The effectiveness of individual interpersonal psychotherapy as a treatment for major depressive disorder in adult outpatients: a systematic review.
ABSTRACT BACKGROUND: This systematic review describes a comparison between several standard treatments for major depressive disorder (MDD) in adult outpatients, with a focus on interpersonal psychotherapy (IPT). METHODS: Systematic searches of PubMed and PsycINFO studies between January 1970 and August 2012 were performed to identify (C-)RCTs, in which MDD was a primary diagnosis in adult outpatients receiving individual IPT as a monotherapy compared to other forms of psychotherapy and/or pharmacotherapy. RESULTS: 1233 patients were included in six eligible studies, out of which 854 completed treatment in outpatient facilities. IPT combined with nefazodone improved depressive symptoms significantly better than sole nefazodone, while undefined pharmacotherapy combined with clinical management improved symptoms better than sole IPT. IPT or imipramine hydrochloride with clinical management showed a better outcome than placebo with clinical management. Depressive symptoms were reduced more in CBASP (cognitive behavioral analysis system of psychotherapy) patients in comparison with IPT patients, while IPT reduced symptoms better than usual care and wait list condition. CONCLUSIONS: The differences between treatment effects are very small and often they are not significant. Psychotherapeutic treatments such as IPT and CBT, and/or pharmacotherapy are recommended as first-line treatments for depressed adult outpatients, without favoring one of them, although the individual preferences of patients should be taken into consideration in choosing a treatment.
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ABSTRACT: Interpersonal therapy (IPT) is a brief, structured psychotherapy initially intended to treat adult depression that was developed in the 1970s and manualized in 1984 by G. Klerman and his team. Two main theories served as a basis for its design: Bowlby's attachment theory and communication theory. Klerman theorized that tensions and problems in interpersonal relationships (i.e. disputes) cause psychological distress in vulnerable individuals that may lead to a major depressive episode. Clinical and epidemiological studies have shown that an insecure attachment style is strongly associated with lifetime depression. Severe depressive episodes have been correlated with avoidant attachment in women. IPT is based on the hypothesis that recent or ongoing disturbances in interpersonal relationships either trigger or follow the onset of mood disorder. In practice, IPT assists patients in analysing their interpersonal relationship modes, correlating their relational states with their mood and in learning to use better communication. Resolving difficulties in interpersonal relationships through the use of better communication skills promotes the improvement of depressive symptoms. Klerman identified four interpersonal areas that seem to be highly correlated with depressive episodes: grief (a close and important personal relation who has died), interpersonal disputes (conflicts with significant people such as a spouse or another close family member), role transition (significant life changes such as retirement, parenthood or chronic and invalidating illness) and interpersonal deficits (patients who have limited social contacts and few interpersonal relations). Classically, IPT is planned around 12-16 weekly sessions. During the initial sessions, the therapist will explore all existing interpersonal relations and any significant dysfunctions, both recent and ongoing. Following this interview, the area the patient considers as driving the current depressive episode will be designated as the focus of therapy. Evaluation of depressive symptoms by a quantitative measure (i.e. Visual Analogue Scale) and qualitative measures (activity, pleasure, quality of life) reoccurs at each session. During the intermediate sessions, therapy uses current situations and events in the designated area that particularly affect the patient's mood. Coping, communication and decision-making skills are gradually improved through a number of techniques. These include non-directive and directive exploration, clarification, encouragement of affect, and communication analysis. The therapeutic relationship is empathetic and encouraging of all progress the patient makes. The final phases close the therapy and help the patient to plan future actions and improvements. Several controlled clinical trials in adult populations have demonstrated the efficacy of IPT in treating Major Depressive Disorder (initial and recurrent episodes). It has been recommended as an appropriate treatment option in several guidelines. It can be provided in individual, couple or group formats. There remains an ongoing discussion of the efficacy of monthly maintenance sessions in recurrent depression. Since its conception, clinical trials have explored its use in specific populations such as adolescents and the elderly. IPT has also been the object of trial in other disorders such as post-partum depression, bipolar disorder, social phobia and eating disorders. This article reviews the basic principles and objectives of this therapeutic model. Theoretical concepts and results from research are also discussed. The approach is briefly described and the various therapeutic phases are discussed. Clinical trials have shown that IPT is effective in treating major depressive disorder in a wide variety of populations. Further trials are necessary to determine its efficacy in other psychiatric disorders.L Encéphale 04/2014; · 0.60 Impact Factor
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ABSTRACT: The improvement of social support promotes the mental health and improves the health status. The study aimed to examine the influence of the social support on symptoms of anxiety and depression among patients with silicosis and provide the scientific basis to further alleviate anxiety and depression and to monitor their whole quality of life. We investigated 324 inpatients with silicosis between April 2011 and September 2011. The HADS (the Hospital Anxiety-Depression Scale) was the major methodology used to evaluate anxiety and depression, and the MSPSS (the Multidimensional Scale of Perceived Social Support) to evaluate the social support level. Among patients with silicosis, 99.1% had anxiety symptoms, and 86.1% had depression symptoms. Meanwhile, the social support significantly influenced symptoms of anxiety and depression. The study suggested that patients with silicosis presented more anxiety and depression symptoms, while the social support levels of the patients were relatively low. The influence of social support on symptoms of anxiety and depression among patients with silicosis implied that improving the level of social support and the effective symptomatic treatment might alleviate anxiety and depression symptoms and improve physical and mental status.TheScientificWorldJournal. 01/2014; 2014:724804.
Article: Abuse and misuse of antidepressants.[Show abstract] [Hide abstract]
ABSTRACT: Rates of prescription drug abuse have reached epidemic proportions. Large-scale epidemiologic surveys of this under-recognized clinical problem have not included antidepressants despite their contribution to morbidity and mortality. The purpose of this review is to look specifically at the misuse of antidepressants and how this behavior may fit into the growing crisis of nonmedical use of prescription drugs.Substance abuse and rehabilitation. 01/2014; 5:107-20.
RESEARCH ARTICLEOpen Access
The effectiveness of individual interpersonal
psychotherapy as a treatment for major
depressive disorder in adult outpatients:
a systematic review
Madelon L J M van Hees1*, Thomas Rotter1,2, Tim Ellermann3and Silvia M A A Evers1,4
Background: This systematic review describes a comparison between several standard treatments for major
depressive disorder (MDD) in adult outpatients, with a focus on interpersonal psychotherapy (IPT).
Methods: Systematic searches of PubMed and PsycINFO studies between January 1970 and August 2012 were
performed to identify (C-)RCTs, in which MDD was a primary diagnosis in adult outpatients receiving individual IPT
as a monotherapy compared to other forms of psychotherapy and/or pharmacotherapy.
Results: 1233 patients were included in eight eligible studies, out of which 854 completed treatment in outpatient
facilities. IPT combined with nefazodone improved depressive symptoms significantly better than sole nefazodone,
while undefined pharmacotherapy combined with clinical management improved symptoms better than sole IPT.
IPT or imipramine hydrochloride with clinical management showed a better outcome than placebo with clinical
management. Depressive symptoms were reduced more in CBASP (cognitive behavioral analysis system of
psychotherapy) patients in comparison with IPT patients, while IPT reduced symptoms better than usual care and
wait list condition.
Conclusions: The differences between treatment effects are very small and often they are not significant.
Psychotherapeutic treatments such as IPT and CBT, and/or pharmacotherapy are recommended as first-line
treatments for depressed adult outpatients, without favoring one of them, although the individual preferences of
patients should be taken into consideration in choosing a treatment.
Keywords: Interpersonal psychotherapy, Major depressive disorder, Systematic review
Major depressive disorder (MDD) is a mental disorder
characterized by a depressed mood, diminished interest or
pleasure, sleeping problems and tiredness, and negative
thoughts . The mean one-year-prevalence of depression
in European inhabitants between 18 and 65 years old is
6.9% , and 16.2-16.6% of US adults develop a major
depressive disorder [3,4]. Furthermore, depression causes a
high burden worldwide, taking fourth place in a ranking of
leading contributors to the burden of diseases in 2000. In
2020, it is estimated that depression will take second place
in the ranking for all ages and sexes . Moreover, depres-
sion is the leading cause of years of life lived with disability,
in all ages and sexes, accounting for 11.9% of all disability
. Since it appears that persons suffering from mental
disorders make more use of health care services , the
increasing prevalence of depression leads to an increase in
health care costs.
Research  and Dutch guidelines  suggest treating
Psychotherapy follows several kinds of methodologies. For
depression, Cognitive (Behavior) Therapy (CBT) and
Interpersonal Psychotherapy (IPT) are often applied. CBT
* Correspondence: email@example.com
1Caphri, School of Public Health and Primary Care; Faculty of Health,
Medicine, and Life Sciences, Maastricht University, Maastricht, the
Full list of author information is available at the end of the article
© 2013 van Hees et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative
Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly cited.
van Hees et al. BMC Psychiatry 2013, 13:22
originates from behavior therapy and cognitive therapy,
and combines elements of both therapies [10-12]. IPT was
originally developed for treating acute depression by
improving the interpersonal functioning with important
others [13-17]. This study will focus on the effectiveness
and efficacy of IPT, since CBT has been subject of many
studies up until now, while IPT has only recently become
a subject of interest.
As a monotherapy for adults, individual IPT appears to
be an effective treatment for depression [18-20], and several
reviews [21-25], and meta-analyses [26-33] have been per-
formed on the effectiveness of all kinds of methodologies of
psychotherapy. Nevertheless, psychotherapy is a broad
concept, and reviews and meta-analyses have often focused
on different combinations of psychotherapy for treating
depression without comparing one specific sole treatment
to another [21,25-30,32,34]. Furthermore, although sole
individual IPTappears to be effective, few reviews focus on
sole individual IPT in adults with MDD as a primary diag-
nosis. Often, dissimilar study populations are compared
with each other, for example adult, adolescent, and elderly
patients in one study [23,25-30,33-35]. Furthermore, several
more types of depression exist: dysthymic disorder or
depression with medical conditions, for example, but this
review will focus only on MDD. Chronic MDD and post-
partum depression (PPD) will be included in this systematic
review, for the following reasons. First of all, treatment for
patients with chronic and non-chronic depression is equal
in terms of content and structure. Therefore, the treat-
ments of these patient groups are comparable. Secondly,
the symptoms of both kinds of depression are comparable
in terms of severity and content, which makes the patients
comparable. Furthermore, women with PPD experience the
same kind of symptoms as patients with MDD.
Since comorbidity is very common in patients suffering
from depression, and this possibly increases the severity of
the depression [36-44], this review will focus on MDD as a
primary diagnosis with possible comorbidity.
Other factors influencing the results of previously
executed systematic reviews include different age groups, in
which form the provided IPT is administered, distinct
settings, and the time periods during which the studies
were executed. IPT is often adjusted for applicability to
elderly  or adolescent  depressed patients, or in the
form of group IPT . Therefore, these kinds of treat-
ments may be hard to compare with each other. That is
why this review focuses on individual IPT. From here on,
when IPT is described in the review, individual IPT is
meant, unless described otherwise. Furthermore, the setting
in which treatment takes place suggests the depression’s
level of severity. It is assumed that inpatients have a more
severe depression, which is harder to treat. In addition,
inpatient care is often multidisciplinary, which makes it
difficult to examine the effects of separate therapies.
Research has been conducted on IPT since the 70s, which
is why the date limit for this review is set on 1970. This
review will give an overview of studies published between
January 1970 and August 2012, with a focus on sole IPT
administered to adults. Since some therapies have an effect
relatively quickly, we did not apply a minimum for duration
of a therapy.
With all of the above in mind, the aim of this study is to
give an overview of recent literature describing the effect-
iveness and efficacy of sole individual IPT in comparison
with standardized forms of treatment for treating patients
with MDD as a primary diagnosis. The following research
question has been formulated: Is individual interpersonal
psychotherapy more preferable in comparison with other
standardized forms of treatment for treating adult outpati-
ents with a primary diagnosis of major depressive disorder?
In order to answer this question, a systematic review will
be performed on RCTs and C-RCTs comparing the effect-
iveness (the outcome of a new treatment compared to
other kinds of treatment(s), usually in a clinical setting) or
efficacy (the outcome of treatments in homogeneous
patient groups, usually in an experimental setting)  of
individual sole IPT with other standardized forms of treat-
ment, for treating adult outpatients with MDD as a primary
This paragraph will outline which steps were taken in
order to perform this systematic review. An overview of
the methods used for data collection, study selection,
and data analysis will be provided.
RCTs about IPT for depression were collected by searching
PubMed and PsycINFO for studies published between
January 1970 and August 2012. The following medical sub-
ject heading (MeSH) categories and keywords were used:
disorder, dysthymic disorder, interpersonal psychotherapy,
treatment outcome, clinical trials. The exact search terms
and MeSH headings can be found in the additional files
(Additional file 1 – Search strategy). All titles and abstracts
were screened, and only studies which met the review
inclusion criteria (see next paragraph and Table 1) were
selected for further review. Citation tracking and snowbal-
ling techniques added studies to the second screening
phase, in which selected studies were screened for eligibility
using a predefined checklist (see Data analysis) (Additional
file 2 – Checklist).
Only studies with sufficient methodological quality meeting
the inclusion criteria were selected for this review. The
van Hees et al. BMC Psychiatry 2013, 13:22
Page 2 of 10
criteria for selection will be described shortly. An overview
of the inclusion and exclusion criteria is provided in
Studies were included if they were randomized or
cluster-randomized evaluations (RCTs or C-RCTs) pub-
lished in English after January 1st, 1970, and took place in
western jurisdictions, to ensure high internal validity.
These studies had to focus on MDD (non-chronic or
chronic) as a primary diagnosis in adults (18–65 years
old). The diagnosis must have been reached using a formal
classification system, such as the Diagnostic and Statistical
Manual of Mental Disorders (DSM) , the International
Classification of Diseases (ICD) , or the Research
Diagnostic Criteria . Bipolar disorders as primary
diagnoses were excluded, as well as cases where the
patients were elderly people or adolescents, or in cases
in which physical conditions might contribute to the
(severity of) depressive symptoms. The proposed inter-
vention must have been individual sole IPT, in comparison
with other psychotherapies, pharmacotherapy, or com-
bined treatment. Group IPTand other kinds of treatments
were excluded. Studies executed in ambulant care or
primary care were included, whereas inpatient care
patients were excluded.
By making the inclusion criteria very strict, a more homo-
geneous group, with a narrower scope, was created, which
made it possible to focus on clinical applicability of the
treatments for these kinds of patients.
Before the data were analyzed for this review, the methodo-
logical quality of the studies included after screening has
been assessed, using a predefined checklist (Additional file
2 – Checklist). This checklist was composed of Delphi-list
questions  and questions assessing the risk of bias in
effect evaluation studies . General questions were
composed for collecting relevant information about the
study, after which the resulting information was entered in
a Microsoft Excel table for a clear overview. This overview
was used to create a table of evidence of the extracted study
data, and to summarize the most important findings. MH
performed the analysis and consulted TR in case of doubt.
In this case, the analyses were double checked and consen-
sus was reached.
The literature search resulted in 3981 studies, of which
3911 were excluded from further review for several reasons,
documented below. Figure 1 shows the flow diagram of
included and excluded studies. Studies were excluded when
they did not meet the inclusion criteria, based on the title
and abstract: i.e. they did not focus on MDD as a primary
diagnosis, on individual sole IPT, or the target group was
anything other than adults. Another 62 were excluded after
reading the full text, leaving 8 articles eligible for this
These 62 full-text articles were excluded for the follow-
ing reasons: being reviews or meta-analyses [21-23,25-
30,32,34,53-60], being a protocol for a study , being a
study based on earlier/other studies [43,45,62-76], there
was no comparison in the study , MDD was not the
primary diagnosis [78-82], the study had the wrong aim
for this review [83-86], there was no research data [87-91],
or one of the interventions was not IPT as described in
the eligibility criteria [35,92-100]. See Additional file 3 –
List of excluded studies for a detailed description of the
reasons for exclusion.
Description of the studies
The main characteristics of the RCT studies included are
summarized in Table 2. One study was carried out in the
Netherlands , one in New Zealand , one in
Table 1 Summary of inclusion and exclusion criteria
Inclusion criteriaExclusion criteria
Type of study
Randomized controlled trial
English languageOther languages
Adults (18–65) Elderly people or adolescents
Major depressive disorder as a primary diagnosisBipolar disorder
Individual sole IPTGroup IPT
IPT combined with other therapy
Other evidence-based psychotherapies, combined treatment,
Alternative therapy, bibliotherapy, complementary therapy,
counseling, psychoeducation, supportive therapy
Outpatient ambulant care, primary careInpatient care
Western jurisdictionsOutside of Western jurisdictions
IPT Interpersonal Psychotherapy.
van Hees et al. BMC Psychiatry 2013, 13:22
Page 3 of 10
Canada , one in the UK , one in Germany ,
and three in the USA [106-108]. All studies clearly
described eligibility criteria and success-of-treatment point.
All but two [103,104] included an intention-to-treat ana-
lysis. Seven studies reported comparable sociodemographic
and psychiatric variables at baseline. One  did not re-
port these variables.
A total of 1233 patients were included in the review,
of whom 854 completed treatment in outpatient facil-
ities. Of the patients included, 392 received IPT, 14
received CBASP (Cognitive Behavioral Analysis System
of Psychotherapy), 160 received CBT, 153 received
pharmacotherapy (nefazodone, nortriptyline hydrochlor-
ide, or venlafaxine hydrochloride), 67 received pharma-
cotherapy plus clinical management, 49 received IPT
and nefazodone, 47 received IPT and a placebo, 34
received a placebo plus clinical management, 92 received
usual care consisting of communication with a physician
for appropriate treatment, and 51 were put on a wait list.
The mean age in seven studies [101,102,104-106] ranged
from 29.4 to 40.2 years old, and the percentage of female
patients varied from 55% to 83%, except for one study,
in which only females participated . One study did
not report these data . All patients were diagnosed
with non-psychotic MDD as a primary diagnosis
according to the DSM-III-R , DSM-IV , or the
Research Diagnostic Criteria .
IPT in all studies was based on a standardized manual
[14,17], as was CBASP  and CBT [12,112,113]. The
number of IPT and CBT sessions varied from 8 to 24 in
a 12- or 16-week period, and most of the sessions were
held weekly. Physicians administering nefazodone or
nortriptyline were instructed to follow a manual.
Patients receiving nefazodone started at 100 mg capsules
per day, and doses were gradually increased to a mini-
mum of 400 mg, with a maximum of 600 mg .
Patients receiving nortriptyline started at 25 mg per day,
aiming for blood levels of 190–570 nmol/liter .
Patients receiving imipramine hydrochloride had a
dosage between 150 and 185 mg. Pharmacotherapists
administering venlafaxine followed an evidence-based
protocol of 37.5 mg twice-daily doses . Pharmaco-
therapy plus clinical management was administered by
a psychiatrist who followed the client for the duration
of the protocol associated with the antidepressant medi-
cation , or as long as the clinical management
would be administered .
Risk of bias
Risk of bias was measured and summarized (see Figure 2)
according to the standards of the Cochrane Collaboration
. Although this was not always described exhaustively,
all studies used randomization and seemed to present
complete outcome data. Therefore, all included studies had
a low risk of selection bias and attrition bias. Nevertheless,
two studies [103,107] had an unclear risk of detection bias
and one of them  had a high risk of reporting bias.
Another study  had a high risk of detection bias. Not-
withstanding these higher levels of bias, these studies have
been included in this review.
Findings on outcome measurements
The outcome of the HAMD showed an overall decrease in
the level of depression over time (p<0.001) between the
four treatment conditions (IPT, nefazodone, IPT and nefa-
zodone, IPT and placebo), but this was not statistically sig-
nificant. A significant difference was found between IPT
and nefazodone and the use of nefazodone without IPT in
favor of the first (for the intent to treat sample: adjusted
OR (95% CI)=3.22 (1.02-10.12), p=0.045). Furthermore, a
significant difference was found in the MADRS scores.
Patients receiving IPT with nefazodone improved more
than did patients receiving nefazodone without IPT. Fur-
thermore, the nefazodone condition showed only a small
improvement after the first six weeks .
management (CM) was significantly superior to placebo
with CM on general level of functioning. Patients receiving
IPT or imipramine hydrochloride with CM appeared to
Figure 1 Flow diagram of included and excluded articles;
reasons in Additional file 3.
van Hees et al. BMC Psychiatry 2013, 13:22
Page 4 of 10
have a better outcome on the HRSD than patients receiving
placebo with CM (p=0.018 and p=0.017). Furthermore,
these patients showed a significantly higher percentage in
the recovery analysis compared to placebo with CM
patients, measured by a score of six or lower on the HRSD
(p=0.010 and p=0.013) .
In the Luty et al. study , depressive symptoms
improved for about 55%. No statistically significant differ-
ences were found between IPT and CBT on the primary
outcome measure MADRS (9.5% mean difference (95%
CI), p=0.059), nor after controlling for baseline severity
HRSD scores were significantly higher in the IPT con-
dition compared to the PHT-CM condition (t(96)=−2.46,
p<0.05, d=−0.50). No significant differences were found
between IPT and CBT conditions (t(96)=−1.19, p=0.46,
d=−0.24), or between CBT and PHT-CM conditions
(t(96)=−1.35, p=0.37, d=−0.28) .
Depressive symptoms, measured by the HAMD and
BDI, improved significantly (p<0.001) in the first six
weeks for patients receiving IPT or venlafaxine .
Although the venlafaxine group showed a slightly better
outcome than the IPT group, no significant differences
were found after six weeks.
Table 2 Summary of the characteristics of the includes studies
Study N included N completed
pre- and post-
Blom et al.
193132Adults with MDD IPT vs.Nefazodone vs.IPT
16 HAMD 12 weeks
Elkin et al.
250 155Adults with MDD IPT vs. CBT vs. IMI-CM vs.
Luty et al.
177159Adults with MDDIPT vs.CBT16 MADRS16 weeks
159102Adults with MDDIPT vs.CBT vs.PHT-CM16HRSD16 weeks
2828Adults with MDDIPT vs.Venlafaxine16HAMD 6 weeks
120 99Women with PPDIPT vs. WLC12 HRSD12 weeks
3029Adults with early
IPT vs.CBASP 16 with
276150Adults with MDDIPT vs.Nortriptyline vs.
CBASP Cognitive Behavioral Analysis System of Psychotherapy; CBT Cognitive Behavior Therapy; HAMD Hamilton Depression Rating Scale; HRSD Hamilton Rating
Scale Depression; IMI-CM imipramine plus clinical management; IPT Interpersonal Psychotherapy; MADRS Montgomery-Åsberg Depression Rating Scale; MDD Major
Depressive Disorder; PHT-CM pharmacotherapy plus clinical management; PLA-CM placebo plus clinical management; WLC wait list condition.
Figure 2 Summary of risk of bias in six studies.
van Hees et al. BMC Psychiatry 2013, 13:22
Page 5 of 10
O’Hara described recovery rates for women with PPD
based on HRSD scores and BDI scores, favoring IPT over
wait list condition (WLC). Based on HRSD scores
(HRSD ≤6), IPT had a recovery rate of 31.7%, compared to
15% of WLC (p=0.03). Based on BDI scores (BDI ≤9), IPT
had a recovery rate of 38.3%, while women in the WLC
group showed a recovery rate of 18.3% (p=0.02) .
In both the IPT and CBASP group , HRSD scores
decreased after 16 weeks, but only in the CBASP group
p=0.004). BDI scores were significantly lower after
16 weeks in both groups (IPT: t(14)=2.34, p=0.034;
CBASP: t(13)=5.01, p<0.001). HRSD scores did not show a
significant difference between the groups, whereas BDI
scores showed a significantly higher reduction in depressive
symptoms in the CBASP group after 16 weeks (mean BDI
score of 10.79 vs. 21.27 in IPT; F(1,26)=4.34, p=0.047, treat-
ment effect size: Cohen’s d=0.87).
Eight months after the start of the treatments (IPT,
nortriptyline, or usual care), all HRSD scores improved
significantly (χ2=816.14, df=6, p<0.001), and a significant
difference was found between the groups (χ2=14.92,
df=2, p=0.001). Post-hoc group t-test comparisons
showed significant differences (p<0.01) in HRSD scores
between nortriptyline and usual care, at most measure-
ment times favoring nortriptyline, and between IPT and
usual care, favoring IPT after eight months. No signifi-
cant difference was found between IPT and nortriptyline
at any moment in time .
Meta-analysis and summary of findings
As can be seen in Table 2, heterogeneity between the
studies exists, which made it difficult to make meta-
analytic comparisons. However, three studies were com-
parable in terms of measuring the effects of IPT and
CBT [102,103,107]. The mean difference between the
treatments was 1.01 (95% CI: -0.34, 2.37) favoring CBT
over IPT, but did not reach a statistically significant
level. See Figure 3 for more detailed information.
Although no further meta-analyses were possible, and
results appeared to be inconsistent, some conclusions
can be drawn from these studies. IPT combined with
nefazodone improved MADRS scores significantly better
than did nefazodone alone . Furthermore, higher
HRSD scores were found in IPT patients in comparison
with PHT-CM patients . IPT patients showed a sig-
nificantly greater decrease of HRSD and BDI scores than
WLC patients . As measured with the BDI, depres-
sive symptoms were reduced more in CBASP patients in
comparison with IPT patients . Finally, IPT patients
produced lower HRSD scores in comparison with
patients receiving usual care .
The results of this systematic review show inconsistent
findings in the eight heterogeneous studies included.
The effectiveness and efficacy of the several treatments
is comparable in most studies, and some conclusions
may be drawn. Overall, the efficacy of IPT and CBT
appears to be equal . Contradictory results were
found in IPT in comparison with pharmacotherapy. IPT
combined with nefazodone appears to have a higher effi-
cacy than sole nefazodone , while pharmacotherapy
combined with clinical management appears to have a
higher efficacy than IPT alone . However, another
study showed comparable results between IPT and im-
ipramine hydrochloride with clinical management (CM),
which both returned a better outcome on the HRSD
compared to placebo with CM . Furthermore, ven-
lafaxine seems to reduce depressive symptoms more
than IPT after six weeks, although this outcome was not
significant . The effects of using sole IPT and sole
nortriptyline do not significantly differ from each other
. IPT and CBASP appear to be very comparable in
efficacy, although scores of the BDI showed a slight pre-
ference for CBASP . Finally, IPT appears to be
more effective than wait list condition , and usual
care after eight months, as does nortriptyline .
These outcomes suggest that several kinds of treat-
ments are effective or efficacious for depressed patients,
although one has to keep in mind the small number of
Figure 3 Comparison of HRSD scores between IPT and CBT. CBT Cognitive Behavior Therapy; IPT Interpersonal Psychotherapy; SD Standard
van Hees et al. BMC Psychiatry 2013, 13:22
Page 6 of 10
included studies. Patients are recommended to choose a
treatment which fits their personal preferences, since
this may affect the outcome of the treatment. Policy
makers are advised to base regulations on the effective-
ness and efficacy of treatments in general, instead of a
slightly different effect between one treatment and the
other, since these studies do not take individual differ-
ences and preferences into account.
This review has a number of limitations. First, this
review included only adult outpatients with unipolar,
non-psychotic major depression as a primary diagnosis.
Although these inclusion criteria were a deliberate choice,
this review has consequences for the generalizability. These
results are not generalizable to children, adolescents, or the
elderly, to patients with other kinds of depression, or to
patients suffering from a combination of depression and
medical conditions, or from depression and substance
abuse. Furthermore, no distinction has been made in the
severity of depression, which causes a higher heterogeneity
in the complete sample, making results more uncertain.
Second, only eight studies with a limited number of parti-
cipants were included in this review. Although most studies
showed a low risk of bias, the small size of the sample may
increase this risk. Furthermore, results are harder to
generalize with a small number of participants, especially
because many different kinds of treatments have been com-
pared with each other (high heterogeneity), which limited
the number of participants in the groups not receiving IPT.
Moreover, the limited number of included studies in this
review, makes one question the applicability of the
Cochrane guidelines for conducting a systematic review
, for clinical treatments in mental health care.
Third, all included patients were outpatients and there-
fore had to be willing and motivated to participate in the
selected studies. This may cause some bias, since not all
types of patients could be included in the studies. For
example, treatment-resistant depressed patients may have
been less motivated than patients who were not treatment-
resistant, and it may not be possible to generalize results
for these patients.
Fourth, pharmacotherapy consisted of different types of
antidepressant medication. Although these medications
may seem to be equally effective, some differences may
exist, which may interfere with the results of this review.
Furthermore, one study  used nefazodone as pharma-
cotherapy, although this medication has been withdrawn
in, amongst other countries, the USA and the Netherlands,
because of hepatotoxicity associated with this drug .
Fifth, some of the findings were based on the scores of
the HRSD [101,103-108]. However, this scale has re-
cently been criticized for having multiple problems, in-
cluding among others the existence of different versions
and not being as sensitive as other scales [115,116].
Despite these flaws, the HRSD has been used in many
studies and the outcomes of this scale can therefore not
be excluded from this review. Furthermore, findings were
also based on the MADRS [101,102], which is more sensi-
tive to treatment effect than the HAMD , and on the
BDI [104,105] which correlates weakly with the HDRS
 and has several advantages and disadvantages ,
but is widely used.
Sixth, one study  measured the efficacy only after six
weeks, without follow-up measurement. This is a very short
period for measuring the efficacy of IPT. Therefore, the
results of this study may be questionable. Furthermore,
these authors did not include an intention-to-treat analysis,
which increases the risk of bias.
Finally, although a profound search has been performed,
there is no complete certainty that all studies eligible for
this review have been found. Furthermore, the search was
directed only at published studies, automatically excluding
unpublished data, causing possible publication bias.
It can be concluded that the differences between the
effects and efficacy of several types of treatment are very
small and they are often not significant. This in turn is
consistent with a study concluding that the effects of
psychotherapy for adult depression in meta-analyses are
overestimated . Nevertheless, usual care, as described
in the study of Schulberg et al. , appears to be inef-
fective and is not recommended as a treatment for MDD.
Therefore, psychotherapeutic treatments such as IPT and
CBT, and/or pharmacotherapy are recommended as first-
line treatments for depressed adult outpatients. This
conclusion is consistent with a previous study , and
review , and previous meta-analyses [28,29,32,33,55],
although, as has been stated in the introduction, these
studies had several limitations as well. Furthermore, it is
recommended that the type of treatment is adjusted to the
individual preferences of the patient.
Future research should focus on a larger sample includ-
ing patients with MDD, while correcting for severity of de-
pression. Since many studies focused on IPT combined
with medication, it is recommended that these studies be
included in future research as well. Furthermore, it is
recommended that future studies included in a review,
have longer follow-up periods. All studies should aim for
the highest quality standards currently set.
Additional file 1: Search strategy.
Additional file 2: Checklist.
Additional file 3: List of excluded studies.
van Hees et al. BMC Psychiatry 2013, 13:22
Page 7 of 10
The authors declare that they have no competing interests.
MH designed the study with the support of SE and TR. MH undertook the
literature search with help from TE, identified potential and final selected
articles, interpreted results, drafted and revised all versions of the manuscript,
supported by SE and TR. In case of doubt during the screening and
analyzing phase, TR was consulted. SE and TR supervised the development
of the manuscript. All authors read and approved the final version.
This study was not funded by any grants. We thank Tim Ellermann and
Henrietta Hazen for help during the development of an adequate search
strategy. MH also thanks SE and TR for their support.
1Caphri, School of Public Health and Primary Care; Faculty of Health,
Medicine, and Life Sciences, Maastricht University, Maastricht, the
Netherlands.2College of Pharmacy and Nutrition, University of Saskatchewan,
Saskoon, Canada.3Institute for Public Health and Nursing Research (IPP),
University of Bremen, Bremen, Germany.4Caphri, School of Public Health and
Primary Care; Department of Health Services Research, Maastricht University,
Maastricht, the Netherlands.
Received: 9 December 2011 Accepted: 7 January 2013
Published: 11 January 2013
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Cite this article as: van Hees et al.: The effectiveness of individual
interpersonal psychotherapy as a treatment for major depressive
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