Although numerous effective antidepressant (AD) strategies are available for the treatment of major depressive disorder (MDD), many patients do not achieve satisfactory treatment response.

The aims of the present European, cross-sectional, multicenter, naturalistic study were (1) to determine the proportion of patients suffering from primary MDD who received additional psychotherapy to their ongoing psychopharmacotherapy and (2) to identify the associated socio-demographic and clinical patterns.

Patients receiving both treatments were compared to those lacking concomitant additional psychotherapy that was manual-driven psychotherapy (MDP) in all cases.

While 68.8% of a total of 1279 MDD patients received exclusively psychopharmacotherapy, 31.2% underwent a psychopharmacotherapy-MDP combination. The latter patient population was rather younger, higher educated, employed, exhibited an earlier mean age of MDD onset, lower severity of current depressive symptoms with lower odds of suicidality and higher rates of melancholic features, and comorbid asthma and migraine, and was generally treated with lower daily doses of their first-line ADs. Whereas agomelatine was more commonly dispensed in these patients, selective serotonin reuptake inhibitors were more often prescribed in MDD patients lacking additional MDP. No significant between-group differences were detected in terms of treatment outcome.

The fact that the employment of additional MDP was not related to better treatment outcome in MDD represents our major and clinically most relevant finding. Generally, MDP was employed in a minority of our patients who experienced rather beneficial socio-demographic and clinical characteristics. This might reflect an inferior accessibility of these psychotherapeutic techniques for patients who are more severely ill and less socio-economically privileged.

References Bartova L, Fugger G, Dold M, Swoboda MMM, Zohar J, Mendlewicz J, Souery D, Montgomery S, Fabbri C, Serretti A, Kasper S. Combining psychopharmacotherapy and psychotherapy is not associated with better treatment outcome in major depressive disor

Adverse swallowing outcomes following head and neck squamous cell carcinoma treatment in the context of late-onset post-radiotherapy changes can occur more than five years post-treatment.

A retrospective study was conducted utilising patient records from March 2013 to April 2015. Patients were categorised into ‘swallow dysfunction’ and ‘normal swallow’ groups. Quality of life was investigated using the MD Anderson Dysphagia Inventory and EuroQol questionnaires.

Swallow dysfunction was seen in 77 (51 per cent) of 152 patients. Twenty-eight patients (36 per cent) in the swallow dysfunction group reported symptoms in year five. Swallow dysfunction was associated with stage IV head and neck squamous cell carcinoma (p < 0.001) and radiotherapy (p < 0.001). MD Anderson Dysphagia Inventory global scores showed significant differences between swallow dysfunction and normal swallow groups (p = 0.01), and radiotherapy and surgery groups (p = 0.03), but there were no significant differences between these groups in terms of MD Anderson Dysphagia Inventory composite or EuroQol five-dimensions instrument scores.

One-third of head and neck squamous cell carcinoma survivors with swallow dysfunction still show symptoms at more than five years post-surgery, a point at which they are typically discharged.

This study aimed to assess the current literature on the safety and impact of in-office biopsy on cancer waiting times as well as review evidence regarding cost-efficacy and patient satisfaction.

A search of Cinahl, Cochrane Library, Embase, Medline, Prospero, PubMed and Web of Science was conducted for papers relevant to this study. Included articles were quality assessed and critically appraised.

Of 19 741 identified studies, 22 articles were included. Lower costs were consistently reported for in-office biopsy compared with operating room biopsy. Four complications requiring intervention were documented. In-office biopsy is highly tolerated, with a procedure abandonment rate of less than 1 per cent. When compared with operating room biopsy, it is associated with significantly reduced time-to-diagnosis and time-to-treatment initiation. It is linked to improved overall three-year survival.

In-office biopsy is a safe procedure that may help certain patients avoid general anaesthetic. It was shown to significantly reduce time-to-diagnosis and time-to-treatment initiation when compared with operating room biopsy. This may have important implications for oncological outcomes. In-office biopsy requires fewer resources and is likely to be cost-saving five-years following introduction. With high rates of sensitivity and specificity, in-office biopsy should be considered as the first-line procedure to achieve tissue diagnosis.

Pharmaceutical treatment and psychotherapy constitute the most common treatment methods for depression and anxiety. Physical training has been shown to have comparable effect to cognitive behavioral therapy in treatment of mild to moderate depression and anxiety. Physically active individuals also show lower risks to develop depression and relapse in depression.

The objectives are to evaluate how physical activity can affect depressive and anxiety symptoms, by examining biomarkers in the blood and from the gut and also by measuring cognitive functions. Hopefully, this can lead to new treatment strategies for patients with depression and anxiety.

102 patients are randomized to two groups and undergo 12 weeks intervention as add-on to standard outpatient psychiatric treatment. The first group will participate in physical training three times per week and the other group will receive relaxation therapy on a weekly basis. Daily activity intensity will be measured before and at the last week of intervention with an accelerometer. Blood and faeces sample collection, symptom grading by clinician together with self-rating scales and cognitive screening will be performed at baseline, week 12 and one year of follow-up. The cognitive screenings are performed digitally in cooperation with Mindmore.

The RCT is currently recruiting patients at the Department of Psychiatry of Örebro University Hospital.

The project aims to be holistic in its approach, combining the defining clinical psychiatric symptoms in patients who have both depression and anxiety with the finding and evaluation of new biomarkers from blood and gut to improve cognitive functions.

No significant relationships.

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.

AstraZeneca funded

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%).

Table 1.Type of recurrence

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.

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.