Older adults with treatment-resistant depression (TRD) benefit more from treatment augmentation than switching. It is useful to identify moderators that influence these treatment strategies for personalised medicine.

Our objective was to test whether age, executive dysfunction, comorbid medical burden, comorbid anxiety or the number of previous adequate antidepressant trials could moderate the superiority of augmentation over switching. A significant moderator would influence the differential effect of augmentation versus switching on treatment outcomes.

We performed a preplanned moderation analysis of data from the Optimizing Outcomes of Treatment-Resistant Depression in Older Adults (OPTIMUM) randomised controlled trial (N = 742). Participants were 60 years old or older with TRD. Participants were either (a) randomised to antidepressant augmentation with aripiprazole (2.5–15 mg), bupropion (150–450 mg) or lithium (target serum drug level 0.6 mmol/L) or (b) switched to bupropion (150–450 mg) or nortriptyline (target serum drug level 80–120 ng/mL). Treatment duration was 10 weeks. The two main outcomes of this analysis were (a) symptom improvement, defined as change in Montgomery–Asberg Depression Rating Scale (MADRS) scores from baseline to week 10 and (b) remission, defined as MADRS score of 10 or less at week 10.

Of the 742 participants, 480 were randomised to augmentation and 262 to switching. The number of adequate previous antidepressant trials was a significant moderator of depression symptom improvement (b = −1.6, t = −2.1, P = 0.033, 95% CI [−3.0, −0.1], where b is the coefficient of the relationship (i.e. effect size), and t is the t-statistic for that coefficient associated with the P-value). The effect was similar across all augmentation strategies. No other putative moderators were significant.

Augmenting was superior to switching antidepressants only in older patients with fewer than three previous antidepressant trials. This suggests that other intervention strategies should be considered following three or more trials.

It remains unclear which individuals with subthreshold depression benefit most from psychological intervention, and what long-term effects this has on symptom deterioration, response and remission.

To synthesise psychological intervention benefits in adults with subthreshold depression up to 2 years, and explore participant-level effect-modifiers.

Randomised trials comparing psychological intervention with inactive control were identified via systematic search. Authors were contacted to obtain individual participant data (IPD), analysed using Bayesian one-stage meta-analysis. Treatment–covariate interactions were added to examine moderators. Hierarchical-additive models were used to explore treatment benefits conditional on baseline Patient Health Questionnaire 9 (PHQ-9) values.

IPD of 10 671 individuals (50 studies) could be included. We found significant effects on depressive symptom severity up to 12 months (standardised mean-difference [s.m.d.] = −0.48 to −0.27). Effects could not be ascertained up to 24 months (s.m.d. = −0.18). Similar findings emerged for 50% symptom reduction (relative risk = 1.27–2.79), reliable improvement (relative risk = 1.38–3.17), deterioration (relative risk = 0.67–0.54) and close-to-symptom-free status (relative risk = 1.41–2.80). Among participant-level moderators, only initial depression and anxiety severity were highly credible (P > 0.99). Predicted treatment benefits decreased with lower symptom severity but remained minimally important even for very mild symptoms (s.m.d. = −0.33 for PHQ-9 = 5).

Psychological intervention reduces the symptom burden in individuals with subthreshold depression up to 1 year, and protects against symptom deterioration. Benefits up to 2 years are less certain. We find strong support for intervention in subthreshold depression, particularly with PHQ-9 scores ≥ 10. For very mild symptoms, scalable treatments could be an attractive option.

Few studies have examined the impact of late-life depression trajectories on specific domains of cognitive function. This study aims to delineate how different depressive symptom trajectories specifically affect cognitive function in older adults.

Prospective longitudinal cohort study

Australia and the United States of America

In total, 11,035 community-dwelling older adults with a mean age of 75 years

Depressive trajectories were modelled from depressive symptoms according to annual Centre for Epidemiological Studies Depression Scale 10 (CES-D-10) surveys. Four trajectories of depressive symptoms were identified: low (“nondepressed”), consistently mild (“subthreshold depression”), consistently moderate (“persistent depression”), and initially low but increasing (“emerging depression”). Global cognition (Modified Mini-Mental State Examination [3MS]), verbal fluency (Controlled Oral Word Association Test [COWAT]), processing speed (Symbol Digit Modalities Test [SDMT]), episodic memory (Hopkins Verbal Learning Test – Revised [HVLT-R]), and a composite z-score were assessed over a subsequent median 2 years.

Subthreshold depression predicted impaired performance on the SDMT (Cohen’s d −0.04) and composite score (−0.03); emerging depression predicted impaired performance on the SDMT (−0.13), HVLT-R (−0.09), 3 MS (−0.08) and composite score (−0.09); and persistent depression predicted impaired performance on the SDMT (−0.08), 3 MS (−0.11), and composite score (−0.09).

Depressive symptoms are associated with later impaired processing speed. These effects are small. Diverse depression trajectories have different impacts on cognitive function.

To test vitamin D3 and omega-3s for late-life depression prevention under the National Academy of Medicine framework for indicated (targeting subthreshold depression) and selective (targeting presence of high-risk factors) prevention.

VITamin D and OmegA-3 TriaL (VITAL) is a 2x2 factorial trial of vitamin D3 (2000 IU/day) and/or omega-3s (1 g/day) for cardiovascular and cancer prevention (enrollment: November 2011-March 2014; end date: December 31, 2017). In this targeted prevention study, we included 720 VITAL clinical sub-cohort participants who completed neurobehavioral assessments at baseline and 2 years (91.9% retention). High-risk factors were: subthreshold or clinical anxiety, impaired activities of daily living, physical/functional limitation, medical comorbidity, cognitive impairment, caregiving burden, problem drinking, and low psychosocial support. Co-primary outcomes were: incident major depression (MDD), adjudicated using DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, 4th edition); change in mood (Patient Health Questionnaire-9 [PHQ-9]). We used exact tests to determine treatment effects on MDD incidence and repeated measures models to determine treatment effects on PHQ-9.

11.1% had subthreshold depression, 60.8% had ≥1 high-risk factors, MDD incidence=4.7% (5.0% among completers), and mean PHQ-9 change=0.02 points. Among those with subthreshold depression, the MDD risk ratio (95% confidence intervals)=0.36 (0.06 to 1.28) for vitamin D3 and 0.85 (0.25 to 2.92) for omega-3s, compared to placebos; results were also null among those with ≥1 high-risk factors [vitamin D3 vs. placebo: 0.63 (0.25 to 1.53); omega-3s vs. placebo: 1.08 (0.46 to 2.71)]. There were no significant differences in PHQ-9 change comparing either supplement with placebo.

Neither vitamin D3 nor omega-3s showed benefits for indicated and selective prevention of late-life depression; statistical power was limited.

To investigate the relationship between lean muscle mass and treatment response in treatment-resistant late-life depression (TR-LLD). We hypothesized that lower lean muscle mass would be associated with older age, higher physical comorbidities, higher depressive symptom severity, and poorer treatment response.

Secondary analysis of a randomized, placebo-controlled trial.

Three academic hospitals in the United States and Canada.

Adults aged 60+ years with major depressive disorder who did not remit following open treatment with venlafaxine extended-release (XR) (n = 178).

We estimated lean muscle mass using dual-energy X-ray absorptiometry (DEXA) scans prior to and following randomized treatment with aripiprazole or placebo added to venlafaxine XR. Multivariate regressions estimated influence of demographic and clinical factors on baseline lean muscle mass, and whether baseline lean muscle mass was associated with treatment response, adjusted for treatment arm.

Low lean muscle mass was present in 22 (12.4%) participants. Older age and female sex, but not depressive symptom severity, were independently associated with lower lean muscle mass at baseline. Marital status, baseline depressive symptom severity, and treatment group were associated with improvement of depressive symptoms in the randomized treatment phase. Baseline lean muscle mass was not associated with improvement, regardless of treatment group.

As expected, older age and female sex were associated with lower lean muscle mass in TR-LLD. However, contrary to prior results in LLD, lean muscle mass was not associated with depression severity or outcome. This suggests that aripiprazole augmentation may be useful for TR-LLD, even in the presence of anomalous body composition.

clinicaltrials.gov Identifier: NCT00892047.

Self-reported activity restriction is an established correlate of depression in dementia caregivers (dCGs). It is plausible that the daily distribution of objectively measured activity is also altered in dCGs with depression symptoms; if so, such activity characteristics could provide a passively measurable marker of depression or specific times to target preventive interventions. We therefore investigated how levels of activity throughout the day differed in dCGs with and without depression symptoms, then tested whether any such differences predicted changes in symptoms 6 months later.

We examined 56 dCGs (mean age = 71, standard deviation (SD) = 6.7; 68% female) and used clustering to identify subgroups which had distinct depression symptom levels, leveraging baseline Center for Epidemiologic Studies of Depression Scale–Revised Edition and Patient Health Questionnaire-9 (PHQ-9) measures, as well as a PHQ-9 score from 6 months later. Using wrist activity (mean recording length = 12.9 days, minimum = 6 days), we calculated average hourly activity levels and then assessed when activity levels relate to depression symptoms and changes in symptoms 6 months later.

Clustering identified subgroups characterized by: (1) no/minimal symptoms (36%) and (2) depression symptoms (64%). After multiple comparison correction, the group of dCGs with depression symptoms was less active from 8 to 10 AM (Cohen’s d ≤ −0.9). These morning activity levels predicted the degree of symptom change on the PHQ-9 6 months later (per SD unit β = −0.8, 95% confidence interval: −1.6, −0.1, p = 0.03) independent of self-reported activity restriction and other key factors.

These novel findings suggest that morning activity may protect dCGs from depression symptoms. Future studies should test whether helping dCGs get active in the morning influences the other features of depression in this population (i.e. insomnia, intrusive thoughts, and perceived activity restriction).

The Hamilton Depression Rating Scale (HAMD) and the Beck Depression Inventory (BDI) are the most frequently used observer-rated and self-report scales of depression, respectively. It is important to know what a given total score or a change score from baseline on one scale means in relation to the other scale.

We obtained individual participant data from the randomised controlled trials of psychological and pharmacological treatments for major depressive disorders. We then identified corresponding scores of the HAMD and the BDI (369 patients from seven trials) or the BDI-II (683 patients from another seven trials) using the equipercentile linking method.

The HAMD total scores of 10, 20 and 30 corresponded approximately with the BDI scores of 10, 27 and 42 or with the BDI-II scores of 13, 32 and 50. The HAMD change scores of −20 and −10 with the BDI of −29 and −15 and with the BDI-II of −35 and −16.

The results can help clinicians interpret the HAMD or BDI scores of their patients in a more versatile manner and also help clinicians and researchers evaluate such scores reported in the literature or the database, when scores on only one of these scales are provided. We present a conversion table for future research.

Distinguishing a disorder of persistent and impairing grief from normative grief allows clinicians to identify this often undetected and disabling condition. As four diagnostic criteria sets for a grief disorder have been proposed, their similarities and differences need to be elucidated.

Participants were family members bereaved by US military service death (N = 1732). We conducted analyses to assess the accuracy of each criteria set in identifying threshold cases (participants who endorsed baseline Inventory of Complicated Grief ⩾30 and Work and Social Adjustment Scale ⩾20) and excluding those below this threshold. We also calculated agreement among criteria sets by varying numbers of required associated symptoms.

All four criteria sets accurately excluded participants below our identified clinical threshold (i.e. correctly excluding 86–96% of those subthreshold), but they varied in identification of threshold cases (i.e. correctly identifying 47–82%). When the number of associated symptoms was held constant, criteria sets performed similarly. Accurate case identification was optimized when one or two associated symptoms were required. When employing optimized symptom numbers, pairwise agreements among criteria became correspondingly ‘very good’ (κ = 0.86–0.96).

The four proposed criteria sets describe a similar condition of persistent and impairing grief, but differ primarily in criteria restrictiveness. Diagnostic guidance for prolonged grief disorder in International Classification of Diseases, 11th Edition (ICD-11) functions well, whereas the criteria put forth in Section III of Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) are unnecessarily restrictive.

The World Health Organization (WHO) International Classification of Disease (ICD-11) is expected to include a new diagnosis for prolonged grief disorder (ICD-11PGD). This study examines the validity and clinical utility of the ICD-11PGD guideline by testing its performance in a well-characterized clinical sample and contrasting it with a very different criteria set with the same name (PGDPLOS).

We examined data from 261 treatment-seeking participants in the National Institute of Mental Health (NIMH)-sponsored multicenter clinical trial to determine the rates of diagnosis using the ICD-11PGD guideline and compared these with diagnosis using PGDPLOS criteria.

The ICD-11PGD guideline identified 95.8% [95% confidence interval (CI) 93.3–98.2%] of a treatment-responsive cohort of patients with distressing and impairing grief. PGDPLOS criteria identified only 59.0% (95% CI 53.0–65.0%) and were more likely to omit those who lost someone other than a spouse, were currently married, bereaved by violent means, or not diagnosed with co-occurring depression. Those not diagnosed by PGDPLOS criteria showed the same rate of treatment response as those who were diagnosed.

The ICD-11PGD diagnostic guideline showed good performance characteristics in this sample, while PGDPLOS criteria did not. Limitations of the research sample used to derive PGDPLOS criteria may partly explain their poor performance in a more diverse clinical sample. Clinicians and researchers need to be aware of the important difference between these two identically named diagnostic methods.

Insomnia increases in prevalence with age, is strongly associated with depression, and has been identified as a risk factor for suicide in several studies. The aim of this study was to determine whether insomnia severity varies between those who have attempted suicide (n = 72), those who only contemplate suicide (n = 28), and those who are depressed but have no suicidal ideation or attempt history (n = 35).

Participants were middle-aged and older adults (age 44–87, M = 66 years) with depression. Insomnia severity was measured as the sum of the early, middle, and late insomnia items from the Hamilton Rating Scale for Depression. General linear models examined relations between group status as the independent variable and insomnia severity as the dependent variable.

The suicide attempt group suffered from more severe insomnia than the suicidal ideation and non-suicidal depressed groups (p < 0.05). Differences remained after adjusting for potential confounders including demographics, cognitive ability, alcohol dependence in the past month, severity of depressed mood, anxiety, and physical health burden. Moreover, greater insomnia severity in the suicide attempt group could not be explained by interpersonal difficulties, executive functioning, benzodiazepine use, or by the presence of post-traumatic stress disorder.

Our results suggest that insomnia may be more strongly associated with suicidal behavior than with the presence of suicidal thoughts alone. Accordingly, insomnia is a potential treatment target for reducing suicide risk in middle-aged and older adults.

There is controversy about whether psychotherapies are effective in the treatment of subclinical depression, defined by clinically relevant depressive symptoms in the absence of a major depressive disorder.

To examine whether psychotherapies are effective in reducing depressive symptoms, reduce the risk of developing major depressive disorder and have comparable effects to psychological treatment of major depression.

We conducted a meta-analysis of 18 studies comparing a psychological treatment of subclinical depression with a control group.

The target groups, therapies and characteristics of the included studies differed considerably from each other, and the quality of many studies was not optimal. Psychotherapies did have a small to moderate effect on depressive symptoms against care as usual at the post-test assessment (g = 0.35, 95% CI 0.23–0.47; NNT = 5, 95% CI 4–8) and significantly reduced the incidence of major depressive episodes at 6 months (RR = 0.61) and possibly at 12 months (RR = 0.74). The effects were significantly smaller than those of psychotherapy for major depressive disorder and could be accounted for by non-specific effects of treatment.

Psychotherapy may be effective in the treatment of subclinical depression and reduce the incidence of major depression, but more high-quality research is needed.

Surrogates involved in decisions to limit life-sustaining treatment for a loved one in the intensive care unit (ICU) are at increased risk for adverse psychological outcomes that can last for months to years after the ICU experience. Post-ICU interventions to reduce surrogate distress have not yet been developed. We sought to (1) describe a conceptual framework underlying the beneficial mental health effects of storytelling, and (2) present formative work developing a storytelling intervention to reduce distress for recently bereaved surrogates.

An interdisciplinary team conceived the idea for a storytelling intervention based on evidence from narrative theory that storytelling reduces distress from traumatic events through emotional disclosure, cognitive processing, and social connection. We developed an initial storytelling guide based on this theory and the clinical perspectives of team members. We then conducted a case series with recently bereaved surrogates to iteratively test and modify the guide.

The storytelling guide covered three key domains of the surrogate's experience of the patient's illness and death: antecedents, ICU experience, and aftermath. The facilitator focused on the parts of a story that appeared to generate strong emotions and used nonjudgmental statements to attend to these emotions. Between September 2012 and May 2013, we identified 28 eligible surrogates from a medical ICU and consented 20 for medical record review and recontact; 10 became eligible, of whom 6 consented and completed the storytelling intervention. The single-session storytelling intervention lasted from 40 to 92 minutes. All storytelling participants endorsed the intervention as acceptable, and five of six reported it as helpful.

Surrogate storytelling is an innovative and acceptable post-ICU intervention for recently bereaved surrogates and should be evaluated further.

Late-life depression may increase the risk of incident dementia, in particular of Alzheimer's disease and vascular dementia.

To conduct a systematic review and meta-analysis to evaluate the risk of incident all-cause dementia, Alzheimer's disease and vascular dementia in individuals with late-life depression in population-based prospective studies.

A total of 23 studies were included in the meta-analysis. We used the generic inverse variance method with a random-effects model to calculate the pooled risk of dementia, Alzheimer's disease and vascular dementia in older adults with late-life depression.

Late-life depression was associated with a significant risk of all-cause dementia (1.85, 95% CI 1.67-2.04, P< 0.001), Alzheimer's disease (1.65, 95% CI 1.42-1.92, P<0.001) and vascular dementia (2.52, 95% CI 1.77-3.59, P<0.001). Subgroup analysis, based on five studies, showed that the risk of vascular dementia was significantly higher than for Alzheimer's disease (P=0.03).

Late-life depression is associated with an increased risk for all-cause dementia, vascular dementia and Alzheimer's disease. The present results suggest that it will be valuable to design clinical trials to investigate the effect of late-life depression prevention on risk of dementia, in particular vascular dementia and Alzheimer's disease.