Introduction In ESCAPE-TRD esketamine nasal spray (ESK-NS) significantly increased the probability of achieving remission at Week (Wk) 8 and being relapse‑free through Wk32 after remission at Wk8 versus (vs) quetiapine extended release (Q-XR) in patients (pts) with treatment resistant depression (TRD) (Reif et al. DGPPN 2022; P-01-04). We report ESK-NS vs Q-XR effects on pt-reported health-related quality of life (HRQoL) over 32 wks. Objectives Evaluate pt-reported HRQoL using the generic 36-item Short-Form Health Survey version 2 (SF-36v2, 4-wk recall, 2009 US population norms) in ESCAPE-TRD. Methods ESCAPE‑TRD (NCT04338321) was a randomised phase IIIb trial comparing the efficacy of ESK-NS vs Q-XR, both alongside an ongoing selective serotonin/serotonin-norepinephrine reuptake inhibitor, in pts with TRD. SF-36v2 was assessed every 4 wks (on-treatment and retrieved dropout visits). Domain scores and change from baseline (CfB) were analysed using a mixed model for repeated measures (MMRM; observed cases) adjusted for age, prior treatment failures, baseline score. Higher scores indicate better HRQoL. P values were not adjusted for multiple testing. Results 336 and 340 pts were randomised to ESK-NS and Q-XR. Baseline domain scores were below general population norms and lowest in Role Emotional, Mental Health and Social Functioning ( Figure 1A). All scores improved to Wk32 in both arms ( Figure 1B). At Wk4, CfB was significantly higher (better HRQoL) with ESK-NS vs Q-XR across domains (all p<0.01). At Wk8, CfB was significantly higher with ESK-NS vs Q-XR across all domains (p<0.05) except Bodily Pain and Role Physical. At Wk32, CfB was significantly higher with ESK-NS vs Q-XR for Mental Health (p=0.014), Role Emotional (p=0.001), Role Physical (p=0.046) and Social Functioning (p=0.006); a trend of numerical advantage was seen for all other domains ( Figure 2). Image: Image 2: Conclusions In addition to the superior clinical benefits provided by ESK-NS vs Q-XR in ESCAPE-TRD, pts receiving ESK-NS experienced significantly greater improvements in HRQoL vs Q-XR over 32 wks. Acknowledgements We thank the patients who participated. Study funding: Janssen, medical writing: Costello Medical, UK. Disclosure of Interest A. Young Grant / Research support from: Received grants from Janssen; independent research funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London; the views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health, Consultant of: Received consulting fees from Allegan, AstraZeneca, Bionomics, Eli Lilly, Janssen, Johnson & Johnson, LivaNova, Lundbeck, Servier, and Sumitomo Dainippon Pharma and Sunovion, Speakers bureau of: Received speaker’s honoraria from Allegan, AstraZeneca, Bionomics, Eli Lilly, Janssen, Johnson & Johnson, LivaNova, Lundbeck, Servier, and Sumitomo Dainippon Pharma and Sunovion, B. Baune Grant / Research support from: Received research grants from private industries or non-profit funds from AstraZeneca, Lundbeck, and Sanofi-Synthélabo; received research grants from the BMBF and BMG Germany, the DFG, Germany, the National Health and Medical Research Council, Australia, and Horizon Europe 2021; received research grants from the Fay Fuller Foundation, and James & Diana Ramsay Foundation, Adelaide, Consultant of: Received consulting fees for roles with the National Health and Medical Research Council, Australia; received honoraria from Angelini, AstraZeneca, Biogen, BMS, Boehringer Ingelheim, Johnson & Johnson, LivaNova, Lundbeck, Otsuka, Pfizer, Roche, Servier, Sumitomo Dainippon Pharma and Sunovion, and Wyeth; served on advisory boards for Biogen, Boehringer-Ingelheim, Janssen-Cilag, LivaNova, Lundbeck, Novartis, and Otsuka, N. Cardoner Grant / Research support from: Received research grants from the Ministry of Health, Ministry of Science and Innovation (CIBERSAM), and the Strategic Plan for Research and Innovation in Health (PERIS) for the period 2016–2020, as well as from Marato TV3 and Recercaixa, Consultant of: Served on advisory boards for Angelini, Esteve, Janssen, Lundbeck, Novartis, Pfizer and Viatris, Speakers bureau of: Received speaker’s honoraria from Angelini, Esteve, Janssen, Lundbeck, Novartis, Pfizer and Viatris, R. Frey Grant / Research support from: Received travel fees from Janssen and LivaNova; received grants or contracts from Alkermes (Principal Investigator), Janssen (Principal Investigator), LivaNova (Principal Investigator) and Medizinisch‑Wissenschaftlicher Fonds des Bürgermeisters von Wien (academic study), Consultant of: Received consulting fees from Boehringer Ingelheim and Janssen, Speakers bureau of: Received speaker’s honoraria from Janssen and Lundbeck, T. Ito Shareolder of: Johnson & Johnson, Employee of: Janssen, Y. Kambarov Employee of: Janssen, A. Lacerda Grant / Research support from: Received grants from Azidus, Biophytis, Boehringer-Ingelheim, Cellavita, Celltrion, CNPq, Eli Lilly, EOM, FAPESP, Genova, IQVIA, Janssen, Nordisk, Novartis, Novo, Parexel and PPD, Consultant of: Received consulting fees from Aché, Apsen, Biogen, Boehringer-Ingelheim, Cristalia, Daiichi, Eurofarma, Sankyo, EMS, Janssen, Libbs, LivaNova, Lundbeck, Sanofi and Torrent, Speakers bureau of: Received speaker’s honoraria from Aché, Apsen, Biogen, Boehringer-Ingelheim, Cristalia, Daiichi, Eurofarma, Sankyo, EMS, Janssen, Libbs, LivaNova, Lundbeck, Sanofi and Torrent, B. Rive Employee of: Janssen, C. von Holt Shareolder of: Johnson & Johnson, Employee of: Janssen, A. Oliveira-Maia Grant / Research support from: Received grants from Compass Pathways, Ltd., Janssen, and Schuhfried GmBH; investigator‑driven research funded by Fundação para Ciência e Tecnologia (PTDC/SAU-NUT/3507/2021; PTDC/MED-NEU/1552/2021; PTDC/MED‑NEU/31331/2017), Fundação para Ciência e Tecnologia and FEDER (PTDC/MED-NEU/30845/2017_LISBOA-01-0145-FEDER-030845; PTDC/MEC-PSQ/30302/2017_LISBOA-01-0145-FEDER-30302), the European Research Council (ERC-2020-STG-Grant 950357), the European Commission Horizon 2020 Research and Innovation program (H2020‑SC1‑ 2017‑CNECT‑2‑777167‑ΒΟUNCE; H2020‑SC1‑DTH‑2019‑875358‑FAITH), and the European Joint Programme in Rare Diseases (Joint Translational Call 2019) through Fundação para Ciência e Tecnologia (EJPRD/0001/2020), Consultant of: Received payment or honoraria from MSD (Portugal), Neurolite AG, and the European Monitoring Centre for Drugs and Drug Addiction; received support for attending meetings from Janssen (Portugal); participated in advisory boards for Angelini (Portugal) and Janssen (Portugal), Employee of: Vice-President of the Portuguese Society for Psychiatry and Mental Health; Head of the Psychiatry Working Group for the National Board of Medical Examination (GPNA) at the Portuguese Medical Association and Portuguese Ministry of Health

Introduction Treatment resistant depression (TRD) is estimated to affect 10–30% of patients with major depressive disorder (Al‑Harbi et al. Patient Prefer Adherence 2012; 6 369–88). Esketamine nasal spray (NS), in combination with a selective serotonin reuptake inhibitor (SSRI) or serotonin norepinephrine reuptake inhibitor (SNRI), increases remission and response rates in patients with TRD compared with placebo plus SSRI/SNRI (Popova et al. Am J Psychiatry 2019; 176 428–38). ESCAPE-TRD (NCT04338321) is the first randomised clinical trial to compare esketamine NS to quetiapine extended-release (XR), an antipsychotic augmentation therapy for patients with TRD. Objectives To explore the efficacy and safety of esketamine NS compared with quetiapine XR in TRD over 32 weeks (wks). Methods In the ESCAPE-TRD phase IIIb open-label, rater-blinded trial, patients were randomised 1:1 to esketamine NS (56/84 mg; twice per wk, weekly or every 2 wks) or quetiapine XR (150–300 mg daily) both in combination with an ongoing SSRI/SNRI. Remission (Montgomery-Åsberg Depression Rating Scale [MADRS] total score of ≤10) and response (≥50% improvement in MADRS total score from baseline or MADRS≤10) rates were analysed over time using last observation carried forward. MADRS change from baseline was analysed using Mixed Models for Repeated Measures (MMRM). The most common adverse events (AEs) leading to discontinuation are reported for patients who received ≥1 dose of study medication. Results At baseline, 336 patients were randomised to esketamine NS and 340 to quetiapine XR. A significantly higher percentage of patients in the esketamine NS group achieved remission (at each visit from Wk6 [p=0.008] onward) and response (at each visit from Day 15 [p<0.001] onward) versus patients treated with quetiapine XR. Esketamine NS significantly improved MADRS score compared to quetiapine XR at each visit from Day 8 onwards, with an average difference over time in the least squares means total MADRS score change from baseline of -2.4 (Figure). The most common AEs leading to treatment discontinuation for esketamine NS were dizziness (n=2, 0.6%), dissociation (n=2, 0.6%) and vomiting (n=2, 0.6%), and for quetiapine XR were sedation (n=7, 2.1%), weight increased (n=6, 1.8%) and somnolence (n=5, 1.5%). Image: Conclusions Esketamine NS increased the percentage of patients achieving response and remission and improved MADRS total score over time compared with quetiapine XR. Rates of discontinuation arising from the most common AEs were generally lower with esketamine NS than quetiapine XR. Acknowledgements We thank participating patients and all who assisted with the study. This study was funded by Janssen; medical writing support was provided by Carolyn Walsh, PhD, Costello Medical, UK. Disclosure of InterestA. Reif Grant / Research support from: Medice, Consultant of: National Care Guidelines (NVL, S3) on major depression, bipolar disorder, ADHD and suicidal behaviour (aided in developing guidelines); board member of DGBS, DGPPN, ECNP and German Depression Foundation, Speakers bureau of: (and participated in advisory boards over the last 3 years) for Cyclerion, Janssen, Medice, SAGE/Biogen and Shire/Takeda; received speaker’s honoraria from Das Fortbildungskolleg; , A. E. Anıl Yağcıoğlu Grant / Research support from: Participated as an investigator for Janssen, Speakers bureau of: (and participated in advisory boards over the last 3 years) for Janssen and Abdi İbrahim Otsuka, A. Luts Speakers bureau of: (or participated in advisory boards for or participated as an investigator) for Janssen-Cilag, Asarina Pharma, Bristol Meyer Squibb, Dr August Wolff GmbH & Co, Eli Lilly, Lundbeck, Pfizer, Allergan, Sunovion and Regeneron., T. Messer Consultant of: National Care Guidelines (NVL, S3) on major depression (aided in developing guidelines), Speakers bureau of: (and participated in advisory boards) for Janssen-Cilag and Otsuka/Lundbeck, R. Nielsen Consultant of: Board member of DSAL and IGSLi, Speakers bureau of: (or participated in advisory boards, received research funds or participated as investigator over the last 3 years) for Boehringer Ingelheim, Compass Pharmaceuticals, Janssen-Cilag, Lundbeck, Otsuka, Sage and Teva Pharmaceuticals, J. Buyze Employee of: Janssen, T. Ito Employee of: Janssen, Y. Kambarov Employee of: Janssen, S. Mulhern Haughey Employee of: Janssen, B. Rive Employee of: Janssen, I. Usankova Employee of: Janssen, C. von Holt Employee of: Janssen, Y. Godinov Employee of: Janssen

Aims For patients with depression, the likelihood of remission decreases with each subsequent treatment failure. Per European Medicines Agency guidance, treatment resistant depression (TRD) is defined as nonresponse to ≥2 consecutive treatments at adequate dosage and duration in the current depressive episode. In ESCAPE-TRD (NCT04338321), esketamine nasal spray (NS) increased the probability of achieving remission and remaining relapsefree, compared with quetiapine extended release (QXR) in patients with TRD. Here, we report the efficacy of esketamine NS vs QXR in patient subgroups with 2 or ≥3 consecutive prior treatment failures (PTFs). Methods ESCAPETRD was a phase IIIb trial comparing the efficacy of esketamine NS with QXR in patients with TRD. Patients (N = 676) were randomised 1:1 to esketamine NS (n = 336; 56/84 mg; twice weekly, weekly, or every 2 weeks [wks]) or QXR (n = 340; 150–300 mg daily, both in combination with an ongoing selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor. Randomisation was stratified by age (18-64 years; 65–74 years) and PTFs (2; ≥3). The primary endpoint of remission (Montgomery-Åsberg Depression Rating Scale total score ≤10) at Wk8 and the secondary endpoint of remaining relapse-free through Wk32 after remission at Wk8, were analysed in PTF patient subgroups and compared between study arms, with treatment discontinuation considered as a negative outcome. The effect on time to remission was assessed using hazard ratios (HR) from a Cox regression model. Results Of the randomised patients, 415 (61.4%; esketamine NS: 204, QXR: 211) had experienced 2 PTFs and 261 (38.6%; esketamine NS: 132, QXR: 129) had experienced ≥3. Of patients with 2 PTFs, 54/204 (26.5%) esketamine NS-treated patients and 46/211 (21.8%) Q-XR-treated patients achieved remission at Wk8 (p = 0.267). Of patients with ≥3 PTFs, 37/132 (28.0%) and 14/129 (10.9%) patients achieved remission at Wk8 in esketamine NS and Q-XR arms, respectively (p < 0.001). Of patients with 2 and ≥3 PTFs, 49/204 (24.0%) and 24/132 (18.2%) of esketamine NS-treated patients and 38/211 (18.0%) and 10/129 (7.8%) of Q-XR-treated patients achieved remission at Wk8 without relapse to Wk32 (p = 0.133 and p = 0.013), respectively. Esketamine NS significantly improved time to remission, with a greater effect in the ≥3 PTF subgroup (2 PTFs: HR = 1.547 [95% confidence interval (CI) 1.210–1.976]; p < 0.001 vs ≥3 PTFs: HR = 2.066 [95% CI 1.469–2.907]; p < 0.001). Conclusion Esketamine NS demonstrated a significantly superior remission rate versus QXR at Wk8 in patients with ≥3 PTFs, and significantly shorter time to remission versus Q-XR in both subgroups.

Treatment resistant depression (TRD) affects 10–30% of patients with major depressive disorder; most patients do not respond to real-world treatments (RWT).1 Esketamine nasal spray (NS), in combination with a selective serotonin or serotonin-norepinephrine reuptake inhibitor (SSRI/SNRI), was recently approved for treatment of TRD. Esketamine NS has demonstrated significant benefit on response and remission versus RWT strategies;2 benefit on daily function remains to be established. An indirect treatment comparison (ITC) study (ICEBERG) was performed using data from two studies of patients with TRD: SUSTAIN-2 (an open-label study of esketamine NS plus SSRI/SNRI) and the European Observational TRD cohort (EOTC; a prospective, non-interventional study in real-world practice). Both studies defined TRD as failure of ≥2 treatments in the current depressive episode. Functional remission was defined as a total Sheehan Disability Scale (SDS) score ≤6, at Month 6. Analyses were conducted using propensity score re-weighting based on 17 covariates. Baseline characteristics were similar across studies, including mean (standard deviation) SDS: 22.5 (5.0) for patients receiving esketamine NS (n=512) and 22.0 (5.5) for RWT (n=226). At Month 6, the probability of functional remission was 25.6% (95% confidence interval [CI] 21.8–29.4) in patients receiving esketamine NS and the adjusted probability for RWT was 12.0% (95% CI 7.3–16.6). The risk difference favoured esketamine NS over RWT for 6-month functional remission (0.136 [95% CI 0.076–0.196], p<0.0001); the number needed to treat was 8 (95% CI 6–14). Results were similar across sensitivity analyses and using alternative re-weighting comparisons. This ITC suggests esketamine NS has a significant functional benefit over 6 months versus RWT for patients with TRD. Following adjustment for multiple covariates, consistent results demonstrate robustness of the comparison.

This post hoc study assessed the evidence-base for esketamine nasal spray for management of treatment-resistant depression (TRD) using number needed to treat (NNT), number needed to harm (NNH), and likelihood to be helped or harmed (LHH).Data sources were four phase III randomized, double-blind studies including two positive studies (acute flexible-dose; maintenance) in patients with TRD. Key efficacy study outcomes: acute response (≥50% decrease from baseline on Montgomery–Asberg Depression Rating Scale [MADRS] total score), acute remission (MADRS scores ≤12). NNT, NNH were calculated for esketamine nasal spray+newly initiated oral antidepressant (esketamine+AD) vs. placebo+AD.In the pivotal acute flexible-dose study, MADRS response (63.4% vs. 49.5%) and remission (48.2% vs. 30.3%) at 4 weeks resulted in NNT of 8 and 6 for esketamine+AD vs. placebo+AD. NNH values <10 included dissociation (26.1% vs. 3.7%), vertigo (26.1% vs. 2.8%), nausea (26.1% vs. 6.4%), dizziness (20.9% vs. 4.6%), and dysgeusia (24.3% vs. 11.9%). Discontinuation rates due to adverse events (AE) (7.0% vs. 0.9%) yielded NNH=17. LHH comparing MADRS remission vs. discontinuation due to AE was 17 vs. 6. Maintenance use of esketamine+AD demonstrated NNT values<10 for relapse and/or maintenance of remission. In maintenance study, discontinuation due to AE (2.6% vs. 2.1%) yielded NNH=178 (non-significant).Only dichotomous outcomes were included.NNT<10 for efficacy outcomes suggests potential benefit of esketamine+AD for both acute and maintenance use. LHH was favorable: esketamine+AD was 3 times likely to result in acute remission vs. discontinuations due to AE.

The administration of multiple esketamine doses has shown efficacy for unipolar and bipolar treatment-resistant depression (TRD). Nevertheless, the probability of responding or not after each dose in the real-world remains unknown. This study aimed to estimate it throughout four doses of esketamine, administrated via subcutaneous (SC).We conducted a retrospective analysis of a case series of 70 patients with TRD who received treatment from the esketamine assistance program at Federal University of Sao Paulo, between April 2017 and December 2018. The SC injections were administrated weekly at a dose of 0.5–1.0 mg/kg, in conjunction with patients' psychotropic drugs. Response was defined as a decrease of at least 50% in the Montgomery-Åsberg Depression Rating Scale between baseline and 24 h after dose. We used hidden Markov modeling in order to estimate de probability of response after each esketamine injection.The probability of a patient that was a "non-responder" to become a "responder" following a SC injection of esketamine was 17.30% and the probability that this patient remains a "non-responder" was 82.70%. The probability of a patient that was a "responder" to remain as a "responder" was 95%.Patients with TRD who had not responded after the first dose of esketamine, still had a chance of responding after the subsequent dose administrated via SC.La administración de dosis múltiples de esketamina ha demostrado su eficacia para el tratamiento de la depresión unipolar y bipolar resistente al tratamiento (TRD). Sin embargo, sigue siendo una incógnita la probabilidad de responder o no tras cada dosis en el mundo real. El objetivo de este estudio fue calcular dicha probabilidad durante la administración vía subcutánea (SC) de cuatro dosis de esketamina.Realizamos un análisis retrospectivo de una serie de casos de 70 pacientes con TRD, que recibieron tratamiento a través del programa de asistencia con esketamina en la Universidad Federal University de Sao Paulo, entre abril de 2017 y diciembre de 2018. Las inyecciones SC se administraron semanalmente, a dosis de 0,5-1 mg/kg, junto con los medicamentos psicotrópicos de los pacientes. Se definió la respuesta como una reducción de al menos el 50% en la Escala de Calificación de la Depresión de Montgomery-Åsberg entre el valor basal y las 24 horas posteriores a la administración de la dosis. Utilizamos el modelo oculto de Markov para calcular la probabilidad de respuesta tras cada inyección de esketamina.La probabilidad de que un paciente que fuera «no respondedor» se convirtiera en «respondedor», tras una inyección SC de esketamina fue del 17,3%, y la probabilidad de que este paciente siguiera siendo «no respondedor» fue del 82,7%. La probabilidad de que un paciente que fuera «respondedor» lo siguiera siendo fue del 95%.Los pacientes con TRD que no han respondido a la primera dosis de esketamina, tienen probabilidad de respuesta tras la administración de las siguientes dosis por vía SC.

Background Caregiving in depression imposes a complex health and economic burden. Moreover, there is a paucity of studies examining the impact of caregiving for adult relatives with unipolar depression (CG-UD). This study assessed the burden among CG-UD in five western European (EUR5) countries (France, Germany, Italy, Spain and the United Kingdom) compared with caregivers of adults with other chronic comorbidities (CG-OD) and general non-caregiving (non-CG) population. Methods A retrospective observational study was conducted using the 2016 National Health and Wellness Survey (NHWS) in EUR5. Differences in humanistic burden (health status and health-related quality of life [HRQoL]) and economic burden (work productivity and activity impairments, health care resource utilization [HRU]) were assessed between CG-UD and CG-OD respondents. Caregiver-specific burden (caregiving responsibilities and caregiver reaction assessment [CRA]) was assessed between caregiver groups. Generalized linear models were used to compare between the groups on the outcomes after adjusting for potential confounders. Results Of the 77,418 survey respondents examined, 1380 identified as CG-UD, 6470 as CG-OD and 69,334 as non-CG. Compared to CG-OD and non-CG, CG-UD, reported significantly lower health status (e.g., EuroQoL-5 Dimensions-5 Levels [EQ-5D-5L]: CG-UD = 0.63, CG-OD = 0.67, and non-CG = 0.73, p < 0.001) and HRQoL (e.g., mental component score: CG-UD = 35.0, CG-OD = 37.8, and non-CG = 40.7, p < 0.001). Although effect sizes were small (d < 0.2), minimal clinically important differences (MCID) were apparent for HRQoL and health status. Increased economic-related burden was observed for work and activity impairment (e.g., absenteeism: CG-UD = 32.6%, CG-OD = 26.5%, and non-CG = 14.8%, p < 0.001) and HRU (e.g., healthcare provider [HCP; mean, past 6 months]: CG-UD = 10.5, CG-OD = 8.6, and non-CG = 6.8, p < 0.001). Caregiving-specific burden was associated with experiencing a greater lack of family support (CG-UD: 2.9 vs CG-OD: 2.8, p < 0.01), impact on finances (CG-UD: 3.0 vs CG-OD: 2.9, p = 0.036), and on the caregiver's schedule (CG-UD: 3.1 vs CG-OD: 3.0, p = 0.048). Conclusion Caregivers of persons with chronic disease experience an excess humanistic and economic burden compared to the general population, with a greater burden confronting caregiver for adults with depression. These findings illustrate the far-reaching burden of depression on both the patient and the relatives who care for them.

Treatment resistant depression (TRD), defined by failure to respond to ≥2 different antidepressants at adequate dose for adequate duration in the same major depressive episode (MDE), is associated with significant morbidity and mortality.1 Despite clear unmet need, few studies report treatment patterns and outcomes for TRD patients in standard clinical practice.2 This study aimed to examine disease burden and treatment outcomes with current standard of care among TRD patients in Europe. A prospective, multicentre, observational cohort study was conducted in adults with current TRD and Montgomery-Åsberg Depression Rating Scale (MADRS) score ≥20, initiating a new treatment for depression. Patient characteristics, medical history and treatment outcomes were collected from medical records, clinician-rated interviews and patient-reported questionnaires. The final analysis set included 411 patients. At baseline, patients scored highly for depression (mean MADRS score: 31.8) and functional impairment (mean Work Productivity and Activity Impairment of overall activity: 73.3%; mean Sheehan Disability Scale total score: 22.4, with 74.2% markedly/extremely functionally impaired). At baseline, 41.4% of new treatments combined ≥2 antidepressants and 40.4% involved ≥1 augmentation drug. By Month 6, 8.6% of patients had been hospitalised (mean: 18.4 total inpatient days/hospitalised patient); 75.2% of patients had ≥1 consultation with a psychiatrist/neurologist, (mean: 4.7 consultations/patient). At Month 6, 16.7% (51/306) of patients were in remission (MADRS score ≤10) and 9.8% (30/306) exhibited response without remission (MADRS score >10, improvement from baseline ≥50%). Among Month 6 responders, 51.7% had relapsed by Month 12. At Month 6, >70% of patients showed no response to standard of care and had high medical resource utilisation. More than half of Month 6 responders relapsed by Month 12. This highlights that, despite complex treatment regimens (i.e. augmentation and combination therapies), there are clear unmet needs in the treatment of TRD. REFERENCES

For patients with TBI, traditional methods such as clinical examination and imaging data are the primary references used for deciding whether to operate or not. Intracranial pressure (ICP) monitoring based on lateral ventricles or parenchymal pressure is a more direct reflection of ICP. However, the research on whether the outcome results of ICP monitoring are better than results based on clinical signs and imaging is sparse. Therefore, we compared treatment results for patients with TBI based on ICP monitoring and traditional methods.This retrospective study included patients with TBI admitted to our collaborative hospitals between January 1, 2012, and December 31, 2013. All patients enrolled were divided into a traditional methods group and ICP monitoring group. Follow-up treatment was determined by ICP monitoring value or traditional methods in the 2 groups. Propensity matching scores were used to ensure that baseline characteristics of patients in the 2 groups were consistent.A significant association was found between the initial ICP value and neurologic deterioration (odds ratio 1.24; P < 0.001), and nonlinear correlation achieved the best fit (R2 = 0.547). Both 6-month good recovery rate and favorable outcome rate were higher in the ICP monitoring group than the traditional methods group by propensity score analysis (P < 0.05).For patients with TBI with cerebral contusion volume >20 mL, both 6-month good recovery rate and favorable outcome rate were significantly higher in the ICP monitoring group than the traditional methods group.

To examine the socio-demographic, disease-related and treatment-related characteristics of patients with treatment resistant depression (TRD) in Europe. A prospective, multicenter, observational cohort study of approximately 400 TRD patients in seven European countries. TRD was defined as a lack of clinically meaningful improvement, with at least 2 different oral antidepressants in the current Major Depressive Episode (MDE), prescribed in adequate dosage and duration. Upon enrolment, patients were followed through an observational period of at least 6 months. Outcomes including baseline characteristics, disease history and symptom severity, treatment patterns, clinical outcomes (such as MADRS) and patient reported outcomes (EQ-5D-5L and Sheehan Disability Scale) were analyzed using descriptive statistics. 243 TRD patients were included in this interim analysis. Patients were on average 50.8 years old and 62.1% were female. On average, they already suffered from depression for 12.6 years, had at least 3 previous episodes, and experienced the current episode for more than a year (average duration of current episode = 2.6 years). Patients failed an average of 2.6 oral antidepressant treatments in the current episode. Further, they were highly depressed (average MADRS score 32.1), had a low quality of life (average EQ-5D-5L of 0.41) and suffered high functional impairment (average SDS of 22.3). 76.5% received at least one SSRI in the current episode, indicating traditional management of MDE. At inclusion, 33.3% started augmentation therapies including booster medications while only 19% had previously been treated with these in the current episode. After 6 months of follow-up, 20% of patients responded to treatment. TRD patients are a highly depressed and impaired population already suffering from depression for more than 10 years and failing available treatments options. While patients in a MDE are mostly treated with oral antidepressants alone, the use of augmentation therapies increases when those patients become TRD.

Existence of fungi and disinfection by-products (DBPs) in public swimming pools water are dangerous since it can seriously affect on health of swimmers. This data study aimed to determine the fungi contamination and DBPs concentration including trihalomethanes (THMs), haloacetic acids (HAAs), halamines and cyanogen halides and haloacetonitriles (HANs) of swimming pools (chlorine based) in Gonabad County, Iran. So, the fungal load and DBPs concentration were investigated in two swimming pools in the middle of spring of 2017 by collecting a number of 9 water samples and 9 samples of lateral facilities of each pool by membrane filtration technique and sterile carpet. The DBPs concentrations were measured by gas chromatograph technique. The results showed that the pools were contaminated with Dermatophyte (trichophyton mentagrophytes and epidermophyton flucosomes), yeasts, and more with opportunistic saprophytic fungi. 24.8%, 22.7%, 16.9%, and 11.4% saprophytic fungi were separated from pool side, locker room, pool water, and shower positions, respectively. 7.4% and 3.2% of yeast fungi as well as 0.23% and 0.2% of dentofacies of causative agents of tinea were separated from the pools water and showers as well as locker room and shower positions, respectively. According to the data, halamines and cyanogen halides had the highest concentrations, followed by HAAs, THMs and HANs respectively. Among the halamines and cyanogen halides, HAAs, THMs and HANs, trichloramine acid was the most dominant species, followed by trichloroacetic acid and dichloramine, respectively.

To examine the excess burden of caregiving for adult patients with unipolar depression (CAPUD) compared to caregiving for adult patients with other diseases (CAPOD) and compared to the general population in Europe. A retrospective, cross-sectional analysis was performed using data from the 2016 Europe National Health and Wellness Survey. CAPUD were compared to caregivers for adults who did not have unipolar depression but had other severe diseases (bipolar disorder, schizophrenia, cancer, chronic kidney disease, COPD, heart disease, diabetes, epilepsy, immune thrombocytopenia, macular degeneration, muscular dystrophy, osteoarthritis, or stroke) and to non-caregivers. Outcomes including health-related quality of life (HRQoL) (EQ-5D-5L), Work Productivity and Activity Impairment (WPAI), and healthcare resource utilization (HRU). Generalized linear models adjusted for covariates were used to estimate marginal means for each outcome. Overall, CAPUD (n=1,380) were younger and female compared to other caregivers (n=6,470) or the general population (n=69,334) (mean age: 44±15, 48±16, and 48±16, respectively; % female: 62%, 58%, and 55%, respectively). Adjusting for covariates, an excess burden translated into lower quality of life for CAPUD, their EQ-5D-5L index was 0.63 versus 0.73 for the general population (p<0.001). Activity Impairment showed an increased burden on CAPUD (65.7%) compared to the general population (40.3%; p<0.001). The incremental burden was also observed in terms of HRU in the past 6 months, with CAPUD experiencing almost three times more emergency room visits compared to the general population (1.22 versus 0.44 visits in the past6 months, p<0.001), more provider visits (10.52 versus 6.82, p<0.001) and more hospitalizations (0,72 versus 0.25, p<0.001) There is an incremental burden on caregivers of adult patients with unipolar depression compared to non-caregivers in terms on quality of life, productivity, and resource utilization and this burden is comparable to the burden on caregivers of adult patients with other severe diseases.

Treatment Resistant Depression (TRD) in major depressive disorder (MDD) is defined as failing to respond to two or more anti-depressant (AD) regimens. The study objective was to describe and compare patient characteristics, physician reported healthcare resource utilization and outcomes between TRD and non-TRD MDD patients. A cross-sectional survey of physicians and their patients was conducted in United States, France, Germany, Italy, Spain and United Kingdom from November 2016 to February 2017 through the Adelphi Depression and Anxiety Disease Specific Programme, which collected patient data from participating physicians and patient-reported outcomes from patients. Two groups were analyzed (TRD vs non-TRD MDD) both diagnosed with MDD (with/without anxiety); TRD defined as currently receiving at least third line of AD therapy after switching from first two lines of treatment due to lack of efficacy. The sample included 784 physicians, providing information on 4764 patients; 277 met TRD criteria (66% female; mean age 53 years) and 4487 non-TRD MDD (63% female; mean age 50 years). TRD patients had longer years of diagnosis (10 vs 3 years non-TRD MDD; p<0.0001) and their depression was more frequently recorded as moderate/severe (36% vs. 20% non-TRD MDD; p<0.0001). Unemployment/retirement due to MDD was more likely in TRD patients (40% vs 25% non-TRD MDD; p=0.0004). Physicians were unsatisfied with MDD control in 62% of TRD patients (42% non-TRD MDD; p<0.0001) and reported 48% as being non-responders (35% non-TRD MDD; p=0.0001). A higher proportion of TRD patients had been hospitalized in the last 6 months (13% vs. 7% non-TRD MDD; p<0.0001) and with longer hospital stay (2.4 vs 1.5 days; p=0.0006). TRD patients reported higher activity impairment (48% vs. 42% non-TRD MDD; p=0.0094). TRD patients had greater symptom severity, with poorer outcomes, resulting in greater unmet medical need and lower physician satisfaction.

To examine the humanistic and economic burden of treatment-resistant depression (TRD) in Europe. A retrospective, cross-sectional analysis was performed using data from the 2017 Europe National Health and Wellness Survey. Amongst patients with major depressive disorder (MDD) (included: self-reported physician-diagnosed depression and currently taking ≥1 medication for depression; excluded: anticonvulsant/antipsychotic monotherapy, bipolar disorder, or schizophrenia), TRD was identified as ≥2 anti-depressant medications (≥3 months), or monoamine oxidase inhibitor monotherapy, or reported they did not respond to previous therapy, and moderate/severe depressive symptoms (PHQ-9 ≥10). TRD patients were compared to (1) non-TRD MDD 'nTRD' and (2) general population controls (without a diagnosis of depression). Outcomes including health-related quality of life (HRQoL) (SF-12v2, EQ-5D), Work Productivity and Activity Impairment (WPAI), and healthcare resource utilization (HRU) were assessed using generalized linear models adjusted for covariates. Differences between TRD and control groups were examined using adjusted differences (AD) or relative risks (RR) and 95% confidence intervals (CI). Our study compared 622 TRD patients to 2686 nTRD patients and to 48,852 healthy controls. TRD compared to nTRD patients reported significant decrements in HRQoL, including the mental (AD=-5.65, 95% CI= -6.50–-4.81) and physical (AR=-2.27, 95% CI= -3.13–-1.41) component scores of the SF-12v2 and EQ-5D (AD=-0.13, 95% CI=-0.16–-0.11), increased in healthcare provider visits (RR=1.54, 95% CI=1.40–1.69), emergency department visits (RR=1.66, 95% CI=1.42–1.95), and hospital admissions (RR=1.47, 95% CI=1.20–1.79). All WPAI scores were higher for TRD than nTRD including, work productivity (RR=1.29, 95% CI=1.12–1.50) and overall activity (RR=1.28, 95% CI=1.17–1.40). Even greater differences were observed for all outcomes when compared to the general population (all statistically significant, p<0.05). These results suggest that TRD represents a substantial additional burden even within the MDD population by having significant impact on quality of life and costs related to work and activity loss and HRU.

To examine the humanistic and economic burden of suicidal ideation (SI) in Europe. A retrospective, cross-sectional analysis was performed using data from the 2017 Europe National Health and Wellness Survey. Amongst patients with major depressive disorder (MDD) (included: self-reported physician-diagnosed depression and currently taking ≥1 medication for depression; excluded: anticonvulsant/antipsychotic monotherapy, bipolar disorder, or schizophrenia), SI was identified as having severe depressive symptoms (Patient Health Questionnaire [PHQ]-9≥15) and a positive response to PHQ-9 question: "Over the past 2 weeks, how often have you been bothered by thoughts that you would be better off dead or of hurting yourself in some way?” SI patients were compared to (1) non-SI MDD 'nSI' and (2) general population controls (without a diagnosis of depression). Outcomes including health-related quality of life (HRQoL) (SF-12v2, EQ-5D), Work Productivity and Activity Impairment (WPAI), and healthcare resource utilization (HRU) were assessed using generalized linear models adjusted for covariates. Adjusted differences (AD) or relative risks (RR) and 95% confidence intervals (CI) were computed. Respondents with SI (n=905) were compared to nSI (n=2403) and to healthy (n=48,752) controls. SI versus nSI patients reported significant decrements in HRQoL, including the mental (AD=−9.20, 95% CI= −9.89–−8.51) and physical (AD=−2.00, 95% CI= −2.75–−1.25) component scores of the SF-12v2 and EQ-5D (AD=−0.18, 95% CI=−.19–−.16), and increases in healthcare provider visits (RR=1.38, 95% CI=1.27–1.50), emergency department visits (RR=1.49, 95% CI=1.29–1.73), and hospital admissions (RR=1.60, 95% CI=1.34–1.92). Work and activity impairments were higher for SI than nSI including, overall activity (RR=1.39, 95% CI=1.28–1.50). Even greater differences were observed for all outcomes when compared to the general population (all statistically significant, p<0.05). Results suggest that SI represents a substantial additional burden even within the MDD population by having significant impacts on HRQoL and costs related to work and activity loss and HRU.