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Efficacy of Pharmacotherapy and Cognitive Therapy, Alone and in

Combination in Major Depressive Disorder

Article  in  Hong Kong Journal of Psychiatry · January 2008

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Farshid Shamsaei
Hamadan University of Medical Sciences
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Hong Kong J Psychiatry 2008;18:76-80
Introduction
Antidepressant medications (ADMs) are the most widely
Dr F Shamsaei, Department of Psychiatric Nursing, Behavioural Disorders &
Drug Substances Research Center, Hamadan University of Medical Sciences,
Iran.
Dr A Rahimi, Department of Psychiatry, Behavioural Disorders & Drug
Substances Research Center, Hamadan University of Medical Sciences, Iran.
Dr MK Zarabian, Behavioural Disorders & Drug Substances Research Center,
Hamadan University of Medical Sciences, Iran.
Dr M Sedehi, Department of Biostatistics, Hamedan University of Medical
Sciences, Iran.
Address for correspondence: Dr F Shamsaei, Faculty of Nursing, Hamadan
University of Medical Sciences, Hamadan 65178, Iran.
Tel: 98-811 8276051; Fax: 98-811 8276052;
E-mail: shamsaei68@yahoo.com
Submitted: 8 February 2008; Accepted: 9 April 2008
76
Original Article
used treatments for major depressive disorder.1 Evidence
from randomised placebo-controlled trials has supported
their efficacy, particularly for more severely depressed
patients.2 Cognitive therapy pioneered by Beck et al has
also shown promise in the treatment of major depressive
disorder.3,4 In a randomised, comparative trial, Rush et al5
reported that cognitive therapy was more effective than
ADM. However, their ADM dosages were low and the
medications were tapered 2 weeks before final outcome
assessment. Despite these shortcomings, their findings
generated enthusiasm for cognitive therapy as an alternative
to ADM for the treatment of depression.
Discussion of the comparative efficacy of ADM and
cognitive behaviour therapy for the treatment of severely
depressed patients has been marked by controversy. Findings
from early comparative studies led many to conclude
© 2008 Hong Kong College of Psychiatrists

that cognitive behaviour therapy is at least as effective as
ADM for the acute treatment for depression.5-8 However,
other reports suggested that it is not an effective treatment
for severely depressed patients.9-13 Findings from yet other
randomised trials of ADM and cognitive behaviour therapy
also need to be considered. Using criteria and measures
employed by Elkin et al,9 Hollon et al14 found a very small
advantage for cognitive behaviour therapy in their more
severely depressed subgroup. This finding was at odds
with the Treatment of Depression Collaborative Research
Program, in which ADM outperformed cognitive behaviour
therapy among the more severely depressed patients.15 To
examine the effects of both pharmacotherapy and cognitive
therapy, we conducted a clinical trial comparing the 3-month
efficacy of cognitive therapy and pharmacotherapy with
that of combined therapy in patients with major depressive
disorder of mild or moderate severity, defined according to
DSM-IV criteria.16
Methods
Study Sample
The study sample consisted of consecutive new patients
referred to 2 outpatient clinics of the Farshchian psychiatric
centre in Hamadan, Iran. Farshchian psychiatric centre is a
large psychiatric facility with several inpatient and outpatient
clinics, covering a third of the population of Hamadan city.
A total of 204 patients were screened. Of the 84 who did
not undergo randomisation, 36 did not meet the study entry
criteria (given below), 19 withdrew their consent, and 29
were excluded for other reasons (failure to return for further
evaluation or non-compliance). One hundred and twenty
patients underwent randomisation—40 were assigned to
receive citalopram, 40 received cognitive therapy, and 40
received combined treatment.
Diagnosis was based on the DSM-IV,16 with the
Structured Clinical Interview for Axis I DSM-IV Disorders.17
The inclusion criteria were: age 18-65 years, first visit after
onset of depressive disorder, and not being in receipt of any
prior therapy. Patients were excluded from the study if they
had any of the following: a history of seizures, abnormal
findings on electroencephalography, severe head trauma, or
stroke; evidence suggesting high risk of suicide; a history
of psychotic symptoms or schizophrenia; bipolar disorder,
an eating disorder (if not in remission for at least 1 year),
obsessive-compulsive disorder, or dementia; antisocial,
schizotypal, or severe borderline personality disorder; a
principal diagnosis of panic, generalised anxiety, social
phobia, or post-traumatic stress disorders or any substance-
related abuse or dependence disorder (except those involving
nicotine) within the last 6 months.
Study Design
This study was approved by the institutional review board
at each study centre. All patients provided written informed
consent. According to a central computerised randomisation
schedule, patients who remained eligible at the end of a 2-
Hong Kong J Psychiatry 2008, Vol 18, No.2
Pharmacotherapy and Cognitive Therapy for Depression
week evaluation period were assigned to receive citalopram,
cognitive therapy, or a combination of citalopram and
cognitive therapy, in a 1:1:1 ratio.
Pharmacotherapy
Pharmacotherapy for mild and moderately depressed patients
was initiated in the outpatient clinic at the standard dosage
of citalopram (20 mg / day) used in Farshchian psychiatric
centre. The treatment continued for 8 weeks, with a focus
on medication management, education about medications,
adjustment of dosage and dosage schedules as necessary,
and discussions about adverse effects.
Cognitive Therapy
This was aimed at reducing the participant’s level of
depression and increasing his / her coping skills, and entailed
8 sessions of therapy. The first half of each session was
devoted to presenting a social learning view of depression
and guidance on learning how to identify and differentiate
mood states. The second half addressed acquiring skills in
3 specific areas: increasing pleasant activities, changing
negative cognitions, and improving social skills to increase
positive social interactions. Each participant was encouraged
to develop a personalised plan to work on problem areas by
means of a participant workbook. Each session entailed a
review of material from the previous session, presentation
of new material, discussion, exercises related to the new
material, and a homework assignment. The treatment was
administered in 60-minute individual sessions by a single
therapist, who was a psychiatric nurse.
Measurement
Patients were assessed with the Beck Depression Inventory
(BDI) before and after treatment.18
Statistical Analysis
Analysis of covariance, including the initial measures as co-
variants, and multivariate analyses of variance were used to
test intra- and inter-group differences. In addition, for each
group pre- and post-effect sizes and comparative effect sizes
were calculated as the standard difference between 2 means,
using the pooled standard deviation as denominator.19-22 The
t test was used for comparative mean scores of the BDI pre-
and post-treatment results in the 3 groups.
Results
The mean age of the participants was 36 years (standard
deviation, 11 years). There was no significant difference in
the demographic, social, and clinical characteristics between
the 3 treatment groups (Table 1).
Mean pre- and post-intervention BDI scores of the 3
treatment groups are shown in Table 2. Analyses revealed
significant improvements in post-intervention scores (after
8 weeks) in all 3 patient groups (t test, p < 0.001).
One-way analysis of variance showed significant
differences between the combined treatment group and those
77
F Shamsaei, A Rahimi, MK Zarabian, et al

Table 1. Demographic, social, and clinical characteristics of the patients.

Characteristic Treatment group (%)*
Pharmacotherapy Cognitive therapy Combined therapy
Gender
Male : female 15 : 85 10 : 90 18 : 83
Age (years)
19-29 31 35 34
30-39 36 34 35
40-49 19 18 19
50-59 10 10 7
60-69 4 3 5
Marital status
Married 49 60 63
Divorced 2 3 2
Widowed 1 2 1
Never married 48 36 35
Education level
Low 22 17 20
Intermediate 49 51 45
High 30 33 35
Duration of present episode
< 1 year 44 60 49
1-2 years 27 19 21
> 2 years 28 21 30
Depressed episodes in the past
5 years
0 36 38 42
1 32 26 29
2 17 19 18
>3 15 17 12
*
Data are shown as percentages, unless otherwise specified. Because of rounding, not all percentages total 100.

Table 2. Pre- and post-treatment Beck Depression Inventory scores.

Treatment group Mean (SD) score p Value
Pre-treatment Post-treatment
Cognitive therapy 40.3 (6.8) 25.6 (5.1) < 0.001 (t = 5.5, df = 39)
Pharmacotherapy 45.8 (5.6) 23.4 (4.2) < 0.001 (t = 3.8, df = 39)
Combined therapy 42.3 (4.9) 19.2 (5.7) < 0.001 (t = 2.9, df = 39)

Table 3. Comparison of cognitive therapy and pharmacotherapy and combined therapy.

Comparison Mean difference Standard error p Value
Combined vs. cognitive 14.03 1.24 0.001
Combined vs. pharmacotherapy 11.78 1.24 0.001
Cognitive vs. pharmacotherapy 2.25 1.24 0.17

who received only cognitive therapy, or only citalopram Discussion

(p < 0.001). However, there was no significant difference
between the citalopram and cognitive therapy groups. The
magnitude of responses was significantly greater in the
combined treatment group than in the pharmacotherapy or
the cognitive therapy groups (p < 0.001; Table 3).
Previous reports suggested that the tricyclic antidepressant,
monoamine oxidase inhibitors, and selective serotonin
reuptake inhibitors are effective in the treatment of
depression. Several reports also highlighted the efficacy

78 Hong Kong J Psychiatry 2008, Vol 18, No.2


of cognitive therapy in the treatment of depression.22-34
The present study confirmed that an 8-week treatment
course with citalopram or cognitive therapy effectively
reduced the symptoms of depression. We also showed that
cognitive therapy alone was similar in efficacy to citalopram
treatment.
We also found that combined treatment (citalopram +
cognitive therapy) offered significant advantages over either
treatment alone. Our results seem to concur with those of
Keller et al,32 who reported a superior efficacy of combined
therapy over psychotherapy. Certain depressive symptom
may respond differently to treatment by cognitive therapy
than to standard ADM.5,35 After successful relief of their
symptoms following pharmacotherapy, many depressed
patients seem to require psychotherapy to cope with the
problems of living arising in relation to their depression.36
Our study should be interpreted in the context of its
limitations. For the BDI, a self-reported questionnaire was
used to measure outcomes (clinical responses). Second,
though randomised treatment allocation to the 3 groups was
used, the present study was non-blinded. Third, an 8-week
treatment may be inadequate to detect delayed responses,
particularly from psychological treatment. Fourth, responses
might have differed with higher doses of antidepressants. In
summary, we found that for patients with major depressive
disorder, the combination of antidepressant pharmacotherapy
and the cognitive therapy was significantly more efficacious
than either treatment alone. The response to either treatment
alone was similar to the rates reported in previous trials for
the treatment of major depression.
Acknowledgement
This research was carried out by a grant from Hamadan
University of Medical Sciences.
Declaration
The authors declare that there was no pharmaceutical
sponsorship in conducting this trial.
References
1. Olfson M, Klerman GL. Trends in the prescription of antidepressants
by office-based psychiatrists. Am J Psychiatry 1993;150:571-7.
2. Thase ME, Kupfer DJ. Recent developments in the pharmacotherapy
of mood disorders. J Consult Clin Psychol 1996;64:646-59.
3. Beck AT, Rush AJ, Shaw BF, Emery G. Cognitive therapy of depression.
New York: Guilford Press; 1979.
4. American Psychiatric Association. Practice guideline for the treatment
of patients with major depressive disorder (revision). Am J Psychiatry
2000;157(4 Suppl):S1-45.
5. Rush AJ, Beck AT, Kovacs M, Hollon S. Comparative efficacy of
cognitive therapy and pharmacotherapy in the treatment of depressed
patients. Cognit Ther Res 1977;1:17-37.
6. Murphy GE, Simons AD, Wetzel RD, Lustman PJ. Cognitive therapy
and pharmacotherapy. Singly and together in the treatment of
depression. Arch Gen Psychiatry 1984;41:33-41.
7. Dobson KS. A meta-analysis of the efficacy of cognitive therapy for
depression. J Consult Clin Psychol 1989;57:414-9.
Hong Kong J Psychiatry 2008, Vol 18, No.2
Pharmacotherapy and Cognitive Therapy for Depression
8. Antonuccio D. Psychotherapy for depression: no stronger medicine.
Am Psychol 1995;50:450-2.
9. Elkin I, Shea MT, Watkins JT, Imber SD, Sotsky SM, Collins JF,
et al. National Institute of Mental Health Treatment of Depression
Collaborative Research Program. General effectiveness of treatments.
Arch Gen Psychiatry 1989;46:971-82.
10. Klein DF. Preventing hung juries about therapy studies. J Consult Clin
Psychol 1996;64:81-7.
11. Jacobson NS, Hollon SD. Cognitive-behavior therapy versus
pharmacotherapy: now that the jury’s returned its verdict, it’s time to
present the rest of the evidence. J Consult Clin Psychol 1996;64:74-80.
12. Jacobson NS, Hollon SD. Prospects for future comparisons
between drugs and psychotherapy: lessons from the CBT-versus-
pharmacotherapy exchange. J Consult Clin Psychol 1996;64:104-8.
13. Elkin I, Gibbons RD, Shea MT, Shaw BF. Science is not a trial (but it
can sometimes be a tribulation). J Consult Clin Psychol 1996;64:92-
103.
14. Hollon SD, DeRubeis RJ, Evans MD. Wiemer MJ, Garvey MJ, Grove
WM, et al. Cognitive therapy and pharmacotherapy for depression.
Singly and in combination. Arch Gen Psychiatry 1992;49:774-81.
15. Elkin I, Gibbons RD, Shea MT, Sotsky SM, Watkins JT, Pilkonis PA,
et al. Initial severity and differential treatment outcome in the National
Institute of Mental Health Treatment of Depression Collaborative
Research Program. J Consult Clin Psychol 1995;63:841-7.
16. Diagnostic and statistical manual of mental disorders, 4th edition:
DSM-IV. Washington D.C.: Am Psychiatric Association; 1994.
17. First MB, Spitzer RL, Gibbon M, et al. Structured clinical interview
for Axis-I DSM-IV disorders: patient edition (SCID-II, version 2.0).
New York: New York State Psychiatric Institute Biometrics Research
Department; 1994.
18. Beck AT, Steer RA: Manual for the revised Beck Depression Inventory.
San Antonio, Tex, Psychological Corp.; 1987.
19. Cohen J. Statistical power analysis for the behavioral sciences. 2nd ed.
Hillsdale, NJ: Lawrence Erlbaum; 1988.
20. Rosnow RL, Rosenthal R. Computing contrasts, effect sizes, and
counternulls on other people’s published data: general procedures for
research consumers. Psychological Methods 1996;1:331-40.
21. Fawcett J, Epstein P, Fiester SJ, Elkin I, Autry JH. Clinical
management—imipramine / placebo administration manual.
NIMH Treatment of Depression Collaborative Research Program.
Psychopharmacol Bull 1987;23:309-24.
22. Friedman RA, Markowitz JC, Parides M, Kocsis JH. Acute response
of social functioning in dysthymic patients with desipramine. J Affect
Disord 1995;34:85-8.
23. Kocsis JH, Zisook S, Davidson J, Shelton R, Yonkers K, Hellerstein
DJ, et al. Double-blind comparison of sertraline, imipramine, and
placebo in the treatment of dysthymia: psychosocial outcomes. Am J
Psychiatry 1997;154:390-5.
24. Marin DB, Kocsis JH, Frances AJ, Parides M. Desipramine for the
treatment of “pure” dysthymia versus “double” depression. Am J
Psychiatry 1994;151:1079-80.
25. Stewart JW, McGrath PJ, Quitkin FM, Rabkin JG, Harrison W, Wager
S, et al. Chronic depression: response to placebo, imipramine, and
phenelzine. J Clin Psychopharmacol 1993;13:391-6.
26. Versiani M, Nardi AE, Figueira IL, Stabl M. Tolerability of
moclobemide, a new reversible inhibitor of monoamine oxidase-A,
compared with other antidepressants and placebo. Acta Psychiatr
Scand Suppl 1990;360:24-8.
27. Pétursson H. Studies of reversible and selective inhibitors of
monoamine oxidase A in dysthymia. Acta Psychiatr Scand Suppl
1995;386:36-9.
28. Vallejo J, Gasto C, Catalan R, Salamero M. Double-blind study
of imipramine versus phenelzine in Melancholias and Dysthymic
Disorders. Br J Psychiatry 1987;151:639-42.
29. Hellerstein DJ, Samstag LW, Cantillon M, Maurer M, Rosenthal
J, Yanowitch P, et al. Follow-up assessment of medication-treated
dysthymia. Prog Neuropsychopharmacol Biol Psychiatry 1996;20:427-
42.
79
F Shamsaei, A Rahimi, MK Zarabian, et al
30. Ravindran AV, Bialik RJ, Lapierre YD. Primary early onset dysthymia,
biochemical correlates of the therapeutic response to fluoxetine: I.
Platelet monoamine oxidase and the dexamethasone suppression test.
J Affect Disord 1994;31:111-7.
31. Ravindran AV, Griffiths J, Waddell C, Anisman H. Stressful life events
and coping styles in relation to dysthymia and major depressive
disorder: variations associated with alleviation of symptoms following
pharmacotherapy. Prog Neuropsychopharmacol Biol Psychiatry
1995;19:637-53.
32. Keller MB, McCullough JP, Klein DN, Arnow B, Dunner DL,
Gelenberg AJ, et al. A comparison of nefazodone, the cognitive
behavioral-analysis system of psychotherapy, and their combination
for the treatment of chronic depression. N Eng J Med 2000;342:1462-
80
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70.
33. Blackburn IM, Bishop S, Glen AI, Whalley LJ, Christie JE. The efficacy
of cognitive therapy in depression: a treatment trial using cognitive
therapy and pharmacotherapy, each alone and in combination. Br J
Psychiatry 1981;139:181-9.
34. de Jonghe F, Hendricksen M, van Aalst G, Kool S, Peen V, Van R, et
al. Psychotherapy alone and combined with pharmacotherapy in the
treatment of depression. Br J Psychiatry 2004;185:37-45.
35. Rush AJ, Beck AT, Kovacs M, Weissenburger J, Hollon SD.
Comparison of the effects of cognitive therapy and pharmacotherapy
on hopelessness and self-concept. Am J Psychiatry 1982;139:862-6.
36. Karasu TB. Psychotherapy and pharmacotherapy: toward an integrative
model. Am J Psychiatry 1982;139:1102-13.
Hong Kong J Psychiatry 2008, Vol 18, No.2