Interpersonal and Social Rhythm Therapy: Managingthe Chaos of Bipolar Disorder

Ellen Frank, Holly A. Swartz, and David J. Kupfer

Interpersonal and social rhythm therapy is an individualpsychotherapy designed specifically for the treatment forbipolar disorder. Interpersonal and social rhythm therapygrew from a chronobiological model of bipolar disorderpostulating that individuals with bipolar disorder have agenetic predisposition to circadian rhythm and sleep–wake cycle abnormalities that may be responsible, in part,for the symptomatic manifestations of the illness. In ourmodel, life events (both negative and positive) may causedisruptions in patients’ social rhythms that, in turn,perturb circadian rhythms and sleep–wake cycles and leadto the development of bipolar symptoms. Administered inconcert with medications, interpersonal and social rhythmtherapy combines the basic principles of interpersonalpsychotherapy with behavioral techniques to help patientsregularize their daily routines, diminish interpersonalproblems, and adhere to medication regimens. It modu-lates both biological and psychosocial factors to mitigatepatients’ circadian and sleep–wake cycle vulnerabilities,improve overall functioning, and better manage the po-tential chaos of bipolar disorder symptomatology.BiolPsychiatry 2000;48:593–604 ©2000 Society of Biologi-cal Psychiatry

Key Words: Psychotherapy, bipolar disorder, mood dis-orders, circadian rhythms, life events, interpersonalpsychotherapy

Introduction

During the second half of the 20th century, newtreatments for bipolar disorder focused primarily on

somatic therapies. The discovery of lithium carbonate as atreatment for “psychotic excitement” by Cade in 1949(Cade 1949) and advances in research supporting theheritability of bipolar disorder led investigators to concep-tualize bipolar disorder as a purely biological processamenable to pharmacotherapy alone. Furthermore, clinicallore mistakenly led practitioners to believe that most

patients with bipolar disorder recover fully from mania ordepression, remain asymptomatic between episodes, andexperience no decline in functional status over time.Psychotherapy for bipolar disorder was considered super-fluous and was largely neglected as a treatment strategyfor many years (Benson 1975). Beginning in the 1980s,however, reports appeared in the literature suggesting thatoutcomes with lithium alone were suboptimal. Cumulativedata suggest that pharmacotherapy alone fails to preventrecurrence in 50 to 70% of patients over a 2- to 3-yearperiod (Markar and Mander 1989; Prien et al 1984) andthat overall functioning of bipolar patients remains loweven after the resolution of fully syndromal episodes(Coryell et al 1993; Goldberg et al 1995). Researchers andclinicians became increasingly cognizant that the chroniccourse of bipolar disorder may, in the absence of appro-priate interventions, lead to unremitting symptoms and adownward psychosocial spiral.

A Disorderly Disorder

As depicted in Figure 1, the course of recurrent unipolardisorder, although often debilitating, is unidirectional andrelatively easy to describe: patients become depressed,recover, have a period of remission, and then may or maynot become depressed again at some point in the future(Kupfer 1991). Although a small percentage of the popu-lation experiences refractory depression, most patients, inthe absence of significant comorbidity, eventually respondto treatment and achieve a euthymic state. By contrast, thecourse of bipolar disorder is typically hectic and variable.A “roller coaster” for both patients and clinicians, extremehighs and lows intermingle with mixed states and subsyn-dromal symptom flurries to create hybrid symptom statesthat defy easy labels. As depicted in Figure 2, hypomaniacan surge into a fully syndromal mania and then plummetinto a debilitating major depression. A fall from mania canlead to endless months of major depression, with briefexcursions into minor depression providing only relativerelief from unrelenting dysphoria, anergia, and hypersom-nia. Treatments for those intolerable depressions may senda patient’s mood back into the manic range, only to plungeback down into depression. Although we distinguishbetween the treatment of acute symptomatology (labeled

From the Department of Psychiatry, University of Pittsburgh, Western PsychiatricInstitute and Clinic, Pittsburgh, Pennsylvania.

Address reprint request to Ellen Frank, Ph.D., University of Pittsburgh MedicalCenter, Western Psychiatric Institute and Clinic, 3811 O’Hara Street, Pitts-burgh PA 15213-2593.

Received March 3, 2000; revised June 14, 2000; accepted June 22, 2000.

© 2000 Society of Biological Psychiatry 0006-3223/00/$20.00PII S0006-3223(00)00969-0

Preliminary Phasein Figure 2) and prophylactic treatmentfollowing remission (labeledPreventative Phase), werecognize that these distinctions are often arbitrary andinaccurate. In fact, patients in a nonacute phase of treat-ment often experience on-going symptom fluctuations.Depressive symptoms, in particular, seem especially dif-ficult to eradicate completely (Hlastala et al 1997). Thus,the holy grail of sustained euthymia in bipolar disordermay remain an elusive goal in the absence of sophisticatedtreatments that address both the biological and psycholog-ical aspects of this disorder.

Pathways to Recurrence

Goodwin and Jamison’s definitive textbook on bipolardisorder (Goodwin and Jamison 1990) acknowledges theimportant interplay between biological and psychosocialfactors in determining the course of bipolar disorder.Recognizing the primacy of biology, they hypothesizedthat “the genetic defect in manic depressive illness in-volves the circadian pacemaker or systems that modulateit” (Goodwin and Jamison 1990, 589) but then furtherpostulated that psychosocial factors will interact with

biology to create three probable pathways to recurrence ofbipolar illness: 1) stressful life events; 2) disruptions insocial rhythms; and 3) medication nonadherence. Asenvisioned by Goodwin and Jamison, these routes toillness are interconnected. Their model suggests thatindividuals with bipolar disorder are fundamentally vul-nerable to disruptions in circadian rhythms. Psychosocialstressors then interact with this biological vulnerability tocause symptoms. For instance, stressful life events disruptsocial rhythms, which causes disturbances in circadianintegrity, which, in turn, may lead to recurrence. Alter-nately, problematic interpersonal relationships or disor-dered schedules contribute to a patient’s difficulty adher-ing to a medication regimen which, again, may lead torecurrence. As a direct consequence of this model, onewould assume that helping patients learn to take theirmedication regularly, lead more orderly lives, and resolveinterpersonal problems more effectively would promotecircadian integrity and minimize risk of recurrence.

Treating Bipolar Disorder

As depicted in Figure 2, bipolar illness is a disorderlydisorder. Characterized by erratic sleep–wake cycles anddramatic symptom fluctuations, the clinical course isunpredictable and rarely static. Needless to say, treatingthis “moving target” creates many interesting—and some-times problematic—challenges. For instance, lithiummonotherapy is still considered the “gold standard” ofpharmacotherapy for bipolar disorder. As patients movethrough the various phases of the disorder, however, mostpsychiatrists find themselves treating patients with a rangeof mood stabilizers in combination with neuroleptics,sedative-hypnotics, and antidepressants (Sachs et al 2000).Efforts to simplify regimens are often thwarted by unsat-isfactory treatment response, resulting in years of complexpolypharmacy. Vacillating symptomatology, impairedpsychosocial functioning, and problematic medication sideeffects converge to create unique clinical challenges forboth patients and health care professionals. Consideringthe complexities of this illness, it is not surprising thatpharmacotherapy alone does not address the multipleneeds of patients with bipolar disorder. Although there aremany excellent review papers discussing extant psychos-ocial approaches to bipolar disorder (Colom et al 1998;Johnson et al 2000; Miklowitz and Frank 1999), there aresurprisingly few data supporting their efficacy (Craigheadet al 1998; Swartz and Frank, in press). The absence ofwell-designed, empirically tested psychotherapies in theliterature led us to develop and test a model of individualpsychotherapy that would be used in conjunction withmedication to enhance functioning and diminish recur-rences in patients with bipolar I disorder.

Figure 1. Response, remission recovery, relapse, and recurrence:phases of treatment in unipolar disorder. (Reproduced withpermission from Kupfer 1991.)

Figure 2. Response, remission, recovery, relapse, and recur-rence: phases of treatment of bipolar disorder.

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Theoretical Context for Interpersonal andSocial Rhythm Therapy

Interpersonal and social rhythm therapy (IPSRT) is atreatment that is specifically designed for patients withbipolar disorder. As elaborated below, the genesis ofIPSRT rests in a psycho-chronobiological theory of affec-tive illness that we articulated in a series of papers in the1980s and early 1990s (Ehlers et al 1988, 1993; Monk etal 1991, 1990). Its design was also strongly influenced bythe instability model of bipolar disorder proposed byGoodwin and Jamison (1990) and our evolving under-standing of the relationship between stressful life eventsand bipolar episodes.

Circadian Rhythms, Sleep–Wake Cycles, and MoodDisorders

Researchers have identified reciprocal relationshipsamong circadian rhythms, sleep–wake cycles and mood.Wehr and colleagues have demonstrated that sleep reduc-tion can lead to mania in bipolar subjects (Leibenluft et al1996; Wehr et al 1987). Sleep deprivation has significant(if transient) antidepressant effects in both unipolar andbipolar depressed subjects (Barbini et al 1998; Leibenluftet al 1993; Leibenluft and Wehr 1992), and PET studieshave demonstrated localized effects of sleep deprivation inthe medial prefrontal cortex (Wu et al 1999). The purposeof IPSRT is to regulate both circadian rhythms andsleep–wake cycles. It must be noted, however, that therelationship between bipolar disorder and circadianrhythms is less well characterized than its relationship tosleep–wake disturbances. By targeting social factors thatmodulate these rhythms, IPSRT is presumed to alter theunderlying neuronal circuitry involved in the pathogenesisof bipolar symptomatology.

The theoretical underpinnings of IPSRT began with ourefforts to better understand the psycho-chronobiologicaldeterminants of unipolar disorder. In 1988, we proposedan etiologic model of major depression that focused on therole of disrupted social rhythms in the emergence of adepressive episode in biologically vulnerable individuals(Ehlers et al 1988). Noting that the established biologicalcorrelates of affective disorder include disrupted sleepelectroencephalogram recordings (Kupfer et al 1991) andphasic changes in the circadian secretions of pituitaryhormones (Carroll et al 1980), we hypothesized thatdisruptions in the social cues that entrain these cycles mayact as triggers for mood episodes. We argued thatsocialZeitgebers,that is, personal relationships, social demands,or tasks that entrain biological rhythms, may serve as thelink between the biological and psychosocial processesthat place an individual at risk for developing moodsymptoms. We hypothesized that losing a social Zeitgeber

could trigger an episode by causing the dysregulation ofbiological rhythms. For instance, the loss of a spousethrough death or divorce results in the loss of a socialZeitgeber that may have previously determined sleep–wake times, rest periods, and meal times. In an individualwith the genetic predisposition to depression, the physio-logic and chronobiological disturbances produced by los-ing the social cues for sleep and meal times could be asimportant in the genesis of an episode as the psychologicdistress generated by the event.

We subsequently extended this model of mood disor-ders to include the concept of Zeitsto¨rers (time disturbers;Ehlers et al 1993). As defined above, social Zeitgebers arepersons, social demands, or tasks that set the biologicalclock. By contrast, Zeitsto¨rers are physical, chemical, orpsychosocial events that disturb the biological clock. Forinstance, travel across time zones represents a prototypicalZeitstorer. The abrupt change in the timing of lightexposure, meal times, and sleep times can produce a rangeof symptoms from mild “jet lag” to a full-blown affectiveepisode in predisposed individuals. Other examples ofpotential Zeitsto¨rers include newborn babies, marital sep-arations, work deadlines (e.g., a college student who staysup all night to complete a term paper), and rotating shiftwork. Each of these disruptions has the potential tosignificantly alter an individual’s circadian and sleep–wake rhythms that we argue, in turn, could result in anaffective episode. In the context of our exploration ofsocial Zeitgebers and Zeitsto¨rers, our group developed aninstrument to quantify an individual’s social rhythms(Monk et al 1990). The Social Rhythm Metric (SRM) wasdesigned as both a means of categorizing interindividualdifferences in social rhythm regularity and as a therapeutictool to track decline into and recovery from an affectiveepisode. We hypothesized that a psychotherapy that helpsregulate social rhythms could help a vulnerable individualreduce the risk of developing mood symptoms.

Stressful Life Events and Mood

We formulated IPSRT at a time when there was a greatdeal of interest in the relationship between stressful lifeevents and bipolar episode onset (Ellicott et al 1990).Given the probable role of circadian rhythm disruption inthe genesis of bipolar episodes, our research group wasparticularly interested in the effects of those life eventsthat caused a significant disruption in social rhythms.These theories, however, had not been subject to method-ologically rigorous testing at the inception of IPSRT.Therefore, simultaneous with our early testing of IPSRT,we began an on-going study to assess the relationshipbetween life events and bipolar episode onset with areliable and valid life stress instrument, the BedfordCollege Life Event and Difficulty Schedule (LEDS).

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In our research program, each life event of any severityidentified by LEDS criteria was subject to an additionalrating devised by our group to reflect the degree to whichany given event is likely to have an acute effect on socialroutines, particularly those that might disrupt the sleep–wake cycle. The Social Rhythm Disruption (SRD) ratings,like the LEDS rating, were contextually determined byconsensus panel and guided by clearly delineated criteriaand a dictionary of examples. In an initial report based on39 subjects with bipolar I disorder who were assessed withthe LEDS/SRD protocol, we found evidence that lifeevents (regardless of severity of threat) characterized by ahigh degree of social disruption were associated with theonset of manic but not depressive episodes (Malkoff-Schwartz et al 1998). Severely stressful life events (re-gardless of SRD rating) were related to the onset of bothmanic and depressive bipolar episodes. In a follow-upstudy, we interviewed bipolar subjects with purely manic(n 5 21), purely depressed (n 5 21), and mixed or cycling(n 5 24) episodes and compared this bipolar sample with44 patients with recurrent unipolar depression (Malkoff-Schwartz et al 2000). We again found that life eventsassociated with a high degree of social disruption occur-ring in the 8 weeks before the onset of an episode weremore frequently associated with the onset of manic epi-sodes relative to bipolar cycling, bipolar depressed, orunipolar depressive episodes. Severely life-threateningevents were more frequently associated with the onset ofmanic episodes relative to bipolar cycling episodes. Weconclude that SRD and severe events are associated withmanic episode onsets in a manner distinct from theassociation between SRD and severe events in bipolardepressed, bipolar cycling, and unipolar depressed onsets.

Origins of Interpersonal and Social RhythmTherapy

Interpersonal Psychotherapy of Depression

Interpersonal psychotherapy (IPT) is a time-limited, fo-cused psychotherapy developed in the 1970s by Klerman,Weissman, and colleagues for the treatment of unipolardepression (Klerman et al 1984). Unlike many otherpsychotherapies, IPT is designed to treat a specific disor-der (depression) and has been systematically evaluated inseveral randomized, controlled research trials. IPT wasenvisioned as an acute (12–16 weeks) treatment fordepression but has also been tested in an 8-month contin-uation study (Klerman et al 1974) and as a long-termmaintenance strategy for patients with recurrent depres-sion (Frank et al 1990). The basis of IPT is the premisethat depression occurs in a psychosocial and interpersonalcontext. Akin to the social Zeitgeber hypothesis, thephilosophy of IPT posits that in biologically vulnerable

individuals, stressful interpersonal events may contributeto the onset of depression. It also argues that depressivesymptoms can interfere with an individual’s capacity tosuccessfully negotiate interpersonal conflict or find con-structive solutions to interpersonal dilemmas. Interper-sonal psychotherapy is a “here and now” treatment thatfocuses on the relationship between the patient’s currentinterpersonal milieu and his or her depressive symptoms.Treatment focuses on one of four IPT problem areas: grief,role disputes, role transitions, or interpersonal deficits.

Integrating the Behavioral, Interpersonal, andPsychoeducational Models

In the context of adapting IPT for the maintenance treatmentof recurrent unipolar depression, we saw the potential utilityof this treatment for another highly recurrent affective illness,bipolar disorder. We established that patients with recurrentunipolar disorder could recover from depression with anacute course of IPT and then decrease the risk of havinganother episode by receiving monthly sessions of mainte-nance IPT (Frank et al 1990). We began to conceptualize asimilar kind of maintenance treatment for bipolar I disorder;however, given extant theories about the relationship be-tween circadian rhythms and bipolar episodes and subsequentdata linking SRD events to mania (Malkoff-Schwartz et al1998, 2000), we decided to augment IPT with behavioralstrategies designed to stabilize daily routines. We borrowedtraditional cognitive-behavioral techniques such as self-mon-itoring, realistic goal-setting, and graded task assignment tohelp patients follow more consistent patterns of eating,sleeping, and social stimulation.

We expected IPT to contribute a specific antidepressanteffect and hypothesized that helping patients stabilize theirsocial rhythms would decrease the risk of new affective(especially manic) episodes. Nonetheless, we were awarethat there is tremendous overlap between interpersonalstress and social rhythm disruption: a disturbance in thesocial milieu (such as a new job or conflict with a spouse)often acts as a Zeitsto¨rer which, in turn, can lead tochanges in daily routines. We therefore envisioned IPSRTas a truly integrated therapy that would allow thesestrategies to function synergistically. Thus, we expectedthat the IPT-induced resolution of interpersonal conflictwould also contribute to more stable rhythms and morestable daily routines would promote more stable lifecircumstances (jobs, relationships, etc.).

The third component of IPSRT is psychoeducation.Recalling that the Goodwin and Jamison model (Goodwinand Jamison 1990) predicts three probable pathways torecurrence in bipolar disorder, including medication non-adherence, a cogent psychotherapy for bipolar disorderalso necessarily addresses medical issues such as side

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effects, discontinuation risks, and relapse warning signs.Psychoeducation helps patients understand bipolar disor-der and their medications, thereby decreasing denial andimproving adherence to pharmacotherapeutic regimens.Indirect routes to medication adherence in IPSRT includeregulating social routines (e.g., routinizing times of daywhen medications are administered) and addressing inter-personal problems (e.g., helping a patient find time fortreatment in the setting of a demanding new job). Thus,IPSRT integrates behavioral, interpersonal, and psycho-educational approaches to prevent the onset of new epi-sodes of bipolar disorder.

Interpersonal and Social Rhythm Therapy:Treatment Description

Interpersonal and social rhythm therapy is a manual-basedpsychotherapy (E. Frank et al, unpublished data, 1999)focusing on 1) the link between mood and life events, 2)the importance of maintaining regular daily rhythms aselucidated by the SRM, 3) the identification and manage-ment of potential precipitants of rhythm dysregulationwith special attention to interpersonal triggers, 4) thefacilitation of mourning the lost healthy self, and 5) theidentification and management of affective symptoms.The therapy process is divided into four phases: initialphase, intermediate phase, preventative phase, and termi-nation. We describe each phase of treatment below.

Initial Phase

In the initial phase, the clinician 1) obtains a history of theillness, 2) conducts an interpersonal inventory, 3) identi-fies an interpersonal problem area, 4) educates the patientabout the disorder, and 5) initiates the SRM. Treatmentmay be initiated while the patient is fully symptomatic,subsyndromal, or euthymic. Because the medical manage-ment of a patient’s acute symptoms may slow the initiationof the key features of IPRST, the duration of the initialphase may vary from several weeks to several months,depending on the severity of the patient’s current symp-toms. During this period, the patient and therapist meetweekly for 45-minute sessions.

The therapist begins by conducting a thorough psychi-atric and medical history. In addition to the traditionalpsychiatric amanuensis, the therapist attempts to elicit ingreat detail the events leading up to current and previousepisodes, searching for evidence of alterations or disrup-tions in the patient’s daily routines and interpersonalinteractions that preceded the development of symptoms.From Malkoff-Schwartz et al (1998), we know that manicepisodes in particular are likely to be preceded by a socialrhythm disrupting event. These historic details will help

the therapist understand the patient’s patterns of illnessand aid in the identification of potential episode triggers.As the therapist elicits this information, he or she begins toclarify for the patient the relationship between the disrupt-ing event and the onset of symptoms.

In accordance with the principles of IPT, the therapistalso conducts an assay of the important individuals in thepatient’s life, known as the interpersonal inventory. Amore interpersonally focused search for an episode pre-cipitant, the interpersonal inventory consists of a review ofall important past and present relationships as they relateto the current episode. The therapist asks about thepatient’s life circumstances and requests a description ofthe important people in his or her life. In addition tooutlining the “cast of characters” in the patient’s life, thetherapist probes the quality of those relationships, askingthe patient to describe satisfying and unsatisfying aspectsof relationships, unmet expectations of others, and aspectsof relationships that the patient would like to change. Thetherapist listens closely for omissions, such as the unem-ployed young adult who lives at home but does notmention his parents, or the “happily” married housewifewho labels her marriage to an absent, high-poweredexecutive as “fine,” but does not volunteer details. Thetherapist listens for perturbations in relationships that maycorrespond temporally to the onset or maintenance ofmood symptoms. Understanding the relationship betweeninterpersonal difficulties and the onset of affective symp-toms will help the therapist identify an appropriate treat-ment focus for the intermediate phase of treatment. In IPT,there are four possible treatment foci or interpersonalproblem areas that are discussed in detail in the sectionentitled “Interpersonal Strategies.”

After establishing a diagnosis, the therapist begins toeducate the patient about his or her disorder. The educa-tional component includes information about bipolarsymptoms, prescribed medications, medication side ef-fects, and so forth. The therapist also begins to help thepatient understand the possible role of social and circadianrhythm disruption in precipitating his or her episode.Finally, the therapist initiates a revised version of the SRM(SRM-II) (Frank et al 1994). This 17-item self-report form(Figure 3) requires patients to record daily activities (e.g.,time out of bed, first contact with another person, mealtimes, bedtime), whether each occurred alone or withothers present, and how stimulating (i.e., quiet vs. inter-active) these others were. The patient also rates his or hermood each day. After becoming familiar with the forms,patients spend 5 to 15 minutes per day completing theSRM. In our experience, most patients (about 85%) arewilling and able to fill out the forms most (about 80%) oftime. Therapists encourage patients to complete the formsby reminding them of their importance in the therapy and

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reviewing the week’s SRM at each session. Working withthe SRM, the patient begins to see the dynamic interplayamong instabilities in daily routines, patterns of socialstimulation, sleep–wake times, and mood fluctuations. In

the initial phase of IPSRT, however, no effort is made toregulate these daily rhythms.

Many individuals with bipolar disorder have sufferedwith their illness for many years before entering treatment

Figure 3. Sample page from the Social Rhythm Metric.

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(Goodwin and Jamison 1990). The toll it takes on one’spsyche cannot be underestimated. Importantly, the initialphase of treatment allows the therapist to establish theso-called “nonspecific” factors of therapy (Frank 1971).The therapist offers the patient hope and a human connec-tion in the midst of an affective storm. Interpersonal andsocial rhythm therapy provides an affectively meaningfulforum in which to begin an exploration of the effects of theillness on the patient’s life trajectory, interpersonal rela-tionships, and self-esteem.

Intermediate Phase

The intermediate phase of treatment is conducted weeklyover several months. During this period, the therapisthelps the patient develop strategies to manage affectivesymptoms, stabilize daily rhythms, and resolve the se-lected interpersonal problem area. The therapist alsoprovides a forum for the patient to mourn lost “highs,”struggle with denial, and find a balance between sponta-neity and stability.

Social Rhythm Strategies

During the intermediate phase of treatment, IPSRT uses abehavioral approach to help the patient alter those activi-ties that promote rhythm irregularities. The patient andtherapist review the first 3 or 4 weeks of “free-running”SRMs to find those rhythms that seem to be particularlyunstable. For example, is the patient going to bed at 10PM

one night, 2AM the next night, and midnight the thirdnight? Is there evidence of regularity during the week butextreme deviation on the weekend? Every effort is made todetermine whether the patient’s social rhythm instabilityresults from untreated/prodromal bipolar symptoms orfrom a self-imposed lifestyle choice. In either case, thetherapist will encourage the patient to work toward stabi-lization. If the rhythm instability is related to symptoms,the therapist helps the patient understand that stabilizinghis or her rhythms can help diminish these symptoms. Thetherapist also encourages the patient to address the issuewith his or her psychiatrist in the event that a medicationchange might help reduce the symptoms. If the therapistdetermines that the rhythm instability is a lifestyle choice,the therapist explains that disrupting circadian integritymay prevent a complete recovery. Therapist and patientdiscuss general strategies for regulating rhythms (e.g.,minimizing overstimulation, monitoring the frequency andintensity of social interactions) and identify specific SRMgoals. Goals are graded and include short term (i.e.,adhering to a 7AM wake-up time for 7 consecutive days),intermediate (i.e., sustaining a regular sleep–wake cyclefor a month), and long-term (i.e., finding regular employ-

ment) objectives. The therapist of course allows formodifications of goals as the therapy proceeds.

Following from our Zeitsto¨rer hypothesis, the therapistattends not only to the patient’s daily rhythms but also tothe larger environmental stressors that might result in acircadian rhythm derailment. The search for triggers ofrhythm disruption leads the IPSRT therapist to comb thepatient’s history in search of external sources of rhythmdisruption (Zeitsto¨rers); IPSRT then encourages the pa-tient to make relatively significant life changes in order toprotect the integrity of his or her circadian rhythms andsleep–wake cycle. For instance, a factory worker whoalternated between a night shift and a day shift becamemanic and needed to be hospitalized following the insom-nia-inducing transition from day shift to night shift. Thepatient and therapist evaluated the risks of rotating shiftwork and determined that the frequent shifts in sleepschedule would be incompatible with reasonably stablesocial rhythms. Ultimately, the patient decided to changeto a slightly less lucrative—but more regular—day job.

At some point in the recovery process, most patientswith bipolar disorder question the need for protecting theintegrity of their social rhythms. To someone with a longhistory of fluctuating mood states and erratic socialrhythms, a very regular lifestyle can seem “boring” andunappealing. The therapist addresses this crucial issue onseveral levels. First, the therapist can help the patient finda healthy balance between stability and spontaneity. Thisprocess requires a spirit of careful experimentation on theparts of both therapist and patient to determine how muchsleep, stimulation, and regularity are associated with anoptimal mood state for each individual. Extreme inactiv-ity, on one hand, can contribute to isolation and depressivesymptoms; excess stimulation, on the other hand, mayprecipitate a mania. It is helpful to pursue this aspect oftreatment over many months because seasonal variation inmood and energy often occurs in bipolar patients (Good-win and Jamison 1990). Some patients, for instance, mayfind they benefit from a busier schedule during the wintermonths when they would typically tend toward depressionbut must learn to curtail these same activities during thesummer months when they are at increased risk for amania.

Changes in routine are an inexorable part of life. Somechanges are predictable (e.g., a vacation or a professionalconference); others are not (e.g., job loss or physicalillness). Another goal in IPSRT is to help patients adapt tochanges in routine. In the event of a predictable change,the therapist can help the patient modify his or her activitylevel to modulate potential disruptions in social rhythms.For example, a young, unemployed woman had finallydemanded that her abusive, substance-abusing boyfriendmove out of her apartment as of a specified date. Although

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both therapist and patient viewed this change as positive,they both recognized that his departure would create greatupheaval in the patient’s routines. She relied on herboyfriend to wake her up in the mornings and scheduledmealtimes around his evening routines. Because of hisjealous nature, she had greatly limited her social contactsduring their relationship. In preparation for his departure,the patient began using an alarm clock to determine herown waking time. She planned social outings during theday that would not involve her boyfriend (e.g., meeting anold friend at the mall) and “practiced” these interactions aspart of planning for the move. Helping the patient togradually entrain her rhythms to a new schedule mitigatedagainst the disruptive effects of the lost social Zeitgeber.Unanticipated changes, however, may require consider-able effort from the therapist to address both the unex-pected alterations in social Zeitgebers and the psycholog-ical meaning of the event.

Interpersonal Strategies

The interpersonal techniques employed in IPSRT aresimilar to those described in Klerman and colleagues’definitive description of IPT for unipolar depression (Kler-man et al 1984). As described previously, the therapistidentifies an interpersonal problem area during the initialphase of treatment that will serve as the interpersonaltreatment focus. Each problem area is associated with a setof IPT techniques that are fully described in the Klermanet al (1984) text. In the section that follows, we will brieflydescribe each problem area and focus on the ways inwhich IPRST employs traditional IPT strategies to meetthe specific needs of patients with bipolar disorder.

1. Grief. Grief or complicated bereavement refers tosymptoms that result from incomplete mourning orunresolved feelings about the death of an importantperson in the patient’s life. Symptoms must exceedin duration and intensity those characteristic of thenormal mourning process. In IPT, the problem areaof grief is not typically invoked when the patientexperiences symbolic losses such as the loss of a jobor loss of function from physical illness. In mostcases, these issues would be handled as role transi-tions. Patients with bipolar disorder, however, fre-quently grieve for the person they were before theillness or the person they could have become if theydid not suffer from bipolar disorder. In IPSRT, wecall this grieving for the lost healthy self and utilizethe IPT techniques associated with grief to help thepatient mourn this loss. The therapist encourages thepatient to express painful feelings about lost hopes,ruined relationships, interrupted careers, and passedopportunities. As the patient mourns the passing of

a “former self,” the therapist encourages the patientto develop new relationships, establish new, morerealistic goals, and focus on future opportunities.

2. Interpersonal role disputes.An interpersonal dis-pute refers to any close relationship in which thereare nonreciprocal expectations. Examples include acollege student who wants to live in the dorms butwhose parents want her to live at home, and aconstruction worker who became symptomatic inthe context of pressure from his girlfriend of 7 yearsto propose marriage. Individuals with bipolar disor-der are frequently involved in interpersonal disputes.Bipolar symptoms may contribute to interpersonaldisputes or interpersonal disputes may overstimulatepatients, which may, in turn, precipitate episodes orexacerbate mood symptoms. The former scenario isillustrated by a treatment-nonadherent man withbipolar disorder who became hypomanic, spentexcessive sums of money on unnecessary computerequipment, and engaged in promiscuous extramari-tal behaviors. Even though the behaviors subsidedwith reinitiation of medication, his angry spousemoved into her mother’s house and threatened toleave the marriage. The therapist helped the patientunderstand the role of medication nonadherence inthe evolution of these behaviors and encouraged thepatient to accept more responsibility for his treat-ment. With the help of his therapist, the patient wasable to express his contrition to his partner andadmit to her his ambivalence about taking medica-tion. The couple was able to reconcile with theunderstanding that the patient would accept andadhere to treatment as part of the terms of themarriage.

3. Role transition.A role transition is any major liferole change. This category subsumes many potentialstressors, including new employment, unemploy-ment, matriculation, graduation, retirement, mar-riage, divorce, giving birth, and so forth. The pro-foundly disruptive nature of bipolar disorder maycause significant interpersonal upheaval in a pa-tient’s life. A destructive mania can result in a jobloss or tremendous financial debt. Entrenched de-pressions can lead to ruptured social ties and loss ofsocioeconomic status. In IPSRT, these life changesare handled under the rubric of role transitions. Thetherapist should be especially sensitive to theseissues and probe for the status of important relation-ships pre- and postepisode. Another transition con-fronting newly stable bipolar patients is the loss ofpreviously pleasurable, baseline hypomania. Theallure of the lost euphoric state may tempt patientsto seek transient mood elevation by either discon-

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tinuing medications or manipulating social rhythmsto produce insomnia. The therapist must help thepatient relinquish this aspect of the “former self” tomaintain overall stability. It is important to remindthe patient of the negative consequences of hypo-mania and to encourage the patient to identifyrewarding life goals (i.e., an enduring and stablemarriage) that may constitute a suitable alternativeto the seductive and dangerous pleasures ofhypomania.

4. Interpersonal deficits.Patients with interpersonaldeficits suffer from a long-standing history of im-poverished or contentious social relationships andare unable to identify a single acute interpersonalstressor associated with the onset of their episode.Most bipolar patients’ problems will fall into one ofthe three categories previously discussed; however,a minority of individuals will benefit from aninterpersonal deficits focus. These patients mayinclude individuals whose illness-dependent grandi-osity, social withdrawal, or extreme mood fluctua-tions contribute to multiple failed relationships,recurrent patterns of conflict with coworkers, orconstricted social networks.

In addition to focusing on the interpersonal meaning ofeach problem area, the therapist attends to the role of thesekinds of problems in promoting or disrupting socialrhythm regularity. For instance, the death of a loved onemay result in complicated bereavement but will also resultin the loss of an important Zeitgeber. The on-goinginterpersonal disputes of a husband and wife may lead toprebedtime fighting and subsequent decrease in sleep. Therequirements of a new job may involve changing waketimes or interfere with previously regular exercise rou-tines. In IPSRT, the therapist generally encourages socialrhythm regularity first and then explores the interpersonalmeaning of an event.

Preventative Phase

Because IPSRT is designed, above all, to prevent futuremood episodes and enhance functioning during relativelyeuthymic periods, the preventative phase is a crucialcomponent of this treatment. In our conceptualization of apreventative therapy, treatment frequency decreases tomonthly and lasts 2 or more years. The patient is providedwith an opportunity to consolidate treatment gains andincrease confidence in his or her capacity to apply IPSRTtechniques outside of sessions. For instance, before enter-ing treatment, an academic scholar developed an episodeof mania during a professional conference in another timezone. She became very stimulated, did not sleep well, andsoon required hospitalization for a psychotic mania. Theacute phase of treatment focused on recovery from the

episode and making lifestyle changes to balance herpersonal and professional lives. During the preventativephase of treatment, the patient wanted to pursue careergoals more intensively. She worked with her therapist tomonitor her career choices to preserve her sleep andmaintain regular social rhythms. For instance, the patientlearned that she could tolerate demanding individualprojects (e.g., writing papers) but became overly stimu-lated in group settings (e.g., committee meetings in herdepartment). A year after the beginning of treatment, thepatient wished to return to the conference that led to herfirst hospitalization. Both patient and therapist were con-cerned about the conference’s potential for provoking arecurrence. The therapist helped the patient develop astrategy for diminishing stimulation at the conference(e.g., attending only selected meetings, avoiding the late-night social events) that permitted her to participate in theevent, but in a controlled manner. Thus, in the preventativephase, the therapist continues to encourage the patient tomaintain regular social rhythms and addresses problems asthey arise. The patient works on his or her interpersonalproblem area(s), although the specific interpersonal focusmay differ from that of the acute phase. The preventativephase of treatment may require occasional additional crisissessions to address either a symptom exacerbation or aninterpersonal dilemma.

Termination

The final phase of treatment facilitates termination of thepsychotherapy. The therapist reviews treatment successes,as well as the patient’s potential vulnerabilities, helpingthe patient identify strategies for future management ofinterpersonal difficulties and symptom flares. Terminationis handled gradually, occurring over four to six monthlysessions. Because bipolar disorder is a chronic condition,patients often approach termination with some trepidation.It is important to remind them about available resourcesfor treatment should symptoms flare in the future whileoffering encouragement about their ability to exercise theirnew skills independently. At the end of treatment, patientscan usually be congratulated on the tremendous stridesthey have made in both relationships and social rhythmstability during the course of IPSRT. In some cases,treatment may continue for an indefinite period at areduced frequency, given the chronic nature of the disor-der and the likelihood that a patient will be maintained onmedications indefinitely.

Empirical Data Supporting the Efficacy ofIPSRT

We are currently conducting an on-going randomizedclinical trial at the University of Pittsburgh testing the

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efficacy of IPSRT as an adjunctive maintenance treatmentfor bipolar I disorder (Maintenance Therapies in BipolarDisorder; MH29618, E. Frank, PI). After giving written,informed consent, acutely ill bipolar patients are treatedwith medication and randomly assigned to either IPSRT orintensive clinical management (CM). Once stabilized,patients are reassigned to either IPSRT or CM (in con-junction with a stable medication regimen) for 2 years ofmonthly preventative treatment. Although the study is notyet complete, we have published several reports of pre-liminary findings from this trial.

As further evidence of the complexities of treatingbipolar disorder, we have discovered that departures fromour protocol pharmacotherapy are the norm rather than theexception. In theory, we attempt to treat all patients withlithium plus specified neuroleptics or antidepressants ad-ministered transiently in the acute phase according to aspecified protocol. Our study design specified a goal oflithium monotherapy in the preventative phase. But,among the first 91 subjects to enter the preventative phase,only 23% entered on lithium alone. Also of interest, only63% of subjects presenting with mania, and 22% ofsubjects presenting with depression were able to followthe specified pharmacotherapy algorithm to achieve stabi-lization. The demands of the disorder routinely resulted insubstantial deviation from our carefully planned model.By contrast, the psychotherapy condition has remainedquite “pure,” with raters who are unaware of treatmentassignment distinguishing reliably between audio tapes ofIPSRT and CM sessions.

Our first published report from the Maintenance Ther-apies in Bipolar Disorder (MTBD) protocol demonstratedthat patients in IPSRT can be taught to maintain stabilityin their daily routines over the course of acute treatment(Frank et al 1997). Over time (up to 52 weeks), subjectsreceiving IPSRT (n 5 18) and CM (n 5 20) hadcomparable changes in symptomatology, but the IPSRTgroup showed significantly greater stability of daily rou-tines with increasing time in treatment (p 5 .047). Themean number of weeks of data included in these analyseswere 24.86 13.8 and 26.76 15.0 for IPSRT and CMsubjects, respectively.

We next reported on 42 subjects treated acutely witheither IPSRT or CM, demonstrating that manic subjectsachieved clinical remission significantly more quicklythan did depressed subjects (Hlastala et al 1997). Althoughwe found no statistically significant effects of treatmentassignment, among the 22 depressed subjects, median timeto remission was 21 weeks with IPSRT versus 40 weekswith CM. This statistically nonsignificant but clinicallyinteresting finding suggests that IPSRT may hasten recov-ery from a depression more effectively than a nonspecific“medication clinic” intervention.

We have most recently reported on the first 82 subjectsto enter the preventative phase of treatment in this protocol(Frank et al 1999). We found that groups of subjects whoreceived the same treatment for both acute and preventa-tive phases (either CM followed by CM or IPSRT fol-lowed by IPSRT) had lower rates of recurrence (,20% vs..40%) and levels of symptomatology over the subsequent52 weeks than those reassigned to the alternate modality(either IPSRT followed by CM or CM followed byIPSRT). The polarity of the episode for which a subjectwas treated before entering the preventative phase did notaffect the relative risk of recurrence in the groups receiv-ing altered versus stable treatments. Subsequent analyses,however, have suggested that the loss (as opposed to gain)of IPSRT put subjects at particular risk for a depressiverecurrence. We concluded that even relatively minordisruptions in the psychosocial treatment plan contributeto worse outcomes in bipolar disorder. These analysesprovide additional data to support the hypothesis thatinstability contributes to morbidity in bipolar disorder.

As described previously, our research has demonstrateda correlation between life events associated with a highdegree of social rhythm disruption and the onset ofmanic—but not depressive—episodes (Malkoff-Schwartzet al 1998). One might predict that a psychotherapypromoting regular social rhythms would have a selectivelyprophylactic effect on mania. Although we are still in theprocess of collecting data, our impression is that theopposite may be true: patients assigned to IPSRT in thepreventative phase seem to suffer fewer depressive symp-toms than those assigned to CM but have the same rate ofmanic recurrences (Frank 1999). These paradoxical find-ings may reflect the multiple sites of action of IPSRT andthe as yet unclear effects of this multifaceted treatment ona complex disorder.

Conclusion

Among medical treatments, psychotherapies have thedubious distinction of being among the least well testedand most “cultish” prescriptions offered to patients. Al-though the field is beginning to redress this wrong, IPSRTis among only a handful of psychotherapies utilizingtechniques derived from sound scientific theory, the effi-cacy of which will be evaluated in a randomized con-trolled trial This rational treatment rests firmly on thecircadian rhythm theory of bipolar disorder and ourexplication of social Zeitgebers and Zeitsto¨rers as theputative “bridges” between biological processes and thepatients’ interpersonal experiences. When the preventativephase of our MTBD study concludes, we will be in aposition to answer the most urgent question: Does IPSRTprevent episode recurrence in patients with bipolar I

602 E. Frank et alBIOL PSYCHIATRY2000;48:593–604

disorder? Until that time, we work with the smaller piecesof the puzzle thus far unearthed.

To date, we have established that IPSRT helps patientsachieve more stable social rhythms (Frank et al 1997). Wealso have demonstrated a clear link between life eventsassociated with social rhythm disruption and the onset ofmanic episodes (Malkoff-Schwartz et al 1998). In anironic twist, the cross-over design of our study hasprovided additional data to support Goodwin and Jami-son’s instability model of bipolar disorder (Frank et al1999). Given these converging reports that continue toimplicate circadian instability as an important precipitantof bipolar episodes and our preliminary data demonstrat-ing that IPRST can help stabilize social rhythms, we havereason to believe that a psychosocial intervention thatpromotes rhythm integrity and aids in the resolution andprevention of interpersonal distress is likely to enhancecourse and outcome in bipolar disorder.

Before the identification of lithium as a treatment forbipolar disorder, pharmacologic options were limited andlargely inadequate. By default, psychotherapy was themainstay of treatment. In the absence of effective medi-cations, psychotherapies of the day (mostly insight-ori-ented therapies) were also unsuccessful (Fromm-Reich-mann 1949). A discouraging era of psychotherapytreatments was followed by a disappointing “biologicalera” in which scientists, abandoning psychotherapy, strug-gled with medications alone to optimize outcomes. Thechallenge facing contemporary investigators of bipolardisorder is to develop treatments that address both thebiological and psychologic aspects of the illness. Thestrength of IPSRT lies in its ability to utilize psychosocialstrategies to address the underlying biology of bipolardisorder. Deployed in combination with thoughtful phar-macotherapy, IPSRT appears to successfully integratebiological and psychosocial models of bipolar disorderand, we hope, ultimately to lessen the impact of thisdevastating illness on patients’ lives.

Supported in part by National Institute of Mental Health Grants Nos.MH-30915 (DJK), MH-29618 (EF), and MH-60473 (HAS).

Aspects of this work were presented at the conference “BipolarDisorder: From Preclinical to Clinical, Facing the New Millennium,”January 19–21, 2000, Scottsdale, Arizona. The conference was spon-sored by the Society of Biological Psychiatry through an unrestrictededucational grant provided by Eli Lilly and Company.

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