Combined Therapy of Major Depression With Concomitant BPD - Comparison of Interpersonal and Cognitive ...

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Original Research
Combined Therapy of Major Depression With
Concomitant Borderline Personality Disorder:
Comparison of Interpersonal and Cognitive
Psychotherapy
Silvio Bellino, MD
1
, Monica Zizza, PhD
2
, Camilla Rinaldi, MD
3
, Filippo Bogetto, MD
4
Objective:
The combination of antidepressants and brief psychotherapies has been proven
more efficacious in treating major depression and is particularly recommended in patients
with concomitant personality disorders. We compare the effects of 2 combined therapies,
fluoxetine and interpersonal therapy (IPT) or fluoxetine and cognitive therapy (CT), on
major depression in patients with borderline personality disorder (BPD).
Method:
Thirty-five consecutive outpatients with a diagnosis of BPD and a major
depressive episode (not bipolar and not psychotic) were enrolled. They were randomly
assigned to 1 of the 2 combined treatments and treated for 24 weeks. Assessment included
a semistructured interview, Clinical Global Impression (CGI) scale, Hamilton Depression
Rating Scale (HDRS), Hamilton Anxiety Rating Scale (HARS), Beck Depression
Inventory-II (BDI-II), Social and Occupational Functioning Assessment Scale (SOFAS),
Satisfaction Profile (SAT-P) for quality of life (QOL), and Inventory of Interpersonal
Problems (IIP-64). Statistical analysis was performed using the univariate General Linear
Model to calculate the effects of duration and type of treatment.
Results:
No significant differences between treatments were found at CGI, HDRS, BDI-II,
and SOFAS score. Combined treatment with CT had greater effects on HARS score and on
psychological functioning factor of SAT-P. Combined treatment with IPT was more
effective on social functioning factor of SAT-P and on domains domineering or controlling
and intrusive or needy of IIP-64.
Conclusions:
Both combined therapies are efficacious in treating major depression in
patients with BPD. Differences between CT and IPT concern specific features of subjective
QOL and interpersonal problems. These findings lack reliable comparisons and need to be
replicated.
(Can J Psychiatry 2007;52:718–725)
Information on funding and support and author affiliations appears at the end of the article.
Clinical Implications
Combined treatments associating fluoxetine with IPT or CT are efficacious in treating major
depression in patients with concomitant BPD.
Combined treatment with CT has greater effects on anxiety symptoms and on patients ’
perception of psychological functioning.
Combined treatment with IPT has more of an impact on patients’ perception of social
functioning and on interpersonal problems.
718
La Revue canadienne de psychiatrie, vol 52, no 11, novembre 2007
Combined Therapy of Major Depression With Concomitant Borderline Personality Disorder: Comparison of Interpersonal and Cognitive Psychotherapy
Limitations
Sample size was relatively small and results need to be replicated.
Study lacked a long-term follow-up to assess if clinical improvement is maintained after the
end of treatment.
Assessment instruments did not include a specific scale for measuring BPD-related symptoms.
Key Words
: major depressive disorder, borderline personality disorder, combined therapy,
interpersonal therapy, cognitive therapy, fluoxetine
T
he combination of ADs and brief psychotherapies is
Clinical data and APA treatment guidelines for major depres-
sion indicate that providing combined therapy is particularly
recommended in patients with concomitant personality disor-
ders.
18,38–40
Kool and colleagues
41
compared the efficacy of
combined therapy with ADs and short psychodynamic sup-
portive psychotherapy and monotherapy with ADs in 72
patients with MDD. They concluded that depressed patients
with comorbid personality disorder appeared to benefit most
from combined therapy. The results were most striking for
cluster C disorders. A recent study of our group
42
included 32
BPD patients who present a major depressive episode (not
bipolar and not psychotic). A combination of fluoxetine and
IPT was found more efficacious than fluoxetine monotherapy
after 24 weeks, on measures of depressive symptoms, subjec-
tive QOL, and interpersonal problems. Although different
psychotherapies have been chosen for combined treatment,
their effects on depressed patients with concomitant personal-
ity disorders have not been compared. In particular, we have
no data to determine if combined treatments with different
psychotherapies can induce specific changes in patients with
MDD and BPD.
This study compares the association of an SSRI with CT or
IPT in treating a group of patients who presented a major
depressive episode with concomitant BPD.
widely used in the treatment of MDD and has been proven
more efficacious than monotherapy with either ADs or psy-
chotherapy in improving depressive symptoms and social
functioning.
1–11
Of the choices of psychotherapy, CT and IPT are 2 time-
limited treatments that were specifically proposed for major
depression and extensively studied in trials of monotherapy or
combined therapy.
1,12–28
Major depression is commonly associated with personality
disorders. In particular, MDD is the most common Axis I
comorbidity in populations with BPD,
29–36
a serious and per-
sistent mental disorder characterized by a pervasive pattern of
instability of interpersonal relationships, affects, and
self-image, as well as marked impulsivity that appears in a
variety of contexts.
37
Abbreviations used in this article
AD
antidepressant drug
APA
American Psychiatric Association
BDI-II
Beck Depression Inventory-II
BPD
borderline personality disorder
CGI
Clinical Global Impression
Method
The study participants were selected from patients attending
the Service for Personality Disorders of the Unit of Psychia-
try, Department of Neurosciences, University of Turin, from
April to December 2005.
We included consecutive outpatients who received a
DSM-IV-TR
37
diagnosis of BPD and then met criteria for a
major depressive episode (that is, mild to moderate).
Diagnoses were made by an expert clinician and were con-
firmed using the Structured Clinical Interview for DSM-IV
Axis I and II disorders.
43,44
We excluded individuals with a lifetime diagnosis of delir-
ium, dementia, amnestic or other cognitive disorders, schizo-
phrenia or other psychotic disorders, and patients whose
major depressive episode was an expression of bipolar
disorder.
CT
cognitive therapy
GLM
General Linear Model
HARS
Hamilton Anxiety Rating Scales
HDRS
Hamilton Depression Rating Scales
IIP-64
Inventory of Interpersonal Problems—64-item version
IPT
interpersonal therapy
MDD
major depressive disorder
QOL
quality of life
SAT-P
Satisfaction Profile
SD
standard deviation
SOFAS
Social and Occupational Functioning
Assessment Scale
SSRI
selective serotonin reuptake inhibitor
The Canadian Journal of Psychiatry, Vol 52, No 11, November 2007
719
Original Research
Exclusion criteria also considered a current diagnosis of sub-
stance abuse disorder and whether an individual was treated
with psychotropic drugs or psychotherapy during the 2
months prior to the study. Female patients of child-bearing
age were excluded if they were not using an adequate method
of birth control (according to the judgment of the clinician).
of patients’ perception of their level of functioning and treat-
ment benefits. Patients were also assessed with IIP-64,
54
a
self-report inventory to identify problematic areas in interper-
sonal relationships. This inventory assesses the severity of
interpersonal problems in 8 domains: domineering or control-
ling; vindictive or self-centred; cold and distant; socially
inhibited; nonassertive; overly accommodating; self-
sacrificing; and intrusive or needy. The IIP-64 has been
widely used to assess psychotherapy outcome.
55–58
Written informed consent was obtained from all patients prior
to their participation. We had ethics board approval and fol-
lowed Declaration of Helsinki guidelines.
Patients included in the study were randomized using the web
program Research Randomizer v3.0 (Urbaniak & Plous,
Social Psychology Network, 2007) and were assigned to one
of 2 treatment groups of combined therapy: IPT plus
pharmacotherapy, or CT plus pharmacotherapy. Patients
underwent their respective treatments for 24 weeks.
All 32 patients included in the study received 20 to 40 mg of
fluoxetine daily. Initially, fluoxetine was prescribed at a fixed
dosage of 20 mg daily with the opportunity to increase the
dosage to 40 mg daily beginning in week 2, depending on clin-
ical judgment. A psychiatrist provided pharmacotherapy. He
was blind to which type of psychotherapy the patients were
receiving. Each patient was given 7 appointments, the first 2
fortnightly and the last 5 monthly.
Sixteen patients received fluoxetine plus IPT, the remaining
16 received fluoxetine plus CT. IPT consisted of weekly ses-
sions lasting 1 hour and was conducted referring to the IPT of
depression manual.
45
Patients in the IPT group were treated by
a psychotherapist who was not the psychiatrist prescribing
medication and who had at least 5 years of experience practis-
ing IPT. CT consisted of weekly 1-hour sessions and were
conducted referring to the manuals of cognitive therapy of
depression.
46,47
Patients in the CT group were treated by a psy-
chotherapist who was neither the psychiatrist prescribing
medication nor the psychotherapist providing IPT, and who
had at least 5 years of experience practising CT. Both psycho-
therapists received supervision during the treatment to assess
their adherence to the psychotherapy manuals. The
pharmacotherapy and both psychotherapies started
simultaneously.
All patients were repeatedly assessed (that is, at baseline,
week 12, and week 24) with the following measures: a
semistructured interview to assess demographic and clinical
characteristics; the Severity and Improvement items of the
CGI scale to assess the level of global symptomatology
48
; the
HDRS and HARS
49,50
; the revised BDI-II, a self-report instru-
ment developed to assess the severity of depression according
to Beck’s cognitive theories
51
; the SOFAS, a self-report scale
that assesses the social and occupational level of function-
ing
52
; the SAT-P,
53
a self-administered questionnaire consist-
ing of 32 scales that provides a satisfaction profile in daily life
and can be considered as an indicator of subjective QOL. The
SAT-P considers 5 different factors: psychological function-
ing; physical functioning; work; sleep, food, and free time;
and social functioning. This questionnaire allows for analysis
The assessments were performed by an investigator who was
blind to the treatment methods. Remission was defined by a
decreased HDRS score (
8, and
a score of 1 (very much improved) or 2 (much improved) on
the Improvement item of the CGI.
40%), with a final score of
We performed statistical analyses using the software system
SPSS, version 13.0 (SPSS Inc, Chicago, Illinois, 2004). Only
those patients who completed the study were included in the
analysis. We used Student
t
test and Fisher’s exact test to com-
pare demographic and clinical characteristics (that is, age,
sex, the Severity item of the CGI, HDRS and HARS scores,
and BDI-II scores) at baseline. The Student
t
test was used to
compare mean daily doses of fluoxetine in the 2 subgroups
and Fisher’s exact test was performed to compare the number
of patients who achieved remission. We used the univariate
GLM to calculate the effects of 2 factors (duration and type of
treatment) on each assessment scale score.
P
values were con-
sidered significant when
P
0.05.
Results
Initially, there were 32 patients enrolled in the study. At
intake, there were no significant differences between the 2
treatment groups concerning age, sex, the Severity item of the
CGI, HDRS and HARS scores, and BDI-II scores. Owing to
noncompliance, 6 patients discontinued treatment during the
first 3 weeks. Of these subjects, 2 were in the IPT group, and 4
were in the CT group. We performed statistical analyses of
outcome measures on the 26 patients (that is, 14 patients in the
IPT group and 12 patients in the CT group) who completed the
24 weeks of treatment. The sample had a mean age of 30.55,
SD 5.75 years. The ratio of men to women was 7 to 19 (2.71).
The mean dosages of fluoxetine were equivalent in the 2
groups: 32.86 mg daily, SD 9.95 mg, in the group treated with
IPT and 30.00 mg daily, SD 10.45 mg, in the group treated
with CT (
P
= 0.48). At the end point, 71.43% (
n
= 10) of the
IPT treated patients and 66.67% (
n
= 8) of CT treated patients
achieved remission. Statistical comparison with the Fisher’s
exact test did not show a significant difference (
P
= 0.56).
Results of the univariate GLM performed on the Severity item
of the CGI, HDRS, HARS, BDI-II, and SOFAS results are
presented in Table 1. On each scale, we found that the time
factor had a significant effect (
P
0.005). The treatment fac-
tor showed a significant effect (
P
= 0.007) only on the HARS,
which indicates a higher score change in the subgroup receiv-
ing fluoxetine and CT.
720
La Revue canadienne de psychiatrie, vol 52, no 11, novembre 2007
Combined Therapy of Major Depression With Concomitant Borderline Personality Disorder: Comparison of Interpersonal and Cognitive Psychotherapy
Table 1 Results of univariate GLM for symptom and social and occupational functioning scales
T0
Mean (SD)
T1
Mean (SD)
T2
Mean (SD)
Rating scale
Treatment
P
Time 0.001
a
Treatment ns
Time
Treatment ns
CGI: Severity item
IPT
3.5 (0.5)
2.5 (0.5)
1.9 (0.9)
CT
3.3 (0.5)
2.3 (0.5)
1.7 (1.1)
Time 0.005
b
Treatment ns
Time
Treatment ns
HDRS
IPT
19.7 (3.4)
16.6 (3.8)
14.1 (5.5)
CT
19.7 (3.4)
16.3 (3.6)
13.7 (5.7)
Time 0.001
a
Treatment 0.007
Time
Treatment ns
HARS
IPT
18.1 (0.8)
16.1 (0.9)
13.7 (2.8)
CT
18.0 (1.1)
13.3 (1.4)
12.5 (1.1)
0.001
b
BDI-II
IPT
22.0 (2.6)
18.9 (3.6)
15.7 (4.5)
Time
CT
21.0 (0.9)
17.7 (1.1)
14.7 (1.9)
Treatment
ns
Time
Treatment ns
0.003
b
SOFAS
IPT
51.7 (5.9)
59.0 (6.2)
65.0 (8.6)
Time
CT
54.0 (7.1)
62.7 (8.4)
70.3 (9.6)
Treatment
ns
Time
Treatment ns
a
T1;
b
T2; ns = not significant
In Table 2, the results of the GLM applied to the 5 factors of
the SAT-P are presented. There was a significant change in 4
of the 5 factors related to the length of treatments, that is, psy-
chological functioning; physical functioning; sleep, food, and
free time; and social functioning (
P
Discussion
Our study compared the efficacy of 2 types of psychotherapy
(that is, IPT or CT) associated with a SSRI (that is, fluoxetine)
in the treatment of patients with a major depressive episode
and preexisting BPD. We chose fluoxetine because it is a
widely used AD
59–61
and it is also recommended by APA treat-
ment guidelines for BPD.
62
Our patients were treated with IPT
or CT because these approaches have been initially proposed
and extensively studied for the treatment of MDD.
1,12–28
In
addition, they are now considered among the effective
psychotherapies for BPD.
42,60,63–69
The combination of
pharmacotherapy and psychotherapy is recommended by
APA guidelines both for treatment of MDD and BPD.
18,60–62
In particular, combined therapy is preferable to monotherapy
when interpersonal problems or personality disorders are
associated with major depression.
18,38–42,70–75
0.007). We found that
the treatment factor had a significant effect (
P=
0.02) on the
psychological functioning factor: combined therapy with CT
was more effective. The treatment factor also had a significant
effect (
P=
0.02) on the social functioning factor: the efficacy
of combined therapy with IPT was greater.
Results of the univariate GLM applied to the 8 domains of the
IIP-64 are described in Table 3. Findings differ depending on
which domain is considered. Neither time nor treatment
factors had a significant effect on any of the following 5
domains: cold or distant; socially inhibited; nonassertive;
overly accommodating; and self-sacrificing. The time factor
had a significant effect (
P
< 0.001) on the vindictive or self-
centred domain. Both the time (
P
In our study, the 2 treatment options did not significantly dif-
fer in rates of remission, improvement of global
psychopathology, social and occupational functioning, and
reduction of depressive symptoms. These findings agree with
other research that found that combined therapy with IPT or
CT are efficacious in depressive disorders.
14,20,25–27
Signifi-
cant differences between the 2 subgroups of our study were
found in measures of anxious symptoms, factors related to
0.001) and the treatment
factor (
P
0.01) had a significant effect on the domineering or
controlling and intrusive or needy domains. These results
indicate that combined therapy with IPT has more of an
impact on these areas than combined therapy with CT.
The Canadian Journal of Psychiatry, Vol 52, No 11, November 2007
721
Original Research
Table 2 Results of univariate GLM for factors of subjective quality of life (SAT-P)
T0
Mean (SD)
T1
Mean (SD)
T2
Mean (SD)
Factor
Treatment
P
Time 0.005
a
Treatment 0.02
Time
Treatment ns
Psychological functioning
IPT
38.7 (10.2)
42.5 (7.1)
56.1 (15.4)
CT
42.3 (4.8)
56.7 (10.8)
63.7 (14.2)
Time 0.007
b
Treatment ns
Time
Treatment ns
Physical functioning
IPT
36.9 (5.3)
46.9 (7.1)
54.4 (14.9)
CT
30.0 (4.5)
46.7 (6.8)
60.0 (7.7)
Work
IPT
38.0 (12.5)
46.2 (15.3)
51.9 (20.2)
Time ns
Treatment ns
Time
Treatment ns
CT
34.2 (7.4)
39.2 (10.2)
39.2 (10.2)
Time 0.003
a
Treatment ns
Time
Treatment ns
Sleep, food, and free time
IPT
36.1 (12.9)
44.7 (9.1)
53.1 (8.8)
CT
41.7 (8.2)
48.3 (6.8)
53.3 (13.7)
Time 0.001
a
Treatment 0.02
Time
Treatment ns
Social functioning
IPT
43.1 (8.8)
53.1 (9.6)
70.0 (12.8)
CT
38.3 (14.7)
45.0 (13.8)
55.0 (14.8)
a
T2;
b
T1; ns = not significant
subjective QOL, and dysfunctional patterns of interpersonal
relationships.
interpersonal problems. Subjective experience of social func-
tioning deals with the quality of social relations in different
contexts in each patient’s life. According to some
research,
68,71,76,77
social functioning is more compromised in
depressed patients with concomitant BPD than in depressed
patients who do not have personality disorders. Difficulties in
handling relationships with family members, colleagues, and
friends provide appropriate targets for the IPT treatment, and
change of dysfunctional interpersonal patterns can improve
the patient’s QOL. The 2 domains domineering or controlling
and intrusive or needy of the IIP-64 refer to areas of interper-
sonal problems that often represent a core feature of patients
with BPD. These patients have a powerful need to feel
engaged with other people and impose their control, because
they cannot tolerate the fear of being abandoned. An improve-
ment in these areas indicates that patients have developed
more functional models for handling interpersonal relation-
ships, reducing their intrusive and controlling attitudes. A
reliable comparison of our results with published research is
not possible.
Concerning the efficacy of combined therapy with CT, our
results showed that it was significantly superior to combined
therapy with IPT in reducing anxious symptoms as measured
by the HARS. These data appear concordant with
Gunderson’s opinion that CT well-structured techniques (that
is, role-playing, instructions, homework, and mental exer-
cises) are useful instruments in reducing anxious symptoms in
BPD patients.
76
Moreover, CT is significantly superior to IPT
in improving the psychological functioning as measured by
the SAT-P scale for QOL. Subjective perception of psycho-
logical functioning deals with self-esteem, psychological
autonomy, problem-solving ability, emotional stability,
self-control, and sense of identity. This finding confirms an
open clinical trial of CT in depressed patients with BPD,
reporting significant reduction in depressive symptoms and
improvement in dysfunctional beliefs concerning self-
perception, dependency, helplessness, and emotional
control.
65
Although IPT and CT have both been widely studied in the
treatment of major depression and are considered promising
options for dealing with patients with BPD, systematic data on
their use in combined therapy of patients with concomitant
BPD and major depression are not available for CT and lim-
ited for IPT. The group treated by Brown and colleagues
65
If we consider the efficacy of combined therapy with IPT, it
was found significantly superior to combined therapy with CT
in improving the social functioning as measured by the
SAT-P, and the 2 domains domineering or controlling and
intrusive or needy as measured by the IIP-64 scale for
722
La Revue canadienne de psychiatrie, vol 52, no 11, novembre 2007
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