The body of evidence of late-life depression: the complex relationship between depressive symptoms, movement, dyspnea and cognition.

BACKGROUND: Physical symptoms play an important role in late-life depression and may contribute to residual symptomatology after antidepressant treatment. In this exploratory study, we examined the role of specific bodily dimensions including movement, respiratory functions, fear of falling, cognition, and physical weakness in older people with depression. METHODS: Clinically stable older patients with major depression within a Psychiatric Consultation-Liaison program for Primary Care underwent comprehensive assessment of depressive symptoms, instrumental movement analysis, dyspnea, weakness, activity limitations, cognitive function, and fear of falling. Network analysis was performed to explore the unique adjusted associations between clinical dimensions. RESULTS: Sadness was associated with worse turning and walking ability and movement transitions from walking to sitting, as well as with worse general cognitive abilities. Sadness was also connected with dyspnea, while neurovegetative depressive burden was connected with activity limitations. DISCUSSION: Limitations of motor and cognitive function, dyspnea, and weakness may contribute to the persistence of residual symptoms of late-life depression.

Antidepressant Drugs Effects on Blood Pressure.

Individuals suffering from depressive disorders display a greater incidence of hypertension compared with the general population, despite reports of the association between depression and hypotension. This phenomenon may depend, at least in part, on the use of antidepressant drugs, which may influence blood pressure through different effects on adrenergic and serotoninergic pathways, as well as on histaminergic, dopaminergic, and cholinergic systems. This review summarizes extant literature on the effect of antidepressant drugs on blood pressure. Selective serotonin reuptake inhibitors are characterized by limited effects on autonomic system activity and a lower impact on blood pressure. Thus, they represent the safest class-particularly among elderly and cardiovascular patients. Serotonin-norepinephrine reuptake inhibitors, particularly venlafaxine, carry a greater risk of hypertension, possibly related to greater effects on the sympathetic nervous system. The norepinephrine reuptake inhibitor reboxetine is considered a safe option because of its neutral effects on blood pressure in long-term studies, even if both hypotensive and hypertensive effects are reported. The dopamine-norepinephrine reuptake inhibitor bupropion can lead to blood pressure increases, usually at high doses, but may also cause orthostatic hypotension, especially in patients with cardiovascular diseases. The norepinephrine-serotonin modulators, mirtazapine and mianserin, have minimal effects on blood pressure but may rarely lead to orthostatic hypotension and falls. These adverse effects are also observed with the serotonin-reuptake modulators, nefazodone and trazodone, but seldomly with vortioxetine and vilazodone. Agomelatine, the only melatonergic antidepressant drug, may also have limited effects on blood pressure. Tricyclic antidepressants have been associated with increases in blood pressure, as well as orthostatic hypotension, particularly imipramine. Oral monoamine-oxidase inhibitors, less frequently skin patch formulations, have been associated with orthostatic hypotension or, conversely, with hypertensive crisis due to ingestion of tyramine-containing food (i.e., cheese reaction). Lastly, a hypertensive crisis may complicate antidepressant treatment as a part of the serotonin syndrome, also including neuromuscular, cognitive, and autonomic dysfunctions. Clinicians treating depressive patients should carefully consider their blood pressure status and cardiovascular comorbidities because of the effects of antidepressant drugs on blood pressure profiles and potential interactions with antihypertensive treatments.

Instrumental assessment of balance and gait in depression: A systematic review.

Psychomotor symptoms of depression are understudied despite having a severe impact on patient outcomes. This review aims to summarize the evidence on motor features of depression assessed with instrumental procedures, and examine age-related differences. We included studies investigating posture, balance and gait ascertained with instrumental measurements among individuals with depressive symptoms or disorders. Studies on subjects with specific physical illnesses were excluded. Methodological quality was assessed with the Newcastle - Ottawa Scale (NOS) and PRISMA guidelines were followed. 33 studies (13 case-control, five cross-sectional, nine longitudinal and six intervention) with overall low-medium quality were included. Different instruments were employed to assess posture (e.g. digital cameras), balance (balance, stepping platform) or gait (e.g. Six-Minute-Walking Test, instrumented walkways). Results suggest that depression in adults is associated with significant impairments of posture, balance and gait. Motor abnormalities among depressed older adults may depend on the interplay of physical diseases, cognitive impairment and mood. Very few intervention studies measured motor symptoms as outcome. Available evidence suggests, however, that antidepressant drugs and physical exercise may be beneficial for motor abnormalities. Despite the lack of high-quality studies, instrumental assessments confirm the presence and importance of motor abnormalities in depression, with potential age-related differences in their pathophysiology.

Physical exercise for late-life depression: Effects on symptom dimensions and time course.

BACKGROUND: Physical exercise is increasingly recognized as a treatment for major depression, even among older patients. However, it is still unknown which depressive symptoms exercise affects most, (e.g. somatic vs. affective) and the timing of its effects. Thus, the aim of this study was to examine the changes of depressive symptoms after treatment with exercise. METHODS: We analyzed data from the SEEDS study, a trial comparing the antidepressant effectiveness of sertraline (S) and sertraline plus exercise (S+EX). Exercise was delivered thrice weekly in small groups and monitored by heart rate meters. Patients with late life depression (n=121) were assessed at baseline, 4, 8, 12 and 24 weeks with the Hamilton Depression Scale. Scores of affective, vegetative, anxiety and agitation/insight factors were analyzed using Multilevel Growth Curve Models and sensitivity analyses (multiple imputation). RESULTS: Compared with the S group, patients in the S+EX group displayed significantly greater improvements of the affective symptom dimension (total effect size = 0.79) with largest changes in the first 4 weeks and last 12 weeks. Improvements were mainly driven by depressed mood and psychomotor retardation. LIMITATIONS: Sample size; lack of an exercise only treatment arm CONCLUSIONS: Adding exercise to antidepressant drug treatment may offer significant advantages over affective symptoms of depression, rather than somatic symptoms or other dimensions of depression. Compared with standard antidepressant treatment, clinical advantages should be expected both at an early (first 4 weeks) and later stage (after 12 weeks).

Physical Exercise in Major Depression: Reducing the Mortality Gap While Improving Clinical Outcomes.

Major depression shortens life while the effectiveness of frontline treatments remains modest. Exercise has been shown to be effective both in reducing mortality and in treating symptoms of major depression, but it is still underutilized in clinical practice, possibly due to prevalent misperceptions. For instance, a common misperception is that exercise is beneficial for depression mostly because of its positive effects on the body ("from the neck down"), whereas its effectiveness in treating core features of depression ("from the neck up") is underappreciated. Other long-held misperceptions are that patients suffering from depression will not engage in exercise even if physicians prescribe it, and that only vigorous exercise is effective. Lastly, a false assumption is that exercise may be more harmful than beneficial in old age, and therefore should only be recommended to younger patients. This narrative review summarizes relevant literature to address the aforementioned misperceptions and to provide practical recommendations for prescribing exercise to individuals with major depression.

Physical exercise for late life depression: effects on cognition and disability.

BACKGROUND: Late-life depression is often associated with cognitive impairments and disability, which may persist even after adequate antidepressant drug treatment. Physical exercise is increasingly recognized as an effective antidepressant agent, and may exert positive effects on these features too. However, few studies examined this issue, especially by comparing different types of exercises. METHODS: We performed secondary analyses on data from the Safety and Efficacy of Exercise for Depression in Seniors study, a trial comparing the antidepressant effectiveness of sertraline (S), sertraline plus thrice-weekly non-progressive exercise (S+NPE), and sertraline plus thrice-weekly progressive aerobic exercise (S+PAE). Exercise was conducted in small groups and monitored by heart rate meters. Patients with late-life depression without severe cognitive impairment were recruited from primary care and assessed at baseline and 24 weeks, using the Montreal Cognitive Assessment (MOCA, total and subdomain scores) and Brief Disability Questionnaire. Analyses were based on Generalized Linear Models. RESULTS: In total, 121 patients (mean age 75, 71% females) were randomized to the study interventions. Compared with the S group, patients in the S+PAE group displayed greater improvements of MOCA total scores (p=0.006, effect size=0.37), visuospatial/executive functions (p=0.001, effect size=0.13), and disability (p=0.02, effect size=-0.31). Participants in the S+NPE group did not display significant differences with the control group. CONCLUSIONS: Adding aerobic, progressive exercise to antidepressant drug treatment may offer significant advantages over standard treatment for cognitive abilities and disability. These findings suggest that even among older patients exercise may constitute a valid therapeutic measure to improve patients' outcomes.

Physical Exercise for Late-Life Depression: Customizing an Intervention for Primary Care.

OBJECTIVES: To identify which individual- and context-related factors influence the translation into clinical practice of interventions based on physical exercise (PE) as an adjunct to antidepressants (AD) for the treatment of late-life major depression (LLMD). DESIGN: Secondary analysis of a randomized controlled trial. SETTING: Primary care with psychiatric consultation-liaison programs (PCLPs)-organizational protocols that regulate the clinical management of individuals with psychiatric disorders. PARTICIPANTS: Individuals aged 65 and older with major depression according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (N = 121). INTERVENTION: Participants with LLMD were randomized to AD (sertraline) or AD plus PE (AD + PE). MEASUREMENTS: Participant characteristics that were associated with greater effectiveness of AD + PE (moderators) were identified, and effect sizes were calculated from success rate differences. Whether the characteristics of the study setting influenced participant flow and attendance at exercise sessions was then explored, and primary care physicians (PCPs) were surveyed regarding their opinions on PE as a treatment for LLMD. RESULTS: The following participant characteristics were associated with greater likelihood of achieving remission from depression with AD + PE than with AD alone: aged 75 and older (effect size 0.32), polypharmacy (0.35), greater aerobic capacity (0.48), displaying psychomotor slowing (0.49), and less-severe anxiety (0.30). The longer the PCLP had been established at a particular center, the more individuals were recruited at that center. After participating in the study, PCPs expressed positive views on AD + PE as a treatment for LLMD and were more likely to use this as a therapeutic strategy. CONCLUSIONS: The combination of PE and sertraline could improve the management of LLMD, especially when customized for individuals with specific clinical features. Liaison programs might influence the implementation of similar interventions in primary care, and PCPs viewed them positively.

Physical Exercise for Late-Life Depression: Effects on Heart Rate Variability.

OBJECTIVES: Late-life major depression is associated with increased cardiovascular risk and impaired autonomic control of the heart, as evident from reduced heart rate variability (HRV). Moreover, antidepressant drug therapy also might be associated with further reductions of HRV. In the SEEDS study, we investigated whether sertraline associated with physical exercise protocols led to improvements of HRV, compared with antidepressant drug therapy alone. DESIGN: Single-blind randomized controlled trial. SETTING: Psychiatric consultation-liaison program for primary care. PARTICIPANTS: Patients aged 65-85 years with major depression, recruited from primary care. INTERVENTIONS: Sertraline plus structured, tailored group physical exercise (S + EX) versus sertraline alone (S) for 24 weeks. MEASUREMENTS: HRV indices (RR, percentage of NN intervals greater than 50 msec [pNN50], square root of the mean squared differences of successive NN intervals [RMSSD], standard deviation of heart rate [SDHR], standard deviation of the NN interval [SDNN], high-frequency band [HF], low-frequency band [LF], and their ratio [LF/HF]) were measured at baseline, week 12, and week 24. Psychiatric and medical assessments. RESULTS: Participants displayed significant improvements of most HRV indices over time, irrespective of the group assignment (pNN50, RMSSD, SDHR, SDNN, HF, LF, and LF/HF). Moreover, patients in the S + EX group displayed greater increases of different HRV indices(RR, pNN50, RMSSD, SDHR, SDNN, HF, and LF) compared with those in the S group. CONCLUSIONS: The combination of structured physical exercise and sertraline might exert positive effects on the autonomic control of the heart among older patients with major depression.

HPA axis and aging in depression: systematic review and meta-analysis.

One of the most consistent findings in the biology of depression is an altered activity of the hypothalamic-pituitary-adrenal (HPA) axis. However, data concerning this issue have never been examined with a focus on the older population. Here we present a systematic review and meta-analysis, based on studies investigating levels of cortisol, adrenocorticotropic hormone (ACTH) and corticotropin-releasing hormone (CRH) in depressed participants older than 60 and compared with healthy controls. We found 20 studies, for a total of 43 comparisons on different indices of HPA axis functioning. Depression had a significant effect (Hedges' g) on basal cortisol levels measured in the morning (0.89), afternoon (0.83) and night (1.39), but a smaller effect on cortisol measured continuously (0.51). The effect of depression was even higher on post-dexamethasone cortisol levels (3.22), whereas it was non-significant on morning ACTH and CRH levels. Subgroup analyses indicated that various methodological and clinical factors can influence the study results. Overall, older participants suffering from depression show a high degree of dysregulation of HPA axis activity, with differences compared with younger adults. This might depend on several mechanisms, including physical illnesses, alterations in the CNS and immune-endocrinological alterations. Further studies are needed to clarify the implications of altered HPA axis activity in older patients suffering from depression. Novel pharmacological approaches might be effective in targeting this pathophysiological feature, thus improving the clinical outcomes.