Journal of Affective Disorders 241 (2018) 627–633

Contents lists available at ScienceDirect

Journal of Affective Disorders

journal homepage: www.elsevier.com/locate/jad

Research paper

Epidemiology of panic attacks, panic disorder and the moderating role of T

age: Results from a population-based study
⁎
Beatriz Olayaa,b,e, , Maria Victoria Monetaa,b,e, Marta Miretc,d,e, José Luis Ayuso-Mateosc,d,e,
Josep Maria Haroa,b,e
a
Research, Innovation and Teaching Unit, Institut de Recerca Sant Joan de Déu, Esplugues de Llobregat, Barcelona, Spain
b
Parc Sanitari Sant Joan de Déu, Universitat de Barcelona, Fundació Sant Joan de Déu, Sant Boi de Llobregat, Barcelona, Spain
c
Department of Psychiatry, Universidad Autónoma de Madrid, Madrid, Spain
d
Department of Psychiatry, Instituto de Investigación Sanitaria Princesa (IP), Hospital Universitario de La Princesa, Madrid, Spain
e
Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain

A R T I C LE I N FO A B S T R A C T

Keywords: Background: The aim of this study was to investigate the prevalence of panic attacks (PA) and panic disorder
Panic attacks (PD) over the lifespan, determine the main correlates and analyze the potential moderating role of age.
Panic disorder Method: We analyzed cross-sectional data from a nationally-representative sample of 4,569 non-institutionalized
Population-based study adults. Three panic groups were created according to results in the CIDI interview: non-panic, PA (without PD)
Older adults
and PD. Panic groups were used as outcomes in adjusted multinomial regression models where several correlates
Young adults
were investigated. Interactions between each covariate and age were explored.
Interaction
Results: The highest prevalence rates of PA (9.5%) and PD (3.3%) were found in people aged 30–39 and 40–49,
respectively. Respondents aged 80 + presented the lowest rates. In the adjusted multinomial model, younger
ages, having depression, and poorer levels of quality of life were significant correlates for both PA and PD,
whereas being female and having 2 or more chronic conditions were only significant for PA (not for PD) and
being a frequent drinker (last 12-months) only for PD. Age significantly interacted with frequent alcohol con-
sumption in the last 12-months for PD. The predicted probability of having PD decreased with age for life-
abstainer or occasional drinkers, whereas the probability increased with older ages for frequent drinkers.
Limitations: Low prevalence of PA and PD resulted in large confidence intervals whereas self-reports could be
affected by recall bias.
Conclusions: Overall, our results suggest that the probability of having PA and PD decreases as people age and
that the significant risk factors are independent of age. However, older adults with a frequent drink pattern seem
to be at higher risk of PD. Future longitudinal studies are needed to determine the trajectories of PD and alcohol
consumption over the lifespan.

1. Introduction prevalence of PA without lifetime PD in high income countries to be

Panic Attacks (PA) are defined as an abrupt surge of intense fear or
intense discomfort that reaches a peak within minutes, and during that
time four or more of 13 symptoms occur (Craske et al., 2010). Ac-
cording to DSM-5 criteria (American Psychiatric Association, 2013), a
diagnosis of panic disorder (PD) requires the presence of recurrent PA
and persistent worry about suffering future attacks and their con-
sequences. Epidemiological studies report a lifetime PD prevalence rate
between 1.4 and 4.1% in the adult general population (Dick et al.,
1994; Eaton et al., 1994; Weissman et al., 1997). The proportion of PA
is somewhat higher; the World Mental Health Survey reports the
14.4% (de Jonge et al., 2016).
PD begins on average in the mid to late-20 s, although onset can
occur at any time from childhood to late life (Antony and
Swinson, 2000). It is suggested that PA and PD tend to decrease with
age (Corna et al., 2007; Lenze and Wetherell, 2011). Some studies in
elderly people report rates of PD ranging from 0.4% to 2.8%, depending
on sample characteristics (Corna et al., 2007; Grant et al., 2006). With
increasing age, PA and PD are more difficult to diagnose and treat
(Lenze and Wetherell, 2011), possibly due to different presentations of
symptoms among the elderly that are not accurately captured by
standard criteria and tools designed for younger adults (Seguí et al.,

⁎
Correspondence to: Research, Innovation and Teaching Unit, Parc Sanitari Sant Joan de Déu, Dr. Antoni Pujadas, 42, 08830 Sant Boi de Llobregat, Spain.
E-mail address: beatriz.olaya@pssjd.org (B. Olaya).

https://doi.org/10.1016/j.jad.2018.08.069
Received 20 October 2017; Received in revised form 25 June 2018; Accepted 12 August 2018
Available online 16 August 2018
0165-0327/ © 2018 Elsevier B.V. All rights reserved.
B. Olaya et al.
2000). Most late-onset PA are related to psychiatric and medical co-
morbidities (Lenze and Wetherell, 2011), which might hamper correct
diagnosis. Age-related changes in brain structures, functions and per-
ipheral physiology could also have an impact on the propensity for
autonomic responses, reducing the odds of PA among the elderly
(Charney et al., 1990; Flint et al., 1998).
Being female and experiencing early stressful life events have con-
sistently been associated with PA and PD in young adults
(Asselmann et al., 2016) and the middle aged (Antony and Swinson,
2000; Moreno-Peral et al., 2014). The association with other psycho-
social factors, such as being separated, divorced or widowed, or having
a low educational level, is still unclear (Moreno-Peral et al., 2014).
Psychiatric and physical comorbidity is frequently observed among
patients with PA and PD (Simon and Fischmann, 2005). Depression,
substance abuse and dependence, agoraphobia and suicidal behavior
have been reported as related to an increased occurrence of PD (Roy-
Byrne et al., 2006). Medical conditions, such as cardiovascular or re-
spiratory diseases, are also commonly associated with PA and PD
(Katerndahl, 2008). Despite the evidence, risk factors might have dif-
fering effects on the probability of suffering from PA and PD over the
lifetime. For instance, hormone changes or psychosocial stressors in
women over the lifetime might impact differently on their psycho-
pathological vulnerability. Investigating the different impacts of several
risk factors across adulthood and late life can help detect potential
targets for early detection and prevention of PA and PD.
The aim of the present study was to describe the prevalence of PA
(without lifetime PD) and lifetime PD in a nationally representative
sample of non-institutionalized adults aged from 18 to 104 years old.
We also examined the association between several covariates (socio-
demographic, life-style, mental health, multimorbidity, and quality of
life) with having PA and PD, and their interaction with age to determine
whether their effects were age-dependent. This study will help elucidate
whether there is a decline with age in the prevalence of PA and PD,
facilitating comparison between young, middle-aged and older adults
by using the same standardized interview based on DSM criteria. Our
results will also shed light on whether the associations with several risk
factors vary over the lifespan by analyzing the interaction with age.
2. Method
2.1. Sample
The present study used Spanish data from COURAGE in Europe
(Leonardi et al., 2014), a cross-sectional household survey of the non-
institutionalized adult population. The survey took place between 2011
and 2012. A stratified multistage clustered design according to geo-
graphical and catchment area sizes was used. Municipalities and census
units were systematically selected with probabilities proportional to the
population size. Age strata were used to select households, and in-
dividuals were randomly selected from inhabitants in a certain age
group within the household. People aged 50 and 80 years old were
oversampled. A total of 4753 persons participated in the study with a
final response rate of 69.9%.
The survey protocol was originally designed in English and trans-
lated into Spanish following World Health Organization translation
guidelines for assessment instruments (WHO, 2014). Interviews were
conducted face-to-face by lay, trained interviewers using Computer-
Assisted Personal Interviewing (CAPI) at respondents' homes. Quality
control procedures were implemented during fieldwork (Üstün et al.,
2005). At the beginning of the interview, the interviewer judged whe-
ther the selected person had cognitive limitations that would prevent
correct understanding of the survey questions. In such cases, a proxy
respondent answered a short version of the interview. Thus, in the
present analyses, we excluded proxy interviews (n = 170). Some 14
participants were also excluded because they had at least one missing
value in the study variables, resulting in a final sample size of 4569.
628
Journal of Affective Disorders 241 (2018) 627–633
Ethical approval was obtained from the Clinical
Investigation Ethics Committee, Parc Sanitari Sant Joan de Déu,
Barcelona (PIC-12-11; PIC-71-12) and from the Clinical
Investigation Ethics Committee, Hospital Universitario la Princesa,
Madrid (PI-364; 2399). Informed consent from each participant was
obtained.
2.2. Measures
2.2.1. Diagnosis
An adapted version of the Composite International Diagnostic
Interview (CIDI version 3.0, Haro et al., 2006) was used to assess the
presence of PA and PD, according to DSM-IV-TR criteria
(American Psychiatric Association, 2000). For the present study, we
used DSM-5 criteria (American Psychiatric Association, 2013) to divide
participants into three groups: (1) no panic attacks (NP) (participants
who did not meet criteria either for panic attack or panic disorder); (2)
panic attack (PA) (people who met criteria for panic attack but not for
panic disorder); and (3) panic disorder (PD) (participants who met
DSM-5 criteria for lifetime or previous 12-month panic disorder). The
CIDI symptoms/items for PA and PD were equivalent to the criteria for
a DSM-5 diagnosis of PA and PD. The DSM-5 criteria for PA include (A)
a discrete period of intense fear or discomfort; (B) four or more of the
following symptoms (palpitations, sweating, trembling or shaking,
shortness of breath or smothering, choking, chest pain or discomfort,
nausea or abdominal distress, dizziness, derealization or depersonali-
zation, fear of losing control or going crazy, fear of dying, paresthesias,
and chills or hot flushes); and (C) symptoms appear abruptly and reach
a peak within 10 minutes. The criteria for PD include: (A) recurrent
unexpected PA (at least two or more); (B) at least one of the attacks
followed by one month (or more) of one or both of the following: a)
persistent concern or worry about having additional attacks or the
implications of the attack and its consequences; (b) significant mala-
daptive change in behavior related to the attacks; and (C) PA are not
due to the direct physiological effects of a substance or a general
medical condition. According to DSM-5 criteria, PA could be expected
or unexpected, whereas PD could happen in the absence of agor-
aphobia.
Depression in the previous 12 months was also measured with an
adapted version of the CIDI 3.0 (Haro et al., 2006). Algorithms were
implemented according to DSM-5 criteria (American Psychiatric
Association, 2013). Due to the sensitive nature of the question, re-
spondents were asked about suicidal ideation through written state-
ments (“You seriously thought about committing suicide” ) and verb-
ally, using labels (“Did experience A ever happen to you?” ). A suicidal
behavior measurement was also adapted from the CIDI 3.0. The re-
spondents who answered this question affirmatively were categorized
as a suicidal ideation case (either lifetime or in the previous 12
months).
2.2.2. Other covariates
Socio-demographic information included age, gender, years of
education, and cohabiting with someone (cohabiting included married
or living with one's partner while not cohabiting included never mar-
ried, separated, divorced or widowed participants). Life-style variables
included current smoking (yes/no) and alcohol-consumption pattern in
the last 12 months (lifetime abstainers or occasional drinkers as the
category of reference and frequent drinkers). Patients were asked about
the presence of chronic conditions (arthritis, asthma, chronic ob-
structive pulmonary disease, angina pectoris, stroke, hypertension),
either by self-reported physician's diagnosis and/or symptom-based
algorithms, while diabetes was detected through a direct question
(Garin et al., 2016). Presence of hypertension was based on self-re-
ported diagnosis or presence of systolic blood pressure ≥ 140 mmHg or
B. Olaya et al. Journal of Affective Disorders 241 (2018) 627–633

diastolic blood pressure ≥ 90 mmHg measured at the time of the in-

terview (Basu and Millett, 2013; Mancia et al., 2013). The number of
chronic conditions (CC) was calculated (0, 1 and 2 or more CCs).
Quality of life was measured with the WHOQOL-AGE (Caballero et al.,
2013), a modified version of the World Health Organization Quality of
Life instrument (WHOQOL) adapted for the elderly population. It has
13 items and a global score can be obtained which ranges from 0
(minimum quality of life) to 100 (maximum quality of life).

2.3. Statistical analysis

Unweighted frequencies, weighted proportions and means were

used for descriptive analyses. Comparisons between panic groups (NP,
PA and PD) were conducted using the Rao-Scott chi-squared test sta-
tistic (which adjusts for complex sample design) (Rao and Scott, 1984)
for categorical variables and one-way ANOVA test for continuous
variables.
Adjusted multinomial regression analyses were conducted, with the
panic variable as outcome, and participants with NP as the reference
group. Covariates included age (centered), gender, years of education
(centered), depression, suicidal thoughts, currently smoking, frequent
drinker, number of chronic conditions and quality of life (centered). To
determine the different effects of these covariates according to age, we
explored the interaction with age as a continuous variable in the adjusted
multinomial regression model. If significant (p < 0.05), we then calcu-
lated marginal effects to plot the predicted probability for each outcome
(i.e., PA and PD) for different ages according to the levels of the modifier.
All analyses were performed using Stata version 13 for Windows (SE
version 13, College Station, TX) taking into account the complex sam-
pling design. Weights were used to adjust for differential probabilities
of selection within households, and post-stratification corrections to the
weights were made to match the samples to the socio-demographic
distributions of the Spanish population. Statistical significance was set
at p < 0.05.
3. Results
Table 1 shows the socio-demographic and clinical characteristics of
the total sample and by panic groups. Mean age of the total sample
(N = 4569) was 47.6 years (95% Confidence Interval, IC = 47–48.3).
The prevalence of lifetime PA in the whole sample was 7.6% (n = 297)
and 96 (2.4%) met criteria for PD (lifetime or previous year). Com-
parison between the three groups (NP, PA and PD) revealed significant
differences in the following sociodemographic and clinical character-
istics: gender (with the highest proportion of women among re-
spondents with PA, p < 0.01), age (younger ages in the PA group, with
Fig. 1. Prevalence rates for individuals with lifetime Panic Attack and Panic
Disorder by age.
Note: PA = Panic attacks; PD = Panic disorder. Unweighted frequencies (n),
weighted proportions (%).
a mean age of 44, 95%CI = 41.9–46.2); people with PD were frequently
not cohabiting with a partner, presented the highest proportion of de-
pression and suicidal ideation, were current smokers and had two or
more chronic conditions. This group also presented the poorest quality
of life score.
The prevalence of PA and PD by age is shown in Fig. 1. The highest
proportion of PA (9.5%, 95%CI = 6.2% − 14.1%) was found in the
30–39 age group, and for PD in people aged 40–49 (3.3%,
95%CI = 1.7% − 6.1%). The lowest prevalence rates of PA and PD
were found in respondents aged 80 + (3.2%, 95%CI = 1.5% − 6.7%,
and 0.5%, 95%CI = 0.1% − 0.6%, respectively). Prevalence rates
started to decline at the age of 50–59. Comparison between the dif-
ferent age groups in terms of proportions of PA and PD showed no
statistically significant differences (χ2 = 1.93, p = 0.063).
Table 2 presents the adjusted odds ratios (ORs) and the 95%CI from
multinomial regression models. Taking the NP group as reference,
younger age (OR = 0.97, 95%CI = 0.95–0.98, p < 0.001), being fe-
male (OR = 1.91, 95%CI = 1.22–2.99, p < 0.01), depression
(OR = 2.96, 95%CI = 1.65–5.31, p < 0.001), having suicidal thoughts
(OR = 5.28, 95%CI = 2.71–10.28, p < 0.001), two or more CCs and
poor quality of life were significantly associated with having PA. For
PD, younger age, depression (OR = 4.19, 95%CI = 1.65–10.60,
p < 0.01), suicidal thoughts (OR = 13.3, 95%CI = 5.77–30.67,
p < 0.001) and poor quality of life (OR = 0.97, 95%CI = 0.95–0.99,

Table 1
Characteristics of the whole sample (N = 4569) and of people with/without panic attack/panic disorder.
Variables Total sample No Panic Attack or Panic Disorder (n = 4,176; 90.1%) Panic Attack Panic Disorder p value
(N = 4,569) (n = 297; 7.6%) (lifetime/last year)
(n = 96; 2.4%)

Females, n (%) 2498 (50.6) 2221 (49.3) 204 (64.2) 73 (58.6) 0.005
Age, mean (95%CI) 47.64 (46.98–48.29) 48.0 (47.31–48.70) 44.04 (41.86–46.22) 45.22 (41.52–48.91) 0.001
Not cohabiting, n (%) 1800 (43.3) 1612 (42.4) 132 (47.3) 56 (67.5) 0.007
Years education, mean (95%CI) 12.71(12.76–13.21) 12.70 (12.19–13.22) 12.90 (11.88–13.93) 12.15 (10.51–3.79) 0.817
Depression last year, n (%) 505 (8.9) 343 (6.4) 110 (29.2) 52 (40.6) < 0.001
Suicidal ideation, n (%) 161 (3.7) 87 (1.7) 47 (17.3) 27 (33.7) < 0.001
Currently smoking, n (%) 1147 (34.3) 1015 (32.8) 98 (47.7) 34 (49.0) < 0.001
Frequent drinker, n (%) 1807 (42.0) 1680 (42.0) 102 (44.6) 25 (31.3) 0.297
N° chronic illnesses, n (%) 0.011
None 1337 (46.3) 1242 (47.0) 73 (36.8) 22 (46.7)
1 1517 (29.4) 1407 (29.7) 88 (29.2) 22 (17.5)
2+ 1715 (24.3) 1527 (23.2) 136 (34.0) 52 (35.8)
Quality of life, mean (95%CI) 74.40 (12.20–13.21) 75.47 (74.57–76.37) 65.40 (63.04–67.77) 62.43 (56.98–67.88) < 0.001

Note: Unweighted frequencies (n), weighted proportions (%) and weighted means with their 95% Confidence Interval (95%CI). Quality of life ranged from 0 to 100.

629
B. Olaya et al. Journal of Affective Disorders 241 (2018) 627–633

Table 2 prevalence of PA (9.5%) and PD (3.3%) was found in those aged 30–39
Adjusted Odds Ratios and Confidence Intervals 95% for Panic Attacks and Panic and 40–49 years old, respectively, whereas the lowest prevalence rates
Disorder. were observed in the oldest participants (aged 80 + ). The proportions
PA PD of PA and PD found in our study are slightly lower than those reported
in other epidemiological studies. For instance, the World Mental Health
Age (continuous) 0.97 (0.95–0.98)*** 0.97 (0.95–1.00)* survey reported a lifetime prevalence rate of PA without PD of 14.4% in
Females 1.91 (1.22–2.99)** 1.18 (0.62–2.26)
high-income countries, and 2.2% lifetime prevalence of PD (de Jonge
Years of education 1.02 (0.99–1.05) 1.02 (0.97–1.07)
Not cohabiting 0.89 (0.55–1.45) 1.94 (0.95–3.95) et al., 2016). However, comparison with previous studies might be
Depression 2.96 (1.65–5.31)*** 4.19 (1.65–10.60)** difficult because of the differences in the instrument used, defining
Suicidal ideation 5.28 (2.71–10.28)*** 13.30 (5.77–30.67)*** criteria for PA and PD, or sample characteristics.
Current smoker 1.45 (0.96–2.19) 1.24 (0.66–2.33)
Our findings confirm the hypothesis that the prevalence of PA and
Frequent drinker 0.89 (0.33–2.40) 0.20 (0.04–0.97)*
Number CC (ref. none)
PD decreases with age. In the adjusted multinomial regression models,
1 CC 1.40 (0.84–2.33) 0.49 (0.19–1.26) each year is related to lower probability of PA and PD. Previous studies
2 + CC 2.29 (1.31–4.01)** 1.18 (0.40–3.48) have shown that PD rarely starts for the first time after the age of 60
Quality of life 0.97 (0.96–0.98)*** 0.97 (0.95–0.99)** (Raj et al., 1993). It has been suggested that lower prevalence among
Age*Frequent drinker 1.01 (0.99–1.03) 1.03 (1.01–1.05)*
older adults might be linked to age-related changes in neurotransmitter
*p < 0.05; ⁎⁎ p < 0.01; ⁎⁎⁎p < 0.001 system structure and function (Flint et al., 1998). According to socio-
Adjusted Odds Ratios and 95% Confidence Intervals are presented. Reference emotional selectivity theory (Carstensen et al., 1999), older adults
category was no panic attacks. In bold, significant associations. would be more likely to experience positive emotions because they
PA = Panic attacks; PD = Panic disorder; CC = Chronic conditions; Quality of adopt a present-focused state of awareness, seek realization of emo-
life score ranges from 0 to 100. tionally meaningful goals and are more selective with their social
company. Thus, they would be less vulnerable to mental health pro-
p < 0.01) were found to be significant predictors. blems. However, it is also possible that the prevalence of PD and PA
Interaction between age and frequent drinking was significant only decreases with age because older participants with a history of PD are
for PD (p < 0.05). Fig. 2 shows the predicted probability of having PA less likely to be in the sample, either because of institutionalization or
and PD, compared with NP, for those who were not frequent drinkers vs premature mortality (Corna et al., 2007). Older cohorts might be less
frequent drinkers, and for different ages. The probability of PA de- vulnerable to mental health problems because of cultural or historical
creased with age in the same pattern for non-drinkers and frequent events they have experienced (Brault et al., 2012; Yang et al., 2007).
drinkers. However, the probability of PD for non-drinkers decreased Longitudinal designs with long follow-up periods can help confirm
with age, whereas the risk for frequent drinkers increased as people got whether the presence of PA or PD genuinely decreases with age.
older. When analyzing the potential moderating role of age in several
sociodemographic and clinical characteristics, we only found a sig-
nificant interaction with frequent alcohol consumption in the last 12
4. Discussion
months. In general, the probability of suffering from PD or PA decreases
in older ages. However, those respondents considered as frequent
The aim of the present study was to investigate the prevalence rates
drinkers (in the last year) were more likely to report PD as they got
of PA and PD in a nationally-representative population-based sample of
older, compared with lifetime abstainers or occasional drinkers. It has
adults and determine whether the effect of several risk factors differed
consistently been shown that PD and alcohol problems are closely re-
according to age. The lifetime prevalence of PA and PD in the total
lated, and that this association seems to be bidirectional (Canan and
sample was 7.6% and 2.4%, respectively. However, the proportion of
Ataoglu, 2008). Some clinical studies found that PD usually precedes
people affected by PA and PD decreased with age. The highest

Fig. 2. Predicted probability and 95% confidence intervals for panic attacks and panic disorder by age and 12-month drinking status.
Note: Probabilities were calculated from the adjusted multinomial model (Table 2), while holding the covariates as constant.

630
B. Olaya et al.
alcoholism (Stockwell et al., 1984; Weiss and Rosenberg, 1985). A
population-based study of young adults also found that PA are asso-
ciated with incident alcohol dependence (Asselmann et al., 2014).
People suffering from panic symptoms might use alcohol to relieve their
anxiety symptomatology (Kushner et al., 1996). Conversely, other stu-
dies reported that the onset of alcohol problems precede the onset of PD
(Krystal et al., 1992; Márquez et al., 2003), in concordance with the
“kindling” effect of alcohol consumption for the risk of PA
(George et al., 1990). Older participants who are frequent drinkers
might have been using alcohol for a long period as self-medication to
reduce their anxiety symptoms, which might result in long-term hazard
effects of alcohol on their brains, and increase their attacks. Further
investigations are needed to confirm these hypotheses.
Depression and suicidal thoughts are shown to be significantly re-
lated to PA and PD in our sample, irrespective of the participants’ ages.
Depression has been shown to be consistently related to PA in both
younger (Kessler et al., 1998) and older adults (Corna et al., 2007). As
for suicidal behavior, a recent meta-analysis reports a significant effect
of PD on suicidal ideation and attempts (Kanwar et al., 2013). It has
been suggested that having suicidal thoughts represents an escape from
negative emotion (Baumeister, 1990). In addition, anxiety is associated
with significant negative emotionality, which has been associated with
suicidal behavior (Stein et al., 1998). Due to the high burden associated
with suicidal behavior, clinicians are encouraged to screen for suicidal
ideation among people with PD but also among people who present PA
even though they represent milder cases than those with full-blown PD.
It is important to evaluate and screen for psychiatric comorbidity as it
has been shown to be a strong predictor of mortality, poor quality of life
and increased burden (Kessler et al., 2005).
In concordance with previous research (Chou, 2010), females are at
higher risk of PA than men. The higher risk of women for mood dis-
orders has been consistently reported (Kornstein and Sloan, 2005) and
is related to greater biological and psychosocial vulnerability than in
men (McLean et al., 2011; Nillni et al., 2011). Suffering from chronic
illnesses is found to be only related to PA after adjusting for the pre-
sence of depression. These results are in line with those of other in-
vestigations that reported a dose-response effect of anxiety on the
number of chronic conditions (Gould et al., 2016). Suffering from more
than one chronic condition decreases quality of life, increases disability
and might be related to stressful situations (e.g., medical tests, ag-
gressive treatments) making them more vulnerable to panic attacks.
There is evidence that PA are frequent in patients with chronic ob-
structive pulmonary disease and arthritis (Livermore et al., 2010;
Murphy et al., 2012), and cognitive misinterpretation of physical
symptoms related to the illness (e.g., shortness of breath) can increase
arousal and create a feedback loop that results in a panic attack
(Livermore et al., 2010). Multimorbidity is common as people get older,
and the presence of PA can add to the psychological burden (Walker
and Druss, 2017). It is therefore recommended that panic is assessed
and treated in the context of multimorbidity.
Finally, both PA and PD are significantly related to lower quality of
life, compared with people with no panic, after adjusting for other
potential covariates and irrespective of age. Previous studies have also
reported major impacts of even subclinical anxiety states on quality of
life (Andlin-Sobocki and Wittchen, 2005; Das-Munshi et al., 2008).
Recent treatment approaches encourage a more holistic emphasis on
well-being, social functioning, quality of life and recovery
(Connell et al., 2014). Our results suggest that this approach should be
considered for both PA and PD over the lifespan, as both conditions are
related to poor quality of life.
There are some limitations that should be considered when inter-
preting the results. First, the prevalence rates of PA, especially with PD,
are very low. Therefore, the magnitude and width of the 95% con-
fidence intervals are large, indicating possible bias. Increasing the
sample size would help decrease this uncertainty. Second, self-report
might be affected by recall bias. Third, other possible confounders
631
Journal of Affective Disorders 241 (2018) 627–633
might explain the relationship between PA and PD with the covariates,
for instance, the presence of other mental disorders that were not as-
sessed in the survey. Fourth, the cross-sectional nature of the study
prevents us from establishing relational causality between the covari-
ates and panic. Longitudinal designs with longer study periods can help
elucidate the trajectories of PA and PD throughout the life span.
PA and PD are more frequently observed among younger in-
dividuals (i.e., 30–39 and 40–49). The probability of suffering from PA
or PD decreases with age, and the effect of several correlates, such as
depression, suicidal thoughts, multimorbidity or quality of life, does not
seem to be modified by age. However, older adults who are frequent
drinkers are also at higher risk for PD. This might be due to either long-
term exposure to the panicogenic effects of alcohol, or that alcohol
consumption is a consequence of suffering PD during their lifetime.
Future studies should try to replicate these results and determine the
directionality of this observed association. Screening for PA and PD by
practitioners and health professionals can help with detection and de-
livery of early treatment that can have an impact on quality of life,
regardless of the age of the individual. Future studies should focus on
determining the trajectories of PA and PD from childhood to late life,
identifying the key risk factors at each stage to design tailored inter-
ventions.
Conflicts of interest
None.
Funding
This work was supported by the Seventh Framework Programme
[grant number 223,071-COURAGE Study]; the Instituto de Salud Carlos
III-FIS [grant numbers PS09/00,295, PS09/01,845, PI12/01,490, and
PI13/00,059]; the European Regional Development Fund (ERDF) “A
Way to Build Europe” [grant numbers PI12/01,490, PI13/00,059,
PI16/00218 and PI16/01073]; Horizon 2020 Research and Innovation
Programme [grant number 635,316-ATHLOS]; and the Centro de
Investigación Biomédica en Red de Salud Mental. BO is thankful to the
PERIS program 2016–2020 “Ajuts per a la Incorporació de Científics i
Tecnòlegs” [grant number SLT006/17/00,066], with the support of the
Health Department from the Generalitat de Catalunya.
Role of the funding sources
The funding sources did not have any role in study design, in the
collection, analysis and interpretation of data, in the writing of the
paper, and in the decision to submit the article for publication.
Authors’ contributions
BO, MVM, MM, JLAM, JM: study design; BO, MM: acquisition of
data; BO, MVM: data analysis; BO, MVM, MM: interpretation of the
data; BO, MVM, MM: preparation of the manuscript; BO, MVM, MM,
JLAM, JM: critical revision of the manuscript. All authors read and
approved the final manuscript.
Acknowledgments
Not applicable.
Supplementary materials
Supplementary material associated with this article can be found, in
the online version, at doi:10.1016/j.jad.2018.08.069.
B. Olaya et al.
References
American Psychiatric Association, 2013. Diagnostic and Statistical Manual of Mental
Disorders, fifth ed. American Psychiatric Association, Washington DC.
American Psychiatric Association, 2000. Diagnostic and Statistical Manual of Mental
Disorders, fourth ed. American Psychiatric Association, Washington DC Text rev.
Andlin-Sobocki, P., Wittchen, H.-U., 2005. Cost of anxiety disorders in Europe. Eur. J.
Neurol. 12, 39–44. https://doi.org/10.1111/j.1468-1331.2005.01196.x.
Antony, M., Swinson, R., 2000. Phobic Disorders and Panic in Adults: A Guide to
Assessment and Treatment. American Psychological Association, Washington, DC.
Asselmann, E., Wittchen, H.-U., Lieb, R., Beesdo-Baum, K., 2016. Risk factors for fearful
spells, panic attacks and panic disorder in a community cohort of adolescents and
young adults. J. Affect. Disord. 193, 305–308. https://doi.org/10.1016/J.JAD.2015.
12.046.
Asselmann, E., Wittchen, H.-U., Lieb, R., Höfler, M., Beesdo-Baum, K., 2014. Associations
of fearful spells and panic attacks with incident anxiety, depressive, and substance
use disorders: A 10-year prospective-longitudinal community study of adolescents
and young adults. J. Psychiatr. Res. 55, 8–14. https://doi.org/10.1016/j.jpsychires.
2014.04.001.
Basu, S., Millett, C., 2013. Social epidemiology of hypertension in middle-income coun-
tries: determinants of prevalence, diagnosis, treatment and control in the WHO SAGE
study. Hypertension 62, 18–26. https://doi.org/10.1161/hypertensionaha.113.
01374.
Baumeister, R.F., 1990. Suicide as escape from self. Psychol. Rev. 97, 90–113.
Brault, M.-C., Meuleman, B., Bracke, P., 2012. Depressive symptoms in the Belgian po-
pulation: disentangling age and cohort effects. Soc. Psychiatry Psychiatr. Epidemiol.
47, 903–915. https://doi.org/10.1007/s00127-011-0398-0.
Caballero, F.F., Miret, M., Power, M., Chatterji, S., Tobiasz-Adamczyk, B., Koskinen, S.,
Leonardi, M., Olaya, B., Haro, J.M., Ayuso-Mateos, J.L., 2013. Validation of an in-
strument to evaluate quality of life in the aging population: WHOQOL-AGE. Health
Qual. Life Outcomes 11, 177.
Canan, F., Ataoglu, A., 2008. Panic disorder after the end of chronic alcohol abuse: a
report of 2 cases. Prim. Care Companion J. Clin. Psychiatry 10, 332–333.
Carstensen, L.L., Isaacowitz, D.M., Charles, S.T., 1999. Taking time seriously. A theory of
socioemotional selectivity. Am. Psychol 54, 165–181.
Charney, D.S., Woods, S.W., Nagy, L.M., Southwick, S.M., Krystal, J.H., Heninger, G.R.,
1990. Noradrenergic function in panic disorder. J. Clin. Psychiatry 51, 5–11 Suppl A.
Chou, K.-L., 2010. Panic disorder in older adults: evidence from the national epidemio-
logic survey on alcohol and related conditions. Int. J. Geriatr. Psychiatry 25,
822–832. https://doi.org/10.1002/gps.2424.
Connell, J., O'Cathain, A., Brazier, J., 2014. Measuring quality of life in mental health: are
we asking the right questions? Soc. Sci. Med. 120, 12–20. https://doi.org/10.1016/j.
socscimed.2014.08.026.
Corna, L.M., Cairney, J., Herrmann, N., Veldhuizen, S., McCabe, L., Streiner, D., 2007.
Panic disorder in later life: results from a national survey of Canadians. Int.
Psychogeriatr. 19, 1084–1096. https://doi.org/10.1017/S1041610207004978.
Craske, M.G., Kircanski, K., Epstein, A., Wittchen, H.-U., Pine, D.S., Lewis-Fernández, R.,
Hinton, D., DSM V Anxiety, OC Spectrum, Posttraumatic and Dissociative Disorder
Work Group, 2010. Panic disorder: a review of DSM-IV panic disorder and proposals
for DSM-V. Depress. Anxiety 27, 93–112. https://doi.org/10.1002/da.20654.
Das-Munshi, J., Goldberg, D., Bebbington, P.E., Bhugra, D.K., Brugha, T.S., Dewey, M.E.,
Jenkins, R., Stewart, R., Prince, M., 2008. Public health significance of mixed anxiety
and depression: beyond current classification. Br. J. Psychiatry 192, 171–177.
https://doi.org/10.1192/bjp.bp.107.036707.
de Jonge, P., Roest, A.M., Lim, C.C.W., Florescu, S.E., Bromet, E.J., Stein, D.J., Harris, M.,
Nakov, V., Caldas-de-Almeida, J.M., Levinson, D., Al-Hamzawi, A.O., Haro, J.M.,
Viana, M.C., Borges, G., O'Neill, S., de Girolamo, G., Demyttenaere, K., Gureje, O.,
Iwata, N., Lee, S., Hu, C., Karam, A., Moskalewicz, J., Kovess-Masfety, V., Navarro-
Mateu, F., Browne, M.O., Piazza, M., Posada-Villa, J., Torres, Y., ten Have, M.L.,
Kessler, R.C., Scott, K.M., 2016. Cross-national epidemiology of panic disorder and
panic attacks in the world mental health surveys. Depress. Anxiety 33, 1155–1177.
https://doi.org/10.1002/da.22572.
Dick, C.L., Bland, R.C., Newman, S.C., 1994. Epidemiology of psychiatric disorders in
Edmonton. Panic Disord. Acta Psychiatr. Scand. Suppl. 376, 45–53.
Eaton, W.W., Kessler, R.C., Wittchen, H.U., Magee, W.J., 1994. Panic and panic disorder
in the United States. Am. J. Psychiatry 151, 413–420. https://doi.org/10.1176/ajp.
151.3.413.
Flint, A.J., Koszycki, D., Vaccarino, F.J., Cadieux, A., Boulenger, J.P., Bradwejn, J., 1998.
Effect of aging on cholecystokinin-induced panic. Am. J. Psychiatry 155, 283.
https://doi.org/10.1176/ajp.155.2.283. –5.
Garin, N., Koyanagi, A., Chatterji, S., Tyrovolas, S., Olaya, B., Leonardi, M., Lara, E.,
Koskinen, S., Tobiasz-Adamczyk, B., Ayuso-Mateos, J.L., Haro, J.M., 2016. Global
multimorbidity patterns: a cross-sectional, population-based, multi-country study. J.
Gerontol. A. Biol. Sci. Med. Sci. 71, 205–214. https://doi.org/10.1093/gerona/
glv128.
George, D.T., Adinoff, B., Ravitz, B., Nutt, D.J., De Jong, J., Berrettini, W., Mefford, I.N.,
Costa, E., Linnoila, M., 1990. A cerebrospinal fluid study of the pathophysiology of
panic disorder associated with alcoholism. Acta Psychiatr. Scand. 82, 1–7.
Gould, C.E., O'Hara, R., Goldstein, M.K., Beaudreau, S.A., 2016. Multimorbidity is asso-
ciated with anxiety in older adults in the health and retirement study. Int. J. Geriatr.
Psychiatry 31, 1105–1115. https://doi.org/10.1002/gps.4532.
Grant, B.F., Hasin, D.S., Stinson, F.S., Dawson, D.A., Goldstein, R.B., Smith, S., Huang, B.,
Saha, T.D., 2006. The epidemiology of DSM-IV panic disorder and agoraphobia in the
United States: results from the national epidemiologic survey on alcohol and related
conditions. J. Clin. Psychiatry 67, 363–374.
632
Journal of Affective Disorders 241 (2018) 627–633
Haro, J.M., Arbabzadeh-Bouchez, S., Brugha, T.S., de Girolamo, G., Guyer, M.E., Jin, R.,
Lepine, J.P., Mazzi, F., Reneses, B., Vilagut, G., Sampson, N.A., Kessler, R.C., 2006.
Concordance of the composite international diagnostic interview version 3.0 (CIDI
3.0) with standardized clinical assessments in the WHO World Mental Health surveys.
Int. J. Methods Psychiatr. Res. 15, 167–180.
Kanwar, A., Malik, S., Prokop, L.J., Sim, L.A., Feldstein, D., Wang, Z., Murad, M.H., 2013.
The association between anxiety disorders and suicidal behaviors: a systematic re-
view and meta-analysis. Depress. Anxiety 30, 917–929. https://doi.org/10.1002/da.
22074.
Katerndahl, D.A., 2008. The association between panic disorder and coronary artery
disease among primary care patients presenting with chest pain: an updated litera-
ture review. Prim. Care Companion J. Clin. Psychiatry 10, 276–285.
Kessler, R.C., Chiu, W.T., Demler, O., Walters, E.E., 2005. Prevalence, severity, and co-
morbidity of twelve-month DSM-IV disorders in the national comorbidity survey
replication (NCS- R). Arch. Gen. Psychiatry 62, 617–627. https://doi.org/10.1001/
archpsyc.62.6.617.
Kessler, R.C., Stang, P.E., Wittchen, H.U., Ustun, T.B., Roy-Burne, P.P., Walters, E.E.,
1998. Lifetime panic-depression comorbidity in the national comorbidity survey.
Arch. Gen. Psychiatry 55, 801–808.
Kornstein, S.G., Sloan, D.M.E., 2005. Depression and gender. In: Stein, D.J., Kupfer, D.J.,
Schatzberg, A.F. (Eds.), The American Psychiatric Publishing Textbook of Mood
Disorders. American Psychiatric Pub, Washington DC, pp. 687–698.
Krystal, J.H., Leaf, P.J., Bruce, M.L., Charney, D.S., 1992. Effects of age and alcoholism on
the prevalence of panic disorder. Acta Psychiatr. Scand. 85, 77–82. https://doi.org/
10.1111/j.1600-0447.1992.tb01447.x.
Kushner, M.G., Mackenzie, T.B., Fiszdon, J., Valentiner, D.P., Foa, E., Anderson, N.,
Wangensteen, D., 1996. The effects of alcohol consumption on laboratory-induced
panic and state anxiety. Arch. Gen. Psychiatry 53, 264–270.
Lenze, E.J., Wetherell, J.L., 2011. A lifespan view of anxiety disorders. Dialog. Clin.
Neurosci. 13, 381–399.
Leonardi, M., Chatterji, S., Koskinen, S., Ayuso-Mateos, J.L., Haro, J.M., Frisoni, G.,
Frattura, L., Martinuzzi, A., Tobiasz-Adamczyk, B., Gmurek, M., Serrano, R.,
Finocchiaro, C., COURAGE in Europe project's consortium, 2014. Determinants of
health and disability in ageing population: the COURAGE in Europe Project (colla-
borative research on ageing in Europe). Clin. Psychol. Psychother. 21, 193–198.
https://doi.org/10.1002/cpp.1856.
Livermore, N., Sharpe, L., McKenzie, D., 2010. Panic attacks and panic disorder in chronic
obstructive pulmonary disease: a cognitive behavioral perspective. Respir. Med. 104,
1246–1253. https://doi.org/10.1016/j.rmed.2010.04.011.
Mancia, G., Fagard, R., Narkiewicz, K., Redón, J., Zanchetti, A., Böhm, M., Christiaens, T.,
Cifkova, R., De Backer, G., Dominiczak, A., Galderisi, M., Grobbee, D.E., Jaarsma, T.,
Kirchhof, P., Kjeldsen, S.E., Laurent, S., Manolis, A.J., Nilsson, P.M., Ruilope, L.M.,
Schmieder, R.E., Sirnes, P.A., Sleight, P., Viigimaa, M., Waeber, B., Zannad, F., 2013.
2013 ESH/ESC Guidelines for the management of arterial hypertension. J. Hypertens.
31, 1281–1357. https://doi.org/10.1097/01.hjh.0000431740.32696.cc.
Márquez, M., Seguí, J., Canet, J., García, L., Ortiz, M., 2003. Alcoholism in 274 patients
with panic disorder in Spain, one of the main producers of wine worldwide. J. Affect.
Disord. 75, 237–245. https://doi.org/10.1016/S0165-0327(02)00054-X.
McLean, C.P., Asnaani, A., Litz, B.T., Hofmann, S.G., 2011. Gender differences in anxiety
disorders: prevalence, course of illness, comorbidity and burden of illness. J.
Psychiatr. Res. 45, 1027–1035. https://doi.org/10.1016/j.jpsychires.2011.03.006.
Moreno-Peral, P., Conejo-Cerón, S., Motrico, E., Rodríguez-Morejón, A., Fernández, A.,
García-Campayo, J., Roca, M., Serrano-Blanco, A., Rubio-Valera, M., Bellón, J.Á.,
2014. Risk factors for the onset of panic and generalised anxiety disorders in the
general adult population: a systematic review of cohort studies. J. Affect. Disord 168,
337–348. https://doi.org/10.1016/j.jad.2014.06.021.
Murphy, L.B., Sacks, J.J., Brady, T.J., Hootman, J.M., Chapman, D.P., 2012. Anxiety is
more common than depression among US adults with arthritis. Arthr. Care Res.
(Hoboken) 64, 968–976. https://doi.org/10.1002/acr.21685. n/a-n/a.
Nillni, Y.I., Toufexis, D.J., Rohan, K.J., 2011. Anxiety sensitivity, the menstrual cycle, and
panic disorder: a putative neuroendocrine and psychological interaction. Clin.
Psychol. Rev. 31, 1183–1191. https://doi.org/10.1016/j.cpr.2011.07.006.
Raj, B.A., Corvea, M.H., Dagon, E.M., 1993. The clinical characteristics of panic disorder
in the elderly: a retrospective study. J. Clin. Psychiatry 54, 150–155.
Rao, J.N.K., Scott, A.J., 1984. On chi-squared tests for multiway contingency tables with
cell proportions estimated from survey data. Ann. Stat. 12, 46–60. https://doi.org/
10.1214/aos/1176346391.
Roy-Byrne, P.P., Craske, M.G., Stein, M.B., 2006. Panic disorder. Lancet 368, 1023–1032.
https://doi.org/10.1016/S0140-6736(06)69418-X.
Seguí, J., Salvador-Carulla, L., Márquez, M., Garcìa, L., Canet, J., Ortiz, M., 2000.
Differential clinical features of late-onset panic disorder. J. Affect. Disord 57,
115–124.
Simon, N.M., Fischmann, D., 2005. The implications of medical and psychiatric co-
morbidity with panic disorder. J. Clin. Psychiatry 66 (Suppl 4), 8–15.
Stein, D., Apter, A., Ratzoni, G., Har-Even, D., Avidan, G., 1998. Association between
multiple suicide attempts and negative affects in adolescents. J. Am. Acad. Child
Adolesc. Psychiatry 37, 488–494. https://doi.org/10.1097/00004583-199805000-
00011.
Stockwell, T., Smail, P., Hodgson, R., Canter, S., 1984. Alcohol dependence and phobic
anxiety states. II. A retrospective study. Br. J. Psychiatry 144, 58–63.
Üstün, T., Chatterji, S., Mechbal, A., Murray, C., 2005. Quality assurance in surveys:
standards, guidelines and procedures. Household Sample Surveys in Developing and
Transtion Countries. United Nations, New York, pp. 199–230.
Walker, E.R., Druss, B.G., 2017. Cumulative burden of comorbid mental disorders, sub-
stance use disorders, chronic medical conditions, and poverty on health among adults
in the U.S.A. Psychol. Health Med. 22, 727–735. https://doi.org/10.1080/13548506.
B. Olaya et al.
2016.1227855.
Weiss, K.J., Rosenberg, D.J., 1985. Prevalence of anxiety disorder among alcoholics. J.
Clin. Psychiatry 46, 3–5.
Weissman, M.M., Bland, R.C., Canino, G.J., Faravelli, C., Greenwald, S., Hwu, H.G.,
Joyce, P.R., Karam, E.G., Lee, C.K., Lellouch, J., Lépine, J.P., Newman, S.C., Oakley-
Browne, M.A., Rubio-Stipec, M., Wells, J.E., Wickramaratne, P.J., Wittchen, H.U.,
Yeh, E.K., 1997. The cross-national epidemiology of panic disorder. Arch. Gen.
633
Journal of Affective Disorders 241 (2018) 627–633
Psychiatry 54, 305–309.
WHO, 2014. Process of translation and adaptation of instruments [WWW Document].
URL. http://www.who.int/substance_abuse/research_tools/translation/en/.
Yang, Y., Marchand, A., Forest, C., Martelin, T., Prattala, R., Hipipi, E., Howes, M.,
Normand, S., Manderschied, R., Walters, E., Zaslavsky, A., 2007. Is Old Age
Depressing? Growth Trajectories and Cohort Variations in Late-Life Depression. J.
Health Soc. Behav 48, 16–32. https://doi.org/10.1177/002214650704800102.