Impact of moderate-to-high-suicide-intent in major depressive disorder: a retrospective cohort study on patient characteristics and healthcare resource utilisation in England.

BACKGROUND: Major depressive disorder (MDD) is a disabling mental illness that can affect all aspects of daily life and is a leading cause of healthcare resource utilisation (HCRU). AIMS: We aimed to characterise patients with MDD with moderate-to-high-suicide-intent, compare their HCRU to patients with MDD without moderate-to-high-suicide-intent, and better understand their patient pathways. METHODS: This retrospective cohort study used data collected from primary care electronic health records from Clinical Practice Research Datalink (CPRD), linked to Hospital Episode Statistics, Mental Health Services Data Set, and Office for National Statistics in England. Adults diagnosed with ≥ 1 MDD diagnosis between 04/2007 and 11/2015 were categorised by suicide intent. RESULTS: 307,476 patients with MDD were included (294,259 patients without moderate-to-high-suicide-intent and 13,217 with moderate-to-high-suicide-intent). Patients with MDD with moderate-to-high-suicide-intent were younger on average (39.0 vs. 44.8 years) and included a lower percentage of females (58% vs. 65%) compared to patients without moderate-to-high-suicide-intent. HCRU was greater among patients with moderate-to-high-suicide-intent than patients without moderate-to-high-suicide-intent during the first follow-up year for general practitioner consultations (38.5 vs. 29.4), psychiatric outpatient visits (1.5 vs. 0.1), psychiatrist visits (3.6 vs. 0.3), emergency visits (1.5 vs. 0.3), and hospitalisations (86% vs. 26%). Overall, 56% of patients with moderate-to-high-suicide-intent had an antidepressant prescription within 30 days from the initial moderate-to-high-suicide-intent. CONCLUSIONS: Patients with MDD and moderate-to-high-suicide-intent were younger, included more males and incurred greater HCRU than those without moderate-to-high-suicide-intent. These results suggest a greater need for effective medical care and appropriate treatments for patients with moderate-to-high-suicide-intent, which could help reduce associated symptoms, mortality, and HCRU.

The humanistic and economic burden of treatment-resistant depression in Europe: a cross-sectional study.

BACKGROUND: A patient is considered to suffer from treatment resistant depression (TRD) when consecutive treatment with two products of different pharmacological classes, used for a sufficient length of time at an adequate dose, fail to induce a clinically meaningful effect (inadequate response). The primary aim of the current study was to examine the humanistic and economic burden of TRD in five European countries, France, Germany, Italy, Spain and the United Kingdom, by comparing with non-treatment resistant depression (nTRD) and general population respondents. METHODS: The sample for this retrospective observational study was taken from the 2017 National Health and Wellness Survey conducted in five European countries. Demographic and patient characteristics were examined for TRD patients compared to respondents with nTRD and to the general population using chi-square tests or one-way analysis of variance for categorical or continuous variables, respectively. Generalized linear models were performed to examine group differences after adjusting these estimates for confounders. RESULTS: A total 52,060 survey respondents were examined, of which 2686 and 622 were considered to have non-treatment resistant and treatment-resistant depression, respectively. Relative to the general population, nTRD and TRD respondents reported significant decrements in health-related quality of life, including lower adjusted mental (- 12.1 vs. -18.1) and physical (- 2.5 vs. -5.4) component scores of the SF-12v2 and increased adjusted relative risk for work (2.2 vs. 2.7) and activity (1.9 vs. 2.5) impairment (all p < 0.001). Additionally, healthcare resource utilization was significantly higher for TRD patients more so than nTRD, compared to the general population, especially for healthcare professional visits (odds ratio nTRD = 5.4; TRD = 15.9, p < 0.001). CONCLUSIONS: In conclusion, TRD patients had significantly lower quality of life, greater work productivity and activity impairment, and increased healthcare resource utilization as compared with nTRD and general population. The study findings suggest an unmet need exists among TRD patients in Europe.

Impacts of X-linked Retinitis Pigmentosa and Patient Pathways in European Countries: Results from the Cross-sectional EXPLORE XLRP-1 Physician Survey.

INTRODUCTION: X-linked retinitis pigmentosa (XLRP) is a rare, incurable, vision-threatening, genetic disease. In this study, we aimed to reveal the real-world burden of this disease from the viewpoint of retina specialists and geneticists involved directly in XLRP care and to identify unique insights that may not otherwise be available through typical clinical studies or health economic research. METHODS: In this exploratory, cross-sectional study (EXPLORE XLRP-1), retina specialists (n = 20) and geneticists (n = 5) in France, Germany, Italy, Spain, and the UK provided anonymized insights on their experiences managing patients with XLRP (n = 80) via an online survey and 60-min telephone interview. RESULTS: Survey respondents reported that patient independence decreased over time, where 37% of patients were considered "completely autonomous" at diagnosis versus 23% at the last consultation. At their last visit, 45% of patients were active in the workforce; 67% (12/18) of "completely autonomous" patients had active working status compared with 13% (1/8) of "completely dependent" patients. The average time from onset of symptoms to diagnosis was 4 years and varied among countries. In 78% of patients, XLRP was confirmed by genetic testing, the rate of which varied among countries (range, 50-94%), taking up to 6 months to receive results. Specialists identified unmet needs in XLRP management including more standardized assessments of quality of life (QoL) as well as easier and earlier access to specialists, genetic testing, patient support programs, and effective treatment options. CONCLUSIONS: The diagnosis, genetic testing, and management pathways among patients with XLRP can vary considerably. There is a need for more standardized diagnosis and management pathways, and QoL assessments, due to the major impact that XLRP has on patients' lives.

The impact of treatment-resistant depression on the lives of carers: A mixed-methods study.

INTRODUCTION: The lived experiences of informal carers of people with depression, particularly those with treatment-resistant depression (TRD), are rarely explored, despite their vital supportive role. METHODS: This mixed-methods study explored the quality of life (QoL) and experiences of carers of individuals with symptomatic TRD (Carers-Sym-TRD; n = 79) or in remission post-TRD (Carers-Rem-TRD; n = 20). Participating carers completed quantitative surveys measuring health-related and broader QoL (EQ-5D-5L/WHOQOL-BREF) and work productivity/activity impairment (WPAI:MM-CG). Interviews were also conducted with 12 Carers-Sym-TRD and 11 Carers-Rem-TRD and analysed thematically. RESULTS: Carers-Sym-TRD had impaired QoL compared with Carers-Rem-TRD, with significantly lower EQ-5D-5L index values (median = 0.84/1.00, respectively; p = 0.020) and WHOQOL-BREF overall score (median = 63.0/70.1; p < 0.001), physical health (median = 15.3/17.3; p < 0.001), psychological health (median = 13.3/14.7; p = 0.017), social relationships (median = 13.3/14.7; p = 0.017) and environment (median = 14.5/16.5; p = 0.011) domain scores. Work productivity/activity impairment was greatest in Carers-Sym-TRD across most WPAI:MM-CG domains, with a higher degree of impairment reported on the presenteeism and work productivity domains, however, there were no significant differences between the carer groups. Interview data suggested that impacts on carers' psychological/emotional wellbeing led to physical problems, which affected cognition and daily performance; Also, successful treatment for the person with depression helped carers worry less and reclaim their independence. LIMITATIONS: Recruitment challenges limited the Carers-Rem-TRD sample; clinical validation of the patient's depression diagnosis was not confirmed for all carers. CONCLUSIONS: TRD has an extensive adverse impact on carers' lives. Carers-Sym-TRD had significantly impaired QoL across a variety of domains compared with Carers-Rem-TRD, suggesting that achieving remission not only benefits patients but also those who care for them.

The lived experience of major and treatment-resistant depression in England: a mixed-methods study.

INTRODUCTION: Major depressive disorder (MDD) is a common, frequently recurrent condition associated with decreased well-being and increased healthcare-related costs. Mixed-methods research provides multiple ways of illustrating the phenomenon to better understand patient experience, including where treatment is not working, referred to here as treatment-resistant depression (TRD). METHODS: A mixed-methods study investigated the experiences of people with symptomatic MDD, symptomatic TRD or TRD in remission, surveying 148 adults recruited from English clinical sites to measure symptom severity (Patient Health Questionnaire-9 [PHQ-9]), HRQoL (EQ-5D-5L/World Health Organisation Brief Assessment of QoL [WHOQOL-BREF]) and work productivity/activity impairment (WPAI:D). Interviews with 26 survey respondents were analysed thematically. Integrated datasets explored areas of convergence and divergence, with concepts mapped against the EQ-5D-5L. RESULTS: Qualitative data explained low WHOQOL-BREF domain scores and the interrelation of psychological, emotional, cognitive and physical difficulties. Tiredness, lack of energy and motivation impacted daily activities, socialising and career goals. Low work performance scores were explained by poor concentration, decision-making and motivation. Participants also described the influence of social support and housing insecurity. Only 19 % of HRQoL qualitative codes mapped to the EQ-5D-5L. Themes dominant in patients with TRD were inability to cope, self-care challenges, dissatisfaction with mental health services and treatment pessimism. LIMITATIONS: Limited data collected on people with TRD in remission. CONCLUSIONS: The EQ-5D-5L and WPAI:D likely underestimate how depression impacts the HRQoL and work of people with MDD or TRD. Qualitative data suggest increased distress for people with TRD compared to those with MDD. Clinical management and treatment access decisions should consider the broader impacts of depression and environmental factors affecting the patient's experience.

Health-related quality of life burden associated with treatment-resistant depression in UK patients: Quantitative results from a mixed-methods non-interventional study.

BACKGROUND: Major depressive disorder (MDD) and its more intractable variant, treatment-resistant depression (TRD), are common conditions that adversely affect patient well-being and health-related quality of life (HRQoL). This study aimed to quantify the impact of MDD and particularly TRD on the HRQoL, functioning and productivity of UK patients to support clinical and reimbursement decisions and policymaking. METHODS: 148 patients with clinician-verified symptomatic (non-treatment-resistant) MDD (Patients-MDD; n = 61) or TRD (Patients-TRD; n = 87) were recruited from ten clinical sites. Participants completed validated patient-reported outcome measures assessing depressive symptom severity (Patient Health Questionnaire-9 [PHQ-9]), HRQoL (EQ-5D-5 L/abbreviated World Health Organization Quality of Life Questionnaire [WHOQOL-BREF]) and work productivity/activity impairment (WPAI:D). RESULTS: Patients-TRD and Patients-MDD reported similar levels of depressive symptom severity (mean PHQ-9 16.2/16.6, respectively). However, HRQoL was significantly poorer for Patients-TRD compared with Patients-MDD, both in the overall cohort (median EQ-5D-5 L utility 0.606/0.721, respectively [p = 0.021]; WHOQOL-BREF overall score 55.2/58.8 [p = 0.024]) and in patients with a PHQ-9 score ≥15 (median EQ-5D-5 L utility 0.415/0.705, respectively [p<0.001]). Although a numerically lower proportion of Patients-TRD were employed (45% vs 57% of Patients-MDD; p = 0.204), employed Patients-MDD reported significantly higher absenteeism and work productivity loss. LIMITATIONS: A minority of patients screened as having symptomatic MDD or TRD self-reported low PHQ-9 symptom severity. This was addressed with a subgroup analysis of patients with more severe depression. CONCLUSIONS: TRD is associated with an added patient HRQoL burden, above that observed for non-treatment-resistant MDD. This highlights the unmet need for greater access to improved treatment, including new treatment options for Patients-TRD.

Current treatments used in clinical practice for major depressive disorder and treatment resistant depression in England: A retrospective database study.

BACKGROUND: Major depressive disorder (MDD) is a chronic recurrent or episodic psychiatric illness that can be successfully treated with oral antidepressants, yet one-in-three patients do not respond to currently-available treatments. According to the FDA and EMA, patients are considered to have treatment-resistant depression (TRD) when their MDD fails to respond adequately to ≥2 successive antidepressants in a single episode. AIMS: To describe current clinical management of patients with MDD and TRD in England, including treatment strategies and referral to secondary mental healthcare. METHOD: A retrospective cohort study of adult patients identified in primary care with diagnosed MDD, including a TRD subgroup (≥2 treatment failures as determined by treatment dynamics) was conducted using the Clinical Practice Research Datalink GOLD primary care database linked to Hospital Episode Statistics and Mental Health Services Data Set data (Protocol 19_019R). RESULTS: 41,375 patients with MDD (mean age 44yrs, 62% female, median follow-up 29mths); and 1,051 (3%) patients with TRD were identified. Mean time-to-TRD was 18 months. Most patients (>99%) received first-line antidepressant monotherapy. Following TRD criteria being met, antidepressant monotherapy use remained most frequent from TRD first-line (70%) to fifth-line (48%). Dual/triple antidepressant use remained constant (range:24%-26%), while augmented antidepressant use increased from TRD first-line (7%) to third-line (17%). Minimal non-pharmacological therapies were observed. CONCLUSIONS: Despite current clinical guidelines recommending a stepwise approach, many patients frequently cycle through numerous antidepressants with similar mechanisms of action and efficacy. These findings indicate a high unmet need for new treatments that improve outcomes in these patient populations.

A retrospective chart review study to quantify the monthly medical resource use and costs of treating patients with treatment resistant depression in the United Kingdom.

INTRODUCTION: Major depressive disorder (MDD) is a globally prevalent chronic psychiatric illness with a significant disease impact. As many as 30% of patients with MDD do not adequately respond to two therapies and are considered to be treatment resistant. This study aimed to quantify healthcare costs associated with treatment resistant depression (TRD) in the UK. METHODS: A retrospective chart review of patients with TRD was conducted in primary and secondary care settings over a 2 year period. Data abstracted from medical records of patients included demographics, clinical characteristics and healthcare resource utilization (HCRU; number of consultations, use of Crisis Resolution and Home Treatment Teams [CRHTTs], non-drug and drug interventions, and hospitalizations). HCRU per patient per month (28 days) was calculated for three health states: major depressive episode (MDE), remission and recovery. Unit costs were from the British National Formulary (BNF) and the Personal Social Services Research Unit (PSSRU). RESULTS: A total of 295 patients with TRD were recruited between January 2016 and May 2018. The mean age of the total sample was 43.3 years; 60.3% were female. Costs per patient, per 28 days, were highest in the MDE state, with the average cost (£992) mainly driven by consultations, non-drug treatment, hospitalizations and CRHTT, with a considerable fall in costs as patients moved into remission and subsequent recovery. CONCLUSION: The results suggest that antidepressant treatments for TRD that are more effective in reducing the time spent in an MDE health state, and helping patients achieve remission and recovery, are essential for reducing the overall HCRU and costs in patients with TRD. Cost of TRD in the UK Strengths and limitations of this study This observational study of TRD is the first to assess the HCRU impact associated with different predefined health states. Using retrospective data from both primary and secondary care physicians from regions across the UK ensures a representative real-world patient population. One limitation is that the selection of patients is based on criteria that define TRD that rely on physician judgement. Although the study captures direct HCRU costs, the indirect costs of lost productivity and care are not included in the overall burden. This study has defined the current clinical management of patients with TRD in the UK and provides an estimate of the associated HCRU and associated costs.

The burden of suicidal ideation across Europe: a cross-sectional survey in five countries.

BACKGROUND: Suicidal ideation (SI) is an associated risk of depression, affecting 30-40% of the depressed population. However, there is a paucity of studies investigating the impact of SI in Europe. This retrospective observational study examined the burden of SI among adults with major depressive disorder (MDD) in the 2017 National Health and Wellness Survey in five European countries: France, Germany, Italy, Spain, and the UK. METHODS: Bivariate analyses evaluated group differences between respondents with MDD with and without SI according to demographic characteristics, self-reported health-related quality of life, work productivity and activity impairment (WPAI), and healthcare resource utilization (HRU). Generalized linear models examined group differences country-wise, after controlling for relevant confounders. RESULTS: Among 52,060 respondents, 3,308 individuals were diagnosed with MDD, comprising SI (n=905) and non-SI (nSI) (n=2403) patients. Adjusted differences (ADs), compared to the general population, were observed using the Medical Outcomes Study Short Form Survey (SF-12v2) mental component summary scores (AD: SI=-20.02, nSI=-10.77), physical component summary scores (AD: SI=-4.49, nSI=-2.50), and EuroQoL-5 Dimensions (AD: SI=-0.34, nSI=-0.15) (for all, p<0.001). Significantly greater WPAI and higher HRU were associated with SI compared to nSI. CONCLUSION: The results illustrate the unique impact of SI within the MDD population and the need to reduce the burden.

Cost-effectiveness of 3-month paliperidone therapy for chronic schizophrenia in the Netherlands.

BACKGROUND: A new depot formulation of paliperidone has been developed that provides effective treatment for schizophrenia for 3 months (PP3M). It has been tested in phase-3 trials, but no data on its cost-effectiveness have been published. PURPOSE: To determine the cost-effectiveness of PP3M compared with once-monthly paliperidone (PP1M), haloperidol long-acting therapy (HAL-LAT), risperidone microspheres (RIS-LAT), and oral olanzapine (oral-OLZ) for treating chronic schizophrenia in The Netherlands. METHODS: A previous 1-year decision tree was adapted, based on local inputs supplemented with data from published literature. The primary analysis used DRG costs in 2016 euros from the insurer perspective, as derived from official lists. A micro-costing analysis was also conducted. For the costing scenario, official list prices were used. Clinical outcomes included relapses (treated as outpatients, requiring hospitalization, total), and quality-adjusted life-years (QALYs). Rates and utility scores were derived from the literature. Economic outcomes were the incremental cost/QALY-gained or relapse-avoided. Model robustness was examined in scenario, 1-way, and probability sensitivity analyses. RESULTS: The expected cost was lowest with PP3M (8,781€), followed by PP1M (10,325€), HAL-LAT (11,278€), RIS-LAT (11,307€), and oral-OLZ (13,556€). PP3M had the fewest total relapses/patient (0.36, 0.94, 1.39, 1.21, and 1.70, respectively), hospitalizations (0.11, 0.46, 0.40, 0.56, and 0.57, respectively), emergency room visits (0.25, 0.48. 0.99, 0.65, and 1.14, respectively) and the most QALYs (0.847, 0.735, 0.709, 0.719, and 0.656, respectively). In both cost-effectiveness and cost-utility analyses, PP3M dominated all other drugs. Sensitivity analyses confirmed base case findings. In the costing analysis, total costs were, on average, 31.9% higher than DRGs. CONCLUSIONS: PP3M dominated all commonly used drugs. It is cost-effective for treating chronic schizophrenia in the Netherlands. Results were robust over a wide range of sensitivity analyses. For patients requiring a depot medication, such as those with adherence problems, PP3M appears to be a good alternative anti-psychotic treatment.

Treatment continuation of four long-acting antipsychotic medications in the Netherlands and Belgium: A retrospective database study.

Achieving greater continuation of treatment is a key element to improve treatment outcomes in schizophrenia patients. However, reported treatment continuation can differ markedly depending on the study design. In a retrospective setting, treatment continuation remains overall poor among patients using antipsychotics. This study aimed to document the difference in treatment continuation between four long-acting injectable antipsychotics based on the QuintilesIMS LRx databases, national, longitudinal, panel based prescription databases of retail pharmacies, in the Netherlands and Belgium. Paliperidone palmitate once monthly, risperidone microspheres, haloperidol decanoate, and olanzapine pamoate were studied. This study demonstrated significantly higher treatment continuation of paliperidone palmitate once monthly compared to risperidone microspheres (p-value<0,01) and haloperidol decanoate (p-value<0,01) in both countries, a significantly higher treatment continuation of paliperidone palmitate once monthly compared to olanzapine pamoate in the Netherlands (p-value<0,01), and a general trend towards better treatment continuation versus olanzapine pamoate in Belgium. Analysing the subgroup of patients without previous exposure to long-acting antipsychotic treatment revealed the positive impact of previous exposure on treatment continuation with a subsequent long acting treatment. Additionally, the probability of restarting the index therapy was higher among patients treated with paliperidone palmitate once monthly compared to patients treated with risperidone microspheres and haloperidol decanoate. The data source used and the methodology defined ensured for the first time a comparison of treatment continuation in a non-interventional study design for the four long-acting injectable antipsychotics studied.

Conceptual framework for outcomes research studies of hepatitis C: an analytical review.

Hepatitis C virus infection is one of the main causes of chronic liver disease worldwide. Until recently, the standard antiviral regimen for hepatitis C was a combination of an interferon derivative and ribavirin, but a plethora of new antiviral drugs is becoming available. While these new drugs have shown great efficacy in clinical trials, observational studies are needed to determine their effectiveness in clinical practice. Previous observational studies have shown that multiple factors, besides the drug regimen, affect patient outcomes in clinical practice. Here, we provide an analytical review of published outcomes studies of the management of hepatitis C virus infection. A conceptual framework defines the relationships between four categories of variables: health care system structure, patient characteristics, process-of-care, and patient outcomes. This framework can provide a starting point for outcomes studies addressing the use and effectiveness of new antiviral drug treatments.