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Journal of Clinical Neuroscience xxx (2015) xxx–xxx

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Journal of Clinical Neuroscience

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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
Department of Nephrology, Xuan Wu Hospital, Capital Medical University, 45 Changshun Street, Xicheng District, Beijing 100053, China
Department of Geriatrics, Xuan Wu Hospital, Capital Medical University, Beijing, China
Department of Emergency, Three Gorges University People’s Hospital, The First People of Yichang, Yichang, China
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)
and a therapy group (amlodipine, 5 mg daily; citalopram, 20 mg daily; n = 35). We compared 24 hour,
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

support the proposal that hypertension is a risk factor for depres-
Depression and hypertension can undermine quality of life sion, with a pooled relative risk of 1.16 when those suffering from
(QOL) and social function, and increase mortality in elderly hypertension were compared with those who were not [11]. Given
patients [1–4]. Hypertension has increasing prevalence in the geri- that it remains unclear as to whether antidepressant medication
atric population [5], and is a principal precursor to cardiovascular can control blood pressure and improve QOL in the elderly, we con-
diseases and a main cause of death globally [6]. The current global ducted a study of 70 elderly Chinese hypertensive patients with
prevalence of hypertension is 26%, and it is projected to rise to 29% depression.
by the year 2025 [7].
Patients with hypertension may experience many negative
emotions that increase their risk of developing mental health dis- 2. Patients and methods
orders, particularly depression [8]. Depression occurs at a higher
rate in patients with hypertension than in the normal population. 2.1. Study population
It has been reported that depressive symptoms lead to poorer con-
trol of hypertension, resulting in the development of complica- The patients were recruited from the Xuan Wu Hospital
tions, which not only affect the treatment outcomes but also between August 2008 and April 2011. All enrolled patients satis-
fied the criteria for major depressive disorder, diagnosed during a
⇑ Correspondence to: Yun Li, Tel./fax: +8601083198707. structured clinical interview as described in the Diagnostic and
E-mail address: (Y. Li). Statistical Manual of Mental Disorders, Fourth Edition-Patient Edi-
Wenjing Fu and Lina Ma have contributed equally to the manuscript. tion. The patient inclusion criteria were advanced age (>60 years),
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
2 W. Fu et al. / Journal of Clinical Neuroscience xxx (2015) xxx–xxx

hypertension and depression. All the participants were either inpa- sure (DBP) P 90 mmHg, current treatment with antihypertensive
tients or outpatients for the management of hypertension, and medication, or a self-reported diagnosis of hypertension.
they did not take antihypertensive medication.
The study exclusion criteria were patients with secondary
2.5. Neuropsychological testing
hypertension, malignant tumors, significant suicidal risk, unstable
physical disorders, dementia, neurological disorders that were sig-
Neuropsychological testing was conducted using the HAMD
nificantly affecting the central nervous system function (including
questionnaire, administered to patients in the presence of two
a history of seizures), a lifetime history of any organic mental dis-
physicians using the generally accepted method of conversation
order, psychotic disorder or mania, substance abuse or dependence
and observation.
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 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-
2.2. Study design
ity, social functioning, emotional role, and mental health. Higher
scores indicated a better QOL.
We conducted a randomized, parallel group study. All study
participants underwent a standardized clinical assessment which
included medical history, physical and neurological examinations, 2.7. Statistical analyses
Hamilton rating scale for depression (HAMD) tests, psychometric
evaluations, an electrocardiogram, complete blood count, urinaly- The statistical analyses were conducted with the paired t-test
sis, blood chemistry screening, and thyroid function tests. The using SPSS software (version 12.0; IBM Corporation, Armonk, NY,
patients were randomly assigned to two groups: a control group USA). The data are expressed as the mean ± standard deviation.
(n = 35), which received conventional medical treatment with The non-normal distributed data were analyzed using the rank
amlodipine capsules (5 mg daily) for hypertension, and a case sum test method. Any differences with a p value <0.05 were con-
group (n = 35), which received conventional amlodipine treatment sidered statistically significant.
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 3. Results
list which was prepared by an independent statistician who was
not involved in the remainder of the study. The statistician respon- 3.1. Comparison of common factors between the two groups
sible for statistical analyses was blinded to the study group alloca-
tions throughout the study. The primary end point of the current We enrolled a total of 70 elderly patients (mean age
study was an improved QOL. The study was approved by the Ethics 72.00 ± 7.00 years) with hypertension and depression. The patient
Committee of Xuan Wu Hospital, Capital Medical University, China response and data recovery rates were 100% at baseline, and the
and all participants provided written informed consent to partici- rate of loss to follow-up was 5.6%. Comparisons between the two
pate. The case intervention patients were blinded to the interven- groups in terms of age, sex, duration of hypertension, body mass
tion and the purpose of the study, and the assessors of the HAMD index, blood pressure, depression symptoms, and QOL are shown
and the 36 item Short Form quality if life questionnaire (SF-36) in Table 1. There were no significant differences in these parame-
were blinded to which group the patient had been allocated to. ters between the groups.
The study participants received a follow-up phone call every
2 weeks to inquire about matters that needed attention, provide
3.2. Comparison of blood pressure before and after treatment
reminders, and follow-up on topics that had been discussed in
the previous calls. Each participant also had a clinical visit in each
Prior to treatment, the differences in blood pressure of the con-
of the first 2 months. At the end of the third month, a clinical
trol and case groups were not statistically significant (Fig. 1). After
follow-up visit was conducted during which the patient received
treatment, the mean blood pressure in both groups was signifi-
a physical examination that included blood pressure, HAMD and
cantly decreased (p < 0.05). Additionally, the blood pressure of
SF-36 tests, which were evaluated by trained physicians.
the case group following treatment was significantly lower than
that of the control group (p < 0.05).
2.3. Data collection

All data were collected on standardized study forms according 3.3. Comparison of depression symptoms before and after treatment
to documented procedures by uniformly trained physicians. Two
individual physicians entered the study data into a clinical data- There was no significant difference between the HAMD scores
base. The data were then checked by another physician. Data qual- of the control and case groups prior to treatment (Fig. 2). However,
ity was ensured through standard data checks, and losses to following treatment, the HAMD scores in the case group were sig-
follow-up were balanced across the two groups. nificantly lower than those in the control group (p < 0.05).

2.4. Ambulatory blood pressure monitoring 3.4. Comparison of QOL scores before and after treatment

Ambulatory blood pressure monitoring was conducted by a There was no significant difference between the QOL scores in
non-invasive blood pressure detection instrument. Systolic blood the control and case groups prior to treatment (Fig. 3). After treat-
pressure (SBP) and diastolic blood pressure (DBP) were recorded, ment, with the exception of physical function, all dimensions of
24 hour, daytime and nighttime. Hypertension was defined as QOL in the case group were significantly higher than those of the
SBP P 140 millimeters of mercury (mmHg), diastolic blood pres- control group (p < 0.05).

Please cite this article in press as: Fu W et al. Antidepressant medication can improve hypertension in elderly patients with depression. J Clin Neurosci
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-
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
Depression was measured using the Hamilton rating scale for depression. of interleukin (IL)-2, IL-6, IL-2 receptor, and IL-6 receptor. High
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

Please cite this article in press as: Fu W et al. Antidepressant medication can improve hypertension in elderly patients with depression. J Clin Neurosci
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 The incidence of depression in elderly hypertensive patients is
of the studies demonstrated that depression was related to high higher than in those without hypertension. Depressive symptoms
blood pressure, a cohort study reported that compared with lead to poor control of blood pressure, and can lead to the develop-
healthy individuals, patients with depression had significantly ment of complications that not only affect efficacy but also dimin-
lower SBP and less risk of developing hypertension. Moreover, ish the QOL. The relationship between hypertension and
compared with healthy persons and patients without treatment, depression has been a matter of debate for a long time, and the
the patients using TCA had significantly higher SBP and DBP, and data remain controversial. No uniform conclusion has been drawn
a much higher risk of developing hypertension [31]. TCA adversely regarding whether antidepressant therapy for elderly hypertensive
affect blood pressure, partly by vagal suppression. Therefore, SSRI patients can reduce blood pressure and improve QOL. Our study
may be the best choice for patients with depression and cardiovas- shows that antidepressant treatment, based on conventional anti-
cular disease, although TCA and NS can be given under careful hypertensive treatment in elderly patients with hypertension and
monitoring of blood pressure. depression, can reduce blood pressure, maintain the control of
Overall, in elderly patients with hypertension and depression, blood pressure and depressive symptoms, and ultimately improve
antidepressant treatment based on conventional antihypertensive QOL.
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 Conflicts of Interest/Disclosures
treatment may abate the symptoms of depression, improve the
compliance with antihypertensive therapy, and promote The authors declare that they have no financial or other con-
rehabilitation. 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
W. Fu et al. / Journal of Clinical Neuroscience xxx (2015) xxx–xxx 5

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Please cite this article in press as: Fu W et al. Antidepressant medication can improve hypertension in elderly patients with depression. J Clin Neurosci