Journal of Clinical Neuroscience xxx (2015) xxx–xxx

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Journal of Clinical Neuroscience

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

Clinical Study

Antidepressant medication can improve hypertension in elderly patients

with depression
Wenjing Fu a,1, Lina Ma b,1, Xiaoling Zhao c, Yun Li b,⇑, Hong Zhu b, Wei Yang b, Chuan Liu b, Jia Liu b,
Rui Han b, Huizhen Liu d
a
Department of Nephrology, Xuan Wu Hospital, Capital Medical University, 45 Changshun Street, Xicheng District, Beijing 100053, China
b
Department of Geriatrics, Xuan Wu Hospital, Capital Medical University, Beijing, China
c
Department of Emergency, Three Gorges University People’s Hospital, The First People of Yichang, Yichang, China
d
Department of Emergency, Beijing Boai Hospital, Beijing, China

a r t i c l e i n f o a b s t r a c t

Article history: We explored the influence of antidepressant therapy on blood pressure and quality of life in elderly
Received 20 December 2014 patients with hypertension. Depression occurs at a higher rate in patients with hypertension than in
Accepted 23 March 2015 the normal population. It has been reported that depressive symptoms lead to poorer hypertension con-
Available online xxxx
trol, resulting in the development of complications. We conducted a randomized, parallel group study. A
total of 70 elderly patients with hypertension in the period of August 2008 to March 2011 were divided
Keywords: into two groups based on their antihypertensive therapy, a control group (amlodipine, 5 mg daily; n = 35)
Antidepressants
and a therapy group (amlodipine, 5 mg daily; citalopram, 20 mg daily; n = 35). We compared 24 hour,
Depression
Elderly
daytime, and nighttime measurements of systolic and diastolic blood pressure, in addition to quality
Hypertension of life, assessed using the Hamilton rating scale for depression, and a 36 item Short Form quality of life
Quality of life questionnaire (SF-36). Both groups were followed for 3 months. At the end of 3 months, all blood pres-
sure levels were significantly lower in the therapy group than in the control group. The other scores (with
the exception of the physical function subcategory of the SF-36 quality of life scale) were significantly
higher. Our study indicates that clinicians should be aware of depressive symptoms in elderly patients
with hypertension, and should consider antidepressant therapy in these patients.
Ó 2015 Elsevier Ltd. All rights reserved.

1. Introduction diminish QOL [9,10]. However, a recent meta-analysis does not

Depression and hypertension can undermine quality of life
(QOL) and social function, and increase mortality in elderly
patients [1–4]. Hypertension has increasing prevalence in the geri-
atric population [5], and is a principal precursor to cardiovascular
diseases and a main cause of death globally [6]. The current global
prevalence of hypertension is 26%, and it is projected to rise to 29%
by the year 2025 [7].
Patients with hypertension may experience many negative
emotions that increase their risk of developing mental health dis-
orders, particularly depression [8]. Depression occurs at a higher
rate in patients with hypertension than in the normal population.
It has been reported that depressive symptoms lead to poorer con-
trol of hypertension, resulting in the development of complica-
tions, which not only affect the treatment outcomes but also
⇑ Correspondence to: Yun Li, Tel./fax: +8601083198707.
E-mail address: liy_xw@sina.com (Y. Li).
1
Wenjing Fu and Lina Ma have contributed equally to the manuscript.
support the proposal that hypertension is a risk factor for depres-
sion, with a pooled relative risk of 1.16 when those suffering from
hypertension were compared with those who were not [11]. Given
that it remains unclear as to whether antidepressant medication
can control blood pressure and improve QOL in the elderly, we con-
ducted a study of 70 elderly Chinese hypertensive patients with
depression.
2. Patients and methods
2.1. Study population
The patients were recruited from the Xuan Wu Hospital
between August 2008 and April 2011. All enrolled patients satis-
fied the criteria for major depressive disorder, diagnosed during a
structured clinical interview as described in the Diagnostic and
Statistical Manual of Mental Disorders, Fourth Edition-Patient Edi-
tion. The patient inclusion criteria were advanced age (>60 years),

http://dx.doi.org/10.1016/j.jocn.2015.03.067
0967-5868/Ó 2015 Elsevier Ltd. All rights reserved.

Please cite this article in press as: Fu W et al. Antidepressant medication can improve hypertension in elderly patients with depression. J Clin Neurosci
(2015), http://dx.doi.org/10.1016/j.jocn.2015.03.067
2 W. Fu et al. / Journal of Clinical Neuroscience xxx (2015) xxx–xxx
hypertension and depression. All the participants were either inpa-
tients or outpatients for the management of hypertension, and
they did not take antihypertensive medication.
The study exclusion criteria were patients with secondary
hypertension, malignant tumors, significant suicidal risk, unstable
physical disorders, dementia, neurological disorders that were sig-
nificantly affecting the central nervous system function (including
a history of seizures), a lifetime history of any organic mental dis-
order, psychotic disorder or mania, substance abuse or dependence
within the previous 6 months, clinical or laboratory evidence of
hypothyroidism without adequate and stable replacement, Parkin-
son’s disease, a family history of mental illness, and antipsychotic
medications.
2.2. Study design
We conducted a randomized, parallel group study. All study
participants underwent a standardized clinical assessment which
included medical history, physical and neurological examinations,
Hamilton rating scale for depression (HAMD) tests, psychometric
evaluations, an electrocardiogram, complete blood count, urinaly-
sis, blood chemistry screening, and thyroid function tests. The
patients were randomly assigned to two groups: a control group
(n = 35), which received conventional medical treatment with
amlodipine capsules (5 mg daily) for hypertension, and a case
group (n = 35), which received conventional amlodipine treatment
supplemented with citalopram (20 mg daily). The patients in both
groups were followed for 3 months. The assignments to the control
or case group were based on a computer-generated randomization
list which was prepared by an independent statistician who was
not involved in the remainder of the study. The statistician respon-
sible for statistical analyses was blinded to the study group alloca-
tions throughout the study. The primary end point of the current
study was an improved QOL. The study was approved by the Ethics
Committee of Xuan Wu Hospital, Capital Medical University, China
and all participants provided written informed consent to partici-
pate. The case intervention patients were blinded to the interven-
tion and the purpose of the study, and the assessors of the HAMD
and the 36 item Short Form quality if life questionnaire (SF-36)
were blinded to which group the patient had been allocated to.
The study participants received a follow-up phone call every
2 weeks to inquire about matters that needed attention, provide
reminders, and follow-up on topics that had been discussed in
the previous calls. Each participant also had a clinical visit in each
of the first 2 months. At the end of the third month, a clinical
follow-up visit was conducted during which the patient received
a physical examination that included blood pressure, HAMD and
SF-36 tests, which were evaluated by trained physicians.
2.3. Data collection
All data were collected on standardized study forms according
to documented procedures by uniformly trained physicians. Two
individual physicians entered the study data into a clinical data-
base. The data were then checked by another physician. Data qual-
ity was ensured through standard data checks, and losses to
follow-up were balanced across the two groups.
2.4. Ambulatory blood pressure monitoring
Ambulatory blood pressure monitoring was conducted by a
non-invasive blood pressure detection instrument. Systolic blood
pressure (SBP) and diastolic blood pressure (DBP) were recorded,
24 hour, daytime and nighttime. Hypertension was defined as
SBP P 140 millimeters of mercury (mmHg), diastolic blood pres-
Please cite this article in press as: Fu W et al. Antidepressant medication can improve hypertension in elderly patients with depression. J Clin Neurosci
(2015), http://dx.doi.org/10.1016/j.jocn.2015.03.067
sure (DBP) P 90 mmHg, current treatment with antihypertensive
medication, or a self-reported diagnosis of hypertension.
2.5. Neuropsychological testing
Neuropsychological testing was conducted using the HAMD
questionnaire, administered to patients in the presence of two
physicians using the generally accepted method of conversation
and observation.
2.6. QOL
The SF-36 scale was used to assess eight areas of QOL including
physical function, physical role, bodily pain, general health, vital-
ity, social functioning, emotional role, and mental health. Higher
scores indicated a better QOL.
2.7. Statistical analyses
The statistical analyses were conducted with the paired t-test
using SPSS software (version 12.0; IBM Corporation, Armonk, NY,
USA). The data are expressed as the mean ± standard deviation.
The non-normal distributed data were analyzed using the rank
sum test method. Any differences with a p value <0.05 were con-
sidered statistically significant.
3. Results
3.1. Comparison of common factors between the two groups
We enrolled a total of 70 elderly patients (mean age
72.00 ± 7.00 years) with hypertension and depression. The patient
response and data recovery rates were 100% at baseline, and the
rate of loss to follow-up was 5.6%. Comparisons between the two
groups in terms of age, sex, duration of hypertension, body mass
index, blood pressure, depression symptoms, and QOL are shown
in Table 1. There were no significant differences in these parame-
ters between the groups.
3.2. Comparison of blood pressure before and after treatment
Prior to treatment, the differences in blood pressure of the con-
trol and case groups were not statistically significant (Fig. 1). After
treatment, the mean blood pressure in both groups was signifi-
cantly decreased (p < 0.05). Additionally, the blood pressure of
the case group following treatment was significantly lower than
that of the control group (p < 0.05).
3.3. Comparison of depression symptoms before and after treatment
There was no significant difference between the HAMD scores
of the control and case groups prior to treatment (Fig. 2). However,
following treatment, the HAMD scores in the case group were sig-
nificantly lower than those in the control group (p < 0.05).
3.4. Comparison of QOL scores before and after treatment
There was no significant difference between the QOL scores in
the control and case groups prior to treatment (Fig. 3). After treat-
ment, with the exception of physical function, all dimensions of
QOL in the case group were significantly higher than those of the
control group (p < 0.05).
 W. Fu et al. / Journal of Clinical Neuroscience xxx (2015) xxx–xxx 3

Table 1 depression doubles the risk of hypertension [13]. Depressed

Comparison of demographic and clinical factors between the study groups before patients not only reduce their physical activities but also incur sig-
treatment
nificant damage to their cognition and activities of daily living
Item Control group Case group [14,15]. The present study shows that after antidepressant treat-
n 34 33 ment, QOL improved in elderly patients with hypertension and
Characteristic depression.
Male sex, n 24 (66.67) 19 (61.29) Depression is a common mental disorder in the elderly, and it
Age, years 71 ± 8 73 ± 7 has become a public health issue [16] that is associated with grow-
Duration of hypertension, years 18 ± 5 18 ± 4 ing medical care burdens on health services use and hospitaliza-
Body mass index, kg/m2 24.3 ± 3.4 24.9 ± 3.9
tion time [17]. Previous studies have found the incidence rate of
Blood pressure, mmHg depression to range from 3–72.5% [18,19]. Depression is associated
24 hour SBP 145.19 ± 8.99 146.26 ± 8.91
24 hour DBP 82.47 ± 7.69 81.90 ± 7.13
with common cardiovascular and cerebrovascular diseases of the
dSBP 148.94 ± 9.60 149.35 ± 8.61 elderly, such as coronary heart disease, stroke, and hypertension
dDBP 85.08 ± 8.24 84.81 ± 7.86 [20]. However, some studies in the general population have failed
nSBP 142.28 ± 8.19 141.84 ± 8.12 to detect a relationship between hypertension and depression, per-
nDBP 79.36 ± 6.65 78.19 ± 5.72
haps due to the varying research methods and measurement stan-
Depression symptoma dards for depression [21].
Anxiety/somatization 7.22 ± 2.68 7.13 ± 2.86
Poor treatment compliance remains a challenge in the manage-
Body quality 1.08 ± 0.91 0.90 ± 0.91
Cognitive impairment 7.19 ± 3.67 7.16 ± 3.87 ment of hypertension [22], the biggest obstacle being the control of
Day and night changes 1.92 ± 0.81 1.77 ± 1.20 blood pressure. In adult American hypertensive patients, 36% who
Block 6.56 ± 3.49 5.61 ± 3.08 received antihypertensive treatment did not reach the targeted
Sleep disorder 2.81 ± 1.24 2.29 ± 1.24 blood pressure level [23]. Recent studies have found that depres-
Hopelessness 6.81 ± 2.16 5.90 ± 2.44
Total score 33.58 ± 7.83 30.77 ± 7.97
sion is related to poor compliance with antihypertensive drugs
[24], and that patients with depression are more prone to poor
Quality of lifeb
Physical function 62.31 ± 8.97 60.26 ± 9.41
treatment compliance than those without depression [25], sug-
Physical role 59.97 ± 9.57 58.84 ± 9.70 gesting that clinicians may improve antihypertensive therapy
Bodily pain 61.28 ± 8.68 59.39 ± 9.86 compliance by helping patients to overcome their depression
General health 48.50 ± 6.93 48.52 ± 7.21 [26,27]. In the present study, antidepressant treatment improved
Vitality 53.44 ± 7.44 53.06 ± 7.28
blood pressure, possibly through the abatement of depressive
Social function 60.69 ± 7.55 61.29 ± 7.96
Emotional role 59.53 ± 8.03 58.55 ± 7.70 symptoms, which improves compliance with the antihypertensive
Mental health 58.53 ± 7.79 57.68 ± 6.48 drugs.
Total score 58.03 ± 3.30 57.20 ± 3.39 Whether the physiological mechanism of depression worsened
All data are reported as the mean ± standard deviation, unless otherwise specified.
the QOL is unclear. Previous studies found that the chronic psycho-
DBP = diastolic blood pressure, dSBP/dDBP = daytime SBP/DBP, mmHg = millimeters logical stress induced by depression led to immune stress in
of mercury, nSBP/nDBP = nighttime SBP/DBP, SBP = systolic blood pressure. patients with first episode depression, resulting in increased levels
a
Depression was measured using the Hamilton rating scale for depression. of interleukin (IL)-2, IL-6, IL-2 receptor, and IL-6 receptor. High
b
Quality of life was measured using a 36 item Short Form questionnaire.
levels of IL-2 and IL-6 can also prompt depressive symptoms
through monoamine neurotransmitters or the hypothalamic pitu-
4. Discussion itary adrenal axis. IL-6 can further increase serotonin levels, lead-
ing to nervous endocrine immune system homeostasis and an
We found that after antidepressant treatment for 3 months, eventual immune system disorder in patients with first episode
blood pressure in the case group decreased significantly compared depression [28,29].
with the control group and, with the exception of physical func- We were unable to analyze the influence of different types of
tion, all other dimensions of QOL were significantly higher in the antidepressant medications on blood pressure and QOL, owing to
case group. Depression is associated with high SBP and DBP [12]. the small sample size. Antidepressant drugs can greatly affect car-
The results of a study of 2992 normotensive adults, who were fol- diac vagal suppression in addition to depression and anxiety [30].
lowed for 6–7 years to determine the relationship between depres- Cardiac vagal suppression has been reported in patients using tri-
sion symptoms and the development of hypertension, showed that cyclic antidepressants (TCA), selective serotonin reuptake inhibi-

Fig. 1. Comparison of blood pressure before and after treatment. The values are presented as the mean ± standard deviation. ⁄Significantly different from before treatment in
control group (p < 0.05), or significantly different from before treatment in the case group. #Significantly different from the control group before treatment, or significantly
different from the control group after treatment (p < 0.05). d = daytime, DBP = diastolic blood pressure, mmHg = millimeters of mercury, n = nighttime, SBP = systolic blood
pressure.

Please cite this article in press as: Fu W et al. Antidepressant medication can improve hypertension in elderly patients with depression. J Clin Neurosci
(2015), http://dx.doi.org/10.1016/j.jocn.2015.03.067
4 W. Fu et al. / Journal of Clinical Neuroscience xxx (2015) xxx–xxx

Fig. 2. Comparison of Hamilton rating scale for depression (HAMD) scores before and after treatment. All values are presented as the mean ± standard deviation.
#
Significantly different from the control group after treatment (p < 0.05).

Fig. 3. Comparison of quality of life (QOL) scores using the 36 item Short Form (SF-36) questionnaire before and after treatment. The values are presented as the
mean ± standard deviation. #Significantly different from the control group after treatment (p < 0.05).

tors (SSRI), and noradrenergic and serotonergic antidepressants 5. Conclusion

(NS). The greatest impact was seen in patients who used TCA,
and experienced significantly increased heart rates. Although most
of the studies demonstrated that depression was related to high
blood pressure, a cohort study reported that compared with
healthy individuals, patients with depression had significantly
lower SBP and less risk of developing hypertension. Moreover,
compared with healthy persons and patients without treatment,
the patients using TCA had significantly higher SBP and DBP, and
a much higher risk of developing hypertension [31]. TCA adversely
affect blood pressure, partly by vagal suppression. Therefore, SSRI
may be the best choice for patients with depression and cardiovas-
cular disease, although TCA and NS can be given under careful
monitoring of blood pressure.
Overall, in elderly patients with hypertension and depression,
antidepressant treatment based on conventional antihypertensive
therapy can reduce blood pressure, relieve depressive symptoms,
and improve QOL. Clinicians should be aware of depressive symp-
toms in elderly patients with hypertension. Early detection and
treatment may abate the symptoms of depression, improve the
compliance with antihypertensive therapy, and promote
rehabilitation.
The incidence of depression in elderly hypertensive patients is
higher than in those without hypertension. Depressive symptoms
lead to poor control of blood pressure, and can lead to the develop-
ment of complications that not only affect efficacy but also dimin-
ish the QOL. The relationship between hypertension and
depression has been a matter of debate for a long time, and the
data remain controversial. No uniform conclusion has been drawn
regarding whether antidepressant therapy for elderly hypertensive
patients can reduce blood pressure and improve QOL. Our study
shows that antidepressant treatment, based on conventional anti-
hypertensive treatment in elderly patients with hypertension and
depression, can reduce blood pressure, maintain the control of
blood pressure and depressive symptoms, and ultimately improve
QOL.
Conflicts of Interest/Disclosures
The authors declare that they have no financial or other con-
flicts of interest in relation to this research and its publication.

Please cite this article in press as: Fu W et al. Antidepressant medication can improve hypertension in elderly patients with depression. J Clin Neurosci
(2015), http://dx.doi.org/10.1016/j.jocn.2015.03.067
 W. Fu et al. / Journal of Clinical Neuroscience xxx (2015) xxx–xxx
Acknowledgments
This work was supported by the Beijing Municipal Health
Bureau Research Fund (Jing 13-02), MOE Project of Humanities
and Social Sciences (12YJCZH146), the Beijing Excellent Talent
Fund (20140000204400001) and the Talent Training Program by
Xuan Wu Hospital, Capital Medical University.
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