Psychological Treatment of Depression in People Aged 65 Years and Over: A Systematic Review of Efficacy, Safety, and Cost-Effectiveness.

OBJECTIVES: Depression in elderly people is a major public health concern. As response to antidepressants is often unsatisfactory in this age group, there is a need for evidence-based non-pharmacological treatment options. Our objectives were twofold: firstly, to synthesize published trials evaluating efficacy, safety and cost-effectiveness of psychological treatment of depression in the elderly and secondly, to assess the quality of evidence. METHOD: The electronic databases PubMed, EMBASE, Cochrane Library, CINAL, Scopus, and PsycINFO were searched up to 23 May 2016 for randomized controlled trials (RCTs) of psychological treatment for depressive disorders or depressive symptoms in people aged 65 years and over. Two reviewers independently assessed relevant studies for risk of bias. Where appropriate, the results were synthesized in meta-analyses. The quality of the evidence was graded according to GRADE (Grading of Recommendations Assessment, Development and Evaluation). RESULTS: Twenty-two relevant RCTs were identified, eight of which were excluded from the synthesis due to a high risk of bias. Of the remaining trials, six evaluated problem-solving therapy (PST), five evaluated other forms of cognitive behavioural therapy (CBT), and three evaluated life review/reminiscence therapy. In frail elderly with depressive symptoms, the evidence supported the efficacy of PST, with large but heterogeneous effect sizes compared with treatment as usual. The results for life-review/reminiscence therapy and CBT were also promising, but because of the limited number of trials the quality of evidence was rated as very low. Safety data were not reported in any included trial. The only identified cost-effectiveness study estimated an incremental cost per additional point reduction in Beck Depression Inventory II score for CBT compared with talking control and treatment as usual. CONCLUSION: Psychological treatment is a feasible option for frail elderly with depressive symptoms. However, important questions about efficacy, generalizability, safety and cost-effectiveness remain.

Efficacy and tolerability of antidepressants in people aged 65 years or older with major depressive disorder - A systematic review and a meta-analysis.

BACKGROUND: There has been a steady increase in the prescription of antidepressants for the elderly. This study comprises a systematic review of randomized, placebo-controlled trials of antidepressants for treatment of depressive disorder in people aged 65 years or more. METHODS: PubMed, EMBASE, Cochrane Library, CINAL, and PsycINFO were searched until May 2016. Where appropriate, the results were synthesized in meta-analyses. RESULTS: Twelve trials met the inclusion criteria. For patients with major depressive disorder, selective serotonin re-uptake inhibitors (SSRI) were not superior to placebo in achieving remission (OR: 0.79, 95% CI: 0.61-1.03) or response (OR=0.86, 95% CI: 0.51-1.10) after 8 weeks of treatment (three trials). However, maintenance treatment with SSRIs was superior to placebo in preventing relapse (OR: 0.22, 95% CI: 0.13-0.36; NNT=5, 95% CI: 3-6; two trials). Duloxetine was superior to placebo in achieving remission (OR: 1.78, 95% CI: 1.20-2.65; NNT=9, 95% CI: 6-20; three trials) and response (OR: 1.83, 95% CI: 1.96-4.08; two trials) in recurrent major depression after 8 weeks, but increased the risk of adverse events that can be problematic in the elderly. LIMITATIONS: The quality of evidence was generally low or moderate, emphasizing the uncertainty of the results. Study populations only partly covered the heterogeneous population of elderly with depressed mood, limiting the generalizability. CONCLUSION: The results underscore the importance of close monitoring of the effects of antidepressants in treatment of elderly patients with a depressive disorder. Methods for early detection of non-responders and effective treatment options for this group are needed.

Antidepressant use and mortality in very old people.

BACKGROUND: Antidepressant treatment may increase the risk of death. The association between antidepressants and mortality has been evaluated in community-dwelling older people, but not in representative samples of very old people, among whom dementia, multimorbidity, and disability are common. METHODS: Umeå 85+/GERDA study participants (n = 992) aged 85, 90, and ≥95 years were followed for up to five years. Cox proportional hazard regression models were used to analyze mortality risk associated with baseline antidepressant treatment, adjusted for potential confounders. RESULTS: Mean age was 89 years; 27% of participants had dementia, 20% had stroke histories, 29% had heart failure, and 16% used antidepressants. In age- and sex-adjusted analyses, antidepressant use was associated with a 76% increased mortality risk (hazard ratio [HR] = 1.76; 95% confidence interval [CI], 1.41-2.19). Adding adjustment for Geriatric Depression Scale score, HR was 1.62 (95% CI, 1.29-2.03). The association was not significant when adjusting for additional confounding factors (HR = 1.08; 95% CI, 0.85-1.38). Interaction analyses in the fully adjusted model revealed a significant interaction between sex and antidepressant use (HR: 1.76; 95% CI, 1.05-2.94). Among male and female antidepressant users, the HRs for death were 0.76 (95% CI, 0.47-1.24) and 1.28 (95% CI, 0.97-1.70), respectively. CONCLUSION: Among very old people, baseline antidepressant treatment does not seem to be independently associated with increased mortality risk. However, the risk may be different in men and women. This difference and the potential risk of initial treatment require further investigation in future cohort studies of very old people.

Symptoms of Depression are Common in Patients With Idiopathic Normal Pressure Hydrocephalus: The INPH-CRasH Study.

BACKGROUND: If patients with idiopathic normal pressure hydrocephalus (INPH) also have depression, this could have important clinical ramifications in assessment and management of their cognitive function and response to shunting. In many dementias, depression is overrepresented, but the prevalence of depression in shunted patients with INPH is unknown. OBJECTIVE: The objective of this case-control study was to assess the prevalence of symptoms of depression in shunted INPH patients compared with population-based controls. METHODS: INPH patients consecutively shunted from 2008 to 2010 in Sweden were analyzed. Patients remaining after inclusion (within 60-85 years and not having dementia, ie, mini-mental state examination ≥23) had a standardized visit to their healthcare provider and answered an extensive questionnaire. Age- and sex-matched population-based controls underwent the same procedure. Symptoms of depression were assessed using the Geriatric Depression Scale 15 (suspected depression defined as ≥5 points, suspected severe depression as ≥12 points). This study is part of the INPH-CRasH study. RESULTS: One hundred seventy-six INPH patients and 368 controls participated. After adjustment for age, sex, cerebrovascular disease, and systolic and diastolic blood pressure, patients had a higher mean depression score (patients: 4.9 ± 3.7 SD, controls: 1.9 ± 2.3 SD; OR 1.4, 95% CI 1.3-1.6, P < .001), more patients had suspected depression (46% vs 13%, OR 6.4, 95% CI 3.8-10.9, P < .001), and more patients had suspected severe depression (7.3% vs 0.6%, OR 14.4, 95% CI 3.0-68.6, P < .005). CONCLUSION: Symptoms of depression are overrepresented in INPH patients compared with the population, despite treatment with a shunt. Screening for depression should be done in the evaluation of INPH patients in order to find and treat a coexisting depression.

Risk factors for depressive disorders in very old age: a population-based cohort study with a 5-year follow-up.

PURPOSE: Depressive disorders are common among the very old, but insufficiently studied. The present study aims to identify risk factors for depressive disorders in very old age. METHODS: The present study is based on the GERDA project, a population-based cohort study of people aged ≥85 years (n = 567), with 5 years between baseline and follow-up. Factors associated with the development of depressive disorders according to DSM-IV criteria at follow-up were analysed by means of a multivariate logistic regression. RESULTS: At baseline, depressive disorders were present in 32.3 % of the participants. At follow-up, 69 % of those with baseline depressive disorders had died. Of the 49 survivors, 38 still had depressive disorders. Of the participants without depressive disorders at baseline, 25.5 % had developed depressive disorders at follow-up. Baseline factors independently associated with new cases of depressive disorders after 5 years were hypertension, a history of stroke and 15-item Geriatric Depression Scale score at baseline. CONCLUSIONS: The present study supports the earlier findings that depressive disorders among the very old are common, chronic and malignant. Mild depressive symptoms as indicated by GDS-15 score and history of stroke or hypertension seem to be important risk factors for incident depressive disorders in very old age.

Platelet serotonin transporter and 5-HT2A receptor binding in adolescents with eating disorders.

The pathogenetic involvement of the serotonergic system in eating disorders is an established finding. Conclusions from platelet studies are based on results from investigations of subjects with a mean age of 20 years or more. The aim was to investigate whether previous findings in adults are valid also for adolescents who are examined within a relatively short interval after the onset of the eating disorder. [(3)H]paroxetine binding to the platelet serotonin transporter and [(3)H]lysergic acid diethylamide ([(3)H]LSD) binding to the 5-HT2A receptor was studied in 15 female adolescents with eating disorders (11 with anorexia nervosa and 4 with clearly anorectic eating behaviour not fulfilling the criteria for anorexia nervosa) and 32 controls. The patients revealed a higher density of serotonin transporters and a lower density of 5-HT2A receptors compared with healthy controls of the same age (775 ± 165 vs. 614 ± 111 fmol/mg protein (p = 0.003) for [(3)H]paroxetine binding and 215 ± 59 vs. 314 ± 151 fmol/mg protein (p = 0.005) for [(3)H]LSD binding). The findings of increased density of platelet serotonin transporters and reduced density of 5-HT2A receptors differ from previous results in older patients. The lower patient age and the short duration of disease in the present study, possibly in conjunction with variations in stress-related psychological and biological factors, may have caused these differences. Although the present findings contradict prevailing evidence, they add further information concerning the nature of serotonergic involvement in eating disorders and indicate that demographic and course-related factors might influence the regulation of the serotonin system in these disorders.

Radioligand binding to brain dopamine and serotonin receptors and transporters in Parkinson's disease: relation to gene polymorphisms.

The influence of variations in genes coding for dopamine and serotonin transporters and receptors on the expression of these structures in the brains of patients with Parkinson's disease (PD) is not known. In order to investigate the significance of dopamine and serotonin transporter and receptor gene polymorphisms on the expression of dopamine and serotonin transporters and the dopamine D(2) and serotonin 5HT(2A) receptors in brain tissue in PD, we conducted a study on brain autopsy material from 16 patients diagnosed with clinical PD and 11 controls. The polymorphisms studied were DAT1 VTNR, DRD2 Taq1A, 5HTTLPR, and 5HTR2A 102 T>C, 516 C>T, His425Tyr, and Thr25Asn. Compared to control subjects, patients with PD had a significantly lowered radioligand binding to the dopamine transporter (DAT) in nucleus caudatus (p = .001) and putamen (p = .008), and to the serotonin transporter in gyrus cingulatus (p = .010) and nucleus caudatus (p = .032). We did not observe any significant associations between genetic polymorphisms and the extent of radioligand binding or between the polymorphisms and a diagnosis of PD. In conclusion, the density of brain dopamine and serotonin transporters in patients with PD was reduced. However, there were no associations between the investigated genotypes and the expression of the corresponding receptors and transporters.

Depression among the very old with dementia.

OBJECTIVES: The aim of this study was to investigate the prevalence of depression among very old individuals with dementia compared to those without dementia and to examine if there were any differences regarding associated factors between people with or without depression in these conditions. METHODS: In a population-based study in Sweden, 363 participants aged 85 years and above, were evaluated for depression and dementia. RESULTS: The prevalence of depression was significantly higher among the people with dementia than without dementia, 43% vs. 24% (p < 0.001). Approximately 2/3 of the depressed in both groups used antidepressants and of those, approximately 50% had responded. Depression in the group without dementia was, among other factors, associated with higher total number of medication, the use of significant more analgesics and benzodiazepines, loneliness, inability of going outside and recent loss of child. The loss of a child was the only factor that was independently associated with depression in those with dementia. CONCLUSIONS: The present study confirms that in the very old, depression is more common among people with dementia than without dementia. A large proportion, both with and without dementia, are under-diagnosed and untreated, and in addition many subjects in both groups studied were non-responders to treatment. Many of the factors associated with depression among people without dementia in this study were not associated with depression among those with dementia, thus supporting the theory that the spectrum of associated factors for depression in dementia seems to be different from that for depression in people without dementia.

Gender differences in depression among the very old.

OBJECTIVES: The aim of this study was to investigate factors associated with depression among men and women aged 85 and over. METHOD: A population-based study was undertaken in northern Sweden. Out of 527 eligible participants, aged 85, 90 or > or = 95, 363 were evaluated for depression. Data were collected from structured interviews, assessments and medical charts and from relatives and caregivers. Depression was screened for using the Geriatric Depression Scale-15 and further assessed using the Montgomerysberg Depression Rating Scale (MADRS). RESULTS: A higher proportion of women were diagnosed with depression (33% vs. 18.6%, p = 0.006). In both men and women experienced loneliness (OR 3.4 vs. 7.0) and not going outside independently (OR 2.6 vs. 26.0) were associated with depression in the final regression model. Depression among men was also independently associated with loss of a child/children during the preceeding ten years (OR 30.0). CONCLUSION: Depression was more common among women than among men. Experienced loneliness and not going outside independently seem to be closely related to depression in both men and women. Loss of a child seems to be the most important factor among men.

Age-correlated decline in [3H]tiagabine binding to GAT-1 in human frontal cortex.

BACKGROUND AND AIMS: In spite of the fact that GABA is a significant transmitter, little is known about the GABA system in aging, compared with other transmitter systems. [(3)H]tiagabine is a ligand for GABAergic neurons, which binds with 10-fold higher affinity to the GABA uptake site than [(3)H]nipecotic acid. The aim of this study was to study the binding of [(3)H]tiagabine to the GABA transporter 1, GAT-1, in human frontal cortex and cingulate cortex from individuals of varying ages. METHODS: [(3)H]tiagabine binding experiments were conducted on post-mortem brain tissue from 19 individuals (age range 17-78 years) without known neurological or psychiatric disorders. Binding data vs age and postmortem interval was analysed by Pearson correlation. RESULTS: The density of [(3)H]tiagabine binding to GAT- 1 decreased significantly with increasing age in the frontal cortex, whereas binding affinity was unchanged. No significant alterations in binding parameters were observed in the cingulate cortex. No correlation was found between post-mortem delay and the number of [(3)H]tiagabine binding sites. CONCLUSIONS: According to the present study, presynaptical alterations in the GABA system are correlated with aging in the frontal cortex of the human brain. Further studies involving a broader range of brain regions seem warranted, to confirm the present findings and to enlarge knowledge about the GABA system in aging.

Efficacy and tolerability of venlafaxine in geriatric outpatients with major depression: a double-blind, randomised 6-month comparative trial with citalopram.

BACKGROUND: The objectives of the study were to compare efficacy and tolerability of venlafaxine ER 75-150 mg/day with that of citalopram 10-20 mg/day in elderly patients with major depression according to DSM-IV criteria. METHODS: A randomised, double-blind, parallel group 6-month study. Efficacy was assessed by MADRS, CGI Global Improvement, CGI Severity of Illness and GDS-20 scores and safety by physical examinations, vital signs, adverse events and UKU side effect rating. Plasma levels of venlafaxine, its major metabolite O-desmethylvenlafaxine and citalopram were followed. RESULTS: One hundred and fifty-one male and female patients (64-89 years) were enrolled and 118 patients completed the study. Comparable improvements in MADRS, CGI Severity of Illness, CGI Global Improvement and GDS-20 were observed during venlafaxine and citalopram treatment. The MADRS remission rate was 19% for venlafaxine and 23% for citalopram. Side effects were common during both treatments but differed in tremor being more common during citalopram and nausea/vomiting during venlafaxine treatment. There were no clinically significant changes in blood pressure or body weight. CONCLUSION: The observed benefits of venlafaxine treatment in elderly patients with major depression were similar to those observed in younger adults as were reported adverse events and side effects. Treatment with venlafaxine ER was well tolerated and induced beneficial effects of similar magnitude as those of citalopram.

Influence of menstrual cycle on platelet serotonin uptake site and serotonin2A receptor binding.

Depression and anxiety are common health problems affecting women, particularly during the reproductive years. Major depression is two to three times as common in women than in men. Neuroendocrine factors are likely to contribute to this overall increased risk for developing mood disorders in women, and the neuroendocrine influence is most obviously seen in women with premenstrual dysphoric disorder (PMDD) as these women experience depressed mood and anxiety premenstrually only during ovulatory cycles. Moreover, dysfunction of serotonergic transmission has been regarded as an important mechanism in several psychiatric disorders and ovarian steroids have been shown to profoundly influence the activity of the serotonergic system. Given these facts, the purpose of this study was to examine whether binding of [3H]paroxetine to the platelet serotonin transporter or binding of [3H]lysergic acid diethylamide ([3H]LSD) to the platelet 5-HT2A receptor are influenced by the cyclical changes in circulating estradiol and progesterone that occur during the menstrual cycle. We examined 28 healthy women, without oral contraceptives and with regular menstrual cycles. In the late follicular phase, Bmax for [3H]paroxetine binding was significantly higher than in the ovulatory (p<0.01), early luteal phase (p<0.05) and mid-luteal phase (p<0.01). Bmax for [3H]LSD binding was significantly higher in the early follicular phase and the early luteal phase compared to the mid-luteal phase (p<0.001 and p<0.05, respectively). In the early follicular phase and the ovulatory phase, significant correlations between estradiol serum concentrations and Kd for [3H]paroxetine were obtained (p<0.001, respectively). In the luteal phase, significant inverse correlations between progesterone as well as estradiol serum concentrations and Kd for [3H]LSD binding were found (p<0.05, respectively).

[(3)H]Tiagabine binding to GABA transporter-1 (GAT-1) in suicidal depression.

BACKGROUND: In depressive disorders, alterations of GABA concentrations and number of postsynaptic GABA related receptor binding sites, as well as antidepressant effects exerted by GABA agonists, suggest a pathogenetic involvement of the GABA system. METHOD: The binding of the presynaptic GABA ligand [(3)H]tiagabine to GABA transporter-1 (GAT-1) was studied in post mortem human frontal cortex and cingulate gyrus from 13 suicide victims and 19 controls without known neurological or psychiatric disorder. RESULTS: No differences were found between the suicide victims and the controls with regard to the number of [(3)H]tiagabine binding sites (B(max)) or apparent affinity (K(d)). LIMITATIONS: The study was limited to two brain regions. CONCLUSION: Findings in other studies of alterations in the GABA system in depression seem according to the present results not to be associated with significant changes in the GABA uptake binding sites in the regions investigated.

Caudate nucleus dopamine d(2) receptors in vascular dementia.

Caudate nucleus dopamine (DA) D(2) receptors were studied in patients with vascular dementia (VaD) and in a control group using [(3)H]raclopride as a radioligand. There was no significant difference in the number of DA D(2) receptors in the VaD group as compared with controls. The binding affinity was significantly lower in the VaD group. When the VaD group was subdivided into subjects with or without neuroleptic treatment, there were no differences in the numbers of receptors as compared with controls, and the significant differences in binding affinity remained for both VaD subgroups. The present results are discussed with reference to the previous finding of a reduced density of caudate nucleus DA uptake sites in the same VaD group and to results from studies on DA D(2) receptors in Alzheimer's disease and Parkinson's disease.