Clinically Meaningful Changes on Depressive Symptom Measures and Patient‐Reported Outcomes in Patients with Treatment‐Resistant Depression

Abstract Background: We assessed the correlation between childhood maltreatment (CM) and severity of depression in an elderly unipolar Treatment-Resistant Depression (TRD) sample. Methods: Patients were enrolled from a longitudinal cohort (FACE-DR) of the French Network of Expert TRD Centres. Results: Our sample included 96 patients (33% of the overall cohort) aged 60 years or above, with a mean age of 67.2 (SD = 5.7). Most of the patients were female (62.5%). The Montgomery and Asberg Depression Rating Scale (MADRS) and Quick Inventory Depression Scale-Self Report (QIDS-SR) mean scores were high, 28.2 (SD = 7.49) [MADRS score range: 0-60; moderate severity≥20, high severity≥35] and 16.5 (SD=4.94) [IDS-SR score range: 0-27; moderate severity≥11, high severity≥16], respectively. Mean self-esteem scores were 22.47 (SD=6.26) [range 0-30]. In an age and sex-adjusted model, we found a positive correlation between childhood trauma (CTQ scores) and depressive symptom severity [MADRS (β=0.274; p=0.07) and QIDS-SR (β=0.302; p=0.005) scores]. We detected a statistically significant correlation between physical abuse and depressive symptom severity [MADRS (β=0.304; p=0.03) and QIDS-SR (β=0.362; p=0.005) scores]. We did not observe any significant correlation between other types of trauma and depressive symptom severity. We showed that self-esteem (Rosenberg scale) mediated the effect of physical abuse (PA) on the intensity of depressive symptoms [MADRS: b=0.318, 95% BCa C.I. [0.07, 0.62]; QIDS-SR: b=0.177, 95% BCa C.I. [0.04, 0.37]]. Preacher & Kelly’s Kappa Squared values of 19.1% (k2=0.191) and 16% (k2=0.16), respectively, indicate a moderate effect. Conclusion: To our knowledge, this is the first study conducted in a geriatric TRD population documenting an association between childhood trauma (mainly relating to PA) and the intensity of depressive symptoms.

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Relationship between childhood physical abuse and clinical severity of treatment-resistant depression in a geriatric population

PLoS ONE ◽

10.1371/journal.pone.0250148 ◽

2021 ◽

Vol 16 (4) ◽

pp. e0250148

Author(s):

Antoine Yrondi ◽

Christophe Arbus ◽

Djamila Bennabi ◽

Thierry D’Amato ◽

Frank Bellivier ◽

...

Keyword(s):

Depressive Symptom ◽

Physical Abuse ◽

Symptom Severity ◽

Self Esteem ◽

Treatment Resistant Depression ◽

Treatment Resistant ◽

High Severity ◽

Depressive Symptom Severity ◽

Resistant Depression ◽

Score Range

Introduction We assessed the correlation between childhood maltreatment (CM) and severity of depression in an elderly unipolar Treatment-Resistant Depression (TRD) sample. Methods Patients were enrolled from a longitudinal cohort (FACE-DR) of the French Network of Expert TRD Centres. Results Our sample included 96 patients (33% of the overall cohort) aged 60 years or above, with a mean age of 67.2 (SD = 5.7). The majority of the patients were female (62.5%). The Montgomery and Asberg Depression Rating Scale (MADRS) and Quick Inventory Depression Scale-Self Report (QIDS-SR) mean scores were high, 28.2 (SD = 7.49) [MADRS score range: 0–60; moderate severity≥20, high severity≥35] and 16.5 (SD = 4.94) [IDS-SR score range: 0–27; moderate severity≥11, high severity≥16], respectively. Mean self-esteem scores were 22.47 (SD = 6.26) [range 0–30]. In an age- and sex-adjusted model, we found a positive correlation between childhood trauma (CTQ scores) and depressive symptom severity [MADRS (β = 0.274; p = 0.07) and QIDS-SR (β = 0.302; p = 0.005) scores]. We detected a statistically significant correlation between physical abuse and depressive symptom severity [MADRS (β = 0.304; p = 0.03) and QIDS-SR (β = 0.362; p = 0.005) scores]. We did not observe any significant correlation between other types of trauma and depressive symptom severity. We showed that self-esteem (Rosenberg scale) mediated the effect of physical abuse (PA) on the intensity of depressive symptoms [MADRS: b = 0.318, 95% BCa C.I. [0.07, 0.62]; QIDS-SR: b = 0.177, 95% BCa C.I. [0.04, 0.37]]. Preacher & Kelly’s Kappa Squared values of 19.1% (k2 = 0.191) and 16% (k2 = 0.16), respectively for the two scales, indicate a moderate effect. Conclusion To our knowledge, this is the first study conducted in a geriatric TRD population documenting an association between childhood trauma (mainly relating to PA) and the intensity of depressive symptoms.

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Treatment resistant depression in the UK: sub-analysis of a European real-world evidence study

BJPsych Open ◽

10.1192/bjo.2021.192 ◽

2021 ◽

Vol 7 (S1) ◽

pp. S55-S55

Author(s):

Jordan Talbot ◽

Donald J MacIntyre ◽

Shanaya Rathod ◽

Joachim Morrens ◽

Allan H Young

Keyword(s):

Real World ◽

Rating Scale ◽

Response Rates ◽

Treatment Resistant Depression ◽

Treatment Resistant ◽

Major Depressive ◽

Madrs Score ◽

Patient Reported ◽

Resistant Depression ◽

The Uk

AimsTreatment resistant depression (TRD) affects ≤20% of patients with major depressive disorder and is defined as failure to respond to ≥2 different antidepressants in the same major depressive episode (MDE). TRD patients’ outcomes are poor and real-world data from the UK are limited. The Treatment Resistant Depression in Europe Cohort was established to study patients being treated in local, routine clinical practice. The analysis presented here aimed to compare UK-specific data with data from other European countries included in the study.MethodA prospective, multicentre, observational cohort study of TRD patients in Italy, Germany, Spain, Portugal, the Netherlands, the UK and Belgium was conducted. Patients aged 18–74 years with current TRD, Montgomery-Åsberg Depression Rating Scale (MADRS) score ≥20, and initiating a new treatment for depression, were eligible. Data from medical records, clinician assessments and patient-reported questionnaires were collected over time, with follow-up of ≥6 months.ResultData from 411 patients were analysed. At baseline, UK patients (n = 49) had similar depression severity to the whole European cohort (34.7% vs 32.6% of patients categorised as severe based on MADRS score, respectively). Patients had experienced the current MDE for a mean (standard deviation [SD]) of 6.1 (7.9) years vs 2.6 (3.9) years and 14.3% vs 4.9% had experienced ≥5 treatment failures during this time in the UK and whole cohort, respectively. Total mean (SD) Sheehan Disability Scale (SDS) scores of 24.5 (5.1) and 22.4 (5.5) were reported for the UK and whole cohort, respectively. Unemployment and long-term sick leave rates were 38.8% and 20.4% in the UK and 30.2% and 19.0% in the whole cohort, respectively. At 6 months, 8.9% of UK patients were in remission, and 82.2% had not responded to treatment, representing the lowest remission and highest non-response rates across all countries.ConclusionUK patients had been ill for longer and had more prior treatment failures than other countries in the study. They had high work and functional impairment, and the worst treatment outcomes of all the countries studied. UK TRD patients experience high disease burden; there is an unmet need for treatment strategies with better response rates.AcknowledgementsWe thank all participating patients. Study, and medical writing (Costello Medical, UK), funded by Janssen. AHY's independent research is funded by the National Institute for Health Research. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health.

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149 Evaluation of Individual Items on the PHQ-9 and SDS in Patients with Treatment-Resistant Depression Treated with Esketamine Nasal Spray

CNS Spectrums ◽

10.1017/s1092852920000656 ◽

2020 ◽

Vol 25 (2) ◽

pp. 295-295

Author(s):

Lysbeth Floden ◽

Stacie Hudgens ◽

Carol Jamieson ◽

Vanina Popova ◽

Wayne Drevets ◽

...

Keyword(s):

Nasal Spray ◽

Odds Ratio ◽

Study Patient ◽

Symptom Improvement ◽

Depression Symptoms ◽

Treatment Resistant Depression ◽

Treatment Resistant ◽

Patient Reported ◽

Resistant Depression ◽

Ratio Range

Abstract:Introduction:Major depressive disorder (MDD) is a global long-term condition and is the leading cause for disability in most countries. The objective of this study was to evaluate individual items of the PHQ-9 and SDS to show differences by treatment arm over the course of treatment.Methods:The TRANSFORM-2 study (NCT02418585) was a Phase 3 short-term trial that evaluated efficacy and safety of flexible esketamine nasal spray (56 mg or 84 mg) doses in combination with newly initiated oral antidepressant (ESK+AD) vs oral AD + placebo nasal spray (AD+PBO) in patients with treatment resistant depression (TRD). The study population, men and women aged 18-64 years, who met the Diagnostic and Statistical Manual of Mental Disorders, Edition 5 diagnostic criteria for single-episode or recurrent MDD, but excluded subjects with suicidal ideation/intent to act within 6 months prior to study. Patient reported outcomes (PROs) were integrated to evaluate the patient perspective of treatment using instruments capturing concepts of importance. The 9-item Patient Health Questionnaire (PHQ-9) is a PRO instrument to assess self-reported depression symptoms, and the SDS a PRO instrument to assess function and disability. Individual items on each of these instruments represent a symptom or aspect of functioning. Respective items for PHQ-9 and SDS, are summed together to generate a total score: 0-27 for the PHQ-9 and 0-30 for SDS. Each total score reflects a single construct of depression severity for the PHQ-9 and functional disability for SDS. Change from baseline in SDS and PHQ-9 total scores at Day 28 were analyzed using a mixed-effects model using repeated measures based on observed case data. Generalized estimation equations of logistic regression models were used to estimate the likelihood of improvement by ≥ 1 point on the individual items of the PHQ-9 and SDS.Results:Full analysis set included 223 patients (ESK+AD: 114; AD+PBO: 109). Change in SDS total score from baseline to Day 28 numerically favored ESK+AD. The LS mean treatment difference (95% CI) was -4.0 (-6.28; -1.64). Change in PHQ-9 total score from baseline to Day 28 numerically favored treatment with ESK+AD. The LS mean difference (95%CI) was -2.4 (-4.18; -0.69). Most patients experienced improvement on all PHQ-9 items and more patients experienced greater improvement in the ESK+AD treatment arm compared to the AD+PBO arm (odds ratio range 1.367-2.767; favoring ESK+AD). Improvements were seen across all items of the Sheehan Disability Scale (odds ratio range from 1.994 – 3.378; favoring ESK+AD).Conclusions:This study shows that while the magnitude of improvement varied on individual items, ESK+AD treatment leads to greater symptom improvement across the multiple symptoms included in the PHQ-9 and SDS compared to the AD+PBO. This assists interpretation of the total scores generated by these PRO measures since total scores on the two measures was not driven by a single item.Funding Acknowledgements:Study was funded by Janssen Global Services, LLC.

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