Curr Psychiatry Rep (2015) 17: 53
DOI 10.1007/s11920-015-0595-8
GERIATRIC DISORDERS (W MCDONALD, SECTION EDITOR)
New Research on Anxiety Disorders in the Elderly and an Update
on Evidence-Based Treatments
Carmen Andreescu 1 & Daniel Varon 1
Published online: 16 May 2015
# Springer Science+Business Media New York 2015
Abstract Anxiety disorders are frequently encountered in the
elderly, but they are largely undetected and untreated. Epide-
miological studies indicate a prevalence ranging from 1.2 to
15 %. With the exception of generalized anxiety disorder and
agoraphobia, which can often start in late life, most anxiety
disorders in older patients are chronic and have their onset
earlier in life. Anxiety disorders are an often unrecognized
cause of distress, disability, and mortality risk in older adults,
and they have been associated with cardiovascular disease,
stroke, and cognitive decline. The mechanisms of anxiety in
older adults differ from that in younger adults due to age-
related neuropathology, as well as the loss and isolation so
prominent in late life. Our review intends to provide a com-
prehensive summary of the most recent research done in the
field of anxiety disorders in the elderly. Recent findings in
clinical research, neuroimaging, neuroendocrinology, and
neuropsychology are covered. An update on treatment options
is discussed, including pharmacological and non-
pharmacological alternatives.
Keywords Anxiety disorders . Elderly . Neurobiological
research . Evidence-based treatment
This article is part of the Topical Collection on Geriatric Disorders
* Carmen Andreescu
Andreescuc@upmc.edu
1
Department of Psychiatry, Western Psychiatric Institute and Clinic,
University of Pittsburgh School Of Medicine, 3811 O’Hara Street,
Pittsburgh, PA, USA
Introduction
One in four adults in the USA will have at least one episode of
an anxiety disorder in their lifetime [1]. Epidemiological stud-
ies showed that most anxiety disorders in the elderly are
chronic and usually occur earlier in life [2], except for gener-
alized anxiety disorder (GAD) and agoraphobia, which often
may have onset later in life [3]. However, late-life GAD is
largely undetected and untreated in primary care. A study
from 2001 estimates the rates of GAD in primary care at about
8 %, while primary care physicians make this diagnosis in
about 0.1 % of cases [4]. Overall, the epidemiological studies
that assessed anxiety in late life [5–8, 9•] give a rather large
range of prevalence for all anxiety disorders in the elderly,
from 1.2 to 15 % (community samples) [10]. The most recent
epidemiological study reports a lifetime prevalence of 11 %
for GAD with 24.6 % of these being late-onset (first episode
after age 50) and only 36.3 % receiving treatment [9•].
Anxiety disorders in the elderly are an often unrecognized
cause of distress, disability, and mortality risk. More recently,
late-life GAD has been linked to increased risk of stroke and
other cardiovascular events, after controlling for other risk
factors [11•, 12], and have also been linked with increased
risk of conversion from mild cognitive impairment to
Alzheimer’s disease [13•].
New Research in Anxiety Disorders in the Elderly
Clinical Research
A recent study from 2015 looked at risk factors for GAD onset
in the elderly in a sample of 1711 individuals 65 and older (the
ESPRIT study) [14]. The authors followed anxiety-free, non-
demented participants for 12 years and reported that the
53 Page 2 of 7
principal predictors of late-onset GAD were gender (female),
recent adverse life events, chronic medical illness (respiratory
disorders, cardiac illness, cognitive impairment), and chronic
mental illness (depression, phobia, and a history of GAD)
[14]. Additionally, poverty, parental loss or separation, a his-
tory of mental illness in the parents, and poor psychological
support during childhood were also independently associated
with incident GAD [14].
Neurobiological
Neuroimaging
With very few exceptions [15–18], most of the evidence re-
garding the neurobiology of late-life anxiety is extrapolated
from midlife studies. Some of the neurobiological findings
implicate structures involved in heightened fear response, es-
pecially hyperactivation in the amygdala and insula in specific
phobia, PTSD, and social anxiety [19]. PTSD has been addi-
tionally linked to hypoactivity in the thalamus, the dorsal and
rostral cingulate, as well as the ventro- and dorsomedial pre-
frontal cortex [19]. GAD has been associated with a more
polymorphic pattern, including heightened amygdala re-
sponse to anticipatory threat [20], increased amygdala-
dorsolateral prefrontal connectivity [21], and greater insula-
orbitofrontal connectivity during induction of worry [22].
However, the neural network abnormalities described in youn-
ger adults might not be entirely translatable into the elderly,
given the various anatomical and pathophysiological changes
observed in the aging brain [23]. The few available studies
have focused mainly on the neurobiology of late-life GAD.
Structural Neuroimaging Studies The only study that ex-
plored the structural neuroanatomy of late-life GAD described
a positive correlation between orbitofrontal cortex volume
correlated and worry severity (as measured by PSWQ) [16],
a finding the authors interpret as pointing toward the role of
OFC in emotional decision-making under uncertain condi-
tions (which is a function of worry). Information regarding
the architecture of the white matter, including the role
macro- or microlesions in the white matter is not explored
with regard to late-life anxiety disorders, a significant litera-
ture gap given the prevalence of disorders such as GAD in the
elderly.
Functional Neuroimaging Studies The few available stud-
ies have reported differences in functional connectivity at rest
between middle age and elderly participants with GAD, with
younger subjects presenting a more robust long-range connec-
tivity in the default mode network than older GAD subjects
[24]. A study that explored the neural basis of emotion regu-
lation in elderly GAD reported that, compared with non-
anxious subjects, the GAD participants failed to engage the
Curr Psychiatry Rep (2015) 17: 53
prefrontal structures during worry reappraisal [17, 18], while
engaging subcortical structures such as the paraventricular
nucleus and the amygdala [18]. These findings suggest that
elderly GAD subjects actually become more anxious when
they attempt to reappraise worry, a finding salient for the psy-
chotherapeutic interventions available for late-life anxiety
(e.g., cognitive reappraisal, a chore part of cognitive-
behavioral therapy, may actually be counterproductive in el-
derly with GAD) [18]. Older GAD also appears to have re-
duced recruitment of the prefrontal attentional control regions,
consistent with a model of top-down deficits in late-life GAD
[15]. These findings suggest treatment strategies such as at-
tentional retraining [25, 26].
Neuropsychological Findings
In older adults, anxiety impairs working memory, attention,
and problem-solving ability [27–30]. Recent investigations
have extended these observations to clinical samples, describ-
ing poorer short-term memory in geriatric GAD [31] and
poorer working memory with greater GAD symptoms [27,
32]. Higher rates of anxiety in participants with mild cognitive
impairment (MCI) have been reported in both population and
clinical samples [33–35]. Longitudinal studies have reported
that anxiety is an independent predictive factor of progression
from MCI to AD [36]. In a 3-year longitudinal study, Palmer
et al. showed that worrying alone was associated with a five-
fold increased risk of AD in elders with MCI compared to
elders with MCI without persistent worrying [37]. A more
recent multicenter, prospective study on 333 healthy older
adults showed that elevated anxiety symptoms moderated
the effect of beta-amyloid on cognitive decline in preclinical
AD, resulting in a more rapid decline [38•]. The relationship
between anxiety and cognitive impairment is probably bidi-
rectional as there is evidence that impaired cognitive perfor-
mance increases anxiety [39]. Thus, some authors have argued
that increased anxiety represents not a risk factor but a conse-
quence of the individual’s self-awareness of cognitive decline
and consequent worry about further degradation in cognitive
status [39].
Neuroendocrinology
Apprehensive anticipations appear to induce limbic and
paralimbic hyperactivation, leading to autonomic hyperactiv-
ity and subsequent higher cortisol levels [40]. Chronically
increased cortisol level has been associated in GAD with in-
creased serotonin uptake [41], with decrease hypothalamus
[42] and hippocampal volume [43] and decreased activation
of the prefrontal cortex [44] (which may contribute to the
deficits in emotion regulation reported in anxiety disorders).
Aging increases the vulnerability to adverse effects of stress
because the homeostatic mechanisms preventing an excessive
Curr Psychiatry Rep (2015) 17: 53
biological stress response are diminished [27, 45, 46]. Late-
life GAD has been associated with increased cortisol levels by
some [47], but not all [48] studies. A double-blind controlled
study has showed that SSRI-treated patients with increased
baseline cortisol had a significantly greater reduction in corti-
sol when compared with placebo-treated elderly GAD [49].
Similar findings were reported after CBT (in younger GAD)
[50]. Recent research shows increases in ß-amyloid-42 pep-
tide (Aß42) production and tau hyperphosphorylation attribut-
able to excessive HPA activation (mediated via corticotropin
releasing factor-1 [CRF1]) suggesting a direct link between
chronic stress, increased CRF production, and the putative
pathogenic steps in Alzheimer’s disease [27, 51–53].
Update on Treatment Options
Current Pharmacological Options
Recommendations for pharmacotherapy in elderly anxious
subjects are usually based on extrapolation of findings from
middle-age adults. However, elderly patients are more suscep-
tible to drug-induced side effects, including anticholinergic
effects (urinary retention, delirium, cognitive impairment),
antiadrenergic effects (orthostatic hypotension), and
antihistaminergic effects (mainly sedation) [54]. Elderly pa-
tients have changes in both pharmacokinetics and pharmaco-
dynamics due to diminished glomerular filtration, reduced he-
patic metabolization, decreased cardiac output, and changes in
the density and activity of target receptors [55]. The evidence
base for pharmacotherapy in older adults is limited and con-
sists mainly of several small clinical trials, many quite old and
in mixed populations [27]. The need for treatment is assessed
based on the severity and duration of the illness, the impact of
quality of life, the presence of comorbid depression or cogni-
tive impairment, as well as the concomitant use of other med-
ications [56•].
SSRIs and serotonin norepinephrine reuptake inhibitors
(SNRIs) remain the first-line medications for both short-term
and long-term treatment. Two small RCTs [57, 58] and a full-
scale RCT [46] demonstrated the efficacy of SSRIs in the
acute treatment of older adults with anxiety disorders, pre-
dominantly GAD. In the latter study, which randomized 177
older adults with GAD, escitalopram was superior to placebo
in cumulative response (69 vs. 51 %). A more recent study
(2010) compared in a randomized, single blind trial the effi-
cacy of sertraline and buspirone for late-life GAD (N=46)
[59]. The authors conclude that both sertraline and buspirone
were efficacious and well tolerated for the treatment of GAD
in the elderly [59]. The SNRIs have proven efficacious in the
treatment of GAD and panic disorder in midlife [56•], but they
appear to be less well tolerated than SSRIs. A retrospective
examination of phase 3 venlafaxine XR and duloxetine data
Page 3 of 7 53
found both medications to be efficacious in older adults, with
a side effect profile similar to younger adults [60, 61]. How-
ever, venlafaxine is associated with dose-dependent increase
in blood pressure, while others have reported orthostatic hy-
potension [92]. Monitoring BP is recommended with higher
doses, especially in the elderly [56•]. Overall, both SSRIs and
SNRIs are relatively well tolerated, but clinicians should as-
sess the potential risks of SSRIs in the elderly population,
including gait impairment increasing risk for falls [62], GI
bleeding [63], bone loss [64], and hyponatremia [65]. Such
reports suggest that the risk-benefit ratio for acute and long-
term SSRI/SNRI use is not the same as in younger adults [27].
Other antidepressant drugs, such as tricyclic antidepres-
sants (TCA) and irreversible monoamine oxidase inhibitors
(MAOI) have proven to be efficacious in some anxiety disor-
ders, but their use in the elderly should be limited to cases
resistant to other treatment options due to their side effect
profile.
The evidence for the efficacy of mirtazapine (Remeron) is
limited and inconsistent [66], but elderly patients may benefit
from its effects on sleep and appetite.
Benzodiazepines are still the most commonly used phar-
macological treatment for geriatric anxiety [67], despite the
association of these medications with falls [68], disability
[69], and cognitive impairment and decline [27, 70]. A recent
survey done in Japan on 796 elderly with anxiety disorders,
showed a very high rate of use of benzodiazepine anxiolytics
in the elderly 71.6 % (mean dose of diazepam 10.3±9.1 mg/
day) [71]. Compared with younger subjects (<50 years old),
older people also received more often benzodiazepines in the
absence of an antidepressant (38–43 % compared to 28–32 %)
[71].
Pregabalin has been proven efficacious both in acute treat-
ment and in the prevention of relapse in midlife GAD [56•]. In
the elderly, a large-scale study (N=273) found pregabalin to
be efficacious and well tolerated in geriatric GAD [72]. Al-
though discontinuation symptoms after abrupt withdrawal of
pregabalin have been reported [56•], these symptoms are rel-
atively infrequent and rebound anxiety has been low (0–6 %)
after interruption of treatment [73]. No such reports were de-
scribed in the elderly.
Antipsychotic drugs have been used in the treatment of
late-life anxiety, mostly off-label. The strongest evidence is
limited to the use of quetiapine in generalized anxiety disor-
der. Until May 2014, nine studies have used quetiapine either
as monotherapy or as adjunctive therapy for midlife GAD
[74]. Quetiapine (either regular or extended release) has
shown efficacy and tolerability in both monotherapy and ad-
junctive treatment trials [74]. One study has studied the effi-
cacy of extended release quetiapine in late-life GAD on a
relatively large sample (N=450) and demonstrated the effica-
cy of quetiapine XR monotherapy (50–300 mg/day) in late-
life GAD with side effects such as somnolence, dry mouth,
53 Page 4 of 7
dizziness, headache, and nausea [75]. The only published aug-
mentation study in late-life anxiety disorders was a small
study with risperidone [76]. The use of atypical antipsychotics
in the elderly raises concerns regarding higher mortality asso-
ciated with antipsychotics compared to placebo in older pa-
tients with dementia. It remains unclear whether these risks
apply to non-demented elderly [27].
Most of the pharmacotherapy trials have focused on geri-
atric GAD. Two studies in late-life panic disorder looked at
treatment response with various SSRIs. Rampello et al. [77]
found evidence for the superiority of escitalopram over
citalopram in time to response, and a small open-label study
found evidence of benefit from sertraline [27, 78].
Psychotherapeutic Interventions
The efficacy of psychological and pharmacological treatments
is relatively similar for the acute treatment of midlife anxiety
disorders [56•]. However, a meta-analysis and one direct ran-
domized comparison of pharmacotherapy and psychotherapy
in late-life anxiety disorders found medications more effective
than CBT in the acute phase of treatment [57, 79].
Most research in psychotherapy for late-life anxiety has
involved CBT for elderly GAD. While some psychotherapy
trials and meta-analyses reported moderate efficacy of CBT in
late-life GAD [80, 81], other trials and meta-analyses [82–84]
have failed to prove an advantage of CBT over supportive
therapy or waiting list.
In elderly persons, the most effective ingredient of CBT
may be relaxation [85]. The cognitive restructuring may be
more difficult given potential decrease in cognitive abilities in
late life [86, 87]. With respect to long-term management of
GAD, naturalistic follow-up studies of older GAD patients
treated with CBT have demonstrated maintenance of gains
for up to 1 year following discontinuation of treatment [27,
81]. Benefits of CBT relative to supportive counseling were
greater at 1 year follow-up than immediately following treat-
ment in a sample of patients who had been treated for at least
3 months with medications prior to receiving CBT, suggesting
that sustained or increasing gains are possible for older adults
receiving CBT for anxiety following an acute course of phar-
macotherapy [27, 88].
A number of innovative psychotherapeutic approaches
have been reported recently. Modular CBT uses a personal-
ized approach, tailored to the specific symptoms of the pa-
tients, allows flexibility to tailor the treatment components to
meet the specific need of each patient [89]. Mindfulness-based
stress reduction for older anxious patients with cognitive dys-
function has also shown promising preliminary results [90].
Acceptance and commitment therapy has also showed im-
provement in worry severity in a relatively recent pilot study
[91]. These approaches show promise but they require further
validation on larger samples.
Curr Psychiatry Rep (2015) 17: 53
Conclusion
Late-life anxiety disorders are chronic and fairly common, but
under-diagnosed and undertreated. Anxiety disorders in the
elderly are an underestimated cause of distress, disability,
and mortality risk. SSRIs continue to remain the first-line
pharmacologic options for acute treatment. Psychotherapeutic
options appear to be less effective for acute treatment in late
life, but CBT may prove advantageous in reducing relapse
rates during maintenance treatment.
Compliance with Ethics Guidelines
Conflict of Interest The authors declare that they have no competing
interests.
Human and Animal Rights and Informed Consent This article does
not contain any studies with human or animal subjects performed by any
of the authors.
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