Klinik Psikofarmakoloji Bülteni-Bulletin of Clinical

Psychopharmacology

ISSN: 1017-7833 (Print) 1302-9657 (Online) Journal homepage: https://www.tandfonline.com/loi/tbcp20

The Effects of Escitalopram Treatment on

Oxidative/ Antioxidative Parameters in Patients
with Depression

Assoc. Prof. Behzat Cimen, Cihan Banu Gumus, Assist. Prof. Ihsan Cetin,
Assoc. Prof. Saliha Ozsoy, Murat Aydin & Leyla Cimen

To cite this article: Assoc. Prof. Behzat Cimen, Cihan Banu Gumus, Assist. Prof. Ihsan Cetin,
Assoc. Prof. Saliha Ozsoy, Murat Aydin & Leyla Cimen (2015) The Effects of Escitalopram
Treatment on Oxidative/ Antioxidative Parameters in Patients with Depression, Klinik
Psikofarmakoloji Bülteni-Bulletin of Clinical Psychopharmacology, 25:3, 272-279, DOI: 10.5455/
bcp.20150215102247

To link to this article: https://doi.org/10.5455/bcp.20150215102247

Published online: 08 Nov 2016.

Submit your article to this journal

Article views: 1141

View related articles

View Crossmark data

Citing articles: 3 View citing articles

Full Terms & Conditions of access and use can be found at

https://www.tandfonline.com/action/journalInformation?journalCode=tbcp21
Original Paper DOI: 10.5455/bcp.20150215102247

The Effects of Escitalopram Treatment on Oxidative/

Antioxidative Parameters in Patients with Depression
Behzat Cimen1, Cihan Banu Gumus2, Ihsan Cetin3, Saliha Ozsoy4, Murat Aydin5, Leyla Cimen6

ABS­TRACT:
The effects of escitalopram treatment on oxidative/antioxidative parameters in
patients with depression
1
Assoc. Prof., 2M.D., Erciyes University,
Objective: In this study, we aimed to investigate the effects of escitalopram, an antidepressant drug of the Faculty of Pharmacy, Department of
selective serotonin reuptake inhibitor group, on lipid peroxidation, nitric oxide (NO) level and superoxide Biochemistry, Kayseri - Turkey
3
Assist. Prof., Batman University, School of
dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities in patients with major Health, Department of Nutrition and
depressive disorder. Dietetics, Batman - Turkey
4
Assoc. Prof., Erciyes University, Faculty of
Method: Eighteen patients (11 women, 7 men) diagnosed with major depressive disorder (MDD) according Medicine, Department of Psychiatry,
Kayseri - Turkey
to DSM-IV criteria and eighteen healthy controls (10 women, 8 men) were included in the study. The relevant 5
M.D., Aydin State Hospital, Psychiatry Clinic,
parameters were measured before and after treatment with 20 mg/day escitalopram for 6 weeks in patients Aydin - Turkey
6
PhD, Erciyes University, Faculty of Medicine,
and only once in the controls. Department of Biochemistry,
Results: Plasma SOD, CAT, malondialdehyde (MDA) and NO levels were significantly higher before treatment Kayseri - Turkey

in patients with major depression compared to healthy controls; there was no significant differences in GPx Corresponding author:
Dr. İhsan Çetin,
levels. Treatment with 20 mg/day escitalopram for 6 weeks reduced plasma SOD, CAT, MDA and NO levels Batman Üniversitesi Merkez Kampüsü,
statistically significantly; it had no effect on GPx levels. Sağlık Yüksek Okulu Beslenme ve Diyetetik
Anabilim Dalı, 72060 Batman - Türkiye
Conclusion: The results provide evidence for the role of oxidative stress in the pathogenesis of MDD and
revealed that subchronic treatment with escitalopram significantly decreased the activity of antioxidant E-ma­il add­ress:
cetiniihsan@gmail.com
enzymes and MDA values. It may be argued that antioxidant enzymes such as SOD, CAT and oxidative stress
Date of submission:
markers such as MDA and NO are state markers of MDD, because values came close to the results of healthy August 12, 2014
subjects after treatment.
Date of acceptance:
February 15, 2015
Keywords: escitalopram, major depression, lipid peroxidation, antioxidant
Declaration of interest:
B.C., C.B.G., I.C., S.O., M.A., L.C.: The authors
Klinik Psikofarmakoloji Bulteni - Bulletin of Clinical Psychopharmacology 2015;25(3):272-9 reported no conflict of interest related to
this article.

INTRODUCTION their efficacy, safety, and tolerability, as they

Major depressive disorder (MDD) is a serious
psychiatric mood disorder resulting in detrimental
effects, including increased health care
expenditure and elevated suicide rates; about one-
third of MDD patients have failed two or more
conventional antidepressant drug trials within the
first year of treatment 1,2 . Selective serotonin
reuptake inhibitor group (SSRI) drugs have been
widely used in the treatment of MDD because of
modify both enzymatic antioxidants and lipid
peroxidation 3,4. Escitalopram is an SSRI whose
absolute bioavailability of about 80% absorption
of escitalopram is independent of food; it is almost
entirely absorbed from the intestine. It takes a
week to raise constant plasma levels 5. Current
evidence suggests that the pathophysiology of
MDD is multifactorial and that inter-related
mechanisms effect genetic, neurotransmitter,
immune, oxidative, and inflammatory systems

272 Klinik Psikofarmakoloji Bulteni - Bulletin of Clinical Psychopharmacology, Volume 25, Issue 3 (September 01, 2015, pp. 209-320)
 Cimen B, Gumus CB, Cetin I, Ozsoy S, Aydin M, Cimen L

with increased production of procytokines6. The antioxidant potential between different

oxidation of catecholamines such as dopamine antidepressants. Considering these aspects, we
and serotonin by monoamino oxidase (MAO) may hypothesized that the oxidative/antioxidant
result in increased radical burden 7. There are activities may be altered by depression; and
numerous studies indicating that reactive oxygen antidepressant therapy with escitalopram may
species (ROS) inducing neuronal damage have an attenuate these activities. Therefore, in this study,
important role in the pathophysiology of we aimed to measure MDA, NO, SOD, CAT, and
depression, probably via membrane omega 3 GPx levels in patients with MDD before and after
polyunsaturated fatty acids (PUFAs) pathology, by treatment with escitalopram.
decreasing the activity of superoxide dismutase
(SOD), catalase (CAT), and glutathione peroxidase MATERIAL AND METHODS
(GPx)4,8-10. Abnormal levels of antioxidant enzymes
and lipid peroxidation in MDD further Subjects
substantiate the role of free radicals in major
depression 4,11 . Insufficient defenses against The study group consisted of 18 patients aged
exposure to excess ROS can lead to neuronal 18-57 years (11 women, 7 men) who were
dysfunction and the death of neurons. Because admitted to the Psychiatry Outpatient Clinic of
ROS have short half-lives, most studies measure Erciyes University School of Medicine. The
the products of oxidative damage. patients were diagnosed with major depressive
Malondialdehyde (MDA) is the most studied disorder according to the Diagnostic and
product of lipid peroxidation. Numerous studies Statistical Manual of Mental Disorders, Fourth
reported increasing levels of MDA and other Edition, (DSM-IV) criteria and met the inclusion
products of lipid peroxidation in depressed criteria for the present study. Eighteen healthy
patients4. Nitric oxide (NO) is responsible for the controls (10 women, 8 men) were included in the
formation of many end products involved in study.
oxidative stress. Increased plasma NO levels have
also been reported in depressive patients12. The Study Design
major antioxidative defenses include both
enzymatic and non-enzymatic antioxidants. The Written informed consents to participate in the
levels of enzymatic antioxidants like SOD, CAT, study was received from the subjects after they
GPx etc. are altered in major depressive disorder head been thoroughly informed about the
patients13. research details. This study has been supported by
Several preclinical and clinical studies have Erciyes University Scientific Research Projects
investigated the effects of antidepressants on the Unit. The research protocol was approved by the
oxidative/antioxidant system. Most of them have Ethics Committee of Medical Ethics at Erciyes
suggested a potential antioxidant effect of University. The study was carried out according to
antidepressants and revealed that treatment with the principles of the Helsinki Convention on
antidepressants can reverse the increased Human Rights and good clinical practice. All
oxidative stress observed in depressive patients14. subjects were included in the study after
However, there are contradictory findings on this evaluation of their baseline laboratory test results
issue. For example, some studies reported a (routine biochemical and hematological tests) in
decrease with antidepressant treatment of addition to physical and psychiatric examinations.
increased MDA and SOD levels in depressive Control group samples were measured only once
patients 4,11 . Others found no effects 15 or any because no drugs were administered to the control
increase in SOD after antidepressant treatment16. group for 6 weeks; thus, we did not expect any
It is also not clear whether there is a difference in changes in the measured parameters.

Klinik Psikofarmakoloji Bulteni - Bulletin of Clinical Psychopharmacology, Volume 25, Issue 3 (September 01, 2015, pp. 209-320) 273
The effects of escitalopram treatment on oxidative/antioxidative parameters in patients with depression
Exclusion criteria were as follows: other
comorbid psychiatric disorders, bipolar disorder,
alcohol and substance use disorder, having
received electroconvulsive therapy within the last
6 months, presence of a severe physical disorder
of neurologic, endocrine, or hematologic nature.
Patients and controls were undergone to standard
clinical evaluation including psychiatric and
physical evaluation on the first day of the study.
Psychiatric diagnosis was determined via clinical
interviews. Patients with first-episode unipolar
depression were included. Patients were included
in the study after a one-week drug washout period
in case they were on any medications. The
patients were assessed by the Montgomery-Asberg
Depression Rating Scale (MADRS) to determine
the severity of the disorder and response to
treatment 17. The patients received 20 mg/day
escitalopram, an SSRI, for 6 weeks; the controls
did not. The patients did not receive any other
medication or non-medication therapies.
Laboratory Measurement
Venous blood samples were collected from the left
forearm vein into 5-ml vacutainer tubes
containing potassium EDTA after overnight fasting
between 7 and 8 AM. Blood specimens were
allowed to clot for 30 min. SOD activity levels were
assayed by the method of Sun et al.18 This method
is based on the reduction of superoxide, which is
produced by the xanthine oxidase enzyme system,
by nitroblue tetrazolium. A unit of SOD was
determined as the amount that decreased
nitroblue tetrazolium reduction by 50%. GSH-Px
activity levels in the hemolysates of erythrocytes
were measured using the method of Paglia and
Valentine, in which GSH-Px activity was coupled
to the oxidation of NADPH by glutathione
reductase19. The oxidation of NADPH was followed
spectrophotometrically at 340 nm at 37°C. The
absorbance at 340 nm was recorded for 5 min.
Activity was observed as the slope of the lines as
μmol of NADPH oxidized per min. CAT activity
was determined by the method described by
Yasmineh et al. The principle of the assay is based
274 Klinik Psikofarmakoloji Bulteni - Bulletin of Clinical Psychopharmacology, Volume 25, Issue 3 (September 01, 2015, pp. 209-320)
on the determination of hydrogen peroxide
decomposition 20. By measuring the absorbance
changes per minute, the rate constant of the
enzyme was determined. Levels of plasma MDA
were measured by the thiobarbituric acid method,
which was modified after the methods of Yoshoiko
et al. Peroxidation was measured as the
production of MDA, which forms a pink
chromogen compound in combination with TBA,
whose absorbance at 532 nm was measured21.
Serum nitrate plus nitrite levels were measured
as an index of NO generation. To measure total
nitrate level, nitrate is converted to nitrite by using
nitrate reductase enzyme. Total nitrite was
measured enzymatically with a modified Griess
method defined by Smarason et al.22. The color
that resulted from the reaction of the nitrite with
Griess reagent was measured. Nitrite, as an end
product, had a pink color and concentration
determined by spectrophotometric absorbance at
548 nm.
Statistical Analyses
Statistical analyses were performed using statistics
packages with SPSS software version 15.0 and
SigmaStat 3.5. Normality of data distribution was
assessed by Kolmogorov-Smirnov test. The mean
values for the groups were compared using
independent-samples t-test. Non-parametric
analysis of the continuous data that did not fit the
normal distribution was done with Mann-Whitney
U test (for between-groups comparisons) and
Wilcoxon test (for within-group comparisons
before and after treatment). Group mean
differences were examined by means of unpaired
(for between-groups comparisons) or paired (for
within-group comparisons before and after
treatment) t-test. The difference in the distribution
of categorical variables was tested using the Chi-
square test. The Pearson correlation test was
performed to investigate the relationship between
oxidative stress parameters and MADRS scores
before and after treatment, respectively. Categorical
variables were expressed as number, and
continuous variables were expressed as mean±SD
 Cimen B, Gumus CB, Cetin I, Ozsoy S, Aydin M, Cimen L

or median (25th-75th percentile), as appropriate. values of patients before and after treatment. The
Statistical significance was set at P value of 0.05. SOD, CAT, MDA and NO levels of the patients
before treatment were found to be significantly
RESULTS higher than those of the controls. The SOD, CAT,
MDA and NO levels in post-treatment were
The demographic and clinical data are significantly lower than those in pre-treatment.
summarized in Table 1. The mean age was After the treatment, SOD and CAT levels were
42.17±10.16 years for patients and 37.89±10.62 higher than those of the controls, and the MDA
years for the controls. There were no significant level was significantly lower than that of the
differences between the patients and controls controls. The NO level of the patients in pre-
(p>0.05) in terms of age, sex, body mass index treatment did not significantly differ from that of
(BMI), smoking, and the amount of time and the controls (Table 2).
smoking status (rate and duration). The duration When the SOD, CAT, MDA and NO levels of the
of education in the control group was significantly patients were compared with regard to gender
higher than in patients (Table 1). differences, there was no statistically significant
Data are expressed as numbers for categorical differences between women and men either
variables and mean±SD or median (25 th -75 th before or after treatment. The GPx levels of
percentile) for continuous variables. women after treatment were found to be
When the distribution of values of the control significantly higher than those of men after
group was analyzed, different variations were treatment (Table 2). There were no correlations
observed. For example, although SOD and MDA between severity of depressive symptoms and
levels of the control group showed more oxidative stress parameters before or after
variability, NO levels showed less variability than treatment.

Table 1: Socio-demographic and clinical characteristics of the patients and controls

Patient (n=18) Controls (n=18) p
Age 42.17±10.16 37.89±10.62 0.182a
Gender (F/M) 11/7 10/8 0.379b
BMI (kg/m2) 27.40±5.31 25.26±3.06 0.120a
Duration of disease (months) 3.93±2.42 - -
Duration of education (years) 8.0 (5.0-11.75) 12.0 (10.5-15.5) 0.005c
Duration of smoking (years) 0.0 (0.0-11.75) 1.0 (0.0-14.5) 0.483c
Number of cigarettes (pcs/day) 0.0 (0.0-10.75) 0.0 (0.0-27.5) 0.267c
Data are expressed as numbers for categorical variables and mean±SD or median (25th-75th percentile) for continuous variables. aVariables were tested using the independent
samples t test, bvariables were tested using the Chi-square test and cvariables were tested using the Mann-Whitney U test. F: Female, M: Male, pcs: Pieces.

Table 2: SOD, CAT, GPx, MDA, and NO levels of the patients and the controls
Patients Comparisons
Controls
Pre treatment Post treatment n=18 Pre treatment- Post treatment- Pre treatment-
n=18 n=18 Control Control Post treatment
MADRS score 36.70±7.93 15.00±5.95 - - - p<0.001
MDA (mmol/ml) 4.90±0.07a 3.70±0.04b,c 3.80±0.08 p<0.001 p<0.001 p<0.001
NO (µmol/L) 52.27±8.22a 43.66±7.89c 42.93±7.15 p<0.001 p=0.764 p<0.001
CAT (U/ml) 3.82±0.10a 3.23±0.11a,c 3.10±0.10 p<0.001 p<0.001 p<0.001
GPx (U/ml) 136.89±6.96 139.45±4.17 140.43±6.07 p=0.113 p=0.584 p=0.127
SOD (U/ml) 10.43 (10.12-10.51)a 8.27 (8.2-8.39)a,c 8.19 (8.15-8.23) p<0.001 p=0.005 p<0.001
Data are expressed as mean±SD or median (25th-75th percentile) for continuous variables. The significance of differences in continuous variables between groups was tested
using independent samples t test or the Mann-Whitney U test for SOD. Comparison of the values in pre-treatment and post-treatment was performed with paired samples t
test and Wilcoxon test for SOD.
a
Higher than those of the controls, bLower than those of the controls, cLower than those in pre-treatment

Klinik Psikofarmakoloji Bulteni - Bulletin of Clinical Psychopharmacology, Volume 25, Issue 3 (September 01, 2015, pp. 209-320) 275
The effects of escitalopram treatment on oxidative/antioxidative parameters in patients with depression
DISCUSSION
Our results provide evidence of an increased
oxidative stress status in MDD as shown by
increased concentrations of MDA. The MDA levels
of the patients before treatment were significantly
higher than those of the controls and significantly
decreased with treatment. After treatment, the
MDA levels of the patients were significantly lower
than those of the controls. Some other studies
found significantly increased MDA levels in
depressive patients, consistent with our results23,24.
Sarandol et al. reported significantly increased
levels of MDA in MDD, but they did not find a
significant difference after treatment15.
It may be suggested that increased production of
lipid peroxidation or decreased detoxification ability
might cause increased oxidative stress in neuronal
and glial cells. Moreover, MDA has an inhibitory
effect on the receptor binding sites of serotonin24. As
a result, it may be tempting to speculate that these
relationships support a possible etiopathogenetic
association between oxidative stress and
monoamine oxidase (MAO) activity in MDD 26.
Catecholamines including dopamine and
norepinephrine are associated with oxidative stress,
thus conditions causing increased catecholamine
metabolism may increase the radical burden as
observed in MDA27. Moreover, it has been reported
that increased free radical production may cause
the destruction of phospholipids and alter viscosity
of neuron membranes, and consequently changes
in membrane viscosity may affect receptor
functions28.
In addition to these results, this study secondly
shows significantly increased stress in MDD with
nitrogen-reactive species. The NO levels of patients
before treatment were found to be significantly
higher than those of controls. NO levels were
significantly decreased by treatment with
escitalopram. Most importantly, the NO levels of
patients after treatment were similar to those of the
control group, which shows the success of
antidepressant therapy in reducing oxidative stress.
Some other studies found significantly decreased
levels of NO in depressed patients with treatment,
276 Klinik Psikofarmakoloji Bulteni - Bulletin of Clinical Psychopharmacology, Volume 25, Issue 3 (September 01, 2015, pp. 209-320)
consistent with our results12,29,30.
Lu et al. reported significantly increased levels
of NO in depressed patients and showed
significantly decreased levels of NO after 2 months
of fluoxetine treatment12. Chrapko et al. reported
significantly increased levels of NO in depressed
patients and showed significantly decreased levels
of NO after 2 months of treatment with
paraoxetine29. Moreno et al. reported that MDD
patients significantly differed from controls in NO
levels 30. Individuals may have an inadequate
antioxidant enzymatic activity that is incapable of
responding to increased free radical production,
which could lead to some of the various
pathological alterations originating from having
MDD.
Our findings provided evidence of an increase
not only of oxidative stress markers but also of
antioxidant activity. However, the other important
finding is the significantly lowering of oxidative
stress markers and antioxidants in MDD after
treatment with escitalopram. The SOD and CAT
levels of patients before treatment were significantly
higher than the SOD and CAT levels of controls. At
the same time, SOD and CAT levels were
significantly decreased with treatment with
escitalopram, but still higher than those of the
controls. Nevertheless, it was not possible to say the
same thing for GPx, which was another antioxidant
examined in our study: There were no statistically
significant differences between the GPx levels of
controls and those of patients before treatment.
When the GPx levels in patients were compared
before and after treatment, there were no
statistically significant differences in terms of GPx
levels. Among the antioxidant enzymes; SOD
dismutates superoxide radicals to form hydrogen
peroxide, which in turn is decomposed to water and
oxygen by GPx and CAT, thereby preventing the
formation of hydroxyl radicals31. Therefore, these
enzymes act cooperatively at different sites in the
metabolic pathway of free radicals. Failure of this
antioxidant defense may lead to oxidative damage
and the initiation of lipid peroxidation. Therefore,
our findings of significantly decreased activity of
two antioxidant defense enzymes (SOD and CAT) in
 Cimen B, Gumus CB, Cetin I, Ozsoy S, Aydin M, Cimen L

treatment with escitalopram in the present study the present study may contribute to the literature
indicate increased oxidative stress in MDD. providing information on oxidative stress and
Sarandol et al. similarly reported significantly antioxidant activity in MDD patients with
increased antioxidant activity of SOD in MDD, but treatment. The treatment for 6 weeks with 20 mg/
they did not find a significant difference after day escitalopram significantly decreased plasma
treatment14. Galecki et al. indicated a statistically levels of SOD, CAT, NO and MDA; on the other
significant decrease in the activity of SOD and CAT hand, GPx levels were unaffected by treatment.
as well as in MDA concentration after combined Post-treatment plasma levels of SOD and CAT
therapy24. were significantly higher, while MDA levels were
Some speculations can be made regarding this significantly lower than those of the controls.
issue. It has been reported that antidepressant Levels of NO and GPx after treatment were not
treatment may suppress immune cells, including significantly different from the controls. After
natural killer cells32. Suppression of immune cells treatment; GPx, CAT, NO, SOD and MDA showed
by means of treatment with escitalopram may 1.8%, 15%, 16.5%, 19.5%, 24% variations,
cause a decrease in oxidative stress. Moreover, respectively. According to these findings, it may
SOD and CAT are two key antioxidant enzymes be speculated that MDA is superior to other
that protect against oxidative tissue damage. It is parameters for predicting treatment response.
therefore conceivable that down-regulation of Increased levels of MDA have been found in
these two enzymes (SOD and CAT) could lead to depression and antidepressant treatment has
further free radical-induced neurotoxicity/ been able to lower the concentrations of lipid
neurodegeneration in MDD. Based on our results, peroxidation 4,11,42. Abdel-Wahab et al. showed
we can say that an increased generation of oxygen that long-term venlafaxine treatment at effective
and nitrogen reactive species in MDD may lead to antidepressant dosages can protect against
an increase in antioxidants. These findings are stress-induced oxidative cellular and DNA
consistent with some recent studies that found damage in male mice43. They also showed that at
significantly increased levels of MDA, SOD and all doses tested, venlafaxine decreased MDA.
GPx activity in patients with MDD and Increased levels of MDA have also been found in
schizophrenia15,33-36. Atmaca et al. found increased our patient group, and escitalopram treatment
levels of MDA, SOD, CAT and GPx activity in has been able to lower the concentrations of
patients with social phobia 37. Moreover, some MDA. Of the many biological targets of oxidative
studies found reduced levels of plasma MDA and stress, lipids are the most susceptible class of
SOD in patients with MDD and biomolecules and MDA serves as a diagnostic
schizophrenia11,38-39, while others failed to find any indicator of lipid peroxidation in many diseases.
difference in SOD, CAT and GPx activity31,34,40,41 Therefore, when we compare them with other
between patients and normal controls. parameters, we may say that MDA is superior to
As can be seen from the literature, the results other parameters for predicting treatment
seem to conflict with one other. Several factors, response due to MDA being the most susceptible
such as differences in techniques of measuring classes of biomolecules.
SOD levels, sampling of patients in different There are several limitations in the present
stages of disease progression (acute or chronic), study. Therefore, it should be considered as a
differences in testing material (red blood cells or preliminary study from our group. The sample size
plasma), exposure to neuroleptic treatment was small and control group samples were not
(currently treated or ceased medication analyzed after treatment, since no differences
treatment), different illness courses of patients or were expected in terms of the control values.
different ethnic origin and lifestyle may be Furthermore, no placebo control group was used.
responsible for the discrepancy. The findings of Our results need to be confirmed by placebo-

Klinik Psikofarmakoloji Bulteni - Bulletin of Clinical Psychopharmacology, Volume 25, Issue 3 (September 01, 2015, pp. 209-320) 277
 The effects of escitalopram treatment on oxidative/antioxidative parameters in patients with depression
controlled studies with a larger number of
samples. Additionally, we were not able to perform
Structured Clinical Interview for DSM Disorders
(SCID) for diagnosis and determination of
specifiers such as melancholic depression. An
association between melancholic depression and
antioxidative enzyme activities and lipid has been
reported4. It is a limitation of the present study
that we were not able to assess anxiety symptom
severity in depressive patients and define
depression subtypes such as melancholic, atypical
etc. Recent studies suggested a relationship
between anxiety and oxidative stress 44. Another
limitation of the study was the short duration of
medication washout. Finally, some confounding
factors that we were not able to notice might have
influenced oxidative stress parameters.
References:
1. Simon GE. Social and economic burden of mood disorders.
Biol Psychiatry 2003;54(3):208-15. [CrossRef]
2. Trivedi MH, Rush AJ, Wisniewski SR, Nierenberg AA, Warden
D, Ritz L, et al. STAR*D Study Team. Evaluation of outcomes
with citalopram for depression using measurement-based
care in STAR*D: implications for clinical practice. Am J
Psychiatry 2006;163(1):28-40. [CrossRef]
3. Anderson IM. SSRIS versus tricyclic antidepressants
in depressed inpatients: a meta-analysis of efficacy and
tolerability. Depress Anxiety 1998;7(Suppl.1):S11-S7.
[CrossRef]
4. Bilici M, Efe H, Koroglu MA, Uydu HA, Bekaroglu M, Deger
O. Antioxidative enzyme activities and lipid peroxidation in
major depression: alterations by antidepressant treatments.
J Affect Disord 2001;64(1):43-51. [CrossRef]
5. Burke WJ. Escitalopram. Expert Opin Investig Drugs
2002;11(10):1477-86. [CrossRef]
6. Felger JC, Lotrich FE. Inflammatory cytokines in depression:
neurobiological mechanisms and therapeutic implications.
Neuroscience 2013;246:199-229. [CrossRef]
7. Thase ME. Bipolar depression: issues in diagnosis and
treatment. Harv Rev Psychiatry 2005;13(5):257-71. [CrossRef]
8. Hakkarainen R, Partonen T, Haukka J, Virtamo J, Albanes
D, Lönnqvist J. Is low dietary intake of omega-3 fatty acids
associated with depression? Am J Psychiatry 2004;161(3):567-
9. [CrossRef]
9. Rao JS, Ertley RN, Lee HJ, DeMar JC Jr, Arnold JT, Rapoport
SI, et al. n-3 polyunsaturated fatty acid deprivation in rats
decreases frontal cortex BDNF via a p38 MAPK-dependent
mechanism. Mol Psychiatry 2007;12(1):36-46. [CrossRef]
278 Klinik Psikofarmakoloji Bulteni - Bulletin of Clinical Psychopharmacology, Volume 25, Issue 3 (September 01, 2015, pp. 209-320)
In conclusion, our results may provide
encouraging evidence for the role of oxidative
stress in the pathogenesis of MDD and suggest
that subchronic treatment with escitalopram may
decrease activity of SOD, CAT enzymes and levels
of MDA and NO. Most importantly, the NO levels
of patients after treatment were closer to the NO
levels of healthy individuals, which shows the
success of antidepressant therapy in reducing
oxidative stress.
Acknowledgements
This research was supported by the scientific
research project unit of Erciyes University (TSY-09-
887). We are grateful to all participants and
everyone who contributed to this research.
10.
Takuma K, Baba A, Matsuda T. Astrocyte apoptosis:
implications for neuroprotection. Prog Neurobiol
2004;72(2):111-27. [CrossRef]
11. Khanzode SD, Dakhale GN, Khanzode SS, Saoji A, Palsodkar
R. Oxidative damage and major depression: the potential
antioxidant action of selective serotonin re-uptake inhibitors.
Redox Rep 2003;8(6):365-70. [CrossRef]
12. Lu YR, Fu XY, Shi LG, Jiang Y, Wu JL, Weng XJ, et al.
Decreased plasma neuroactive amino acids and increased
nitric oxide levels in melancholic major depressive disorder.
BMC Psychiatry 2014;14:123. [CrossRef]
13. Ozcan ME, Gulec M, Ozerol E, Polat R, Akyol O. Antioxidant
enzyme activities and oxidative stress in affective disorders.
Int Clin Psychopharmacol 2004;19(2):89-95. [CrossRef]
14. Stefanescu C, Ciobica A. The relevance of oxidative stress
status in first episode and recurrent depression. J Affect
Disord 2012;143(1-3):34-8. [CrossRef]
15. Sarandol A, Sarandol E, Eker SS, Erdinc S, Vatansever E, Kirli
S. Major depressive disorder is accompanied with oxidative
stress: short-term antidepressant treatment does not alter
oxidative-antioxidative systems. Hum Psychopharmacol
2007;22(2):67-73. [CrossRef]
16. Herken H, Gurel A, Selek S, Armutcu F, Ozen ME, Bulut
M, et al. Adenosine deaminase, nitric oxide, superoxide
dismutase, and xanthine oxidase in patients with major
depression: impact of antidepressant treatment. Arch Med
Res 2007;38(2):247-52. [CrossRef]
17. Montgomery SA, Asberg M. A new depression scale designed
to be sensitive to change. Br J Psychiatry 1979;134(4):382-9.
[CrossRef]

18. Sun Y, Oberley LW, Li Y. A simple method for clinical assay
of superoxide dismutase, Clin Chem 1988;34(3):497-500.
19. Paglia DE, Valentine WN. Studies on the quantitative and
qualitative characterization of erythrocyte glutathione
peroxidase. J Lab Clin Med 1967;70(1):158-69.
20. Yasmineh WG, Kaur TP, Blazar BR, Theologides A. Serum
catalase as marker of graft-vs-host disease in allogeneic
bone marrow transplant recipients: pilot study. Clin Chem
1995;41(11):1574-80.
21. Yoshioka T, Kawada K, Shimada T, Mori M. Lipid peroxidation
in maternal and cord blood and protective mechanism
against activated-oxygen toxicity in the blood. Am J Obstet
Gynecol 1979;135(3):372-6.
22. Smarason AK, Allman KG, Young D, Redman CW. Elevated
levels of serum nitrate, a stable end product of nitric
oxide, in women with pre-eclampsi, Br J Obstet Gynaecol
1997;104(5):538-43. [CrossRef]
23. Moylan S, Maes M, Wray NR, Berk M. The neuroprogressive
nature of major depressive disorder: pathways to disease
evolution and resistance, and therapeutic implications. Mol
Psychiatry 2013;18(5):595-606. [CrossRef]
24. Gałecki P, Szemraj J, Bieńkiewicz M, Florkowski A, Gałecka
E. Lipid peroxidation and antioxidant protection in patients
during acute depressive episodes and in remission after
fluoxetine treatment. Pharmacol Rep 2009;61(3):436-47.
[CrossRef]
25. Britt SG, Chiu VW, Redpath GT, VandenBerg SR. Elimination
of ascorbic acid-induced membrane lipid peroxidation
and serotonin receptor loss by Trolox-C, a water soluble
analogue of vitamin E. J Recept Res 1992;12(2):181-200.
[CrossRef]
26. Pandey GN, Sharma RP, Janicak PG, Davis JM. Monoamine
oxidase and cortisol response in depression and
schizophrenia. Psychiatry Res 1992;44(1):1-8. [CrossRef]
27. Graham DG. Oxidative pathways for catecholamines in
the genesis of neuromelanin and cytotoxic quinones. Mol
Pharmacol 1978;14(4):633-43.
28.
van Vliet IM, den Boer JA, Westenberg HG.
Psychopharmacological treatment of social phobia; a
double blind placebo controlled study with fluvoxamine.
Psychopharmacology (Berl) 1994;115(1-2):128-34.
[CrossRef]
29. Chrapko W, Jurasz P, Radomski MW, Archer SL, Newman SC,
Baker G, et al. Alteration of decreased plasma NO metabolites
and platelet NO synthase activity by paroxetine in depressed
patients. Neuropsychopharmacology 2006;31(6):1286-93.
30. Moreno J, Gaspar E, López-Bello G, Juárez E, Alcázar-
Leyva S, González-Trujano E, et al. Increase in nitric oxide
levels and mitochondrial membrane potential in platelets
of untreated patients with major depression. Psychiatry Res
2013;209(3):447-52. [CrossRef]
31. Yao JK, Reddy R, van Kammen DP. Reduced level of plasma
antioxidant uric acid in schizophrenia. Psychiatry Res
1998;80(1):29-39. [CrossRef]
Klinik Psikofarmakoloji Bulteni - Bulletin of Clinical Psychopharmacology, Volume 25, Issue 3 (September 01, 2015, pp. 209-320)
Cimen B, Gumus CB, Cetin I, Ozsoy S, Aydin M, Cimen L
32. Ravindran AV, Griffiths J, Merali Z, Anisman H. Lymphocyte
subsets associated with major depression and dysthymia:
modification by antidepressant treatment. Psychosom Med
1995;57(6):555-63. [CrossRef]
33. Gama CS, Salvador M, Andreazza AC, Kapczinski F,
Silva Belmonte-de-Abreu P. Elevated serum superoxide
dismutase and thiobarbituric acid reactive substances in
schizophrenia: a study of patients treated with haloperidol
or clozapine. Prog Neuropsychopharmacol Biol Psychiatry
2006;30(3):512-5. [CrossRef]
34. Herken H, Uz E, Ozyurt H, Sogut S, Virit O, Akyol O.
Evidence that the activities of erythrocyte free radical
scavenging enzymes and the products of lipid peroxidation
are increased in different forms of schizophrenia. Mol
Psychiatry 2001;6(1):66-73. [CrossRef]
35. Kunz M, Gama CS, Andreazza AC, Salvador M, Ceresér KM,
Gomes FA, et al. Elevated serum superoxide dismutase
and thiobarbituric acid reactive substances in different
phases of bipolar disorder and in schizophrenia. Prog
Neuropsychopharmacol Biol Psychiatry 2008;32(7):1677-81.
[CrossRef]
36. Zhang Z, Zhang X, Hou G, Sha W, Reynolds GP. The
increased activity of plasma manganese superoxide
dismutase in tardive dyskinesia is unrelated to the Ala-9Val
polymorphism. J Psychiatr Res 2002;36(5):317-24. [CrossRef]
37. Atmaca M, Tezcan E, Kuloglu M, Ustundag B, Tunckol H.
Antioxidant enzyme and malondialdehyde values in social
phobia before and after citalopram treatment. Eur Arch
Psychiatry Clin Neurosci 2004;254(4):231-5. [CrossRef]
38. Akyol O, Herken H, Uz E, Fadillioglu E, Unal S, Sogut S, et al. The
indices of endogenous oxidative and antioxidative processes
in plasma from schizophrenic patients. The possible role of
oxidant/antioxidant imbalance. Prog Neuropsychopharmacol
Biol Psychiatry 2002;26(5):995-1005. [CrossRef]
39. Raffa M, Mechri A, Othman LB, Fendri C, Gaha L,
Kerkeni A. Decreased glutathione levels and antioxidant
enzyme activities in untreated and treated schizophrenic
patients. Prog Neuropsychopharmacol Biol Psychiatry
2009;33(7):1178-83. [CrossRef]
40. Reddy R, Sahebarao MP, Mukherjee S, Murthy JN. Enzymes
of the antioxidant defense system in chronic schizophrenic
patients. Biol Psychiatry 1991;30(4):409-12. [CrossRef]
41. Sofic E, Rustembegovic A, Kroyer G, Cao G. Serum
antioxidant capacity in neurological, psychiatric, renal
diseases and cardiomyopathy. J Neural Transm 2002;109(5-
6):711-9. [CrossRef]
42. Kotan VO, Sarandol E, Kirhan E, Ozkaya G, Kirli S. Effects of
long-term antidepressant treatment on oxidative status in
major depressive disorder: a 24-week follow-up study. Prog.
Neuropsychopharmacol Biol Psychiatry 2011;35(5):1284-90.
[CrossRef]
43. Abdel-Wahab BA, Salama RH. Venlafaxine protects against
stress-induced oxidative DNA damage in hippocampus
during antidepressant testing in mice. Pharmacol Biochem
Behav 2011;100(1):59-65. [CrossRef]
44. Salim S. Oxidative stress and psychological disorders. Curr
Neuropharmacol 2014;12(2):140-7. [CrossRef]
279