Family-Focused Treatment Versus Individual Treatment for Bipolar
Disorder: Results of a Randomized Clinical Trial
Margaret M. Rea
University of California, Los Angeles
Martha C. Tompson
David J. Miklowitz
University of Colorado, Boulder
Michael J. Goldstein, Sun Hwang, and Jim Mintz
University of California, Los Angeles
Recently hospitalized bipolar, manic patients (N ? 53) were randomly assigned to a 9-month, manual-
based, family-focused psychoeducational therapy (n ? 28) or to an individually focused patient treatment
(n ? 25). All patients received concurrent treatment with mood-stabilizing medications. Structured
follow-up assessments were conducted at 3-month intervals for a 1-year period of active treatment and
a 1-year period of posttreatment follow-up. Compared with patients in individual therapy, those in
family-focused treatment were less likely to be rehospitalized during the 2-year study period. Patients in
family treatment also experienced fewer mood disorder relapses over the 2 years, although they did not
differ from patients in individual treatment in their likelihood of a first relapse. Results suggest that
family psychoeducational treatment is a useful adjunct to pharmacotherapy in decreasing the risk of
relapse and hospitalization frequently associated with bipolar disorder.
The quality of outpatient treatment for bipolar disorder ad-
vanced considerably with the introduction of lithium carbonate in
the 1960s and the anticonvulsants in the 1980s. Whereas patients
with bipolar disorder tended to follow deteriorating courses in the
pre-pharmacological era (Cutler & Post, 1982), lithium- or
anticonvulsant-treated patients remain out of the hospital for ex-
tended periods (Goodwin & Jamison, 1990). At least 60% of
patients with bipolar disorder respond to lithium (Goodwin & Zis,
1979) and a comparable number respond to the anticonvulsants
(McElroy & Keck, 2000). Moreover, lithium nonresponders fre-
quently respond to the anticonvulsants (American Psychiatric As-
sociation, 1994; Bowden, 1996).
Nonetheless, there is increasing recognition that pharmacolog-
ical treatment does not fully control the symptomatic fluctuations
of bipolar illness. In a community follow-up, Gitlin, Swendsen,
Heller, and Hammen (1995) found that 37% of bipolar patients
relapsed in one year despite maintenance pharmacotherapy and
73% relapsed over 5 years. Gelenberg et al. (1989) reported a
similar rate (40%) over 1 year among lithium-treated patients, even
with drug compliance assured. Patients with bipolar disorder also
experience considerable psychosocial and occupational deficits
despite pharmacotherapy (Coryell et al., 1993; Dion, Tohen, An-
thony, & Waternaux, 1988; Goldberg, Harrow, & Grossman,
1995). Further, studies suggest that as many as 75% of individuals
with bipolar disorder experience inter-episode residual symptoms
despite pharmacotherapy (Gitlin et al., 1995; Kalbag, Miklowitz,
& Richards, 1999; Keller et al., 1986).
At least a part of this variability in illness course can be
attributed to psychosocial stressors. Specifically, patients who
return to a stressful family milieu after a hospitalization are more
likely to relapse in 9-month to 1-year community follow-ups than
those who return to less stressful family environments (Miklowitz,
Goldstein, Nuechterlein, Snyder, & Mintz, 1988; O’Connell,
Mayo, Flatow, Cuthbertson, & O’Brien, 1991; Priebe, Wildgrube,
& Mueller-Oerlinghausen, 1989). Furthermore, episodes of bipolar
disorder are often precipitated by significant life events, particu-
larly those events that disrupt patients’ sleep–wake cycles or that
promote goal directedness (Ellicott, Hammen, Gitlin, Brown, &
Jamison, 1990; Johnson & Roberts, 1995; Johnson et al., 2000;
Malkoff-Schwartz et al., 1998).
The overall pattern of these findings suggests the possibility that
pharmacotherapy can be augmented by psychosocial interventions
Margaret M. Rea, Department of Psychiatry, University of California,
Los Angeles; Martha C. Tompson, Department of Psychology, Boston
University; David J. Miklowitz, Department of Psychology, University of
Colorado, Boulder; Michael J. Goldstein, Department of Psychology, Uni-
versity of California, Los Angeles; Sun Hwang and Jim Mintz, Department
of Psychiatry and Biobehavioral Sciences, University of California, Los
Margaret M. Rea is now at the Department of Psychiatry, University of
Michael J. Goldstein died in March 1997. We gratefully acknowledge
his essential contributions to this research.
This research was supported by National Institute of Mental Health
(NIMH) Training Grant MH-14584, NIMH Grant MH-42556, and the
University of California, Los Angeles, Clinical Research Center for the
Study of Schizophrenia, NIMH Grant MH-30911.
Special thanks go to Emily Altman, Jeffrey Ball, Steven Erhardt, Jodie
Halpern, Constance Hammen, Jennifer Christian-Herman, Robin Kissell,
Robert Liberman, Sandra Malik, Keith Neuchterlein, Noosha Niv, Sumie
Okazaki, Meg Racenstein, Irwin Rosenfarb, Angus Strachan, Joseph
Ventura, Amy Weisman, Stephanie Woo, and Sibyl Zaden for their
Correspondence concerning this article should be addressed to Martha
C. Tompson, Department of Psychology, Boston University, 648 Beacon
Street, 4th Floor, Room 407, Boston, Massachusetts 02215.
Journal of Consulting and Clinical Psychology
2003, Vol. 71, No. 3, 482–492
Copyright 2003 by the American Psychological Association, Inc.
0022-006X/03/$12.00 DOI: 10.1037/0022-006X.71.3.482
whose objectives include decreasing family stress and improving
psychosocial functioning, compliance with medication, and the
patients’ ability to cope with environmental triggers (Miklowitz,
1996). Although promising results have been published, the psy-
chosocial treatment literature for bipolar disorder is in its infancy
(for reviews, see Craighead & Miklowitz, 2000; Huxley, Parikh, &
Baldessarini, 2000; Miklowitz & Craighead, 2001). Studies of
individual therapy have included a controlled trial by Cochran
(1984), who demonstrated that bipolar outpatients who received
lithium and brief cognitive therapy were more compliant with
medications at a 6-month follow-up, and had fewer medication
noncompliance-associated relapses of mood disorder, than patients
who received only lithium. Perry, Tarrier, Morriss, McCarthy, and
Limb (1999) found that medication administered with an individ-
ual cognitive–behavioral therapy aimed at early recognition of
prodromal symptoms was more effective in delaying manic re-
lapses over an 18-month follow-up than a medication-only inter-
vention. Frank et al. (1997) demonstrated the positive benefits of
individual–interpersonal and social rhythm therapy on patients’
capacities to regulate their daily routines and sleep–wake cycles.
Preliminary data also suggest that patients treated with mainte-
nance interpersonal therapy and medication are more likely to
maintain stable mood states than patients treated with an intensive
clinical management intervention and medication (Frank, 1999).
Models of family-based interventions for bipolar disorder have
been informed by the literature on psychoeducational treatments
for schizophrenic disorders. Falloon et al. (1985) demonstrated the
utility of a behavioral family intervention for schizophrenic pa-
tients over an individual supportive intervention, in terms of re-
ductions in relapse rates and improvements in psychosocial func-
tioning over 2 years. Hogarty et al. (1986, 1991) showed that a
family psychoeducational treatment and pharmacotherapy had
more lasting effects—in terms of community survivorship—than
individual social skills training and pharmacotherapy in 1- and
2-year follow-ups of schizophrenic patients. Involving the family
in the outpatient management of schizophrenia has received strong
support from the empirical literature, although questions remain
about which forms of family treatment are most effective (Gold-
stein & Miklowitz, 1995).
Bipolar disorder shares many of the clinical characteristics of
schizophrenia, including a relapse–remission course, significant
psychosocial impairment, the need for maintenance medication
and associated issues of noncompliance, and the negative impact
of family stress on clinical outcomes. Thus, a natural step in
examining psychosocial intervention for bipolar disorder is to test
the efficacy of family-based treatments that have proven effica-
cious with schizophrenia. Clarkin, Carpenter, Hull, Wilner, and
Glick (1998) showed that individuals with bipolar disorder who
received a marital psychoeducational intervention in conjunction
with pharmacotherapy had better medication adherence and global
functioning scores over 1 year of treatment than those who had
pharmacotherapy alone, despite no group differences in symptom-
atic outcome. Miklowitz and colleagues (Miklowitz et al., 2000;
Simoneau, Miklowitz, Richards, Saleem, & George, 1999) re-
ported the 1-year results of a University of Colorado trial compar-
ing family-focused psychoeducational treatment (FFT; Miklowitz
& Goldstein, 1997) and pharmacotherapy to a crisis management
intervention, also with pharmacotherapy. Among bipolar patients
followed over 1 year, family-focused treatment was associated
with longer delays prior to mood disorder relapses, more dramatic
improvements in depression symptoms, and higher levels of pos-
itive family communication than the crisis management interven-
tion. The results remained robust even when individual differences
in pharmacotherapy regimes, and compliance with those regimes,
were statistically controlled.
The results of the Colorado trial, while encouraging, must be
interpreted in light of the fact that the two psychosocial treatments
were not matched on number of therapist contact hours. The family
treatment consisted of 21 sessions over a 9-month period, whereas
the crisis management intervention condition consisted of two
family education sessions and crisis intervention sessions offered
as needed, also over a 9-month period. Thus, it is possible that the
superior outcomes of patients in the family treatment were in part
a function of the greater attention they received from project
clinicians. In addition, the effects of the family treatment could
reflect the impact of intensive psychosocial treatment more gen-
erally, and not the influence of family intervention specifically.
The present study evaluated, in a randomized design, the effects
of FFT and pharmacotherapy against a comparably paced, indi-
vidually focused patient treatment, which included education, case
management, and problem solving alongside standard pharmaco-
therapy. This trial, conducted at the University of California, Los
Angeles (UCLA), matched the two psychosocial treatments on
number of therapy contacts (21 sessions over 9 months). All
patients (N ? 53) were offered 12 months of study-based phar-
macotherapy from study psychiatrists working in a specialty out-
patient clinic. The impact of the two psychosocial interventions
was compared in terms of the timing and rates of relapse and
rehospitalization over a 1-year interval of active treatment and a
1-year posttreatment follow-up. We predicted that patients in FFT
would experience fewer rehospitalizations and fewer symptom
relapses, and demonstrate better compliance with medications,
than patients in individual treatment.
Participants were recruited from the inpatient services of three large
hospitals in the Los Angeles area. Criteria for inclusion in the study were
(a) a diagnosis of bipolar disorder, manic type; (b) between age 18 and 45;
(c) competency to give written informed consent; (d) currently taking
mood-regulating medications (lithium carbonate, divalproex sodium, car-
bamazepine, or a combination of these medications); and (e) availability of
at least one close family member to participate with the patient. Subjects
were excluded if they showed evidence of organic central nervous system
disorder or chronic alcohol or substance abuse/dependence. All but one of
the patients was approached by research staff members while hospitalized.
If time permitted, the diagnostic interview was conducted with the patient
prior to his or her discharge. At the initial patient contact, research staff
obtained written permission to speak with relatives.
Of those patients approached and evaluated, 76 met the above criteria.
However, 20 of these were not assigned to psychosocial treatment for the
following reasons: The patient refused all follow-up care (n ? 11), the
family refused (n ? 3), the patient reported transportation problems (n ?
5), or the patient needed extended inpatient care (n ? 1). Three additional
participants were dropped from the study when further evaluation of the
patients’ symptoms revealed a change of the diagnosis to a schizophrenic
or schizoaffective disorder. Thus, 53 families participated in the random-
FAMILY-FOCUSED TREATMENT FOR BIPOLAR DISORDER
The 53 patients ranged from 18 to 46 years of age (M ? 25.6; SD ? 6.4),
and had, on average, 14.2 years (SD ? 2.2) of education. Sixty percent
were Caucasian (n ? 32), 23% (n ? 12) were African American, 9% (n ?
5) were Asian American, and the remaining 9% (n ? 4) were from other
ethnic groups. The majority of the patients lived with their relatives at
study entry (n ? 38; 72%). Forty percent (n ? 21) had experienced only
one episode of mania, and 60% (n ? 32) had a history of multiple episodes
of mania. Sixty-six percent of the patients (n ? 35) had only one relative
who participated in the study, and 34% (n ? 18) had multiple relatives (i.e.,
mother and father). Relatives (n ? 74) included 29 mothers, 22 fathers, 1
stepfather, 9 spouses, 7 siblings, 1 grandmother, 1 uncle, and 4 aunts.
agement sessions with a staff research psychiatrist for 1 year. Patients were
prescribed at least one of the major mood-regulating medications used in
the treatment of bipolar disorder (lithium carbonate, carbamazepine, or
divalproex sodium). Treatment was individually tailored to the patient’s
clinical state and at times included antipsychotics, anticholinergics, anti-
depressants, and anxiolytic agents. The two treatment groups did not differ
in medication protocols at any point during the 1-year study period (see
Table 1; for all comparisons, p ? .10).
In addition to the medication management sessions, the patients were
randomly assigned to either family-focused treatment (n ? 28) or individ-
ually focused patient treatment (n ? 25). Patients and relatives were
informed of treatment assignments following the pretreatment baseline
assessments described below. Contact with the psychiatrist and the psy-
chosocial intervention team was more intensive in the early stages of the
year-long treatment protocol and became less frequent as patients became
increasingly stable. Thus, both medication management and psychosocial
intervention (family or individual) sessions took place weekly for the first
3 months of participation, every other week for the second 3 months of the
study, and monthly thereafter. In order to provide optimal care, psychia-
trists conducting the medication management sessions and therapists con-
All patients received individual medication man-
ducting the psychosocial sessions communicated with each other on a
weekly basis about all patients. Thus, psychiatrists were aware of patients’
psychosocial treatment assignments.
Psychosocial intervention sessions were scheduled for a total of 9
months (21 sessions), and medication management sessions continued for
the remainder of the 3 months of the 1-year active treatment period.
Patients in family treatment had two cotherapists, whereas those in indi-
vidual patient treatment had one therapist. At the end of the study year,
participants were referred to treatment providers in the community, and
considerable effort was made to assist in this transition. As might be
anticipated, the intensity of this continuation treatment varied from patient
to patient. However, the two treatment groups were equal with regard to the
proportion of patients who pursued psychiatric treatment after the 12-
month active treatment phase. At a 24-month follow-up, 71% (12 of 17) of
the individual treatment patients, and 71% (15 of 21) of the family
treatment patients, had pursued and had become engaged in continuing
The research staff contacted patients approximately 1 year following the
active study treatment period to obtain follow-up data on clinical and
psychosocial outcomes. Data from this evaluation will be referred to as the
posttreatment follow-up. Typically, patients received this final follow-up
interview at 24 months after entry into the study. However, several patients
could not be contacted for follow-up interviews at that point. Patients in the
two treatment groups did not differ in the length of the follow-up interval,
FFT group: M ? 128.7 weeks, SD ? 34.5; individual group, M ? 123.2
weeks, SD ? 31.6; t(37) ? 0.52, p ? .10. Furthermore, an approximately
equal proportion of patients in the family-focused treatment (16 of 28, or
57%) and in the individually focused treatment (13 of 25, or 52%) were
contacted and interviewed after the 24-month point. Given that survival
modeling is ideally suited for data in which follow-up times vary, we have
included in survival analyses all outcome data for patients in the sample
regardless of their length of follow-up.
Patients were informed at the outset of the study that they would not be
able to continue in the psychosocial protocol if they chose to discontinue
Medication Protocols During Study Treatment
points. FFT ? family-focused treatment; IPT ? individually focused patient treatment.
aOne patient in this cell was receiving antipsychotic medication alone.
Medication protocols did not differ across the two treatment groups (p ? .10) at any of the evaluation
REA ET AL.
their medications. Patients who did discontinue medications were assisted
in obtaining psychiatric care outside of the study. Forty-two of the 53
patients (79%) completed the full 9-month psychosocial treatment proto-
col. Of those who did not complete treatment, 6 participated in the
family-focused intervention and 5 in the case management condition—a
nonsignificant difference in rates of attrition, ?2(1, N ? 53) ? 0.02, p ?
.10. Of the 11 who did not complete treatment, 7 dropped out during the
first 3 months of treatment (3 patients moved out of the area, 2 families
refused further involvement, 1 patient refused all further psychosocial
sessions and pharmacotherapy, and 1 required long-term inpatient care),
and 4 dropped out during the second 6 months (2 refused all treatment, 1
chose to see a private psychiatrist, and 1 refused further family
Follow-up data, including symptom, psychosocial, and medication
regimen–compliance ratings, were obtained on 9 of the 11 patients who did
not complete 9 months of psychosocial treatment. Of these 9 individuals,
one patient had 9 months of follow-up data, 3 had 6 months of data, and 5
patients had 3 months of data. Consistent with the intent-to-treat design of
the study, data from all patients were included in the survival analyses
regardless of whether they completed the treatment protocol.
The FFT was modeled after the original
structure of Falloon, Boyd, and McGill (1984) behavioral family manage-
ment for patients with schizophrenia but substantially modified by Mik-
lowitz and Goldstein (1997) for individuals with bipolar disorder and their
families. The 21 sessions were an hour in length and included three primary
components: psychoeducation about bipolar disorder, communication en-
hancement training, and problem-solving skills training. Allocation of time
to each component was dependent on the individual family’s needs and
preparation, given their prior knowledge of bipolar disorder, current family
difficulties, and the patient’s clinical status. The psychoeducation compo-
nent included information about the symptoms, course, causes, and treat-
ment of bipolar disorder. Information was presented within a vulnerability–
stress framework, with careful attention paid to risk factors (e.g., drug use,
poor sleep patterns) and protective factors (e.g., medication compliance,
social support) in the course of bipolar disorder. Second, family members
were taught communication skills, including active listening, giving one
another structured positive and negative feedback, and making positive
requests for changes in one another’s behavior. Communication training
included in-session role playing and homework assignments that required
between-session rehearsal. Third, family members learned problem-
solving techniques, including identification of specific problems, brain-
storming of solutions, evaluating the advantages and disadvantages of each
proposed solution, and implementing self-selected solutions. Although
topics in the problem-solving component were geared toward each family’s
specific concerns, all families completed a “relapse drill,” in which
problem-solving focused on planning a family-wide response should the
patient’s symptoms return. Finally, crisis intervention was available to
families on an as-needed basis (see Miklowitz & Goldstein, 1997).
Therapists were trained in conducting FFT in three ways. First, all new
therapists reviewed an initial version of the Miklowitz and Goldstein
(1997) treatment manual and studied case examples in detail. Second, they
viewed a set of training tapes outlining the steps for conducting FFT. Third,
all new therapists were apprenticed to a senior FFT therapist. Only after
successfully conducting therapy with two families could the new FFT
therapist be considered senior and able to train new therapists. To ensure
that treatment delivery was uniform and adhered to the manualized proto-
col, an experienced family therapist, the first author, viewed all treatment
sessions either live or on videotape and provided regular supervision. In
addition, all therapists and psychiatrists met in weekly group supervision
sessions in which cases were reviewed.
The therapists’ competence with and adherence to the FFT treatment
manual were evaluated by a separate group of raters who viewed the
videotaped sessions and applied ratings using the 13 Likert-type Therapist
Competency/Adherence Scales (see Weisman et al., 1998). These scales
measure treatment fidelity in five domains: providing psychoeducation,
implementing communication training, teaching problem-solving skills,
general therapeutic skills, and therapist cooperation. Ratings for the study
therapists averaged 5.61 (SD ? 0.73) across the 13 scales, each of which
could range from 1 (low) to 7 (high), indicating that, on average, therapists
delivered the FFT manual with skill and consistency.
Individually focused patient treatment.
patient treatment condition, patients met with a therapist for 30-min ses-
sions, also titrated over 9 months (12 weekly, 6 biweekly, 3 monthly). The
treatment was supportive, problem-focused, and educational. The goals
were to educate the patient about the illness, monitor and increase the
patient’s awareness of symptoms, conduct crisis intervention, and reduce
ongoing life stress. In the initial phase of treatment (Sessions 1–8) the
patient and therapist reviewed the symptoms of the index episode and the
precipitating life circumstances. Therapists acquainted patients with the
importance of regular sleep patterns, medication effects and side effects,
and the role of alcohol or street drugs in precipitating symptom exacerba-
tions. In the middle phases of treatment (Sessions 9–18), sessions focused
on problem solving concerning ongoing life stressors, establishing realistic
short-term goals, and exploring feelings about the illness and its stigma.
The final sessions focused on problem solving about likely future stressors
and disposition plans for the period immediately following completion of
The individual therapists were trained in the goals of the intervention
prior to conducting the treatment. Group supervision for therapists was
conducted weekly, and audiotapes of sessions were monitored regularly.
No standardized measures of treatment adherence were used to evaluate the
individually focused treatment. However, the same therapists conducted
both the family-focused and individually focused interventions and were
supervised in both modalities by the same experienced clinicians. As a
result, levels of therapist training and experience with bipolar patients were
standardized across conditions.
Shortly after referral to the study, the patient’s diagnosis
according to the Diagnostic and Statistical Manual of Mental Disorders—
Third Edition, Revised (DSM–III–R; American Psychiatric Association,
1987) was confirmed by use of the Present State Examination (PSE; Wing,
Cooper, & Sartorius, 1974) with supplementary mania items from the
Structured Clinical Interview for the DSM–III–R (SCID; Spitzer, Williams,
Gibbon, & First, 1990). Any additional information needed for diagnostic
purposes was obtained through chart reviews and/or information from the
relatives. Interviewers who were trained by the Diagnostic and Psychopa-
thology Unit of the University of California, Los Angeles Intervention
Research Center for Major Mental Disorders conducted all diagnostic
assessments. Training consisted of (a) scoring videotapes of diagnostic
interviews with accompanying ratings; (b) conducting diagnostic inter-
views while an expert diagnostician co-rated the interviews; and (c) par-
ticipating in biannual fidelity checks to prevent rater drift (Ventura, Liber-
man, Green, Shaner, & Mintz, 1998).
Two interrater reliability statistics were calculated to measure diagnostic
agreement. First, kappa statistics compared agreement on the presence or
absence of each critical PSE/SCID item. All interviewers met the minimum
standards of acceptable symptom agreement, with an overall kappa of .75,
a specificity of .75, and a sensitivity of .75. Second, the study interviewers
achieved high interrater reliability in the differential diagnosis of mood
disorder versus schizophrenia and schizoaffective disorder, with an overall
kappa of .88, a sensitivity of .88, and a specificity of .88.
To determine whether participants in the two treatment conditions were
from comparable clinical populations, a number of demographic and clin-
ical variables were assessed on entry into the study. These included gender,
age, years of education, current marital status, employment, and socioeco-
nomic status (SES; based on the Amherst Modification of the
Hollingshead–Redlich Scale; Watt, 1976). Clinical variables included age
at illness onset, presence–absence of previous episodes of mania, total
duration of illness, and premorbid social adjustment. The latter was mea-
In the individually focused
FAMILY-FOCUSED TREATMENT FOR BIPOLAR DISORDER
sured with the UCLA Social Attainment Scale (SAS; Goldstein, 1978), a
seven-item face-to-face interview that assesses social and sexual adjust-
ment during adolescence (ages 16–20 years).
Assessment of patients’ outcomes.
in three domains: symptomatic functioning, rehospitalization, and medica-
tion compliance. All measures were administered at the outset of treatment
and every 3 months throughout the patients’ participation in the 1-year
active treatment phase of the study. Further, patients and relatives were
contacted for a final follow-up interview at least 2 years after entering the
study. Project staff members assessed patients’ symptoms using the Brief
Psychiatric Rating Scale (BPRS; Lukoff, Nuechterlein, & Ventura, 1986)
and supplementary items from the Schedule for Affective Disorders and
Schizophrenia—Change Version (SADS-C; Endicott & Spitzer, 1978),
which provides more detailed assessments of changes (both major and
subclinical) in levels of depression and mania. The supplementary SADS-C
items included neurovegetative symptoms (i.e., lack of energy, poor appe-
tite, weight loss, increased activity, increased energy, and less sleep),
affective symptoms (loss of interest), and cognitive symptoms (discour-
agement, negative self-evaluation).
Raters who were blind to patients’ psychosocial treatment conditions
conducted the BPRS/SADS-C interviews. In addition to rigorous training
in BPRS administration and scoring, all raters attended yearly group and
individual quality assurance sessions to maximize their consistency with
the BPRS scoring manual. These methods have been shown to greatly
improve rater reliability and decrease rater drift (Ventura, Green, Shaner,
& Liberman, 1993). Intraclass correlation coefficients across all BPRS
items were computed between each rater and a criterion rater on a mini-
mum of nine interviews and ranged from .83 to .93 (for all, p ? .01). In
making BPRS/SADS-C ratings covering the interval from the end of active
treatment (12 months) to the final posttreatment follow-up, interviewers
followed the manual-based instructions to use all sources of information,
including data from patients, family members, and, where possible, med-
ical records (Ventura et al., 1993).
For each 3-month follow-up period, participants were placed in one of
the following clinical outcome categories: (a) relapse, defined as a rating
of 6 or 7 on the BPRS/SADS-C core symptoms of depression (depressed
mood, loss of interest), mania (hostility, elevated mood, grandiosity), or
psychosis (unusual thought content, suspiciousness, hallucinations, con-
ceptual disorganization) and at least two ancillary symptoms (suicidality,
guilt, sleep disturbance, appetite disturbance, lack of energy, negative
evaluation, discouragement, increased energy–activity), or (b) nonrelapse,
defined as a score of 5 or below on all relevant BPRS/SADS-C core
symptoms during the 3-month interval. For each relapse, approximate dates
of symptom onset and resolution were noted. In addition to relapse,
rehospitalization was an important outcome variable for the study. Data on
rehospitalization were collected at each time point using patients’ and
relatives’ reports. Inpatient medical records were consulted, where possi-
ble, to verify that rehospitalizations had occurred.
Medication compliance was rated every 3
months by the patient’s psychiatrist, using a standardized form which
included detailed information about the current medication regimen and
associated blood serum levels as well as any changes in the medication
protocol since the last visit. The psychiatrist made ratings of compliance on
a 7-point Likert scale ranging from full compliance (1) to discontinued
medication against medical advice (7), using all available compliance
information, including patients’ reports, psychiatrists’ observations, and
medication blood levels. Although interrater reliability evaluations of the
psychiatrists’ medication compliance ratings were not undertaken for this
study, past research conducted with this scale has demonstrated a high level
of rater agreement (Miklowitz et al., 1988). In that study, medication
compliance was evaluated longitudinally among 23 bipolar patients who
originated from the same inpatient hospital as the patients in the present
study. The Pearson correlation coefficient between two independent raters
using this 7-point scale was .97.
Patients’ outcomes were measured
In examining patient outcomes, two central questions were
addressed. First, were there differences between the treatment
groups in the probability of symptom relapse and rehospitalization
during the 1-year active treatment period and the posttreatment
interval? We predicted that, compared with the individual-focused
patient treatment, FFT would be associated with a lower risk of
relapse and rehospitalization. Second, does participation in family,
as opposed to individual, treatment improve compliance with
Prior to examining the outcome data, preliminary analyses were
conducted to determine how successful the randomization had
been in yielding equivalent groups on demographic characteristics
(age, ethnicity, gender, marital status, employment status, SES,
education) and clinical variables (age of onset, premorbid adjust-
ment, and history of prior episodes). Student’s t tests were used to
examine group differences on continuous variables, and likelihood
ratio chi-square analyses were used to examine group differences
on categorical variables. As Table 2 indicates, there were no
differences between the treatment groups on any variable except
age at illness onset and premorbid adjustment.
Treatment Group Differences on Demographic
and Clinical Variables
(n ? 25)
(n ? 28)
First manic episode
Age at onset
aThe groups were significantly different at p ? .05.
SES ? socioeconomic status.
REA ET AL.
Despite the randomization, patients in individual treatment had
a significantly younger age of illness onset and poorer premorbid
adjustment than patients in family-focused treatment (for both, p ?
.05). However, age of illness onset was not significantly associated
with premorbid adjustment (Pearson’s r ? .10, p ? .10). Given the
difference between the treatment groups on these clinical vari-
ables, subsequent analyses were conducted controlling for each
Description of Clinical Outcomes
During the 1-year active treatment period, 26 of the 53 (49%)
participants experienced a total of 32 relapses. Nine of the partic-
ipants experienced an episode of depression, 12 experienced a
single episode of mania, 2 had two episodes of mania, 2 had one
episode of mania and one episode of depression, and 1 had three
episodes of mania. During the posttreatment follow-up interval, 19
of the 39 available individuals (49%) experienced a total of 24
relapses. Eight had a single episode of mania, 6 had a single
episode of depression, 3 had two episodes of mania and 2 had
episodes of both depression and mania. To ascertain the degree to
which the measure of relapse had clinical significance, we exam-
ined the association between relapse and rehospitalization. Of
those 26 patients experiencing relapses during the active treatment
year, 18 (69%) were rehospitalized for a total of 20 rehospitaliza-
tions. Twelve individuals had a single rehospitalization for ma-
nia, 4 were rehospitalized for depression, and 2 experienced two
separate rehospitalizations for mania. Of those 19 patients who
experienced a relapse during the posttreatment follow-up pe-
riod, 16 (84%) were rehospitalized for a total of 19 rehospitaliza-
tions. Ten had a single rehospitalization for mania, 3 had a single
rehospitalization for depression, 2 individuals were rehospitalized
twice for mania, and 1 had separate rehospitalizations for mania
and depression. Although there was a significant association be-
tween having had a relapse and having been hospitalized during
the 1-year active treatment period, ?2(1, N ? 53) ? 28.3, p ? .01,
and during the posttreatment follow-up interval, ?2(1, N ?
39) ? 23.0, p ? .01, a proportion of the patients (31% during the
intervention and 16% in the follow-up period) were not rehospi-
talized despite a symptom relapse. Thus, relapse and rehospital-
ization represented overlapping but different categorical outcomes
and were examined separately.
Treatment Group and Clinical Outcome
Survival analyses examined the relationships between treatment
group, relapse, and rehospitalization. First, we used survival
curves based on the Kaplan–Meier method (Kalbfleisch & Pren-
tice, 1980) to estimate the risk of relapse–rehospitalization (time to
first relapse or rehospitalization) in each of the treatment groups,
and log-rank chi-square tests were conducted to evaluate the
equivalence of the resultant survival curves. Second, because we
continued to follow and treat patients after they relapsed, partici-
pants could (and did) have multiple relapses and rehospitalizations
during the 1-year active treatment period and the posttreatment
follow-up period. These multiple events were analyzed with the
Andersen and Gill (1982) counting process approach, a method of
proportional hazard survival regression analysis that permits entry
of multiple events of the same type. Participants were included in
the analysis regardless of whether they completed the full year of
psychosocial treatment. For all analyses, two-tailed tests were
Figure 1 demonstrates the cumulative probability of symptom
relapse during the entire 1-year treatment period and posttreatment
follow-up interval together. Calculated with the Kaplan–Meier
method, the probability of having an episode of mood disorder did
not differ between the FFT and individually focused patient treat-
ment groups, ?2(1, N ? 53) ? 0.50, p ? .10. However, when
multiple relapses were examined with the Andersen–Gill model,
results indicated a treatment group effect. Those in FFT had fewer
relapses during the entire follow-up interval (intervention year and
posttreatment follow-up together) than did those in individual
treatment, ?2(1) ? 5.04, p ? .05.
Why should an analytic strategy that includes multiple events
reveal differences between the treatment groups, whereas an anal-
ysis that considers only the time until a first incident does not
reveal such differences? Given that the majority of the second
events occurred in the posttreatment interval, separate survival
models examined the 1-year active treatment and the posttreatment
follow-up intervals independently. During the active treatment
year, there were no differences between the treatment groups in
risk of relapse according to either survival method: Kaplan–Meier,
?2(1, N ? 53) ? 0.47, p ? .10; Andersen–Gill, ?2(1) ? 0.85, p ?
.10. Forty-six percent of patients in FFT and 52% of patients in
individual treatment experienced at least one relapse during the
active treatment year, ?2(1, N ? 53) ? 0.16, p ? .10; h ? 0.11.
However, patients who had participated in FFT were much less
likely to relapse in the posttreatment follow-up period than were
patients in individual treatment: Kaplan–Meier, ?2(1, N ?
39) ? 4.05, p ? .05; Andersen–Gill, ?2(1) ? 5.13, p ? .05. During
the posttreatment follow-up period, 28% of patients in FFT expe-
rienced at least one relapse compared with 60% of patients in
individual treatment, ?2(1, N ? 39) ? 4.66, p ? .05; h ? 0.66.
Given the pretreatment group differences on premorbid adjust-
ment scores and age at illness onset, separate analyses were con-
ducted, controlling for each. First, we examined whether premor-
bid adjustment could account for the relationships observed
between treatment group and time to relapse. Premorbid adjust-
ment period and follow-up interval.
Cumulative probability of symptom relapse over 1-year treat-
FAMILY-FOCUSED TREATMENT FOR BIPOLAR DISORDER
ment, treatment group, and their interaction term were entered into
Cox proportional hazards regression models for each of the two
study periods (the 1-year active treatment year and the posttreat-
ment follow-up interval). The regression model for the year of
study treatment revealed a significant interaction of treatment
group and premorbid adjustment in predicting relapse, ?2(1, N ?
51) ? 4.73, p ? .05. To further examine this interaction, subjects
were placed into high and low premorbid groups with a median
split on the UCLA Social Attainment Scale, and separate survival
models were tested for both premorbid groups (good vs. poor
premorbid adjustment). Whereas patients with good premorbid
adjustment were equally likely to relapse during the first year
whether in family or individual treatment, ?2(1, N ? 31) ? 1.68,
p ? .10, being in family treatment decreased the odds of relapse
threefold among poorer premorbid patients, in comparison with the
individual treatment, ?2(1, N ? 20) ? 3.56, p ? .06. The gender
of the patient was not associated with relapse, ?2(1, N ?
53) ? 0.20, p ? .10, nor did its inclusion in the model improve
prediction of relapse.
During the posttreatment follow-up period, there was no inter-
action between treatment group and premorbid adjustment and no
significant effect of premorbid adjustment on relapse risk. How-
ever, inclusion of premorbid adjustment, ?2(1, N ? 39) ? 0.80, p
?.10, in the regression model reduced the predictive significance
of treatment group, ?2(1, N ? 39) ? 2.46, p ? .12, during the
Second, in parallel analyses we examined whether age of illness
onset could account for the relationships observed between treat-
ment group and time to relapse. Age of illness onset was not
associated with relapse risk during either the 1-year active treat-
ment period or the posttreatment follow-up interval, and its inclu-
sion in multiple regression models did not reduce the predictive
significance of treatment group.
The cumulative probability of rehospitalization for the two
treatment groups during the entire study period (active treatment
and follow-up) is depicted in Figure 2. Kaplan–Meier survival
analysis revealed that individuals who participated in FFT were
less likely to be hospitalized over the entire study interval than
were individuals who participated in individual treatment, ?2(1,
N ? 53) ? 3.87, p ? .05. When multiple rehospitalizations were
considered in an Andersen–Gill survival model, these treatment
group differences were equally evident, ?2(1) ? 4.21, p ? .05.
Next, Kaplan–Meier survival analyses separately examined rehos-
pitalizations for the year-long treatment period and the posttreat-
ment follow-up. No effect of treatment group was observed during
the 1-year active treatment period, ?2(1, N ? 53) ? 1.38, p ? .10.
Twenty-nine percent of patients in FFT and 40% of patients in
individual treatment were rehospitalized during the active treat-
ment year, ?2(1, N ? 53) ? 0.76, p ?.10; h ? .24. Nonetheless,
those patients who received FFT had a much lower risk of rehos-
pitalization during the posttreatment follow-up period than those
patients who received individual treatment, paralleling the findings
for relapse, ?2(1, N ? 39) ? 10.32, p ? .01. Indeed, during the
posttreatment follow-up period, 12% of patients in FFT were
rehospitalized compared with 60% of patients in individual treat-
ment, ?2(1, N ? 39) ? 11.52, p ? .01; h ? 1.06.
Separate Cox proportional hazards regression models were con-
ducted to control for premorbid adjustment and age of illness
onset. Neither premorbid adjustment, treatment group, nor their
interaction predicted the likelihood of rehospitalization during the
treatment year. However, both premorbid adjustment, ?2(1, N ?
39) ? 4.65, p ? .03, and treatment group, ?2(1, N ? 39) ? 4.90,
p ? .03, were separate and statistically reliable predictors of
rehospitalization during the posttreatment follow-up interval. As
expected, good premorbid patients were less likely to be rehospi-
talized during the posttreatment interval than poor premorbid
As in our analyses of relapse, age of illness onset was not
associated with rehospitalization for either study interval. Further-
more, its inclusion in regression models did not attenuate the
effects of treatment group on rehospitalization.
The above findings suggested that the impact of the family
intervention was stronger for rehospitalization than for symptom-
atic relapse. To further understand the relationship between treat-
ment, relapse, and rehospitalization, we divided the participants
into those who had not been rehospitalized when they relapsed
versus those who were rehospitalized at least once during a re-
lapse, when considering the entire follow-up period (study year
and follow-up together). A chi-square test revealed that patients in
the family treatment were significantly less likely to be hospital-
ized at the time of relapse than patients in the individual treatment
(55% vs. 88%, respectively), ?2(1, N ? 35) ? 4.57, p ? .03; h ?
.76. These findings suggest that the family intervention had its
greatest impact on assisting patients and their families to avoid the
need for rehospitalization during a period of symptomatic
The findings indicate that patients who participated in family
treatment had a lower risk of rehospitalization and relapse than
those in individual patient treatment during the posttreatment
follow-up interval, but not during the treatment itself. Could these
results be accounted for by the patients’ utilization of mood-
stabilizing medications, either their specific regimens or compli-
ance with these regimens? As indicated earlier, medication regi-
mens for the two groups were comparable at each individual
assessment point (for all, p ? .10; Table 1). We next examined the
period and follow-up interval.
Cumulative probability of hospitilization over 1-year treatment
REA ET AL.
7-point Likert-type physician’s ratings on medication compliance
across the treatment year using repeated measures analyses of
variance (ANOVAs) and found no main effect for treatment group,
F(1, 49) ? 0.98, p ? .10, no effect of time, F(3, 117) ? 0.76, p ?
.10, and no Treatment Group ? Time interaction, F(3,
117) ? 0.09, p ? .10. Means for the two treatment groups at each
follow-up point are displayed in Table 3.
A Student’s t test compared the treatment groups on medication
compliance during the posttreatment follow-up interval (a single
assessment) and found no differences, t(34) ? 0.25, p ? .10. On
the whole, the participants were quite compliant with their medi-
cation, with at least 78% of the patients scoring within the com-
pliant range at each assessment point.
This study examined the efficacy of psychosocial treatment as
an adjunct to standard pharmacological maintenance in preventing
relapses of bipolar disorder. The findings indicate that an outpa-
tient family-based treatment can lead to a reduced risk of relapse
and rehospitalization, as compared with a comparably paced indi-
vidual therapy program. Group differences were particularly ap-
parent in the year following participation in the treatment program
when 28% of those who had received family-based intervention
relapsed, as opposed to 60% of those in individually based treat-
ment. Results for rehospitalization during the posttreatment
follow-up period were even more striking: Twelve percent of
patients in family-based treatment were rehospitalized, compared
with 60% in individually based treatment.
The findings add to the growing literature suggesting that psy-
choeducational treatment of the family plays an important role in
the comprehensive outpatient management of bipolar disorder
(Miklowitz & Craighead, 2001). Specifically, the findings are
consistent with the Miklowitz et al. (2000) trial, which found that,
over a 1-year active treatment and follow-up period, FFT and
medication led to longer delays prior to relapse than a comparison
group that received medication, two sessions of family education,
and crisis support as needed.
Interestingly, in this study, the impact of FFT was strongest after
completion of the treatment protocol but did not appear during the
year of active intervention. The differential impact of the two
treatment conditions in the first study year may have been diluted
in several ways. First, unlike the study by Miklowitz et al. (2000),
the FFT and the individual comparison treatments were matched
on amount of therapist–patient contacts. Thus, a high level of
intervention was available for both psychosocial treatment groups,
including intensive medication management, frequent monitoring
of emergent symptoms, family education, 24-hr staff availability to
family members and patients, and thorough medical and psycho-
social follow-up of missed appointments. Second, there were high
rates of compliance to medication and psychotherapy in both
treatment groups during the first study year. These rates of com-
pliance are in contrast to the poor compliance often associated with
bipolar disorder (Cochran, 1986). Although there was not a
pharmacotherapy-only contrast group in this study, the finding of
high compliance in both psychosocial treatment groups may sug-
gest that a relatively intensive psychosocial intervention, either
family- or individually based, may help assure consistency with
drug regimens among bipolar patients. Alternatively, the study
may have inadvertently sampled patients who were more medi-
cally compliant. In summary, a high intensity of psychosocial
intervention and medication management may have led to compa-
rable rates of relapse and rehospitalization in both psychosocial
treatment groups during the 12-month active treatment phase.
If treatment with FFT did not lead to better medical adherence
among patients than individually focused patient treatment, then
what might account for the better clinical status of FFT-treated
patients over the 2-year course of the study? Possibly, the skills
that patients and family members develop through participation in
FFT, including a greater knowledge of bipolar disorder and effec-
tive communication and problem-solving skills, may be brought to
bear in managing the illness. This possibility is supported by the
finding that the impact of the family intervention was greatest after
the year-long participation in the study, a point at which family
members no longer had regular contact with the study’s clinical
team and had to rely on the tools they developed in family
treatment, such as early symptom identification, appropriate use of
mental health resources, and problem solving. Although the pa-
tients in individual treatment were taught skills for better illness
management, family members were not brought into treatment as
sources of support. For example, participants in the family treat-
ment were encouraged to engage in anticipatory planning for
future symptom recurrences, including developing a written con-
tract regarding how a relapse could be handled. Bipolar patients
may benefit from the assistance of a knowledgeable social system
when their own coping strategies are compromised by their clinical
state. The notion that family support leads to improved manage-
ment of the disorder is underscored by the finding that, even in the
face of symptomatic relapse, just over half of the patients in family
treatment were rehospitalized, whereas almost 90% of patients in
individual treatment were rehospitalized.
An unanticipated finding was that premorbid social adjust-
ment—an established predictor of outcome in schizophrenic and
other disorders (e.g., Houlihan, 1977)—interacted with treatment
group in predicting patients’ outcomes during the year of partici-
pation in the study-based treatment. During this period, poor
premorbid patients were protected from relapse in the family
treatment group but not in the individual therapy group. The
gender of the patient did not moderate this interaction. In the
1-year period following the conclusion of the intervention, how-
ever, treatment group and premorbid adjustment were independent
predictors of rehospitalization. Good premorbid patients had lower
rates of rehospitalization following the study regardless of treat-
Physicians’ Medication Compliance Ratings
M SDM SD
the two treatment groups (p ? .10) at any of the evaluation points.
Physicians’ ratings of medication compliance did not differ across
FAMILY-FOCUSED TREATMENT FOR BIPOLAR DISORDER
ment condition. In an early study of family crisis-oriented treat-
ment for schizophrenia, Goldstein, Rodnick, Evans, May, and
Steinberg (1978) found interactions between type of psychosocial
treatment, premorbid adjustment, and gender. Premorbid adjust-
ment was unrelated to relapse rates among females with schizo-
phrenia. In contrast to the present findings, good premorbid males
with schizophrenia had lower rates of relapse than poor premorbid
males when treated with family therapy and phenothiazine
Few studies have examined the relationship between premorbid
adjustment and outcome in bipolar disorder. Glick, Clarkin, Haas,
and Spencer (1993) examined prehospital functioning, a variable
conceptually similar to premorbid adjustment, in evaluating the
effects of a six-session family-based treatment for hospitalized
individuals with schizophrenia and affective disorders. Among
patients with affective disorders, positive benefits of family treat-
ment were generally limited to female patients but did not vary
with prehospital functioning. Results among patients with schizo-
phrenia were somewhat different. At hospital discharge, those with
good prehospital functioning appeared to benefit most from family
treatment. However, results at 18 months after hospital discharge
were similar to the present findings in that family treatment ap-
peared to have its greatest impact on those with poor prehospital
functioning. Taken as a whole, these studies underscore the com-
plex relationships between type of treatment, diagnosis, and pre-
morbid functioning. Future studies of the psychosocial treatment
of bipolar disorder should examine premorbid psychosocial adjust-
ment as a moderator of the impact of interventions during periods
of active treatment and follow-up.
There are several limitations to the current study. First, the
design did not allow for control over medication regimens. Stan-
dard drug treatments for bipolar disorder often consist of complex
combinations of mood stabilizers, antipsychotics, and antidepres-
sants. Medication regimens were clinically determined for individ-
ual patients, leading to a wide range of drug combinations and
dosing patterns. Furthermore, it was not possible to keep physi-
cians unaware of patients’ psychosocial treatment assignments.
This design precludes the analysis of potential interactions be-
tween specific types of medications or dosing protocols and psy-
chosocial intervention strategies.
Second, although the study compared two treatments of equal
duration (9 months) and number of sessions (21), there were
nonetheless systematic differences between the treatments. Specif-
ically, patients in the family-focused treatment had two therapists
and attended 60-min sessions, whereas those in individually fo-
cused treatment had one therapist and attended 30-min sessions.
Indeed, the individual treatment had more limited goals, and did
not include a focus on the quality of family interactions or the
coping styles of caregiving family members. Possibly, a more
rigorous test of the difference between these two treatments would
occur in a study in which both interventions were delivered by
single providers and matched on the length of the treatment sessions.
Third, although therapists’ adherence to the family-focused
treatment was evaluated and revealed consistent fidelity to the
treatment manual, similar measures of adherence were not ob-
tained for therapists administering the individually focused treat-
ment. The same therapists administered both treatments and re-
ceived equally frequent supervision from the same, experienced
clinicians. Nonetheless, it was not possible to determine whether
the treatments were conducted with the same degree of skill or
enthusiasm. Future randomized studies of bipolar disorder and
psychosocial treatment need to document equivalence of thera-
pists’ fidelity and skill in delivering all study-based experimental
Fourth, this study was restricted to those patients who were
willing to take mood stabilizers. The impact of the family inter-
vention on unmedicated patients cannot be determined. Fifth, the
findings are only applicable to patients who had families willing to
be involved in treatment. Although this inclusionary criterion may
have led to overselection of better prognosis bipolar patients with
high levels of social support, rates of relapse over the first year
(49%) were comparable to rates observed in other longitudinal or
randomized treatment studies of bipolar patients (e.g., 37%, Gitlin
et al., 1995; 44%, Miklowitz et al., 2000). Finally, this study
included only patients whose index study episode was manic and,
in all cases but one, hospitalized. Thus, the applicability of the
findings to bipolar, depressed, mixed, rapid cycling, or bipolar II
patients is less clear.
The current study lends strong support to the nascent literature
on the role of psychosocial treatment generally, and family treat-
ment specifically, in the comprehensive outpatient management of
bipolar disorder. However, a number of challenges remain. First,
the mechanisms underlying the impact of these treatments require
further study. Prior studies have shown positive effects of individ-
ual or family psychosocial interventions on the stability of sleep–
wake schedules and social routines (Frank et al., 1997), medication
adherence (Cochran, 1984), and the efficiency of family commu-
nication and problem-solving behavior among patients with bipo-
lar disorder (Simoneau, Miklowitz, Richards, Saleem, & George,
1999). Yet, we know little about how changes in these mediating
variables alter a patient’s vulnerability to episodes of mood disor-
der. Second, although a number of psychosocial interventions for
bipolar disorder exist, it is not clear which subgroups of patients
(e.g., depressed versus manic patients, medically noncompliant
versus compliant, good versus poor premorbid) respond best to
each and at which stages of their disorder.
Third, research needs to consider the barriers to implementing
family or other psychosocial interventions for bipolar patients in
community settings. Studies of patients with schizophrenia suggest
the importance of including family interventions in comprehensive
outpatient management protocols (Schooler et al., 1997). Family
interventions, however, have rarely been implemented in commu-
nity settings in the United States, due in part to the costs of such
programs. The strongest finding of the current study was the
notable group differences in rehospitalization rates, perhaps the
most costly of treatment options. Possibly, the cost of a family-
based treatment may be offset by the decreased rehospitalization
risk conferred by the treatment over time. The cost-effectiveness of
family-focused and other psychosocial treatments in a variety of
community settings serving different patient populations—as is
being done in the Systematic Treatment Enhancement Program for
Bipolar Disorder (Sachs, in press)—should provide more compre-
hensive answers to these questions.
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Received June 19, 2001
Revision received May 6, 2002
Accepted May 7, 2002 ?
REA ET AL.