Post-traumatic stress disorder and medication adherence: Results from the Mind Your Heart Study.
ABSTRACT BACKGROUND: Patients with post-traumatic stress disorder (PTSD) are at increased risk for adverse outcomes from comorbid medical conditions. Medication non-adherence is a potential mechanism explaining this increased risk. METHODS: We examined the association between PTSD and medication adherence in a cross-sectional study of 724 patients recruited from two Department of Veterans Affairs Medical Centers between 2008 and 2010. PTSD was assessed using the Clinician Administered PTSD Scale. Medication adherence was assessed using a standardized questionnaire. Ordinal logistic regression models were used to calculate the odds ratios (ORs) for medication non-adherence in patients with versus without PTSD, adjusting for potential confounders. RESULTS: A total of 252 patients (35%) had PTSD. Twelve percent of patients with PTSD reported not taking their medications as prescribed compared to 9% of patients without PTSD (unadjusted OR 1.85, 95% CI 1.37-2.50, P<0.001). Forty-one percent of patients with PTSD compared to 29% of patients without PTSD reported forgetting medications (unadjusted OR 1.90, 95% CI 1.44-2.52, P<0.001). Patients with PTSD were also more likely to report skipping medications (24% versus 13%; unadjusted OR 2.01, 95% CI 1.44-2.82, P<0.001). The association between PTSD and non-adherence remained significant after adjusting for demographics, depression, alcohol use, social support, and medical comorbidities (adjusted OR 1.47, 95% CI 1.03-2.10, P=0.04 for not taking medications as prescribed and 1.95, 95% CI 1.31-2.91, P=0.001 for skipping medications). CONCLUSIONS: PTSD was associated with medication non-adherence independent of psychiatric and medical comorbidities. Medication non-adherence may contribute to the increased morbidity and mortality observed in patients with PTSD.
- JAMA Internal Medicine 12/2013; · 13.25 Impact Factor
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ABSTRACT: Gender differences in post-traumatic stress disorder (PTSD) rates were confirmed across different DSM editions as well as the role of bipolar disorder (BD) comorbidity on prevalence and course, but little data is available upon new DSM-5 criteria, including maladaptive behaviors. The aim of this study was to investigate gender differences in DSM-5 PTSD in a sample of young adult earthquake survivors and the impact of lifetime mood spectrum comorbidity. Five hundred twelve young adult survivors from the L'Aquila 2009 earthquake were evaluated by Trauma and Loss Spectrum-Self Report (TALS-SR) and Mood Spectrum-Self Report (MOODS-SR). Females showed significantly higher DSM-5 PTSD prevalence rates than men. Similarly, female survivors with DSM-5 PTSD showed significantly higher scores in several of the MOODS-SR and TALS-SR domains with respect to males. Males showed significantly higher scores in the TALS-SR maladaptive coping domain only. A significant positive association between the MOODS-SR manic-hypomanic component and TALS-SR potentially traumatic events and maladaptive coping domains emerged in the whole sample, particularly among men. This study allows a first glimpse on gender differences in DSM-5 PTSD criteria in a sample of earthquake survivors. Further, possible correlations with subthreshold manic-hypomanic comorbidity are suggested among males, showing a significant trend particularly for lifetime trauma exposure and for the newly introduced maladaptive behaviors.Annals of General Psychiatry 01/2014; 13:28. · 1.53 Impact Factor
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ABSTRACT: Abstract We conducted a study of alcohol use biomarkers and cognitive performance among 85 veterans with problematic alcohol use and posttraumatic stress disorder (PTSD). All analyses were adjusted for demographics, depression, anxiety, and PTSD symptoms. Elevated levels of aspartate aminotransferase (AST) were associated with worse performance on the Trail Making Test Part A and Hopkins Verbal Learning Test. Two other biomarkers were not associated with any neurocognitive measures. Indirect alcohol use biomarkers (e.g., AST) may have a specific role in identifying those veterans with problematic alcohol use and PTSD who show a change in psychomotor speed and immediate verbal memory performance.Journal of Addictive Diseases 04/2014; · 1.46 Impact Factor
Post-traumatic stress disorder and medication adherence: Results from the Mind
Your Heart Study
Ian M. Kronisha,*, Donald Edmondsona, Yongmei Lib, Beth E. Cohenb,c
aCenter for Behavioral Cardiovascular Health, Columbia University Medical Center, New York, NY, USA
bGeneral Internal Medicine, Department of Veterans Affairs Medical Center, San Francisco, CA, USA
cDepartment of Medicine, University of California, San Francisco, CA, USA
a r t i c l e i n f o
Received 29 April 2012
Received in revised form
7 June 2012
Accepted 14 June 2012
Post-traumatic stress disorder
a b s t r a c t
Background: Patients with post-traumatic stress disorder (PTSD) are at increased risk for adverse
outcomes from comorbid medical conditions. Medication non-adherence is a potential mechanism
explaining this increased risk.
Methods: We examined the association between PTSD and medication adherence in a cross-sectional
study of 724 patients recruited from two Department of Veterans Affairs Medical Centers between
2008 and 2010. PTSD was assessed using the Clinician Administered PTSD Scale. Medication adherence
was assessed using a standardized questionnaire. Ordinal logistic regression models were used to
calculate the odds ratios (ORs) for medication non-adherence in patients with versus without PTSD,
adjusting for potential confounders.
Results: A total of 252 patients (35%) had PTSD. Twelve percent of patients with PTSD reported not taking
their medications as prescribed compared to 9% of patients without PTSD (unadjusted OR 1.85, 95% CI
1.37e2.50, P<0.001). Forty-one percent of patients with PTSD compared to 29% of patients without PTSD
reported forgetting medications (unadjusted OR 1.90, 95% CI 1.44e2.52, P<0.001). Patients with PTSD
were also more likely to report skipping medications (24% versus 13%; unadjusted OR 2.01, 95% CI 1.44
e2.82, P <0.001). The association between PTSD and non-adherence remained significant after adjusting
for demographics, depression, alcohol use, social support, and medical comorbidities (adjusted OR 1.47,
95% CI 1.03e2.10, P ¼0.04 for not taking medications as prescribed and 1.95, 95% CI 1.31e2.91, P ¼0.001
for skipping medications).
Conclusions: PTSD was associated with medication non-adherence independent of psychiatric and
medical comorbidities. Medication non-adherence may contribute to the increased morbidity and
mortality observed in patients with PTSD.
? 2012 Elsevier Ltd. All rights reserved.
Post-traumatic stress disorder (PTSD) is a common, typically
chronic anxiety disorder with a prevalence of 8e12% in the general
population and 13e31% in veterans (Kessler, 2000; Kessler et al.,
1995; Boscarino, 2006; Dohrenwend et al., 2006; Friedman,
2004). PTSD comes at a profound cost in terms of disabling
psychological distress, elevated risk for suicide, and inability to
work (Yehuda, 2002). A growing body of research also demon-
strates that PTSD, in both veterans and civilians, increases the risks
and consequences associated with comorbid medical conditions
(Beckham et al., 1998; Jordan et al., 2011; Wisnivesky et al., 2011;
Hoge et al., 2007; Jakupcak et al., 2008; Ahmadi et al., 2011;
Pietrzak et al., 2012). For example, patients with PTSD are at
increased risk of recurrent cardiovascular events (Edmondson et al.,
2011; Shemesh et al., 2004), and among patients with diabetes,
those with PTSD have poorer glycemic control and worse prognosis
(Miller et al., 2011; Trief et al., 2006). The mechanisms explaining
the associations between PTSD and adverse outcomes frommedical
illness remain poorly understood (Dedert et al., 2010).
Medication adherence represents one of the most essential
health behaviors for preventing complications from medical
conditions. While some studies have shown that individuals with
PTSD engage in increased smoking (Fu et al., 2007) and decreased
physical activity (Zen et al., 2011), far less is known about the
impact of PTSD on medication-taking behavior. Studies that have
examined medication adherence in PTSD thus far have restricted
* Corresponding author. Columbia University Medical Center, 622 West 168th
Street, PH9-311, New York, NY 10032, USA. Tel.: þ1 212 342 1335; fax: þ1 212 342
E-mail address: email@example.com (I.M. Kronish).
Contents lists available at SciVerse ScienceDirect
Journal of Psychiatric Research
journal homepage: www.elsevier.com/locate/psychires
0022-3956/$ e see front matter ? 2012 Elsevier Ltd. All rights reserved.
Journal of Psychiatric Research 46 (2012) 1595e1599
their analysis to populations with specific medical illnesses that
may directly induce PTSD, including acute coronary events and HIV
diagnosis (Shemesh et al., 2004; Vranceanu et al., 2008). PTSD that
develops related to myocardial infarction or HIV may have different
associations with medication non-adherence than PTSD due to
more general types of traumatic events.
Accordingly, we sought to better understand the relationship
between PTSD and medication adherence in a group of outpatients
recruited without regard to specific disease status or trauma
exposure. We hypothesized that patients with PTSD would have
lower rates of medication adherence, even after accounting for
depression and other potential confounders.
The Mind Your Heart Study is a prospective cohort study
designed to examine the association between PTSD and health
outcomes. Patients were recruited between February 2008 and
June 2010 from outpatient clinics affiliated with two Department of
Veterans Affairs (VA) Medical Centers (San Francisco VA Medical
Center and the VA Palo Alto Health Care System, California).
Patients were excluded if they planned on leaving the area in three
years or did not have contact information for follow-up. Potential
patients were also excluded if they were unable to walk one block
or had a myocardial infarction in the prior six months as a cardiac
treadmill test was done for the study and would be contraindicated
in these cases. All patients provided written informed consent and
appropriate institutional review boards approved the research
Overall,1020 patients were assessed for eligibility. One hundred
and four patients (10.2%) were found ineligible, primarily due to
lacking contact information for follow-up (n¼82). Of the remain-
ing 916 eligible patients, 172 (18.8%) declined to participate or did
not show up for the baseline interview such that 744 patients were
ultimately enrolled in the study. Ten patients were excluded from
these analyses because they did not complete full PTSD assess-
ments or because the supervising study psychologist had concerns
about the accuracy of the PTSD diagnosis. Another 10 patients were
excluded because they reported not taking any medications,
leaving 724 patients for these analyses.
We evaluated PTSD with the Clinician Administered PTSD Scale
(CAPS) using criteria from the Diagnostic and Statistical Manual of
Mental Disorders IV (DSM-IV) (APA, 2000). The CAPS is the most
widely used structured interview for diagnosing PTSD (Blake et al.,
1995; Weathers et al., 2001) and has excellent testeretest reliability
(Weathers et al., 2001). The CAPS was also used to identify the
categories of trauma exposure that were common in patients with
and internalconsistency (alpha¼0.80e0.90)
2.3. Medication adherence
We assessed medication adherence using a standardized ques-
tionnaire based on the one used to measure adherence in the
CARDIA (Coronary Artery Risk Development in Young Adults) study
(Gehi et al., 2005; Cutter et al., 1991). Cut-points for determining
whether someone was non-adherent were chosen according to
convention (Gehi et al., 2005). Overall medication adherence was
assessed by asking patients “Overall, in the past month, how often
did you take your medications as the doctor prescribed?” Possible
responses were less than half of the time, about half of the time,
most of the time, nearly all of the time, and all of the time; overall
non-adherence was defined as taking medication as prescribed half
of the time or less. Forgetting to take medications was assessed by
asking “In the past month, how often did you forget to take one or
more of your prescribed medications?” Possible responses were
never, once in the last month, 2 to 3 times in the last month, about
once per week, several times per week, or nearly every day; non-
adherence was defined as forgetting medications once per week
or more. Deciding not to take medications was evaluated with the
question “In the past month, how often did you decide to skip one
or more of your medications?” Possible responses were never, once
in the last month, 2 to 3 times in the last month, about once per
week, several times per week, or nearly every day; non-adherence
was defined as skipping medications once per week or more.
We administered a self-report questionnaire to all patients to
determine age, sex, ethnicity, income, education, and medical
history (Whooley et al., 2008). We used the Alcohol Use Disorders
Identification Test-consumption questions (AUDIT-C), a validated
screening questionnaire, to measure alcohol use, and used recom-
mended cut-off scores of 3 for women and 4 for men to identify
patients with possible problematic alcohol use (Bradley et al.,1998;
Bush et al.,1998). We assessed social support with the validated 12-
item Multidimensional Scale of Perceived Social Support (MSPSS)
(Dahlem et al.,1991; Zimet et al.,1990). We used the 9-item Patient
Health Questionnaire (PHQ-9) to evaluate depressive symptoms.
This self-report instrument measures the frequency of depressive
symptoms corresponding to the 9 symptom criteria in the DSM-IV.
A standard cut-point of ?10 is used to define depression and has
demonstrated excellent validity when compared with a mental
health interview with a sensitivity of 88% and a specificity of 88%
(Kroenke et al., 2001).
2.5. Statistical analysis
We compared differences in characteristics between patients
with and without PTSD using t tests or ManneWhitney U tests for
continuous variables and chi-square tests for dichotomous vari-
ables. Given the ordinal nature of our medication adherence vari-
ables, for our main analyses, we used separate ordinal logistic
regression models to evaluate the association of PTSD with the
three medication adherence outcomes. These models yield single
odds ratios for the association of the predictor variable (PTSD) with
each combination of higher versus lower-risk outcome categories
(for example, skipping medications nearly every day vs. other
categories; nearly every day or several times per week vs. other
categories; nearly every day, several times per week, or about once
per week vs. other categories; etc.). We adjusted for patient char-
acteristics from Table 1 that were associated with PTSD at P<0.20
using staged models. Covariates included in the final models
included sex, depression, alcohol use, social support, and history of
hypertension, elevated cholesterol, diabetes, myocardial infarction,
or chronic obstructive pulmonary disease. The proportional odds
assumption was verified for all models. To determine if there were
differences in the strength of the association between PTSD and
type of non-adherence (forgetting to take and deciding to skip
medications), we transformed the odds ratios for the association
between PTSD and non-adherence into r-scores and then derived
a Z-statistic according to the method recommended by Steiger
(1980). For our secondary analyses, we used the pre-defined cut-
points to determine whether patients were or were not adherent
and then used chi-squared to test for differences in the proportion
I.M. Kronish et al. / Journal of Psychiatric Research 46 (2012) 1595e1599
of patients with and without PTSD who were non-adherent. All
11 (StataCorp; College Station, Texas) to perform all analyses.
Of the 724 patients analyzed, 251 (35%) had PTSD. The mean age
of patients was 58 years, 6% were women, and 58% self-identified
their race as white. Among patients with PTSD, the most
common types of trauma exposures were combat-related (55%),
sexual assault (12%), physical assault (8%), non-combat military
trauma (3%), accident (2%), and unexpected death of close friend or
relative (2%). Compared to patients without PTSD, those with PTSD
were more likely (P<0.05) to be female, to have depression, to
have lower social support, and to have at-risk alcohol use (Table 1).
Patients with PTSD also had higher rates of several comorbid
chronic medical conditions.
In unadjusted analyses, patients with PTSD had nearly twice the
odds of not taking their medications as prescribed as compared to
patients without PTSD (Table 2). The association between PTSD and
this measure of medication adherence remained significant even
after controlling for potential confounders, including demo-
graphics, depression, alcohol use, and medical comorbidities
As compared to patients without PTSD, patients with PTSD were
also more likely to report forgetting their medications and skipping
their medications (Fig. 1). In fully adjusted regression analyses,
there was a strongerassociation between PTSD and deciding toskip
medications (adjusted OR 1.95, 95% CI 1.31e2.91; P¼0.001) as
compared to PTSD and forgetting medications (adjusted OR 1.32,
95% CI 0.95e1.83; P¼0.09), and the difference in these adjusted
ORs was statistically significant (P<0.001).
We found that PTSD was associated with lower medication
adherence in our sample of 724 patients, even after controlling for
depression and other potential confounders. In addition, we found
that patients with PTSD were more likely to report forgetting and
deciding to skip their medications. This establishes PTSD as an
independent risk factor for medication non-adherence in patients
recruited from general medicine clinics and expands upon prior
studies in this area.
Prior investigators have shown that PTSD was associated with
lower adherence to medications prescribed for specific medical
illnesses. For example, Shemesh et al. enrolled 73 patients with
a recent history of myocardial infarction and reported that patients
with PTSD had a higher prevalence of medication non-adherence
than patients without PTSD (Shemesh et al., 2004). This analysis,
Associations between post-traumatic stress disorder and non-adherence to medications among medical outpatients.
Type of non-adherence UnadjustedAdjusted for age, sex Fully adjusteda
OR (95% CI)
OR (95% CI)
OR (95% CI)
Overall, do not take
medications as prescribed
Forget to take medications
Decide to skip medications
<0.001 1.47 (1.03e2.10)0.04
Abbreviations: OR, odds ratio; CI, confidence interval; PHQ-9, Patient Health Questionnaire-9 item version.
aAll variables from Table 1 that were associated with post-traumatic stress disorder (PTSD) at P<.20 were entered into ordinal logistic regression models to evaluate the
association of PTSD with the three medication adherence outcomes. Covariates included in each of the three fully adjusted models include age, sex, depression, social support
score, alcohol use, and history of hypertension, elevated cholesterol, diabetes, myocardial infarction, and chronic obstructive pulmonary disease. Other variables significantly
associated with not taking medications as prescribed included age (OR 0.98, 95% CI 0.97e0.99), female gender (OR 2.53, 95% CI 1.29e4.94), and diabetes (OR 1.52, 95% CI
1.01e2.29). Other variables significantly associated with forgetting to take medications included depression (PHQ-9 score?10) (OR 2.09; 95% CI 1.48e2.94); hypercholes-
terolemia (OR 1.43, 95% CI 1.07e1.92); and diabetes (OR 1.55, 95% CI 1.07e2.25). Other variables associated with deciding to skip medications included age (OR 0.98, 95% CI
0.96e0.99), at risk alcohol use (OR 1.60, 95% CI 1.12e2.27), and diabetes (OR 1.95, 95% CI 1.25e3.06).
Characteristics of 724 study patients according to post-traumatic stress disorder
Age, mean (SD), in years
Annual income <$20,000
Depression (PHQ-9 ?10)
MSPSS social support
score, mean (SD)
At-risk alcohol use (AUDIT-C ?3
in women, ?4 in men)
207 (44.7)88 (36.4)0.03
Prior heart attack
Abbreviations: PTSD, post-traumatic stress disorder; MSPSS, multidimensional scale
of perceived social support; PHQ-9, 9-item patient health questionnaire; AUDIT-C,
alcohol use disorders identification test consumption questions.
*Data are presented as number (%) unless otherwise specified.
Fig.1. Percentage of patients with and without post-traumatic stress disorder who are
non-adherent to medications. Abbreviations: PTSD, post-traumatic stress disorder.
I.M. Kronish et al. / Journal of Psychiatric Research 46 (2012) 1595e1599
however, was limited by its small sample size and was not adjusted
for depression or other potential confounders. In a larger sample,
Zen et al. showed that PTSD was associated with decreased medi-
cation adherence in patients with stable coronary heart disease,
however this association did not remain significant after adjusting
for depression (Zen et al., 2011). PTSD has also been associated with
decreased adherence in patients with HIV, but the comorbidity
between PTSD and depression was so high in one study that
investigators were unable to test whether PTSD was associated
with non-adherence independent of depression (Boarts et al.,
2006). In contrast, our study examines the association between
PTSD and medication adherence in a broad group of outpatients
without any specific medical illnesses and includes sufficient
patients without comorbid depression to test the independent
association of PTSD and medication adherence.
There are several potential explanations for why we found an
association between PTSD and adherence that was independent of
depression, whereas others have not. The severity of PTSD may
have been higher in this VA population as compared to other
samples (Brinker et al., 2007). In addition, we used the gold-
standard psychiatric interview to identify PTSD whereas prior
studies utilized briefer survey measures or interviews. This may
have led to more accurate PTSD categorization and more clear
delineation between depression and PTSD in our sample.
Currently, most plausible mechanisms to explain how PTSD may
influence medication adherence are rooted in PTSD-specific
cognitive and behavioral symptoms. Avoidant symptoms are one
of the hallmarks of PTSD and patients with PTSD may not adhere to
medical treatments that remind them of their initial trauma or of
their own mortality more generally (Shemesh et al., 2004). Also,
prior work has demonstrated that patients with PTSD may have
impairments in cognitive function (Stafford et al., 2008; Hekler
et al., 2008), and cognitive dysfunction has been linked with
medication non-adherence in prior studies (Lovejoy & Suhr, 2009).
Interestingly, nearly 41% of patients with PTSD reported regularly
forgetting their medications in our study. Accordingly, PTSD-
related deficits in cognitive function may lead to increased unin-
Compared to non-adherence due to forgetting medications, we
found an even stronger association between PTSD and skipping
medications. As described above, this could relate to avoidance
symptoms in patients with PTSD. However, it is also possible that
patients with PTSD after stroke have unfavorable illness beliefs
that, in turn, lead to decreased medication adherence (Stafford
et al., 2008; Hekler et al., 2008). For example, PTSD has been
associated with a sense of foreshortened future (Greenwell &
Cosden, 2009; Rodriguez et al., 2008) and a lack of personal
control over the illness that triggered PTSD (Wikman et al., 2011);
these distinct illness representations may lead affected patients to
miss preventive medications out of a fatalistic sense that such
medications are not worth taking, particularly for asymptomatic
conditions like hypertension or hyperlipidemia. Although some
researchers have begun to look at the association between PTSD
and beliefs about PTSD treatment (Spoont et al., 2005), we could
find no published studies that explored beliefs about treatment for
medical conditions in patients with PTSD.
Our findings should be interpreted in light of several potential
limitations. First, the cross-sectional nature of the data prevents us
from ascribing causal attributions to the association of PTSD and
medication adherence, though reverse causality (medication non-
adherence causing PTSD) is less plausible. Second, medication
adherence was measured using self-report and no objective
measures of adherence were available to confirm responses.
Nevertheless, self-report measures are often highly correlated with
objective measures (Krousel-Wood et al., 2009) and have been
reliable predictors of poor outcomes in multiple studies (Gehi et al.,
2007; Rasmussen et al., 2007). If anything, self-reports may have
underestimated the true prevalence of non-adherence in these
patients (Shi et al., 2010). Third, the study population was majority
men and was recruited from VA medical centers, which may reduce
generalizability. Nevertheless, patients in this study were recruited
from general outpatient clinics and included patients with PTSD
from a variety of causes. Hence, this study broadens the literature
pertaining to the association of PTSD and medication adherence
that has previously been restricted to disease-specific or trauma-
The results of this study suggest that PTSD may be putting
patients at increased risk for adverse outcomes from comorbid
medical conditions as a result of decreased medication adherence.
As depression, socioeconomic status, and medical comorbidities
did not explain these associations, future studies should explore
other mechanisms, such as differences in beliefs about medications
or cognitive dysfunction. In the meantime, clinicians should care-
fully assess for adherence problems in patients with PTSD.
The Mind Your Heart Study was supported by the National
Heart, Lung, and Blood Institute (K23 HL 094765-0), the Irene
Perstein Foundation, and Departmental funds from the University
of California, San Francisco. Dr. Kronish was supported by the
National Heart, Lung, and Blood Institute (K23 HL098359). Dr.
Edmondson was supported by grant KM1CA156709 from the
National Institutes of Health. The sponsors had no role in the design
or conduct of the study, nor in the collection or interpretation of
data, nor in the preparation of the manuscript.
Conflicts of interest
This manuscript represents original work and is not under
consideration for publication elsewhere. All authors had access to
the data and a role in writing the manuscript.
We wish to thank the Mind Your Heart Study participants and
gratefully acknowledge the contributions of the Mind Your Heart
Study staff and co-Investigators, particularly Dr. Mary Whooley.
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