Journal of Affective Disorders 108 (2008) 159 – 164

www.elsevier.com/locate/jad

Brief report
Treatment of depression and anxiety in infertile women: Cognitive
behavioral therapy versus fluoxetine
Mahbobeh Faramarzi a,⁎, Ahmad Alipor b , Seddigheh Esmaelzadeh c , Farzan Kheirkhah a ,
Karamolah Poladi d , Hagar Pash e
a
Department of Psychiatry, Faculty of Medicine, Babol University of Medical Sciences, Gang Afroz Street, Babol, Iran
b
Department of Psychology, Tehran Payam Noor University, Tehran, Iran
c
Department of Obstetric and Gynecology, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran
d
Department of Psychology, University of Shahid Chamran, Ahvaz, Iran
e
Department of Midwifery, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran
Received 24 June 2007; received in revised form 3 September 2007; accepted 6 September 2007
Available online 23 October 2007

Abstract

Background: Infertility is a stressful event that can give rise to psychological difficulties. Both psychotherapy and pharmacotherapy
are well-established treatments for depression and anxiety. The aim of this study was to compare the effectiveness of cognitive
behavioral therapy with fluoxetine in the resolution or decreasing of depression and anxiety in infertile women.
Method: In a randomized controlled clinical trial, 89 mild to moderate depressed infertile women (Beck scores 10–47) were recruited
into three groups; cognitive behavior therapy (CBT), antidepressant therapy, and a control group. Twenty-nine participants in the CBT
method received relaxation training, restructuring, and eliminating of negative automatic thoughts and dysfunctional attitudes to
depression for 10 sessions. Thirty participants in the pharmacotherapy group took 20 mg fluoxetine daily for 90 days. Thirty control
subjects did not receive any intervention. All participants completed the Beck Depression Inventory and Cattell Anxiety Inventory at
the beginning and end of the study. X 2 test, paired t-test, and ANOVA were used to analyze the data.
Results: The resolution of depression in the three groups was: fluoxetine group 50%, CBT 79.3%, and control 10%. The mean of the
Beck scores at the beginning and end of the study was respectively: fluoxetine 23.2 ± 8.6 versus 14.3 ± 8.5(p b 0.001), CBT 20.1 ± 7.9
versus 7.7 ± 4.8 (p b 0.001), and control 19.8 ± 8.5 versus 19.7 ± 8.4 (p = 0.9). Although both fluoxetine and CBT decreased significantly
the mean of BDI scores more than that of the control group, the decrease in the CBT group was significantly more than fluoxetine group.
The CBT method decreased significantly the mean of the Cattell scores more than the fluoxetine and control groups, but the decrease in
the anxiety mean scores of that fluoxetine group was no more than that of control group.
Conclusion: CBT was not only a reliable alternative to pharmacotherapy but also was superior to fluoxetine in the resolution or reducing
of depression and anxiety of infertile women. Fluoxetine was superior to no therapy in the treatment of depression but not anxiety.
© 2007 Elsevier B.V. All rights reserved.

Keywords: Infertility; Cognitive behavior therapy; Anxiety; Depression; Fluoxetine

1. Introduction

⁎ Corresponding author. Tel.: +98 9113230822(Mobile); fax: +98
1113264925.
E-mail address: mahbob330@yahoo.com (M. Faramarzi).
0165-0327/$ - see front matter © 2007 Elsevier B.V. All rights reserved.
doi:10.1016/j.jad.2007.09.002
Infertility is defined as 1 year of unprotected inter-
course without pregnancy. Infertility has been charac-
terized as creating of form of chronic stress that can rise
160 M. Faramarzi et al. / Journal of Affective Disorders 108 (2008) 159–164
due to a variety of psychological difficulties. Patients
with infertility experience psychological symptoms
similar to those associated with cancer, hypertension,
and cardiac rehabilitation (Domar et al., 1993). Overall
prevalence of psychological problems in infertile
couples ranges between 25 and 60% (Seibel and Taymor,
1982). Infertility sometimes is accompanied by crises
and emotional tensions such as depression, anxiety,
interpersonal problems, suppressed anger, frustration,
feelings of inferiority, and unconscious feelings of guilt
(Kofman and Sheiner, 2005; Gox et al., 2006).
Cognitive behavior therapy (CBT) and medications
are two major developments in the past 40 years con-
cerning the treatment of depression. A recent compre-
hensive review of a meta-analysis of treatment outcomes
for a variety of psychiatric disorders concluded that CBT
is effective for adult unipolar depression, and furthermore,
there was significant evidence for long-term effectiveness
following cessation of treatment (Butler et al., 2006).
Numerous studies suggest that psychotherapy, particular-
ly CBT, is at least as effective as medication in the treat-
ment of depression (Jacobson and Hollon, 1996; Mc
Bride et al., 2006).
Despite widespread belief in the worthiness of CBT in
the treatment of depression and anxiety, relatively few
studies have evaluated the effectiveness of psychosocial
interventions in the field of infertility. There have been
no published, randomized controlled prospective trials to
adequately compare the impact of group psychological
inventions with pharmacotherapy on the promotion of
mental health of infertile women. The following study
will answer this question of whether CBT is a reliable
alternative to fluoxetine in the treatment of depression
and anxiety in infertile women.
2. Materials and method
A randomized controlled clinical trial was conducted
in the Fatemeh Alzahra Infertility Center of the Babol
University of Medical Sciences from September 2006 to
June 2007. Women who had been trying to conceive for
more than 2 years were recruited for this study. They
were patients at the infertility center who did not decide
to undergo fertility treatment until 3 months afterward.
Eligible women who had more than 5 years education
and were not currently practicing any relaxation tech-
niques, were not participating in any support group, were
not currently taking any psychotherapy, and were not
currently undergoing any assisted reproductive therapy
were invited to enter the study. Five midwives of the
center conducted structured telephone invitations with
potential participants. Of 350 invitations, 200 patients
accepted to enter the study and were referred to the
center. Subsequent to completing the demographic ques-
tionnaire and the Beck Depression Inventory (BDI), a
psychologist conducted a face-to-face interview using
the Structured Clinical Interview for DSM-III-R (Spitzer
et al., 1990). Women who met one of the following
conditions were excluded from the study: a score ≤ 9 or
N47 on the BDI, or meeting the criteria for clinical severe
depression on the clinical interview. Thus, only women
with minimal, mild, and moderate depression (Beck
score 10–47) were included the study. Fig. 1 shows
the flow diagram of participants through each stage of
randomized, controlled trial. Finally, 89 participants re-
mained until the end of the study (29 CBT, 30 fluoxetine,
30 control).
All participants completed the BDI and the Cattell
Anxiety Inventory at the beginning and end of the study.
The BDI used was a translated and validated Persian
version. Gasemzadeh et al. (2005) reported that the
BDI Persian had high internal consistency (Cronbach's
alpha = 0.87) and acceptable test–retest reliability
(r = 0.74). A full 21-item BDI was administered. Each
item describes a specific behavioral manifestation of
depression. Scores on each item can range from 0, in-
dicating no depressive symptomatology, to 3, indicating
a severe level of symptomatology. Total scores can thus
range from 0 to 63. The classification of depression
scores involves: index score of ≤ 9 is considered to
between normal range, a score 10 to 15 shows minimal
depressive symptomatology, a score of 16–31 points
shows mild depression, a score of 32–47 is in favor of
moderate depression, and a score of N47 indicates severe
depression (Beck et al., 1988). The Cattell Anxiety
Inventory is a 40-item self-report measure of anxiety.
This test was a translated and validated Iranian version of
the Cattell Anxiety Inventory. Scores can range from 0 to
80, with scores of 41or above demonstrating anxiety
(Cattell, 1962). Classification of the anxiety score in-
volves: 0–40 (normal anxiety), 41–44 (mild anxiety),
45–49 (moderate anxiety), and 50–80 (severe anxiety).
Participants in the CBT group were engaged in a
10-week, two-hour group cognitive behavior therapy
program. Progressive muscle relaxation was added to
sessions 5–10. Groups consisted of 8–12 members and
the therapist was an expert psychologist who trained
for the CBT program. Therapy was conducted at the
Psychiatry Department of the Babol University of
Medical Sciences and was especially adapted for in-
fertile women (Beck et al., 1979; Free, 1999; Newton
et al., 1999). The therapist considered social, sexual,
and relationship concerns of the infertile women for
restructuring and eliminating in CBT sessions. The first
 M. Faramarzi et al. / Journal of Affective Disorders 108 (2008) 159–164 161

Fig. 1. Flow diagram of participants through each stage of randomized, controlled trial. ⁎Some of 40 depressed women who refused to enter the study
denied their mood disorders, and some of them believed that they could find relief from depression without medication intervention. Some of them
worried if they began their treatment course, their family would mark them as mental patients. ⁎⁎As stressful events such as family death, heavy
accidents, pregnancy, etc. affected the depression or anxiety tests, these women excluded the analysis.

three sessions provided patients with a general orien- 1999). For home practicing, subjects read a relaxation
tation to cognitive therapy and the causes of infertility. A book and listened to a 20-minute pre-recorded CD two
gynecologist participated in the first three sessions for times daily over a period of 5 weeks.
30 min and explained the cause of infertility for each The pharmacotherapy group took a capsule of flu-
patient. Cognitive interventions have been based on the oxetine (20 mg) daily for 90 days. Participants in the
premise that both negative automatic thoughts and dys-
functional attitudes to depression require restructure,
eliminating the diathesis to depression (Gloaguen et al., Table 1
1998). The following three sessions (sessions 4–6) Demographic characteristics of infertile women in three groups
included the identification and challenging of core dys- Criteria Fluoxetine CBT a Control F b p-value
functional or irrational beliefs that underlie automatic
Mean Mean Mean
negative thoughts about the infertility. Finally, sessions (SD) (SD) (SD)
7–10 taught participants varying techniques (e.g.
Age (year) 29.8 (5.3) 28.3 (3.8) 28.4 (5.3) 0.8 0.4
countering, self-reward) for maintaining the change of Education (year) 9.4 (4.2) 9.2 (2.4) 9.8 (3.9) 0.4 0.2
their dysfunctional beliefs about infertility (Oei and Duration of 6.3 (3.4) 5.4 (3.9) 5.7 (4.4) 0.3 0.6
Sullivan, 1999). In addition to the above program, infertility (year)
sessions 5–10 taught participants progressive muscle a
Cognitive behavior therapy.
b
relaxation in a group setting. (Vickers and Zollman, ANOVA was performed to compare the means of groups.
162 M. Faramarzi et al. / Journal of Affective Disorders 108 (2008) 159–164
control group completed two questionnaires at the
beginning of the study and 3 months after the interview.
All analyses were performed using SPSS software
(11). Paired t-tests were used to compare the mean
scores of depression and anxiety tests in each study
group separately before and after interventions. Analysis
of variance was performed to compare the mean scores
of the tests in the three study groups at the beginning and
also, at the end of the study.
3. Results
The demographic characteristics of the study sample
are summarized in Table 1. There were no statistically
significant differences among the three groups in age,
highest education level, and the duration of infertility.
Also, there was no significant difference in causes of
infertility among three groups. Infertility diagnoses in
fluoxetine, CBT, and the control group were respec-
tively: male factor (23%, 26%, and 24%), female factors
(37%, 38%, and 34%), both female and male factors
(25%, 24%, and 26%), and unknown (15%, 12%, 16%).
These results show that resolution of depression in
the three groups was: fluoxetine 50%, CBT 79.3%, and
control group 10%. Table 2 shows that the mean of the
Beck scores in CBT and fluoxetine group decreased
after interventions, but changes in the control group was
not significant. Also, although the three groups did not
have a meaningful difference in the mean of the BDI
scores with ANOVA analysis at the beginning of the
study, the differences were significant at the end of the
study. A Tockey test showed that although both
fluoxetine and CBT decreased significantly the mean
of the BDI scores more than the control group, and the
decrease in the CBT group was significantly more than
that in the fluoxetine group.
A comparison of the mean of the Cattell scores with
paired t-test at the beginning and end of the study shows
that both CBT and fluoxetine decreased the mean of
Table 2
The mean of Beck scores in three groups of infertile women at beginning
and end of the study
Groups At beginning At ending ta
Mean (SD) Mean (SD)
Fluoxetine 23.2 (8.6) 14.3 (8.5) 5.6
CBT b 20.1 (7.9) 7.7 (4.8) 7.5
Control 19.8 (8.5) 19.7 (8.4) 0.08
a
Pair t-test was used to compare the mean of scores, before and after
inventions.
b
Cognitive behavior therapy.
Table 3
The mean of Cattell Anxiety Scores a in three groups of infertile
women at beginning and end of the study
Groups At beginning At ending tb p-value
Mean (SD) Mean (SD)
Fluoxetine 41.7 (10.5) 36.7 (10.5) 2.8 0.008
CBT c 42.3 (8.6) 30.6 (8.6) 7.5 b0.0001
Control 38.1 (9.1) 39.9 (8.8) − 1.5 0.1
a
The Cattell Anxiety Inventory is a 40-item self-report measure of
anxiety. Classification of anxiety score involves: 0–40 (normal
anxiety), 41–44 (mild anxiety), 45–49 (moderate anxiety), 50–80
(severe anxiety).
b
Pair t-test was used to compare the mean of each group, before and
after interventions.
c
Cognitive behavior therapy.
anxiety (Table 3). Also, an ANOVA test showed that
although the three groups did not have a meaningful
difference in mean scores of the anxiety at the beginning
of the study, the differences were significant at the end of
the study (p b 0.05). A Tockey test showed that the CBT
method could decrease significantly the mean of the
Cattell scores more than fluoxetine or no intervention,
but the decrease of the mean scores in the fluoxetine
group was not more than that of the control group.
4. Discussion
The first result from this data suggested that CBT was
a reliable method for the resolution of depression and
anxiety in infertile women. There are many studies that
support this finding (Hasson et al., 2007). Terzioglu
(2001) showed that couples who received daily
information and support during treatment lowered
their anxiety and depression scores and indicate higher
life satisfaction than controls. Boivin (2003) reviewed a
number of papers to determine whether psychosocial
interventions improved well-being in infertile people. It
was found that group interventions were significantly
more effective than counseling interventions. In contrast
with the results of this study, few studies showed that
psychological interventions for infertile women did not
improve mental health of the patients (Olga and Van
den, 2005; Strauss et al., 2002).
p-value Another result suggested that CBT was superior to
fluoxetine in the resolution or reduction of depression and
anxiety in infertile women. Some studies support this
b0.0001
b0.0001 finding (Mc Bride et al., 2006; Westbrook and Kirk,
0.9 2005). Antonuccio et al. (1997) in a comprehensive re-
view showed that fluoxetine alone result in 23% higher
expected costs than individual CBT treatment. In contrast,
a few studies have reported that CBT showed no more
 M. Faramarzi et al. / Journal of Affective Disorders 108 (2008) 159–164
effectiveness than pharmacotherapy in the treatment or
prevention of depression or anxiety )Hollon et al., 2005;
Austin et al., 2008). However, the version of CBT used in
this study was a novel amalgamation of different
approaches, and many have tried to do too much in an
overly structured fashion. Therefore, this novel model,
especially in the infertility field, may explain the different
results of this study with others.
There were a number of limitations in this study. The
first limitation of the study was the disproportionate num-
ber of dropouts from the experimental and control groups.
The second limitation was the issue of referring. Although
severe depressed women were referred to psychiatric center
for treatment, many women did not go to that center.
This study implies that some cultural issues affect
the treatment of depression and anxiety in infertile women.
Previous studies reported that the prevalence of depression
and anxiety in Iranian infertile women was 30–40%
(Ramezanzadeh et al., 2004). However, in this study, some
patients who suffered from depression refused to partici-
pate in the study to treat their problem, as they were worried
that their family might consider them to be psychosis
patients. Cultural worries of infertile women forced them to
deny their mood disorders or suppose that they could treat
themselves. Thus, this study suggests that it is necessary to
increase the knowledge of infertile women about the
advantages of treatment of mental disorders.
Results of this study were very beneficial for the
Fatemeh Alzahra center. After publishing the findings of
the report, the administrators of the center approved that
Fatemeh Alzahra needed a psychologist. This center
planned to consider the adjunct of psychological inter-
vention to medical treatment in the future. Also, this project
will continue in the future, and the subjects will follow up
for 1 year to investigate the spontaneous pregnancy rate
and reoccurrence of depression in the three groups.
In conclusion, CBT was superior to fluoxetine in the
resolution of depression and anxiety of infertile women.
Fluoxetine was superior to the control group in the
resolution of depression but not anxiety. This project
proposed that it is necessary to investigate the effective-
ness of routine CBT to prevent depression and anxiety in
infertile couples.
Role of funding source
Funding for this study was provided by the Research Center of
Babol University of Medical Sciences. The Research Center had no
further role in study design; in the collection, analysis and
interpretation of data; in the writing of the report; and in the decision
to submit the paper for publication.
Conflict of interest
All authors declare that they have no conflicts of interest.
163
Acknowledgments
The authors thank all the participants who attended
this study. Also, the authors thank Mrs. Afshar for
cooperation in the relaxation class and the midwives of
Fatemeh Alzahra hospital who invited and encouraged
women for attending in this study: Ghofrani, Asef,
Mahoti, Firozpour, Golsorkhtabar, Rastegar and Rabian.
The authors thank Dr. Mostafazadeh for financial
support of the project.
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