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412 The APA Publishing Textbook of Mood Disorders, Second Edition
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as effective as tricyclic ADMs in alleviating MDD among outpatients. CBT compared
favorably to ADMs when study physicians were free to prescribe the ADM of their
choice (and free to switch medications during the treatment trial), provided that they
prescribed at or above the established therapeutic dosages (Blackburn and Moore
1997). Additionally, CBT was as effective as the monoamine oxidase inhibitor
phenelzine and was more effective than pill placebo in the treatment of atypical de
pression (Jarrett et al. 1999).
As noted earlier, the American Psychiatric Association published guidelines in
1993 (revised in 2010) stating that psychosocial interventions are not as appropriate as
antidepressants for severely depressed individuals. At the time of that publication,
CBT had not yet been compared with selective serotonin reuptake inhibitor (SSRI)
ADMs. Additionally, unlike trials of ADMs, most studies demonstrating that CBT was
an efficacious treatment for depression had not included pill-placebo control groups.
Thus, considerable questions remained as to whether CBT could be considered
equally as efficacious as ADMs with the same types of depressed subjects; moreover,
one could not draw definitive conclusions about the relative efficacy of CBT compared
with pill placebo (Klein 1996). As a result, various investigators in the early part of this
century undertook studies with more severely depressed patients and compared CBT
with SSRIs in pill-placebo controlled studies.
DeRubeis and colleagues (DeRubeis et al. 2005; Hollon et al. 2005) conducted perhaps the most illustrative and appropriately controlled acute treatment study that also
included a long-term follow-up. They conducted an RCT (N=240 depressed patients)
comparing CBT, paroxetine, and pill placebo. The paroxetine treatment arm included
a flexible dosing strategy reflective of clinical practice with ADMs—that is, dosages
could be increased up to 50 mg/day; patients who were unresponsive at 50 mg/day
could have their treatment augmented with lithium or desipramine; and in cases in
which paroxetine was intolerable, a switch could be made to another SSRI. For ethical
reasons, the study was designed so that after 8 weeks of treatment, the “double blind”
was broken and the pill-placebo condition was terminated. Data analyses conducted
at that time showed that paroxetine was superior to pill placebo. Active treatments
with paroxetine or CBT were continued for a total of 16 weeks. At the end of the 16week acute treatment phase, participants who had responded to either treatment were
continued in active treatment for 1 year. During the 1-year follow-up, one-half (ran
domly selected) of the paroxetine patients had their medication tapered to pill placebo, and the other half continued to receive the medication to which they had been
responsive. CBT patients received three booster sessions, at least 1 month apart,
during the 1-year follow up period. At the 1-year follow-up, all patients were terminated from treatment and followed naturalistically for an additional year.
The primary acute treatment finding was that ADMs and the CBT treatments were
equally efficacious, with a categorical response rate of 58% for both treatments and re
mission rates of 46% for the ADM and 40% for CBT. The authors concluded, “It appears that cognitive therapy can be as effective as medications, even among more
severely depressed outpatients, at least when provided by experienced cognitive
therapists” (DeRubeis et al. 2005, p. 415). In the long-term follow-up phase of this
study, CBT conferred greater maintenance of treatment gains among those who had
responded to acute treatment (Hollon et al. 2005). Specifically, the relapse rate for the
CBT condition was significantly lower than that of the patients who were successfully
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treated with ADM but then had the medication withdrawn at the end of 16 weeks
(30.8% vs. 76.2% relapse), and CBT was as effective (30.8% relapse) as ADM for those
who continued the ADM for a full year (47.2% relapse). This latter finding is particu
larly relevant for translating these results to real-world settings, because the typical
period for which ADMs are prescribed is up to 1 year, but the average length of time
that outpatients take prescribed ADMs is less than 16 weeks (Hirschfeld et al. 1997;
Katon and Schulberg 1992; Keller et al. 1986). Moreover, fewer than 10% of outpatients with MDD complete an adequate course of ADM treatment (Venturini et al.
1999). Taken together, the findings reported by DeRubeis and Hollon and their col
leagues suggest that CBT is at least as effective as an SSRI for moderate and severe
depression, and that 16 weeks of treatment with CBT provides a sustained treatment
effect for longer periods of time than does an ADM.
Comprehensive reviews of the relevant treatment literatures (David et al. 2018;
DeRubeis et al. 2008) corroborate the conclusions reached in the preceding studies.
Comparable effect sizes were reported for CBT and citalopram in the Sequenced
Treatment Alternatives to Relieve Depression (STAR*D) study, the largest trial of
antidepressants conducted to date (Trivedi et al. 2006). A series of meta-analyses have
reached the same conclusions as the general clinical reviews; namely, both CBT and
ADMs (most recently SSRIs) are equally effective for moderate and severe depression
(see, e.g., Bortolotti et al. 2008; Cuijpers et al. 2016; Driessen et al. 2010). Finally, liter
ature reviews and meta-analyses have reported that 1) the combination of CBT and
ADMs is more effective than either monotherapy alone, but this may hold true only
for severely depressed patients (Hollon et al. 2016); and 2) CBT and ADM combination
treatment does not decrease the sustainable maintenance effects conferred by CBT for
depression (e.g., W.E. Craighead and Dunlop 2014; Cuijpers et al. 2016). It should be
noted, however, that all the reviewed treatment studies excluded inpatients and imminently suicidal outpatients.
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Summary
Approximately 30%–35% of MDD patients who complete a course of CBT are largely
asymptomatic and are considered “remitted.” Another 30%–35% of CBT-treated pa
tients have a 50% reduction in depressive symptoms and their symptoms no longer
meet full criteria for MDD at posttreatment; these patients are typically referred to as
“responders.” Furthermore, among the studies reported herein, CBT appeared to
confer some enduring prophylactic effects, with only 20%–30% of those successfully
treated experiencing a relapse or recurrence during the first year following treatment.
Indeed, 16 weeks (16–20 sessions) of CBT have consistently produced a 1-year followup success rate equal to that achieved by a full year of ADM treatment (Kennedy et
al. 2018). Furthermore, CBT’s maintenance effects are superior to short-term (16
week) ADM treatment (Cuijpers et al. 2016; Zhang et al. 2018).
Future Directions
Recent research has moved from comparisons of the relative effectiveness of CBT and
other treatments to seeking knowledge regarding the moderators and mediators of
treatments for MDD. Newer studies, consequently, focus on the identification of the
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mechanisms of treatment effectiveness, and they offer potential information regarding personalizing treatment. A particularly promising avenue of research has investigated the differential and overlapping neural pathways and connectivity among
depressed patients who respond to CBT in comparison to those who respond to
ADMs. Recent findings indicate that connectivity levels in at least one neural circuit
may moderate differential outcomes when treating depressed patients with CBT versus ADMs (escitalopram or duloxetine) (Dunlop et al. 2017). These data also indicated
how psychotherapeutic and somatic interventions may be complementary and addi
tive in the alleviation of human suffering when depression is treated with the combination of CBT and ADMs. Replication of these preliminary findings may advance
knowledge of the mechanisms of clinical change. In the best-case scenario, clinicians
can eventually assess patient characteristics (e.g., biomarkers) adequately to allow de
pression treatment choices to be evidence-based rather than based simply on trial and
error. Finally, applications of machine learning and artificial intelligence (Ewbank et
al. 2019) within the scientific clinical setting are likely to further enhance the knowl
edge obtained in studies of moderators and mediators of CBT and other efficacious
treatments.
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CHAPTER 24
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Interpersonal
Psychotherapy
for Depressive Disorders
John C. Markowitz, M.D.
Mood disorders are where interpersonal psychotherapy (IPT) began. In the
1970s, the late Gerald L. Klerman, M.D., Myrna M. Weissman, Ph.D., and colleagues
were planning a randomized trial comparing pharmacotherapy and placebo for outpatients with major depressive disorder (MDD). Recognizing that many depressed
patients received psychotherapy as part of their treatment, Klerman and Weissman
decided to add psychotherapy to the study. Realizing that they had no gauge of what
constituted typical psychotherapy in the community, these researchers decided to
devise their own standardized treatment, which they hoped would not be too
removed from community practice and which rely on interpersonal theory and, more
particularly, on empirical research on interpersonal aspects of depression.
Klerman et al. (1984) developed a manual for this treatment and trained therapists
to use it. The resultant psychotherapy worked as well as tricyclic antidepressant med
ication and better than control conditions, and the combination of this psychotherapy
with pharmacotherapy had advantages over either modality alone (Klerman et al.
1974). Moreover, patients who received this interpersonally focused therapy developed new social skills over time, whereas patients who received medication alone did
not. What became known as IPT has subsequently shown efficacy for MDD in repeated randomized controlled trials (RCTs) (Cuijpers et al. 2011) and for other subtypes of mood, and increasingly for nonmood, disorders as well (Cuijpers et al. 2016;
Weissman et al. 2000). In this chapter I review basic aspects of IPT and its application
to acute and chronic unipolar mood disorders.
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History and Early Work
The history of IPT records a series of randomized clinical trials, beginning with trials
in mood disorders. For many years, IPT paradoxically was very well researched but
little practiced: it was almost purely a research intervention. Its research successes and
recommendation by treatment guidelines (e.g., American Psychiatric Association
2010; Depression Guideline Panel 1993; Karasu et al. 1993), however, led to increasing
interest and demand for training from clinicians. IPT has spread to different diagno
ses, formats, and cultures. One of the relatively few empirically validated antidepressant psychotherapies, IPT has been tested in key studies such as the National Institute
of Mental Health (NIMH) Treatment of Depression Collaborative Research Program
(Elkin et al. 1985, 1989). The IPT manual (Weissman et al. 2018) has been translated
into several languages, and this treatment has proved transportable to European,
South American, and African, Australian, and Asian settings. Originally developed as
an individual psychotherapy, IPT also shows promise in group, couples, and telether
apy formats.
Theoretical Model and Hypothesized Mechanisms
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An eclectic treatment, IPT derives from several sources. One root is the interpersonal
theory that arose in the United States after World War II. In contrast to the then-prevail
ing intrapsychically focused psychoanalytic thinking, psychiatrists such as Adolf
Meyer, Harry Stack Sullivan (1953), Erich Fromm, and Frieda Fromm-Reichmann em
phasized the status of humans as social beings and the effects of environment and current life events on psychopathology. Bowlby (1973, 1988) underscored the importance
of attachment to primary caregivers as the basis for understanding affective re
sponses to stress and to attachment in adult relationships. This theory provides a
background for understanding IPT.
Research on psychosocial aspects of mood disorders confirmed the importance of
life events as both precipitants and consequences of depression and indicated that so
cial supports protect against depressive episodes (Brown and Harris 1978). Furthermore, research has connected the onset of mood disorders with life events such as the
deaths of significant others (complicated bereavement), struggles with significant others
(role disputes), and important life changes such as geographic moves, marriage or divorce, and beginning or ending jobs (role transitions) (Klerman et al. 1984). Negative
life events are even more likely to follow the onset of depression than to precede it.
Depressed patients withdraw socially, talk less to other people, and function less well
in social and work settings. Regardless of whether a life event triggers a depressive
episode, negative life events tend to follow its onset, confirming the patient’s sense
that life is spiraling downward and out of control.
IPT was developed as a simple, practical treatment by researchers. Its structure followed the logic of extant research on interpersonal aspects of depression. Patients are
given the diagnosis of MDD according to standard diagnostic criteria (American Psychiatric Association 2013). Treatment focuses on problem areas defined as stressful
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triggers or consequences of depressive episodes: complicated bereavement following
the death of a loved one, a struggle with a significant other, a major life change, or so
cial isolation. The treatment does not demand a causal relation between mood event
and life situation—the etiology of all psychiatric syndromes remains unknown and is
surely multifaceted—but simply notes the association of the two. This connection be
tween life situation and mood is one that many depressed patients forget; they guiltily blame themselves for their illness, its symptoms, and what is going wrong in their
lives. IPT therapists encourage patients to see that by handling a situation well, they
can make life go right and thereby improve their mood.
The mechanisms that make IPT efficacious are unknown. Research on IPT has been
largely outcome research, designed to test whether the treatment works, rather than
dismantling or process research to explore why it works; hence, more is known about
appropriate target diagnoses for IPT than about its active ingredients. Nonetheless,
IPT provides several likely helpful factors:
• The IPT therapist names the illness (e.g., MDD) and explicitly reassures the patient
that what he or she is experiencing is a treatable illness and is not the patient’s
fault. This medical model gives the patient a temporary “sick role” (Parsons 1951)
and shifts blame for symptoms from the overly guilty depressed patient to the
syndrome.
• IPT helps the patient to understand connections between affects and actions in the
interpersonal arena and to put them to effective use. This is a relatively simple and
plausible central focus that even a depressed patient with concrete thinking and
poor ability to concentrate can grasp.
• IPT focuses on building interpersonal skills such as self-assertion, effective expres-
sion of anger, and social risk-taking. Many depressed patients lack these important practical skills.
• The focus on understanding and confronting current interpersonal difficulties leads
to “success experiences,” that is, victorious interpersonal encounters (Frank 1971).
These successes give the patient a greater sense of competence, agency, and con
trol over his or her environment.
• IPT therapists assign no homework. This means that patients cannot fail to com-
plete assignments, a frequent occurrence in other therapies that makes noncompliant patients feel like failures. Instead, the therapist primes the patient for encounters using role-play, then lets the time pressure of time-limited treatment
push the patient toward eventual action.
• IPT focuses outside the office rather than on the therapeutic relationship. This has
at least two positive consequences. First, therapists foster a positive therapeutic
alliance; avoiding interpretations of the therapeutic relationship minimizes the
risk of therapeutic ruptures (Safran and Muran 2000). Second, as termination approaches, patients can clearly see that they have done the hard work on, and hence
deserve the credit for, their improved daily functioning and symptomatic gains.
• Therapeutic optimism, an important aspect of the IPT therapist’s stance, is bol-
stered by research that IPT works.
• Preliminary recent research suggests that IPT may work through the repair of dys-
regulated affect and attachment (Milrod et al. 2020).
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