individual antidepressants were escitalopram (18.4%), venlafaxine (15.2%), sertraline (12.9%), paroxetine (9.1%), mirtazapine (8.2%), duloxetine (7.0%), and fluoxetine (6.5%). Among the patients, 59.4% were treated with polypsychopharmaceutical medications (mean: 2 drugs) and for the number of individual drugs, we found a significant correlation with the present MADRS total score and the MADRS total score change during the current depressive episode.
Consistent with surveys investigating primarily municipal psychiatric treatment centers, we could replicate the observation that SSRIs are the most commonly used antidepressants in MDD for the first time for European university centers.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Major depressive disorder (MDD) is the second leading cause of disability in China.
To analyze functioning during the course of treating MDD in China, Taiwan and Hong Kong.
To study the influence of pain and clinical remission on functioning.
This was a post-hoc analysis of a 6-month, prospective, observational study (n = 909) with 422 patients enrolled from China (n = 205; 48.6%), Taiwan (n = 199; 47.2%) and Hong Kong (n = 18; 4.2%). Functioning was measured with the Sheehan Disability Scale (SDS), pain with the Somatic Symptom Inventory, and severity of depression with the Quick Inventory of Depressive Symptomatology-Self Report 16 (QIDS). Patients were classified as having no pain, persistent pain (pain at any visit) or remitted pain (pain only at baseline). A mixed model with repeated measures was fitted to analyze the relationship between pain and functioning.
At baseline, 40% of the patients had painful physical symptoms. Patients with pain had a higher QIDS and lower SDS (P < 0.05) at baseline. At 6 months, patients with persistent pain had lower functioning (P < 0.05). The regression model confirmed that clinical remission was associated with higher functioning at endpoint and that patients with persistent pain had lower functioning at endpoint when compared with the no pain group.
Patients presenting with pain symptoms had lower functioning at baseline. At 6 months, pain persistence was associated with significantly lower functioning as measured by the SDS. Clinical remission was associated with better functional outcomes. The course of pain was related to the likelihood of achieving remission.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.