1

Effect of short term use of anti-depressant drugs on HbA1c and renal function markers in
postmenopausal women
“A hospital based cross sectional study from Khyber Pakhtunkhwa”
By
Mohammad Yousaf 1 ⃰, Sundus Nayab2, Laila Akbar2, Farheen khanum2, Saleem Nawaz2,
Sajjad Ahmad 2,Attaurahman3, Faiza Javed3
1, 2,3
Deptt of Chemistry Islmai college KPK Peshawar Pakistan.
2
Saidu group of teaching hospitals KPK Pakistan
⃰ For Corresponding:yousaf672010@hotmail.com
#:03009077940

Abstract
The present study was conducted to find the relationship between antidepressant drugs use,
diabetes and renal functions in postmenopausal women in Khyber Pakhtunkhwa.
The patients Group (PG) consists of 140 postmenopausal women using various anti-depressant
drugs for more than 03 months and less than 06 months while 140 postmenopausal women were
taken as Control Group (CG) from the general population of Khyber Pakhtunkhwa. Serum Urea
was measured by Kinetic UV method and Serum Creatinine by modified Jaffe method while
Glycohemoglobien (HbA1c) was determined by Fast ion-exchange resin separation method.

The mean age of control group was 51.65 ± 5.81 years, for Selective Serotonin Reuptake
Inhibitor (SSRI) group was 43.09± 6.28 years and for Tricyclic Antidepressant (TCA) in PG was
45.33± 5.15 years. The mean BMI of CG, SSRI and TCA groups was 25.42 ± 5.04 30.49±7.25
and 28.71±7.78 Kg/m2 respectively. The mean serum urea of CG, SSRI and TCA group was
27.07±7.78, 30.17±30.39 and 21.40±3.56mg/dL respectively. The mean serum Creatinine of CG,
SSRI and TCA groups was 0.85±0.21, 0.70±0.28 and 0.67±0.09 mg/dL respectively. The mean of
HbA1c for CG, SSRI and TCA groups was 6.06 ± 0.59, 5.67 ± 0.56, and 5.45 ± 0.49 %
respectively. The mean of average glucose level for CG, SSRI and TCA group was 85.37 ± 8.34,
79.96 ± 7.85, and 76.96 ± 7.04 mg/dL respectively.
Conclusion: The results of this study showed that short term use of antidepressant drugs like
SSRI and TCA have no effect on HbA1c and renal function markers in postmenopausal women.
Key words: Urea, Creatinine, Anti-depressant, post-menopausal.

INTRODUCTION
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Antidepressants drugs are used to treat various signs of depressive syndromes by rectifying
disparities of chemical messenger with in the brain. Chemical disorders could also be imputable
for creating changes in mood and also in behavior [1].
Antidepressants are in a variety of different types; though all types are used by impacting the
chemical messengers (neurotransmitters) in the brain, like serotonin and nor epinephrine.
Antidepressants play a very important role to treat those patients having mild or unadorned
depression. The primary antidepressants given to the patients during the initial stage of their
treatment must be to cure the symptoms of disorder, though if it does not give any relief from the
sign of depression so it causes various side effects on the individual [2].
In order to avoid side effects caused by using wrong type of antidepressant for specific
syndrome, we must have to analyze the right antidepressants based on patient health condition[3-
5].
Antidepressant drugs may cause various ill effects on a particular individual[6].The approving
adverse effect profiles of the advance antidepressant medications, particularly the Selective
Serotonin Re-uptake Inhibitors (SSRIs) compared with the older drugs such as Tricyclic
Antidepressants (TCAs) has probably contributed to their popularity in between prescribers and
patients[7]. A no of recent publications show that antidepressant drugs may enhance the risk of
diabetes because of long-term safety use of these medications [8- 11].One study based on the UK
General Practice Research Database reported that those individuals who had used antidepressants
for a long period of time more than 24 months had increased risk of diabetes [12].While other
studies find a less important and weak connection in between the antidepressants use and risk of
diabetes [10]. National Centre for Health Statistics in 2012 observed that a large population
sample of adults using antidepressant for depressive symptoms had no risk of diabetes. The
sample was drawn from several years of the US National Health and Nutrition Examination
Survey (NHANES). Moreover, the study took improvement of deviations in frequency of blood
testing in the general population to assess glycemic measures among antidepressant users who
did not have recent blood sugar testing and thus did not have any opportunity to be detected [13].
Kivimaki and Batty, have suggested two approaches for addressing the limitation of past
research, first to examine the association of antidepressant use with undiagnosed diabetes; and
second to examine the association of antidepressant use with blood sugar levels in non-diabetic
individuals[ 14].
Shulman KI et al, Al Jurdi RK et al, Rej S et al. reported in their studies that lithium as an
antidepressant have very little prescription to older peoples having depression because of its
greater association with adverse renal disorders, including Chronic Kidney Disease (CKD,
previously called as chronic renal failure), Acute Kidney Injury (AKI, previously called as acute
renal failure) and Nephrogenic Diabetes Insipidus (NDI) [15-17]. Rej S et al, Hendric HC et al.
suggested that those older adults who had used lithium as an antidepressant have a very high
problem of co morbid disorders, including hypertension, diabetes and cardiovascular diseases,
then these all disorders lead to create problem of CKD and AKI [17,18].Rej S et al, Hendric HC
et al, McKnight RF et al. proposed a very small evidence supported the association between the
antidepressant type lithium and renal diseases in the older adults[ 17-19].
The present cross sectional study was carried out to study the effects of various antidepressant
drugs use on the HbA1c level and serum biochemical markers of renal functions postmenopausal
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women of Northern Pakistan in the province of Khyber Pakhtun Khawa which is affected more
by terrorism than any other province of Pakistan.

METHODS
Patients and methods
The study was carried out in KTH (Khyber Teaching Hospital) and Shafique psychiatric clinic
Peshawar from February 19, 2016 to May 15, 2018. The study was approved by the ethical
committee of Khyber Teaching Hospital through its letter no 766/KTH/E-111, dated 13-6-16. By
using simple random sampling technique as guided per CONSORT guidelines a data of 140
patients was collected who fulfilled the inclusion and exclusion standard. Age matched 140
postmenopausal women were taken as Control Group (CG) from the general population of
Khyber Pakhtunkhwa. These were further grouped into two classes. Inclusion Criteria for the PG
was postmenopausal women the using antidepressants drugs for short period. Subjects suffering
from hypertension, diabetes and renal disorders were excluded from the study.

Data collection
Data from the patients and control group regarding their age, weight and medical history was
collected on a well-designed proforma at their consent. All human dignity was respected in
accordance with international norms involving human as an experimental subjects. Exclusion
criteria were maintained throughout the study.
Fresh venous fasting blood sample was collected from each patient. Blood sample was then
transferred to a tube in order to avoid its clotting. The blood sample was then assayed in the
central Pathology laboratory of KTH for the required biochemical parameters using standard kits
and protocols.

Biochemical tests
Renal function
Serum urea and creatinine levels were determined on autoanalyser (Erbamannhein chemistry
autoanalyser, Germany) using standard Erba kits. Serum Urea was measured by Kinetic UV
method [20] and Serum creatinine by modified Jaffe method [21]. The normal ranges were 05-45
mg/dl for Urea and 0.5-1.5 mg/dl for Creatinine.

HbA1c determination
HbA1c was determined by Fast ion-exchange resin separation method [22].

Statistical analysis
Statistical analysis of the data was performed on SPSS for windows 21.0 software (SPSS Inc.
Chicago, IL, USA) and Microsoft Excel. Values were expressed as Mean ± Standard Deviation
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(SD). Pearson’s correlation was applied to look for association between required variables. A
two-tailed p value<0.05 was considered statistically significant.

RESULTS
Baseline characteristics of control and patient groups
The mean age of control group was 51.65 ± 5.81 years, for SSRI group was 43.09± 6.28 years
and for TCA was 45.33± 5.15 years. The mean BMI of control group was 25.42±5.04 Kg/m2, for
SSRI was 30.49±7.25 Kg/m2 and for TCA was 28.71±7.78 Kg/m2.
Table 1. Base line characteristics of control and patient groups

S.No Group ID Age(years) BMI(Kg/m2)

Mean S.D Mean S.D

1 CG
(n= 140)
51.65 5.81 25.42 5.04

SSRI
2 PG n= 71 43.09 6.28 30.49 7.25
(n= 140)

TCA
n= 69 45.33 5.15 28.71 7.78

TCA=Tricyclic Antidepressant SSRI=Selective Serotonin Reuptake Inhibitor

CG= Control Group PG= Patient Group

Comparison of renal markers Serum urea/serum Creatinine and diabetic markers of

Control and Patient Group
The mean serum urea of control group was 27.07±7.78mg/dL, for SSRI group was
30.17±30.39mg/dL and for TCA group was 21.40±3.56mg/dL.
The serum urea of SSRI group was higher than both the TCA and control group while TCA
group was lower than the control group.
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The mean serum Creatinine of control group was 0.85±0.21 mg/dL, for SSRI group was
0.70±0.28 mg/dL and for TCA group was 0.67±0.09 mg/dL.
The serum Creatinine of SSRI group was lower than both the TCA and control group while TCA
was lower than the control group.
The mean of HbA1c for control group was 6.06 ± 0.59, for SSRI (PG) 5.67 ± 0.56, and for TCA
(PG) it was 5.45 ± 0.49 %.
The HbA1c level of SSRI (PG) was higher than TCA (PG) while lower than control group.
The mean of Average glucose level for control group was 85.37 ± 8.34, for SSRI (PG) 79.96 ±
7.85, and for TCA (PG) it was 76.96 ± 7.04 mg/dl.
The Average glucose level of SSRI (PG) was higher than TCA (PG) while lower than control
group.
Table-2.Comparison of renal markers serum Urea/ serum Creatinine and diabetic markers
of Control and Patient Group

Group ID Serum Serum HbA1c % Average

Urea(mg/dL) Creatinine(mg/dL) Glucose
S. Level
N
o (mg/dL)

1 Mean S.D Mean S.D Mean S.D Mean S.D

CG
(n= 140)
27.07 7.78 0.85 0.21 6.06 0.59 85.37 8.34

2 PG SSRI 30.17 30.39 0.70 0.28 5.67 0.56 79.96 7.85

n= 71
(n=140)

TCA 21.40 3.56 0.67 0.09 5.45 0.49 76.97 7.04

n=69

TCA=Tricyclic Antidepressant SSRI=Selective Serotonin Reuptake Inhibitor

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CG= Control Group PG= Patient Group

Correlation analysis of Renal and Diabetic Marker in patients group

Correlation analysis of renal markers and HbA1c with various parameters like age, BMI, Dosage
in mg per day and duration in months was carried out. The results are shown in table 3.
Serum urea was negatively correlated with BMI, duration in month, dosage in mg per day while
positively correlated with age in significant way in SSRI group (ρ = 0.001).
Serum urea was negatively correlated with BMI, duration in month while positively correlated
with age and dosage in mg per day in TCA group in non-significant way.
Serum creatinine was positively correlated with age in significant way (ᵱ = 0.01) while
negatively correlated with BMI, duration in month, dosage in mg per day in SSRI group.
Serum creatinine was negatively correlated with age in significant way (ᵱ = 0.03) while
negatively correlated with duration in month in non-significant way while positively correlated
with BMI and dosage in mg per day in TCA group in non-significant way.
The age and Dosage in mg/day variables were negatively correlated with HbA1c of SSRI (PG) in
non-significant way, while BMI and Duration in month variables were positively correlated with
HbA1c of SSRI (PG) in non-significant way.
Age, duration in month and Dosage in mg/day variables were negatively correlated with Average
glucose level of SSRI (PG) in non-significant way, while BMI was positively correlated with
Average glucose level of SSRI (PG) in non-significant way.
Age and duration in month variables were negatively correlated with HbA1C of TCA (PG) in
non-significant way, while BMI and Dosage in mg/day variables were positively correlated with
HbA1c of TCA (PG) in non-significant way.
Age and Duration in month variables were negatively correlated with average glucose level of
TCA (PG) in non-significant way, while BMI and Dosage in mg/day variables were positively
correlated with Average glucose level of TCA (PG) in non-significant way.
No significant correlation was found in between HbA1C and Average glucose level and in other
parameters with in any of the group (SSRI and TCA).
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Table-3.Pearson’s Correlation analysis of renal and diabetic marker in patients group

S.No Group ID Parameters Renal Markers Diabetic Markers

PG Serum Urea Serum HbA1c % Average
Creatinine Glucose
n =140 r (p) r(p) Level
r (p) (mg/dl)
r(ρ)

Age
0.86** (0.001) 0.73*(0.01) -0.02(0.94) -0.02(0.94)
SSRI group
n= 71
BMI
1 -0.25 (0.45) -0.04 (0.90) 0.25(0.42) 0.25(0.42)

Duration
in months
-0.25 (0.46) -0.34 (0.31) 0.34(0.25) -0.34(0.25)

Dosage in -0.13 (0.71) -0.01 (0.98) -0.21(0.49) -0.21(0.49)

mg

Age
0.02 (0.95) -0.72* (0.03) -0.56(0.19) -0.56(0.19)
TCA group
BMI
n= 69 -0.01 (0.98) 0.33 (0.39) 0.70(0.08) 0.70(0.08)
2 Duration
in months
-0.34 (0.38) -0.14 (0.71) -0.20(0.66) -0.20(0.66)
 8

Dosage in 0.17 (0.66) 0.48 (0.20) 0.10(0.83) 0.10(0.82)

mg

Discussion
Mental health problems in Pakistan are linked to both the current violence in the country [23]
and also disruption in the social fabric of the society[24]. Mental disorders are supposed to affect
one in every five individuals[25].World Health Organization (WHO) projects that mental
disorder will be one of the leading causes of disability worldwide by 2020 [26].
There are no, large, population-based studies on the prevalence of mental disorders and
depression in Pakistan. The available studies show a prevalence rate to be between 10% and
50%[27, 28].
About one-third of the people suffering from mental disorders are using anti-depressant drugs,
including Selective Serotonin Reuptake Inhibitors (SSRIs), Tricyclic Anti-depressants (TCAs),
and Monoamine Oxidase Inhibitors (MAOIs) [29].
The long term use of these drugs is believed to cause diabetes and irreversible damage to
kidneys.
A no of recent publications show that antidepressant drugs enhance the risk of diabetes because
of long-term safety use of these medications [30].
The present cross sectional study was carried out to study the effects of various antidepressant
drugs on the HbA1c level and serum biochemical markers of renal functions in postmenopausal
women population of Northern Pakistan in the province of Khyber Pakhtunkhaw which is
affected more by terrorism than any other province of Pakistan. We found in our study that the
HbA1c level of SSRI (PG) was higher than TCA (PG) while lower than control group. This
result is in good agreement with Lust man et al. 2006 study, who found that level of HbA1c is
reduced during the open treatment stage and remains reduced during depression-free
maintenance, regardless of the type of antidepressant used for the treatment of the patient [31].
Pyykkonen et al. 2011 recently found and examined the relation of antidepressants medication
use with glycemic control in adults without the diagnosing of diabetes with mixed results [32].
One study based on the UK General Practice Research Database reported that those individuals
who had used antidepressants for a long period of time more than 24 months had increased risk
of diabetes [33].
The serum urea of SSRI group was higher than both the TCA and control group while TCA
group was lower than the control group. The serum creatinine of SSRI group was lower than
both the TCA and control group while TCA was lower than the control group. Serum creatinine
was positively correlated with age in significant way (ρ = 0.01) while negatively correlated with
BMI, duration in month, dosage in mg per day in SSRI group.
 9

Serum creatinine was negatively correlated with age in significant way (ρ = 0.03).
Van Wyck Fleet J et al. reported in their study that antidepressant type (bupropion) causes
various genitourinary symptoms, including polyuria (2-5 %), urinary urgency (< 2%), urinary
incontinence (< 1 %) and urinary retention (< 1 %)[34].
Turpeinen M, Koivuviita N, Tolonen A, et al. reported that Bupropion may lead to increase level
of serum creatinine without increasing other signs of renal injury [35].

Limitations
The study has got some unavoidable limitations. The first and foremost is the small sample size
including only 280 post-menopausal women visiting only two tertiary care health Centers in
Peshawar city. As the population of this city is highly heterogeneous in nature, because of the
influx of Afghan refugees and hence the outcome of this finding cannot be the true representative
of the local inhabitants. Secondly the study period was also short due to lack of finances. Further
studies are required involving lager populations for better results.

Conclusion
The results of this study showed that short term use of antidepressant drugs like SSRI and TCA
have no effect on HbA1c and renal function markers in postmenopausal women.

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