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Background: Cognitive behavioural therapy (CBT) is the most researched psychological therapy for anxiety disorders in adults, and known to be effective in this population. However, it remains unclear whether these results apply to older adults, as most studies include participants between 18 and 55 years of age. This systematic review aims to provide a comprehensive and up-to-date synthesis of the available evidence on CBT and third wave approaches for older adults with anxiety and related disorders., Objectives: To assess the effects of Cognitive Behavioural Therapy (CT, BT, CBT and third-wave CBT interventions) on severity of anxiety symptoms compared with minimal management (not providing therapy) for anxiety and related disorders in older adults, aged 55 years or over. To assess the effects of CBT and related therapies on severity of anxiety symptoms compared with other psychological therapies for anxiety and related disorders in older adults, aged 55 years or over., Search Methods: We searched the Cochrane Common Mental Disorders Controlled studies Register (CCMDCTR), CENTRAL, Ovid MEDLINE, Ovid Embase and Ovid PsycINFO to 21 July 2022. These searches were updated on 2 February 2024. We also searched the international studies registries, including Clinicalstudies.gov and the WHO International Clinical Trials Registry Platform (ICTRP), to identify additional ongoing and unpublished studies. These sources were manually searched for studies up to 12 February 2024., Selection Criteria: We included randomised controlled trials (RCTs) in older adults (≥ 55 years) with an anxiety disorder, or a related disorder, including obsessive compulsive disorder (OCD), acute stress disorder and post-traumatic stress disorder (PTSD), that compared CBT to either minimal management or an active (non-CBT) psychological therapy. Eligible studies had to have an anxiety-related outcome., Data Collection and Analysis: Several authors independently screened all titles identified by the searches. All full texts were screened for eligibility according to our prespecified selection criteria. Data were extracted and the risk of bias was assessed using the Cochrane tool for RCTs. The certainty of evidence was evaluated using GRADE. Meta-analyses were performed for outcomes with quantitative data from more than one study., Main Results: We included 21 RCTs on 1234 older people allocated to either CBT or control conditions. Ten studies focused on generalised anxiety disorder; others mostly included a mix of clinical diagnoses. Nineteen studies focused on the comparison between CBT and minimal management. Key issues relating to risk of bias were lack of blinding of participants and personnel, and participants dropping out of studies, potentially due to treatment preference and allocation. CBT may result in a small-to-moderate reduction of anxiety post-treatment (SMD -0.51, 95% CI -0.66 to -0.36, low-certainty evidence). However, compared to this benefit with CBT immediately after treatment, at three to six months post-treatment, there was little to no difference between CBT and minimal management (SMD -0.29, 95% CI -0.59 to 0.01, low-certainty evidence). CBT may have little or no effect on clinical recovery/ improvement post-treatment compared to minimal management, but the evidence is very uncertain (RR 1.56, 95% CI 1.20 to 2.03, very low-certainty evidence). Results indicate that five people would need to receive treatment for one additional person to benefit (NNTB = 5). Compared to minimal management, CBT may result in a reduction of comorbid depression symptoms post-treatment (SMD -0.57, 95% CI -0.74 to -0.40, low-certainty evidence). There was no difference in dropout rates post-treatment, although the certainty of the evidence was low (RR 1.19, 95% CI 0.80 to 1.78). Two studies reported adverse events, both of which related to medication in the control groups (very low-certainty evidence, no quantitative estimate). Only two studies compared CBT to other psychological therapies, both of which only included participants with post-traumatic stress disorder. Low-certainty evidence showed no difference in anxiety severity post-treatment and at four to six months post-treatment, symptoms of depression post-treatment, and dropout rates post-treatment. Other outcomes and time points are reported in the results section of the manuscript., Authors' Conclusions: CBT may be more effective than minimal management in reducing anxiety and symptoms of worry and depression post-treatment in older adults with anxiety disorders. The evidence is less certain longer-term and for other outcomes including clinical recovery/improvement. There is not enough evidence to determine whether CBT is more effective than alternative psychological therapies for anxiety in older adults., (Copyright © 2024 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: To examine the mortality risk of current and life-time depressive as well as anxiety disorders, whether this risk is moderated by sex or age, and whether this risk can be explained by lifestyle and/or somatic health status., Methods: A cohort study (Lifelines) including 141,377 participants (18-93 years) which were followed-up regarding mortality for 8.6 years (range 3.0-13.7). Baseline depressive and anxiety disorders according to Diagnostic and Statistical Manual of Mental Disorders, fourth edition criteria were assessed with the Mini International Neuropsychiatric Interview and lifetime diagnoses by self-report. All-cause mortality was retrieved from Statistics Netherlands. Cox-regression was applied to calculate proportional hazard ratios, adjusted for lifestyle (physical activity, alcohol use, smoking, and body mass index) and somatic health status (multimorbidity and frailty) in different models., Results: The mortality rate of depressive and anxiety disorders was conditional upon age but not on sex. Only in people below 60 years, current depressive and anxiety disorders were associated with mortality. Only depressive disorder and panic disorder independently predicted mortality when all mental disorders were included simultaneously in one overall model (hazard ratio [HR] = 2.18 [95% confidence intervals (CI): 1.56-3.05], p < 0.001 and HR = 2.39 [95% CI: 1.15-4.98], p = 0.020). Life-time depressive and anxiety disorders, however, were independent of each other associated with mortality. Associations hardly changed when adjusted for lifestyle characteristics but decreased substantially when adjusted for somatic health status (in particular physical frailty)., Conclusions: In particular, depressive disorder is associated with excess mortality in people below 60 years, independent of their lifestyle. This effect seems partly explained by multimorbidity and frailty, which suggest that chronic disease management of depression-associated somatic morbidity needs to be (further) improved.

Objective: Studies on the course of depression often ignore comorbid anxiety disorders or anxiety symptoms. We explored predictors of complete remission (no depression nor anxiety diagnoses at follow-up) and of the course of comorbid anxiety symptoms. We additionally tested the hypothesis that the course of anxiety disorders and symptoms in depressed patients is explained by negative life-events in the presence of high neuroticism or a low sense of mastery., Methods: An observational study of 270 patients (≥60 years) diagnosed with major depressive disorder and 2-year follow-up data, who participated in the Netherlands Study of Depression in Older persons (NESDO). Sociodemographic, somatic, psychiatric, and treatment variables were first explored as possible predictors. A multiple logistic regression analysis was used to examine their predictive value concerning complete remission. Subsequently, negative life-events, personality and their interaction were tested as potential predictors. Linear Mixed Models were used to assess whether the personality traits modified the effect of early and recent life-events, and time and their interactions on the course of the anxiety symptoms., Results: A total of 135 of 270 patients achieved complete remission. Depressed patients with a comorbid anxiety disorder at baseline less often achieved complete remission: 38 of 103 (37.0%) versus 97 of 167 (58.1%). The severity of depressive and anxiety symptomatology, the presence of a comorbid anxiety disorder, and a poorer physical health at baseline predicted nonremission. In line with our hypothesis, a less favorable course of self-reported anxiety symptoms was associated with more recent negative life-events, but only among patients with a high level of neuroticism or a low level of mastery., Conclusion: Comorbid anxiety in depression as a negative impact on complete remission at 2-year follow-up. The course of anxiety severity seems dependent on the interaction of personality traits and life-events., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Anxiety sensitivity is associated with the onset of panic attacks, anxiety, and other common mental disorders. Anxiety sensitivity is usually seen as a relative stable trait. However, previous studies were inconclusive regarding the longitudinal stability of anxiety sensitivity and differed in study designs and outcomes. The current study examines the stability of anxiety sensitivity over time and its longitudinal associations with severity of anxiety symptoms. Participants from the Netherlands Study of Depression and Anxiety with and without an anxiety, depressive, or comorbid anxiety-depressive disorder diagnosis were included (N = 2052). Stability in anxiety sensitivity over two year follow-up and the longitudinal association between the change in anxiety sensitivity and change in severity of anxiety symptoms were tested. Results indicated that two-year stability of anxiety sensitivity was high (r = 0.72), yet this test-retest estimate leaves room for changes in anxiety sensitivity in some individuals as well. Change in anxiety sensitivity was positively associated with change in severity of anxiety symptoms (B = 0.64 in univariable analysis and B = 0.52 in multivariable analysis). The longitudinal association of anxiety sensitivity with severity of anxiety symptoms indicates that targeting anxiety sensitivity may be of additional benefit in clinical practice.

Background: Following remission of an anxiety disorder or a depressive disorder, antidepressants are frequently discontinued and in the case of symptom occurrence reinstated. Reinstatement of antidepressants seems less effective in some patients, but an overview is lacking. This systematic review aimed to provide insight into the magnitude and risk factors of response failure after reinstatement of antidepressants in patients with anxiety disorders, depressive disorders, obsessive-compulsive disorder (OCD), or posttraumatic stress disorder (PTSD)., Method: PubMed, Embase, and trial registers were systematically searched for studies in which patients: (1) had an anxiety disorder, a depressive disorder, OCD, or PTSD and (2) experienced failure to respond after reinstatement of a previously effective antidepressant., Results: Ten studies reported failure to respond following antidepressant reinstatement. The phenomenon was observed in 16.5% of patients with a depressive disorder, OCD, and social phobia and occurred in all common classes of antidepressants. The range of response failure was broad, varying between 3.8 and 42.9% across studies. No risk factors for failure to respond were investigated. The overall study quality was limited., Conclusion: Research investigating response failure is scarce and the study quality limited. Response failure occurred in a substantial minority of patients. Contributors to the relevance of this phenomenon are the prevalence of the investigated disorders, the number of patients being treated with antidepressants, and the occurrence of response failure for all common classes of antidepressants. This systematic review highlights the need for studies systematically investigating this phenomenon and associated risk factors., (© 2018 The Author(s) Published by S. Karger AG, Basel.)

Background: Self-rated general health has been associated with worse outcome after a myocardial infarction (MI). Previously, however, concurrent depression or anxiety was not taken into account., Objective: To evaluate the effect of physical health complaints post-MI on cardiac prognosis adjusting for cardiac disease severity, depression, and anxiety., Methods: The somatic subscale of the Health Complaints Scale was administered to 424 patients with MI at 3 and 12 months post-MI. Types and trajectories of health complaints were identified with latent transition analysis. The prognostic effect of Health Complaints Scale sum-score at 3 months, and of types and trajectories of health complaints on combined end points (new cardiac events and mortality) was evaluated with Cox regression. Adjustments were made for age, sex, education level, living alone, history of MI, left ventricular ejection fraction, depressive symptoms, and generalized anxiety disorder., Results: Overall, 189 (44.9%) patients with MI had a cardiac event or died during a mean follow-up of 5.7 (3.1) years. In the fully adjusted model, Health Complaints Scale sum-score predicted outcome (hazard ratio [HR] = 1.02 [95% CI: 1.00-1.05]). Latent transition analysis distinguished 5 groups at 3 and 12 months characterized by (1) no/minimal complaints, (2) cardiac complaints, (3) lack of energy, (4) sleep problems, and (5) mixed health complaints, resulting in 25 transition classes. Patients with cardiac and energy complaints at 3 months (HR cardiac = 1.55 [1.15-2.10] and HR energy = 1.35[1.00-1.81]) and those with new or persistent cardiac, energy, and mixed complaints over time had a worse prognosis (HR cardiac = 1.55 [1.11-2.16], HR mixed = 1.71 [1.19-2.47], and HR energy = 1.51 [1.09-2.08])., Conclusions: Physical health complaints are predictors of cardiac outcome independent from cardiac disease, depression, and anxiety. Type and trajectories of health complaints may have additional prognostic significance., (Copyright © 2017 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: Comorbid anxiety in depression increases the risk of suicidal ideation and behavior, although data on death by suicide are scarce. We compared characteristics of depressed elderly patients with and without anxiety disorders who died by suicide., Methods: From a 16-year clinical survey of all suicides in the UK (n = 25,128), we identified 1909 cases aged ≥60 years with a primary diagnosis of depression and no comorbidity other than anxiety disorders. Clinical characteristics of cases with (n = 333, 17.4%) and without (n = 1576) comorbid anxiety disorders were compared by logistic regression adjusted for demographic differences., Results: Compared with cases without comorbid anxiety disorders, cases with comorbid anxiety disorders were more likely to have a duration of illness over 1 year (OR(1-5 years)  = 1.4 [95% CI: 1.0-1.9], p = 0.061; OR(≥5 years)  = 1.4 [95% CI: 1.6-2.8], p < 0.001), were more frequently prescribed psychotropic drugs other than antidepressants, lithium, and antipsychotics (OR = 2.1 [95% CI: 1.6-2.7], p < 0.001) and were more distressed during their last contact with services (OR = 1.3 [95% CI: 1.0-1.7], p = 0.037). In contrast, clinicians estimated the immediate and long-term suicidal risks lower in those with comorbid anxiety disorders (OR = 0.6 [95% CI: 0.3-0.9], p = 0.011 and OR = 0.7 [95% CI: 0.6-1.0], p = 0.028, respectively)., Conclusion: Among depressed suicide cases, a comorbid anxiety disorder was identified in one out of six cases and associated with a higher prevalence of several suicide risk factors. This is important, as the detection of anxiety disorders comorbid to depression seems rather low and even when recognized clinicians rated such individuals as at low suicide risk., (Copyright © 2015 John Wiley & Sons, Ltd.)

Background: Physical symptoms significantly impair health-related quality of life (HRQoL), but age effects and differential effects of medically unexplained symptoms (MUS) and medically explained symptoms (MES) have hardly been examined. Our objective was to determine the effect of age on the impact of MUS and MES on HRQoL., Methods: In a population-based cohort (n = 946, aged 28-75 years), MUS and MES were measured using the Composite International Diagnostic Interview and HRQoL using the EuroQol-5 dimensions (EQ-5D). Using multiple linear regression, we regressed MUS, MES and their interaction with age on HRQoL, adjusted for socio-demographic variables and the presence of depressive and anxiety disorders. In case of significant interaction terms, age-stratified results will be presented., Results: In the whole study population, the association between MUS and HRQoL was stronger (β = -0.35; p < 0.001) than between MES and HRQoL (β = -0.26; p < 0.001). Adjusted for depressive and anxiety disorders, differences between these associations decline (MUS: β = -0.28, p < 0.001; MES: β = -0.25, p < 0.001). Age significantly interacted with number of MUS in explaining variance in HRQoL but not with the number of MES. The impact of MUS on HRQoL is much larger in people aged below 65 years (β = -0.39, p < 0.001) versus those aged 65 years and over (β = -0.21, p = 0.002). In the older group, the association between MUS and HRQoL lost significance when adjusted for depressive and anxiety disorders (β = -0.12 p = 0.062)., Conclusion: Our results show that age affects the association between MUS and HRQoL, which suggest that older persons cope better with MUS than younger persons., (Copyright © 2014 John Wiley & Sons, Ltd.)

Background: Anxiety in depression is challenging as it results in more functional impairment and a worse prognosis. No consensus exists on the definition of anxious depression., Methods: In 359 older patients with major depressive disorder, we examined the agreement between anxious depression based on different combinations of comorbid anxiety disorders and anxious depression based on high level of anxiety symptoms measured by self-report questionnaires., Results: Agreement between the definitions of anxious depression was poor, as indicated by κ statistics ranging between 0.06 and 0.23., Conclusion: Accepted criteria for anxious depression classify completely different patients as being anxious depressed. This may explain inconsistent results of previous studies on anxious depression. Moreover, progress in this research field is hampered, as studies using different definitions cannot be pooled in meta-analyses., (Copyright © 2014 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objective: To examine the interplay between subclinical atherosclerotic disease and neuroticism in explaining variance in late-life depressive symptoms., Methods: This study was part of the Nijmegen Biomedical Study, a population-based survey; 1,517 participants aged 50-70 years were included. Depressive symptoms were measured by the Beck Depression Inventory (BDI). Principal components analysis of the BDI items yielded two factors, representing a cognitive-affective symptom cluster and a somatic-affective symptom cluster. Atherosclerotic disease was measured by the intima media thickness (IMT) of the carotid arteries and neuroticism by the revised Eysenck Personality Questionnaire., Results: Multiple linear regression analyses using different measures of depressive symptoms as the dependent variable showed that neuroticism was strongly and significantly associated with the sum score of the BDI and with the two depressive symptom clusters. IMT, however, was only significantly associated with the somatic-affective symptom cluster but not with the cognitive-affective symptom cluster. Interestingly, we found a significant negative interaction between neuroticism and IMT in explaining the severity of the cognitive-affective symptom cluster but not with respect to the somatic-affective symptom cluster., Conclusion: The negative interaction between neuroticism and atherosclerosis indicates that neuroticism is less strongly associated with cognitive-depressive symptoms in the presence of more severe atherosclerosis. This may be explained by apathy due to cerebrovascular disease and fits with a hypothesis of vascular apathy., (Copyright © 2014 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Tolerance towards the effects of benzodiazepines is observed in various animal and human studies. Therefore, it is assumed that patients who use benzodiazepines for a longer period of time need to increase their dose over time to experience the same effect., Objective: To observe whether long-term benzodiazepine users increase their dose over time., Methods: From the Dutch National Information Network of Family Practices, a group of long-term benzodiazepine users was identified. This group was divided into an incident long-term benzodiazepine users group (N = 113) and a prevalent long-term benzodiazepine users group (N = 992). Long-term use of benzodiazepines was defined as usage for at least 6 months. The main outcome was a change in prescribed dose from baseline until 24 months after baseline. Linear regression analysis was performed to evaluate dose change., Results: Neither incident long-term benzodiazepine users nor prevalent long-term benzodiazepine users were prescribed increasing dosages during follow-up., Conclusion: There is no increase in prescribed dose among long-term users, as might be expected due to the development of tolerance to the effects of benzodiazepines.

Objectives: Whereas animal models indicate that brain-derived neurotrophic factor (BDNF) plays a role in anxiety-related behaviour, little is known about BDNF in patients with an anxiety disorder. We tested the hypothesis that serum BDNF levels are low in patients with an anxiety disorder as compared to healthy controls. We further examined the associations of gender and some of the clinical characteristics of anxiety with BDNF levels., Methods: Serum BDNF levels were determined in 393 unmedicated, non-depressed patients with social anxiety disorder, panic disorder, agoraphobia, and generalised anxiety disorder (66.7% females) and in 382 healthy controls (62.0% females)., Results: Overall, there were no differences in BDNF levels among patients and controls, regardless of type of anxiety disorder. Analyses stratified by gender revealed that female patients had lower levels of BDNF relative to female controls (P < 0.05, d = 0.19), which was stronger in female patients with > 1 anxiety disorder (P < 0.01, d = 0.32). BDNF levels were similar among male patients and controls and unrelated to the clinical characteristics of anxiety., Conclusion: Our results mirror preclinical findings indicating that gender plays a role in the association between BDNF and anxiety and suggest that BDNF might play a role in the pathophysiology of anxiety in women.

Aim: To collect empirical evidence concerning the effectiveness of the treatment of anxiety disorders in the elderly., Method: Meta-analysis and randomised controlled trials., Results: Meta-analysis showed that cognitive behavioural therapy (CBT) was more successful than waiting-list control or active control as a treatment for older persons with anxiety disorders. In a direct comparison of the treatment of older persons with panic disorder (PD) both CBT an paroxetine were found to be more effective than waiting-list control. CBT was more successful in reducing avoidance behaviours in older persons with PD. Older persons with reported fewer and less severe agoraphobic cognitions than younger patients, but there was no difference between the severity of agoraphobic avoidance in older patients with PD and younger patients with PD., Conclusion: There is sufficient empirical evidence to support the effectiveness of CBT in the treatment of older persons with anxiety disorders. In assessing the severity of PD in the elderly, one should carefully consider the severity of avoidance behaviours. Because no difference was found between the effectiveness of CBT and paroxetine for the treatment of PD in the elderly and because was more effective in reducing avoidance behaviours in older patients with PD than in younger patients with pd, there seems to be a slight preference for CBT in the case of older patients with PD. Older age is not associated with a poorer outcome of treatment with CBT.

Objective: To examine and estimate the efficacy of cognitive-behavioural therapy (CBT) for late-life anxiety disorders., Method: A systematic review and meta-analysis of randomized controlled trials comparing CBT with i) a waiting-list control condition and ii) an active control condition controlling for non-specific effects in patients aged over 60 years and suffering from an anxiety disorder. The main outcome parameter of individual studies, i.e. effect on anxiety, was pooled using the standardized mean difference (SMD)., Results: Seven papers fulfilled the inclusion criteria, including nine randomized controlled comparisons for 297 patients. Anxiety symptoms were significantly more reduced following CBT than after either a waiting-list control condition [SMD = -0.44 (95 CI: -0.84 -0.04), P = 0.03] or an active control condition [SMD = -0.51 (95 CI: -0.81, -0.21), P<0.001]. Additionally, CBT significantly alleviated accompanying symptoms of worrying and depression., Conclusion: Cognitive-behavioural therapy is efficacious for the treatment of late-life anxiety disorders.