Interpersonal and Social Rhythm Therapy: Managing
                     the Chaos of Bipolar Disorder
                     Ellen Frank, Holly A. Swartz, and David J. Kupfer
                     Interpersonal and social rhythm therapy is an individual                               patients with bipolar disorder recover fully from mania or
                     psychotherapy designed specifically for the treatment for                              depression, remain asymptomatic between episodes, and
                     bipolar disorder. Interpersonal and social rhythm therapy                              experience no decline in functional status over time.
                     grew from a chronobiological model of bipolar disorder                                 Psychotherapy for bipolar disorder was considered super-
                     postulating that individuals with bipolar disorder have a                              fluous and was largely neglected as a treatment strategy
                     genetic predisposition to circadian rhythm and sleep–                                  for many years (Benson 1975). Beginning in the 1980s,
                     wakecycle abnormalities that may be responsible, in part,                              however, reports appeared in the literature suggesting that
                     for the symptomatic manifestations of the illness. In our                              outcomeswithlithium alone were suboptimal. Cumulative
                     model, life events (both negative and positive) may cause                              data suggest that pharmacotherapy alone fails to prevent
                     disruptions in patients’ social rhythms that, in turn,                                 recurrence in 50 to 70% of patients over a 2- to 3-year
                     perturb circadian rhythms and sleep–wake cycles and lead
                     to the development of bipolar symptoms. Administered in                                period (Markar and Mander 1989; Prien et al 1984) and
                     concert with medications, interpersonal and social rhythm                              that overall functioning of bipolar patients remains low
                     therapy combines the basic principles of interpersonal                                 even after the resolution of fully syndromal episodes
                     psychotherapy with behavioral techniques to help patients                              (Coryell et al 1993; Goldberg et al 1995). Researchers and
                     regularize their daily routines, diminish interpersonal                                clinicians became increasingly cognizant that the chronic
                     problems, and adhere to medication regimens. It modu-                                  course of bipolar disorder may, in the absence of appro-
                     lates both biological and psychosocial factors to mitigate                             priate interventions, lead to unremitting symptoms and a
                     patients’ circadian and sleep–wake cycle vulnerabilities,                              downward psychosocial spiral.
                     improve overall functioning, and better manage the po-
                     tential chaos of bipolar disorder symptomatology.                          Biol        A Disorderly Disorder
                     Psychiatry 2000;48:593–604 © 2000 Society of Biologi-                                  As depicted in Figure 1, the course of recurrent unipolar
                     cal Psychiatry                                                                         disorder, although often debilitating, is unidirectional and
                     Key Words: Psychotherapy, bipolar disorder, mood dis-                                  relatively easy to describe: patients become depressed,
                     orders,      circadian      rhythms, life events, interpersonal                        recover, have a period of remission, and then may or may
                     psychotherapy                                                                          not become depressed again at some point in the future
                                                                                                            (Kupfer 1991). Although a small percentage of the popu-
                                                                                                            lation experiences refractory depression, most patients, in
                     Introduction                                                                           the absence of significant comorbidity, eventually respond
                            uring the second half of the 20th century, new                                  to treatment and achieve a euthymic state. By contrast, the
                     Dtreatments for bipolar disorder focused primarily on                                  course of bipolar disorder is typically hectic and variable.
                     somatic therapies. The discovery of lithium carbonate as a                             A“roller coaster” for both patients and clinicians, extreme
                     treatment for “psychotic excitement” by Cade in 1949                                   highs and lows intermingle with mixed states and subsyn-
                     (Cade 1949) and advances in research supporting the                                    dromal symptom flurries to create hybrid symptom states
                     heritability of bipolar disorder led investigators to concep-                          that defy easy labels. As depicted in Figure 2, hypomania
                     tualize bipolar disorder as a purely biological process                                can surge into a fully syndromal mania and then plummet
                     amenable to pharmacotherapy alone. Furthermore, clinical                               into a debilitating major depression. A fall from mania can
                     lore mistakenly led practitioners to believe that most                                 lead to endless months of major depression, with brief
                                                                                                            excursions into minor depression providing only relative
                                                                                                            relief from unrelenting dysphoria, anergia, and hypersom-
                     From the Department of Psychiatry, University of Pittsburgh, Western Psychiatric       nia. Treatments for those intolerable depressions may send
                          Institute and Clinic, Pittsburgh, Pennsylvania.                                   a patient’s mood back into the manic range, only to plunge
                     Address reprint request to Ellen Frank, Ph.D., University of Pittsburgh Medical
                          Center, Western Psychiatric Institute and Clinic, 3811 O’Hara Street, Pitts-      back down into depression. Although we distinguish
                          burgh PA 15213-2593.
                     Received March 3, 2000; revised June 14, 2000; accepted June 22, 2000.                 between the treatment of acute symptomatology (labeled
                     ©2000 Society of Biological Psychiatry                                                                                                            0006-3223/00/$20.00
                                                                                                                                                                 PII S0006-3223(00)00969-0
                 594       BIOL PSYCHIATRY                                                                                               E. Frank et al
                           2000;48:593–604
                                                                                      biology to create three probable pathways to recurrence of
                                                                                      bipolar illness: 1) stressful life events; 2) disruptions in
                                                                                      social rhythms; and 3) medication nonadherence. As
                                                                                      envisioned by Goodwin and Jamison, these routes to
                                                                                      illness are interconnected. Their model suggests that
                                                                                      individuals with bipolar disorder are fundamentally vul-
                                                                                      nerable to disruptions in circadian rhythms. Psychosocial
                                                                                      stressors then interact with this biological vulnerability to
                                                                                      cause symptoms. For instance, stressful life events disrupt
                 Figure 1. Response, remission recovery, relapse, and recurrence:     social rhythms, which causes disturbances in circadian
                 phases of treatment in unipolar disorder. (Reproduced with           integrity, which, in turn, may lead to recurrence. Alter-
                 permission from Kupfer 1991.)                                        nately, problematic interpersonal relationships or disor-
                                                                                      dered schedules contribute to a patient’s difficulty adher-
                                                                                      ing to a medication regimen which, again, may lead to
                 Preliminary Phase in Figure 2) and prophylactic treatment            recurrence. As a direct consequence of this model, one
                 following remission (labeled Preventative Phase), we                 would assume that helping patients learn to take their
                 recognize that these distinctions are often arbitrary and            medication regularly, lead more orderly lives, and resolve
                 inaccurate. In fact, patients in a nonacute phase of treat-          interpersonal problems more effectively would promote
                 ment often experience on-going symptom fluctuations.                 circadian integrity and minimize risk of recurrence.
                 Depressive symptoms, in particular, seem especially dif-
                 ficult to eradicate completely (Hlastala et al 1997). Thus,          Treating Bipolar Disorder
                 the holy grail of sustained euthymia in bipolar disorder             As depicted in Figure 2, bipolar illness is a disorderly
                 mayremainanelusivegoalintheabsenceofsophisticated                    disorder. Characterized by erratic sleep–wake cycles and
                 treatments that address both the biological and psycholog-           dramatic symptom fluctuations, the clinical course is
                 ical aspects of this disorder.                                       unpredictable and rarely static. Needless to say, treating
                                                                                      this “moving target” creates many interesting—and some-
                 Pathways to Recurrence                                               times problematic—challenges. For instance, lithium
                 Goodwin and Jamison’s definitive textbook on bipolar                 monotherapy is still considered the “gold standard” of
                 disorder (Goodwin and Jamison 1990) acknowledges the                 pharmacotherapy for bipolar disorder. As patients move
                 important interplay between biological and psychosocial              through the various phases of the disorder, however, most
                 factors in determining the course of bipolar disorder.               psychiatrists find themselves treating patients with a range
                 Recognizing the primacy of biology, they hypothesized                of mood stabilizers in combination with neuroleptics,
                 that “the genetic defect in manic depressive illness in-             sedative-hypnotics, and antidepressants (Sachs et al 2000).
                 volves the circadian pacemaker or systems that modulate              Efforts to simplify regimens are often thwarted by unsat-
                 it” (Goodwin and Jamison 1990, 589) but then further                 isfactory treatment response, resulting in years of complex
                 postulated that psychosocial factors will interact with              polypharmacy. Vacillating symptomatology, impaired
                                                                                      psychosocial functioning, and problematic medication side
                                                                                      effects converge to create unique clinical challenges for
                                                                                      both patients and health care professionals. Considering
                                                                                      the complexities of this illness, it is not surprising that
                                                                                      pharmacotherapy alone does not address the multiple
                                                                                      needs of patients with bipolar disorder. Although there are
                                                                                      many excellent review papers discussing extant psychos-
                                                                                      ocial approaches to bipolar disorder (Colom et al 1998;
                                                                                      Johnson et al 2000; Miklowitz and Frank 1999), there are
                                                                                      surprisingly few data supporting their efficacy (Craighead
                                                                                      et al 1998; Swartz and Frank, in press). The absence of
                                                                                      well-designed, empirically tested psychotherapies in the
                                                                                      literature led us to develop and test a model of individual
                                                                                      psychotherapy that would be used in conjunction with
                 Figure 2. Response, remission, recovery, relapse, and recur-         medication to enhance functioning and diminish recur-
                 rence: phases of treatment of bipolar disorder.                      rences in patients with bipolar I disorder.
                Interpersonal and Social Rhythm Therapy                                                              BIOL PSYCHIATRY        595
                                                                                                                     2000;48:593–604
                Theoretical Context for Interpersonal and                         could trigger an episode by causing the dysregulation of
                Social Rhythm Therapy                                             biological rhythms. For instance, the loss of a spouse
                Interpersonal and social rhythm therapy (IPSRT) is a              through death or divorce results in the loss of a social
                treatment that is specifically designed for patients with         Zeitgeber that may have previously determined sleep–
                bipolar disorder. As elaborated below, the genesis of             wake times, rest periods, and meal times. In an individual
                IPSRT rests in a psycho-chronobiological theory of affec-         with the genetic predisposition to depression, the physio-
                tive illness that we articulated in a series of papers in the     logic and chronobiological disturbances produced by los-
                1980s and early 1990s (Ehlers et al 1988, 1993; Monk et           ing the social cues for sleep and meal times could be as
                al 1991, 1990). Its design was also strongly influenced by        important in the genesis of an episode as the psychologic
                the instability model of bipolar disorder proposed by             distress generated by the event.
                Goodwin and Jamison (1990) and our evolving under-                   We subsequently extended this model of mood disor-
                standing of the relationship between stressful life events        ders to include the concept of Zeitsto¨rers (time disturbers;
                and bipolar episodes.                                             Ehlers et al 1993). As defined above, social Zeitgebers are
                                                                                  persons, social demands, or tasks that set the biological
                                                                                  clock. By contrast, Zeitsto¨rers are physical, chemical, or
                Circadian Rhythms, Sleep–Wake Cycles, and Mood                    psychosocial events that disturb the biological clock. For
                Disorders                                                         instance, travel across time zones represents a prototypical
                Researchers     have identified    reciprocal   relationships     Zeitsto¨rer. The abrupt change in the timing of light
                among circadian rhythms, sleep–wake cycles and mood.              exposure, meal times, and sleep times can produce a range
                Wehr and colleagues have demonstrated that sleep reduc-           of symptoms from mild “jet lag” to a full-blown affective
                tion can lead to mania in bipolar subjects (Leibenluft et al      episode in predisposed individuals. Other examples of
                1996; Wehr et al 1987). Sleep deprivation has significant         potential Zeitsto¨rers include newborn babies, marital sep-
                (if transient) antidepressant effects in both unipolar and        arations, work deadlines (e.g., a college student who stays
                bipolar depressed subjects (Barbini et al 1998; Leibenluft        up all night to complete a term paper), and rotating shift
                et al 1993; Leibenluft and Wehr 1992), and PET studies            work. Each of these disruptions has the potential to
                havedemonstratedlocalized effects of sleep deprivation in         significantly alter an individual’s circadian and sleep–
                the medial prefrontal cortex (Wu et al 1999). The purpose         wake rhythms that we argue, in turn, could result in an
                of IPSRT is to regulate both circadian rhythms and                affective episode. In the context of our exploration of
                sleep–wake cycles. It must be noted, however, that the            social Zeitgebers and Zeitsto¨rers, our group developed an
                relationship   between bipolar disorder and circadian             instrument to quantify an individual’s social rhythms
                rhythms is less well characterized than its relationship to       (Monketal 1990). The Social Rhythm Metric (SRM) was
                sleep–wake disturbances. By targeting social factors that         designed as both a means of categorizing interindividual
                modulate these rhythms, IPSRT is presumed to alter the            differences in social rhythm regularity and as a therapeutic
                underlying neuronal circuitry involved in the pathogenesis        tool to track decline into and recovery from an affective
                of bipolar symptomatology.                                        episode. We hypothesized that a psychotherapy that helps
                   The theoretical underpinnings of IPSRT began with our          regulate social rhythms could help a vulnerable individual
                efforts to better understand the psycho-chronobiological          reduce the risk of developing mood symptoms.
                determinants of unipolar disorder. In 1988, we proposed           Stressful Life Events and Mood
                an etiologic model of major depression that focused on the
                role of disrupted social rhythms in the emergence of a            We formulated IPSRT at a time when there was a great
                depressive episode in biologically vulnerable individuals         deal of interest in the relationship between stressful life
                (Ehlers et al 1988). Noting that the established biological       events and bipolar episode onset (Ellicott et al 1990).
                correlates of affective disorder include disrupted sleep          Given the probable role of circadian rhythm disruption in
                electroencephalogram recordings (Kupfer et al 1991) and           the genesis of bipolar episodes, our research group was
                phasic changes in the circadian secretions of pituitary           particularly interested in the effects of those life events
                hormones (Carroll et al 1980), we hypothesized that               that caused a significant disruption in social rhythms.
                disruptions in the social cues that entrain these cycles may      These theories, however, had not been subject to method-
                act as triggers for mood episodes. We argued that social          ologically rigorous testing at the inception of IPSRT.
                Zeitgebers, that is, personal relationships, social demands,      Therefore, simultaneous with our early testing of IPSRT,
                or tasks that entrain biological rhythms, may serve as the        we began an on-going study to assess the relationship
                link between the biological and psychosocial processes            between life events and bipolar episode onset with a
                that place an individual at risk for developing mood              reliable and valid life stress instrument, the Bedford
                symptoms. We hypothesized that losing a social Zeitgeber          College Life Event and Difficulty Schedule (LEDS).
                596      BIOL PSYCHIATRY                                                                                     E. Frank et al
                         2000;48:593–604
                  In our research program, each life event of any severity     individuals, stressful interpersonal events may contribute
                identified by LEDS criteria was subject to an additional       to the onset of depression. It also argues that depressive
                rating devised by our group to reflect the degree to which     symptoms can interfere with an individual’s capacity to
                any given event is likely to have an acute effect on social    successfully negotiate interpersonal conflict or find con-
                routines, particularly those that might disrupt the sleep–     structive solutions to interpersonal dilemmas. Interper-
                wakecycle. The Social Rhythm Disruption (SRD) ratings,         sonal psychotherapy is a “here and now” treatment that
                like the LEDS rating, were contextually determined by          focuses on the relationship between the patient’s current
                consensus panel and guided by clearly delineated criteria      interpersonal milieu and his or her depressive symptoms.
                and a dictionary of examples. In an initial report based on    TreatmentfocusesononeoffourIPTproblemareas:grief,
                39subjects with bipolar I disorder who were assessed with      role disputes, role transitions, or interpersonal deficits.
                the LEDS/SRD protocol, we found evidence that life
                events (regardless of severity of threat) characterized by a   Integrating the Behavioral, Interpersonal, and
                high degree of social disruption were associated with the      Psychoeducational Models
                onset of manic but not depressive episodes (Malkoff-
                Schwartz et al 1998). Severely stressful life events (re-      In the context of adapting IPT for the maintenance treatment
                gardless of SRD rating) were related to the onset of both      of recurrent unipolar depression, we saw the potential utility
                manic and depressive bipolar episodes. In a follow-up          of this treatment for another highly recurrent affective illness,
                study, we interviewed bipolar subjects with purely manic       bipolar disorder. We established that patients with recurrent
                (n 5 21), purely depressed (n 5 21), and mixed or cycling      unipolar disorder could recover from depression with an
                (n 5 24) episodes and compared this bipolar sample with        acute course of IPT and then decrease the risk of having
                44 patients with recurrent unipolar depression (Malkoff-       another episode by receiving monthly sessions of mainte-
                Schwartz et al 2000). We again found that life events          nance IPT (Frank et al 1990). We began to conceptualize a
                associated with a high degree of social disruption occur-      similar kind of maintenance treatment for bipolar I disorder;
                ring in the 8 weeks before the onset of an episode were        however, given extant theories about the relationship be-
                more frequently associated with the onset of manic epi-        tweencircadianrhythmsandbipolarepisodesandsubsequent
                sodes relative to bipolar cycling, bipolar depressed, or       data linking SRD events to mania (Malkoff-Schwartz et al
                unipolar depressive episodes. Severely life-threatening        1998, 2000), we decided to augment IPT with behavioral
                events were more frequently associated with the onset of       strategies designed to stabilize daily routines. We borrowed
                manic episodes relative to bipolar cycling episodes. We        traditional cognitive-behavioral techniques such as self-mon-
                conclude that SRD and severe events are associated with        itoring, realistic goal-setting, and graded task assignment to
                manic episode onsets in a manner distinct from the             help patients follow more consistent patterns of eating,
                association between SRD and severe events in bipolar           sleeping, and social stimulation.
                depressed, bipolar cycling, and unipolar depressed onsets.        Weexpected IPT to contribute a specific antidepressant
                                                                               effect and hypothesized that helping patients stabilize their
                Origins of Interpersonal and Social Rhythm                     social rhythms would decrease the risk of new affective
                Therapy                                                        (especially manic) episodes. Nonetheless, we were aware
                                                                               that there is tremendous overlap between interpersonal
                Interpersonal Psychotherapy of Depression                      stress and social rhythm disruption: a disturbance in the
                Interpersonal psychotherapy (IPT) is a time-limited, fo-       social milieu (such as a new job or conflict with a spouse)
                cused psychotherapy developed in the 1970s by Klerman,         often acts as a Zeitsto¨rer which, in turn, can lead to
                Weissman, and colleagues for the treatment of unipolar         changes in daily routines. We therefore envisioned IPSRT
                depression (Klerman et al 1984). Unlike many other             as a truly integrated therapy that would allow these
                psychotherapies, IPT is designed to treat a specific disor-    strategies to function synergistically. Thus, we expected
                der (depression) and has been systematically evaluated in      that the IPT-induced resolution of interpersonal conflict
                several randomized, controlled research trials. IPT was        would also contribute to more stable rhythms and more
                envisioned as an acute (12–16 weeks) treatment for             stable daily routines would promote more stable life
                depression but has also been tested in an 8-month contin-      circumstances (jobs, relationships, etc.).
                uation study (Klerman et al 1974) and as a long-term              The third component of IPSRT is psychoeducation.
                maintenance strategy for patients with recurrent depres-       Recalling that the Goodwin and Jamison model (Goodwin
                sion (Frank et al 1990). The basis of IPT is the premise       and Jamison 1990) predicts three probable pathways to
                that depression occurs in a psychosocial and interpersonal     recurrence in bipolar disorder, including medication non-
                context. Akin to the social Zeitgeber hypothesis, the          adherence, a cogent psychotherapy for bipolar disorder
                philosophy of IPT posits that in biologically vulnerable       also necessarily addresses medical issues such as side