DOI: 10.1111/bdi.

12621

ORIGINAL ARTICLE

Randomized trial comparing caregiver-­only family-­focused

treatment to standard health education on the 6-­month
outcome of bipolar disorder

Deborah A Perlick1,2  | Carlos Jackson1,2 | Savannah Grier1,2 | 

Brittney Huntington1,2 | Andrew Aronson2 | Xiaodong Luo1,2 | David J Miklowitz3

1
JJ Peters, Department of Veterans Affairs
Medical Center and VISN 2, South Mental
Illness Research, Education and Clinical
Center, Bronx, NY, USA
2
Department of Psychiatry, Icahn School of
Medicine at Mount Sinai, New York, NY, USA
3
Division of Child & Adolescent
Psychiatry, UCLA Semel Institute, David
Geffen School of Medicine, University of
California, Los Angeles, CA, USA
Correspondence
Deborah A. Perlick, Icahn School of
Medicine at Mount Sinai, One Gustave L.
Levy Place, New York, NY, USA.
Email: deborah.perlick@mssm.edu
Funding information
National Institute of Mental Health, Grant/
Award Number: R34 MH071396
Abstract
Objectives: Caregivers of people with bipolar disorder often have depression and
health problems. This study aimed to evaluate the sustained effects of a 12-­15 week
psychoeducational intervention on the health and mental health of caregivers of per-
sons with bipolar disorder. We also evaluated the effects of the intervention on pa-
tients’ mood symptoms over 6 months post-­treatment.
Methods: Caregivers of 46 persons with bipolar disorder were randomized to 12-­
15 weeks of a caregiver-­only adaptation of family-­focused treatment (FFT), in which
caregivers were instructed on self-­care strategies and ways to assist the patient in
managing the illness, or to 8-­12 sessions of standard health education. Independent
evaluators assessed caregivers’ depression and physical health and patients’ mood
symptoms before treatment, immediately after the treatment, and at 6 months
post-­treatment.
Results: Randomization to FFT was associated with greater decreases in depression
for both caregivers and patients over a 6-­month follow-­up period post-­treatment.
Reductions in patients’ depression scores over 6 months post-­treatment were medi-
ated by reductions in caregivers’ depression scores (z = −2.74, P < .01).
Conclusions: Interventions that are effective in reducing mood symptoms and im-
proving health behavior in caregivers may have important health and mental health
benefits for patients with bipolar disorder. Specifically, a treatment focused on car-
egiver education about bipolar disorder and the need for the caregiver to attend to
his/her own health and mental health can benefit patients, even without their direct
participation.

KEYWORDS
bipolar disorder, family depression, family education, patient bipolar mood symptoms

1 | I NTRO D U C TI O N
Research on family members of persons with bipolar disorder has
focused on interventions to provide education and communication
and problem-­solving skills to enhance family members’ effectiveness
as caregivers and improve patient outcomes.1 Studies of the impact
of caregiving on family members’ own mental, physical and financial
health, often referred to as ‘caregiver burden’, 2 show that 89%-­91%
of family caregivers of people with bipolar disorder report moder-
ate to high levels of burden.3–6 Higher levels of caregiver burden are

622  |  wileyonlinelibrary.com/journal/bdi

© 2018 John Wiley & Sons A/S. Bipolar Disorders. 2018;20:622–633.
Published by John Wiley & Sons Ltd
PERLICK et al.
associated with adverse effects for caregivers, including sleep dis-
7,8
turbance, chronic medical conditions and depressive symptoms,
well as with higher levels of caregiver health and mental health care
service use.8 Interventions targeting health behavior have demon-
strated improved health and/or mental health status for caregivers
of persons with dementia,9–12 cancer13,14 and anorexia nervosa,15
but aside from our preliminary work, described below,16 evidence-­
based treatments for bipolar disorder have not explicitly targeted
caregiver health, mental health or burden to date.
Importantly, caregiver burden has been associated with adverse
effects for the relatives with bipolar disorder as well.17,18 Persons
with bipolar disorder whose caregivers are highly burdened and/
or exhibit health problems report poorer medication adherence17
and are at greater risk for relapse and/or suicidal behavior than per-
sons with bipolar disorder whose caregivers report low levels of
7,17–19
burden.
To address these adverse effects of caregiver burden on care-
giver and patient outcomes, we developed a ‘caregiver only’ varia-
tion of family-­focused therapy (FFT) for bipolar disorder1 targeting
caregivers’ own health and mental health needs through definition of
self-­care goals and use of cognitive behavioral strategies to promote
self-­care implementation, as well as education about management
of bipolar disorder. Both FFT and Family-­Focused Treatment-­Health
Promoting Intervention (FFT-­HPI) seek to reduce the risk of patient
relapse by replacing negative patient-­
caregiver interactions with
more adaptive communications, but the approaches differ. FFT in-
volves bidirectional communication between the patient and care-
giver and familial problem solving, while FFT-­HPI is an individual or
couples treatment for caregivers that focuses on caregivers’ interac-
tions with the patient using cognitive and behavioral strategies, as
well as on caregiver self-­care. This study evaluates the efficacy of
this 12-­15 session intervention, FFT-­HPI, over the course of treat-
ment and 6 months post-­treatment compared to a health education
(HE) comparison treatment. A preliminary report examined changes
observed over the course of treatment only,16 finding reductions in
mood symptoms for both caregivers and patients, but did not eval-
uate the maintenance of these treatment gains, or the association
of caregiver and patient reductions in mood symptoms over time.
Based on the positive findings from health-­promoting interventions
for other disorders cited above, we hypothesized that caregivers
randomized to FFT-­HPI would show reductions in health and mental
health problems (primary outcomes) and health behavior and subjec-
tive burden (secondary outcomes) compared to caregivers random-
ized to HE over the 12-­week course of the treatment and 6-­month
follow-­up. Because caregiver burden has been found to mediate or
16,17
moderate patient clinical outcomes in bipolar disorder, we also
hypothesized that patients associated with caregivers randomized to
FFT-­HPI would show decreased mood symptoms compared to those
associated with caregivers randomized to HE during this time frame,
and that improvement in patient mood symptoms would be medi-
ated by treatment-­related improvements in caregiver health and
mental health outcomes. Finally, based on extensive literature show-
ing high rates of distress and anxiety among caregivers4,8,20,21 and
|
      623
a high correspondence between symptoms of anxiety and depres-
as sion in caregivers, 21 we hypothesized that reductions in caregiver
depression would be correlated with treatment-­related reductions
in anxiety level among caregivers.
2 | PATI E NT S A N D M E TH O DS
2.1 | Participants
Eligible caregivers: (a) were aged ≥18 years, (b) identified as the pri-
mary caregiver of a relative with bipolar I or II disorder who also
consented to participate in the study, and (c) demonstrated current
problems with mental health or health behavior. The primary car-
egiver met at least three of five criteria established by Pollak and
Perlick 22: (1) is a spouse or parent, (2) has more frequent contact
than any other caregiver; (3) helps to support the patient finan-
cially; (4) is contacted by treatment staff for emergencies; (5) has
been involved in the patient’s treatment. Caregiver health behavior
and mental health problems were defined as scoring positive for at
least one health risk behavior on the Health Risk Behavior Scale23
and either scoring ≥10 on the Center for Epidemiological Studies
for Depression Scale24 or scoring positive on at least four burden
areas on the Social Behavior Assessment Schedule. 25 Patients were
diagnosed based on the Structured Clinical Interview for DSM-­IV
(SCID). 26 The study was approved by the Internal Review Boards
of the Icahn School of Medicine at Mount Sinai and the Bronx VA
Medical Center.
2.2 | Recruitment
Caregiver participants were recruited from the Mount Sinai
Outpatient Mental Health Clinic, New York, NY (n = 5); from the
Bronx Veterans Affairs Medical Center, Bronx, NY (n = 2); and from
the Mood Disorders Support Group of New York (MDSG), New York,
NY (n = 36). At the mental health facilities, clinicians referred pa-
tients who agreed to participate and had an interested family mem-
ber to the study team. Caregivers were recruited at weekly MDSG
support group meetings via fliers, by referral from peer group lead-
ers, or through a brief presentation by study staff at weekly ‘Family
and Friends’ group meetings. Prospective participants were told the
study aimed to evaluate an intervention for family members that fo-
cused on education about bipolar disorder and on improving family
member health practices. The study principal investigator (DP) met
with all clinician-­and self-­referred caregivers and patients individu-
ally to explain study procedures, answer questions and obtain writ-
ten informed consent. Forty (80%) of 50 caregivers referred from
the MDSG and 100% of their relatives with bipolar disorder agreed
to participate. Fourteen (54%) of 26 patients referred from the men-
tal health facilities agreed to participate; of these, 12 (71.4%) of their
caregivers agreed as well. Differential patient participation rates
in the support group vs mental health clinics were likely related to
both the differential recruitment procedures described above (con-
tacted by clinician vs family member who required patient’s consent
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624       PERLICK et al.
to participate) and overall referral rates (26 from clinics vs 50 from
support group).
All consenting caregivers and patients were screened for eligibil-
ity, according to the criteria described above. Three caregivers were
subsequently excluded because they did not meet criteria for health
risk behavior, and one caregiver’s relative did not meet diagnostic
criteria on the SCID.
2.3 | Design and randomization
The study was a two-­arm randomized controlled trial with an active
control group. Interested caregivers from all sources who consented,
met inclusion/exclusion criteria and completed the baseline assess-
ment were randomized to receive either the experimental treat-
ment, FFT-­HPI, or a control treatment providing education about
bipolar disorder and health problems common among caregivers
(HE). Randomization was performed by an independent researcher
using a random numbers table where all even numbers were as-
signed to FFT-­HPI and odd numbers to HE. Treatment assignments
were placed into sealed envelopes numbered sequentially and were
opened by the project director at the weekly meeting immediately
following completion of the baseline assessment. Parents of young
adults who were equally involved in caregiving were randomized as
one unit. The small number of subjects did not allow for a blocking/
stratification procedure: Three parental couples were randomized to
FFT-­HPI and one to HE. Overall, 25 caregivers were assigned to FFT-­
HPI and 21 were assigned to HE.
2.4 | Interventions
2.4.1 | FFT-­HPI
The FFT-­HPI model is an individual or couples treatment for car-
egivers of persons with bipolar disorder. It is based on three prem-
ises supported by extensive research and theory: (1) negative and
dysfunctional automatic thoughts, feelings and core beliefs about
caregiving contribute to and sustain depressive symptoms and per-
27,28
ceived burden among caregivers; (2) depressive symptoms in
particular interfere with caregiver self-­care and ability to manage
the demands and stress associated with caregiving skillfully;29–31 (3)
because caregiver depression symptoms interfere with management
of caregiving demands, level of caregiver symptoms also impacts the
patient’s level of mood symptoms.1,16,17 FFT-­HPI is designed to cor-
rect this dysfunctional sequence by combining education about op-
timal illness management with cognitive reframing of the caregiver’s
core beliefs about caregiving and definition and implementation of
self-­care goals to boost emotional and physical health and resilience.
The intervention consisted of two phases. The initial phase,
Psychoeducation and Goal Setting (sessions 1-­4), (1) provided educa-
tion on the etiology and treatment of bipolar disorder, relapse pre-
vention and communication strategies as described by Miklowitz1,2
and (2) helped caregivers to set goals for promoting self-­care and
improving the relationship with the patient. A particular treatment
focus was helping caregivers define both appropriate levels of sup-
port relative to the patient’s mental status and realistic expectations
for his/her functional outcome, in order to promote more autono-
mous functioning for both patient and caregiver.
The second phase, Behavioral Analysis of Self-care Barriers (ses-
sions 5-­12), used cognitive behavioral therapy (CBT) and problem-­
solving strategies to (1) identify situations where caregiving demands
and/or subjective strain and associated cognitions served as barriers
to the caregivers’ implementation of illness management and self-­
care goals, and (2) implement corrective solutions formulated as spe-
cific behaviors tracked via a daily diary. Strategies for this treatment
phase were derived from pilot data provided by the responses of 28
caregivers of patients with bipolar disorder participating in an inter-
view study6 who were asked whether, and in what ways, caregiv-
ing interfered with self-­care. Based on informal qualitative analysis
of these responses and their combined clinical experience, DP and
DJM identified three common barriers to self-­care: (1) demands for
service or support by the bipolar relative; (2) conflict with the bipolar
relative; (3) caregiver anxiety and/or depression. They then devel-
oped modules designed to address these barriers to self-­care and
facilitate adoption of health-­promoting behavior. ‘Support diversi-
fication’ focused on broadening the patient and caregiver support
networks and increasing patient self-­reliance. ‘Conflict resolution’
utilized problem-­solving and communication skills training and in-
cluded an optional one to three sessions with the bipolar relative.
‘Efficacy and expectations’ challenged depressogenic cognitions
and used positive self-­statements, exercise and sleep hygiene to
increase caregivers’ self-­
efficacy. Clinicians and caregivers could
also opt to combine interventions from more than one module. In
this case caregivers were offered an additional three sessions (up
to 15 sessions) to accommodate more than one module. To gain ad-
ditional input on this approach, DP and study clinician NL co-­led a
focus group with seven caregivers of patients with bipolar disorder
recruited from MDSG/NY. Participants in this group discussed, con-
firmed and elaborated on the barriers identified in our pilot study,
and helped identify and refine strategies to address them, based on
their own lived experience.
Phase 2 of the intervention was initiated with a collaborative
discussion with each caregiver which integrated findings from the
assessment (e.g. depression score) with caregivers’ perceptions, re-
sulting in assignment to one of the three treatment modules. Beliefs
about caregiving targeted for ‘support diversification’ included,
‘I think I just accept that I can’t do things because of my mother’s
needs’. Examples of targets for ‘conflict resolution’ included, ‘He
becomes angry if I ask him if he’s taken his meds, yet other days
he is angry if I don’t ask’, and core beliefs targeted for ‘efficacy and
expectations’ were, ‘I am so depressed I don’t have the energy to do
anything…despite medication’, ‘I feel guilty’ and ‘I want to be asleep
to cope…it’s just too heavy to think about’.
Sessions were 45 minutes in duration and delivered on a weekly
basis. Across all modules, the therapist and caregiver defined a spe-
cific goal in each of three areas: (1) interpersonal (i.e. improving their
interactions with their relative); (2) affective (i.e. reducing their own
PERLICK et al.
emotional distress); (3) health/self-­care (i.e. monitoring their physical
health and adopting a healthier lifestyle in at least one area, such as
exercise or diet). These goals served as a treatment plan. Specific
strategies and/or plans towards attaining these broader goals were
defined (e.g. schedule appointment for physical exam), and progress
in implementing the plan was monitored through a daily diary, focus-
ing on one plan at a time. All sessions in all modules followed a stan-
dard CBT format, including setting an agenda, review of homework
(i.e. review of self-­care plan log), behavioral analysis and problem-­
solving and/or use of cognitive reframing to address barriers to
implementation of self-­care plan, and assignment of homework. A
more detailed description of the treatment is provided in Perlick
et al.19 (treatment manual available upon request).
2.4.2 | Health education
The HE comparison treatment adopted a didactic approach to edu-
cating family members about bipolar disorder and health problems
identified as common among caregivers, e.g. depression, anxiety
and sleep disorders. Health information was delivered by a trained
clinical research associate, using eight to 12 commercially produced
DVDs selected for this purpose, with each tape focusing on a single
health problem such as chronic pain or heart disease. In session 1,
participants viewed a DVD that provided education about bipolar
disorder. In sessions 2-­7 they viewed a core set of six 25-­30 minute
tapes (one per session) describing the most common health prob-
lems experienced by caregivers based on prior studies. They then
selected up to five additional tapes of their own choice. The clinical
research associate paused the tapes at standardized break points
to review the material and ensure the caregiver understood the in-
formation. However, research associates refrained from answering
questions that addressed the caregivers’ or patients’ own health or
mental health. Scripted questions were used to ensure adherence to
the structured protocol. Questions included, ‘What are the risk fac-
tors associated with heart disease?’ and ‘What treatments are avail-
able for insomnia?’ Sessions were 45 minutes in duration.
2.4.3 | Treatment fidelity
The treatment was delivered by two experienced clinicians trained
in FFT and CBT and was supported by weekly peer supervision
and monthly supervision by DJM. All sessions were audiotaped to
evaluate treatment fidelity and ten randomly selected sessions were
rated by two independent raters using an adaptation of the 11-­item
32
Therapy Competence and Adherence Scales. Of 10 sessions rated
by two raters, 90% (18/20) were rated at or above a preselected
adherence threshold. Agreement between the two raters was good
(kappa = 0.91).
2.5 | Patient and caregiver assessments
Caregivers and patients were assessed pre-­and immediately post-­
treatment and 6 months post-­treatment. Assessors were blind to
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treatment condition and participants were instructed not to discuss
their treatment experience with the assessors. All patient and di-
agnostic assessments were performed by two master’s level clinical
doctoral students who administered the first three diagnostic and
clinical symptom scales together with the first author (DP): both cli-
nicians’ diagnostic interview ratings corresponded 100% with DP’s,
and clinical symptom scales differed from DP’s by no more than one
point. All additional measures were administered in interview for-
mat, even where a self-­report option was available, to reduce missing
data and improve reliability. In addition to diagnostic and outcome
measures described below, data on patient clinical history and pa-
tient and caregiver sociodemographics (e.g., age, gender, race/eth-
nicity, marital and employment status, and socioeconomic status of
both patients and caregivers) were collected.
2.6 | Patient assessment
The patient’s lifetime diagnosis of bipolar disorder and current
episode status were assessed using the mood and psychosis mod-
ules from SCID. 26 Current symptom level was evaluated using the
Hamilton Rating Scale for Depression (HAM-­D)33 and the Young
Mania Rating Scale (YMRS).34 Internal consistency reliability in the
present study was 0.849 for the HAM-­D and 0.852 for YMRS.
2.7 | Caregiver assessment
The caregiver’s lifetime diagnosis and current episode status were
evaluated by the Mini International Neuropsychiatric Interview
(MINI Plus, version 5.0), a semi-­structured interview designed to
identify current major Axis I disorders.35 The MINI was developed
to meet the need for a brief, reliable, and valid structured diagnos-
tic interview and has good concordance with SCID-­P diagnoses of
MDD (kappa = 0.84).35 The primary caregiver outcomes, health and
mental health, were evaluated by the Mental Outcomes Studies
36-­Item Short-­Form Health Survey (SF-­36)36 and the Center for
D). 24 The SF-­
Epidemiological Studies of Depression Scale (CES-­
36 is a valid and reliable instrument comprised of eight subscales
which yield a total Mental Component Score (MCS) and Physical
Component Score (PCS) evaluating physical functioning, role limi-
tations due to physical health problems, role limitations due to
emotional problems, energy/fatigue, emotional well-­
being, social
functioning, bodily pain, and general health. The SF-­36 has dem-
onstrated reliability (internal consistency coefficients) of ≥0.8,
and is sensitive to change.36–38 The CES-­D is a 20-­item interview
or self-­report scale assessing depressive symptoms which corre-
lates highly with other self-­report depression measures (Cronbach’s
alpha = 0.93). We chose the CES-­D over the HAM-­D to evaluate
depressive symptoms among caregivers because it has been used
to evaluate caregiver depression in prior studies, with 30%-­4 0% of
caregivers of patients with schizophrenia and bipolar disorder scor-
ing positive for depression, using the traditional cut-­off of ≥16.39,40
It has also demonstrated sensitivity to change in interventions de-
signed to improve mental health among caregivers of persons with
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626       PERLICK et al.
civilian traumatic brain injury (TBI),41 combat-­related mild TBI and
42
post-­traumatic stress disorder (PTSD), and Alzheimer’s disease.
The CES-­
D demonstrated high internal consistency reliability
(Cronbach’s alpha = 0.93) in the present study.
Secondary outcomes, caregiver burden and health behavior,
were evaluated by The Social Behavior Assessment Scale (SBAS)
and the Health Risk Behavior Scale (HRB). 23 The SBAS is a semi-­
structured interview assessing objective and subjective burden in
three domains: patient problem behaviors (e.g. violence and unpre-
dictability); patient role dysfunction at work and at home; and ad-
verse effects on others (the impact of the illness on the caregiver’s
work, social and leisure time). To measure objective burden, caregiv-
ers rated the degree to which each problem was present on a scale
of ‘0’, none, ‘1’, moderate or ‘2’, severe; to measure subjective bur-
den, caregivers rated the degree of distress experienced in relation
to each item rated as objectively present, also on a three-­point scale.
Subjective items were coded as ‘not applicable’ (i.e. when the objec-
tive burden was rated as ‘0’ analyses). Gibbons et al.44 reported inter-
rater reliability (weighted kappa) coefficients of 0.97, 0.83 and 0.98
for subjective burden ratings on domains 1-­3 above respectively;
comparable coefficients were obtained for ratings of objective bur-
den. The total subjective burden score across 56 items (Cronbach’s
alpha = 0.88) was used to evaluate burden in the present study, as
this measure represents the purer measure of perceived strain. The
HRB is a nine-­item scale developed to assess behavioral health risks
associated with caregiving (e.g. eating fewer than three meals a day,
not getting enough rest, forgetting to take medications, and miss-
ing doctors’ appointments), which correlates with perceptions of
general health23 and demonstrated adequate internal consistency
reliability in the present study: Cronbach’s alpha = 0.78. The Brief
Symptom Index (BSI) 45 anxiety scale was included in order to evalu-
ate our exploratory hypothesis that decreases in caregiver depres-
sion were mediated by decreases in anxiety. The BSI is a self-­report
inventory designed to assess the psychological symptom status of
patients and non-­patients. The anxiety dimension items reflect a set
of symptoms usually associated with high manifest anxiety, such as
restlessness, nervousness, and tension. Each item on the BSI is rated
on a five-­point scale of distress (0-­4), ranging from ‘not at all’ to ‘ex-
tremely’ (Cronbach’s alpha = 0.85).
2.8 | Data analytic strategy
First, the treatment and control groups were compared on pretreat-
ment sociodemographic and clinical characteristics using t tests or
Fisher’s exact tests to ensure that randomization resulted in balanced
groups on these variables in view of the relatively small sample size.
Next, mixed effects linear regression models46 evaluated the impact
of treatment assignment on the primary and secondary outcomes for
caregivers (SF-­36, CES-­D, SBAS and HRB) and primary outcomes for
patients (HAM-­D and YMRS) over the treatment and post-­treatment
periods. For outcomes showing a significant group × time interaction,
differences between treatment groups at each follow-­up assessment
and within groups from pre-­to post-­treatment and from pre-­to 6
months post-­treatment were evaluated using t tests and paired t
43
tests, respectively. All principal analyses were conducted based on
the intention-­to-­treat principle using all available data for analysis.
Models included group, time, group-­by-­time and the pretreatment
value of each outcome. Because YMRS pretreatment scores showed
25
a bimodal distribution, indicating either no symptoms or very many,
they were dichotomized into scores above and below the median,
and the YMRS model also included a term for the YMRS pretreat-
ment score being above vs below the median score. The Sobel test47
was used to evaluate the hypothesis that treatment-­related reduc-
tions in patient depression and mania were mediated by treatment-­
related improvements in caregiver health and mental health during
follow-­up, as well as the hypothesis that treatment-­related reduc-
tions in caregiver depression level were mediated by reductions in
caregiver anxiety level during the follow-­up period.
3 | R E S U LT S
3.1 | Attrition and adherence
Figure 1 displays the participant flow through the trial. Of the 46
participants who completed outcome measures at baseline and
were randomized to treatments, 43 (93%) completed measures at
both post-­treatment and 6-­month follow-­up. One FFT-­HPI partici-
pant withdrew because the caregiver moved out of state, and two
HE participants withdrew after one or two sessions (i.e. prior to
phase 2); in one case the caregiver died, and in another the family
no longer desired participation (Figure 1). All participants who began
phase 2 of the treatment completed the treatment and both follow-
­up assessments and were included in all analyses, bringing the final
sample to 24 FFT-­HPI and 19 HE participants (N = 43). To boost re-
tention, patients and caregivers assigned to both conditions were
routinely invited to lectures or meetings held by each site.
Table 1 displays the sample characteristics. Treatment groups did
not differ significantly on any of the 13 baseline sociodemographic
and clinical variables evaluated. Participants in both conditions were
seen weekly for a mean ± standard deviation 14.3 ± 1.6 sessions in
FFT-­HPI and 8.1 ± 2.4 sessions in HE. All caregivers completed the
minimum number of sessions (12 in FFT-­HPI and eight in HE) except
for one FFT-­HPI caregiver who completed seven sessions and one
HE participant who completed four. While gender did not differ be-
tween treatment groups, the overall percentage of female caregivers
(84%) was high although not inconsistent with the literature, where
the percentage of caregivers who are female has ranged from 65%
to 91%.6,18,48,49
3.2 | Caregiver outcomes
Table  2 displays the mean, standard deviation, parameter estimates
and significance levels for the mixed models described above, and
Figure 2 displays the slopes for the primary outcomes with con-
fidence intervals set at the 95th percentile for each assessment
point. Significant group-­by-­time interactions were observed for
PERLICK et al.
F I G U R E   1   Consolidated Standards
of Reporting Trials (CONSORT) diagram.
FFT-­HPI, Family-­Focused Treatment-­
Health Promotion Intervention; HE, health
education [Colour figure can be viewed at
wileyonlinelibrary.com]
caregiver depressive symptoms and overall psychological distress,
assessed on the SFMCS over the course of treatment and follow-
­up (Table 2). Caregivers treated with FFT-­HPI showed a reduction
in depressive symptoms of nearly 48% during the treatment and
follow-­up period, compared to caregivers in the HE condition who
showed reductions of 22% (Figure 2). Similarly, FFT-­HPI caregivers
demonstrated a 41% improvement in overall psychological health
(SFMCS) over the course of treatment and follow-­up, compared
to a 21% improvement observed for HE caregivers, which levelled
off immediately post-­t reatment. The largest change was observed
for the ‘role limitations due to emotional problems’ subscale,
where FFT-­HPI participants improved by 134% from baseline to
6 months post-­treatment vs a more modest 33% improvement
observed for HE participants. A significant group-­by-­time inter-
action was also observed for the burden measure, with FFT-­HPI
caregivers reporting experiencing less burden over the course of
treatment and follow-­up relative to HE caregivers (Table 2). The
hypothesized group-­by-­time interactions for the SF-­36 PCS and
HRB scales were not significant at the .05 level (Table 2). Paired
t tests for the HPI group demonstrated significant pre-­to post-­
treatment decreases for the CES-­D which were maintained over
the 6-­m onth follow-­up period, while for the SF-­M CS, SBAS and
BSI significant improvements were observed from immediately
post-treatment to 6 months post-treatment as well as during the
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treatment itself (P values < .05; Table 2). Comparisons between
groups using t tests showed significant differences immediately
post-­t reatment for the BSI anxiety scale and for the BSI, CES-­D,
and SF-­M CS 6 months post-­t reatment.
3.3 | Patient outcomes
Patients associated with caregivers treated with FFT-­HPI demon-
strated a significant decrease in depressive symptoms on the HAM-­D
compared to patients associated with caregivers in the HE condi-
tion (group-­by-­time interaction, z = −2.08, P = .04; Table 3) over the
course of treatment and follow-­up. The group-­by-­time interaction
for YMRS was significant, with the baseline score dichotomized
into high vs low based on a median split (group-­by-­time-­by-­YMRS-­
baseline dichotomized score, z = −2.30, P = .021), demonstrating
an advantage of FFT-­HPI over HE in reducing symptoms of mania/
hypomania, particularly for those patients who started out with
higher YMRS scores (Figure 3). Paired t tests for the HPI group
demonstrated significant pre-­to post-­treatment decreases on the
HAM-­D and YMRS which were maintained across the 6-­month fol-
low-­up (P values < .05; Table 3). Comparisons between groups using
t tests showed significant differences for the HAM-­D and YMRS
both immediately post-­treatment and 6 months post-­treatment (P
values < .05).
 |
628       PERLICK et al.

TA B L E   1   Demographic and illness characteristics of persons

with bipolar disorder (BD) and their family caregiversa

Caregivers Persons with BD

Variable (n = 43) (n = 40)

Age, mean ± SD 52.9 ± 12.4 34.2 ± 14.8

Female sex 36 (83.7) 25 (62.5)
Race
Caucasian 33 (76.7) 30 (75)
African American 2 (4.7) 3 (7.5)
Other 1 (2.3) 0 (0)
Hispanic ethnicity 12 (27.9) 7 (17.5)
Marital status
Married/cohabitating 19 (44.2) 6 (15)
Widowed/divorced/separated 14 (32.6) 12 (30)
Never married 10 (23.3) 22 (55)
Employment status
Full time 22 (51.2) 7 (17.5)
Part time 11 (25.6) 7 (17.5)
Retired/unemployed/student 10 (23.3) 26 (65)
Relationship of caregiver to patient
Parent 30 (69.8)
Spouse/significant other 6 (14)
Adult child 6 (14)
Friend or neighbor 1 (2.3)
Living with patient 28 (65.1)
Socioeconomic statusb
I or II 23 (53.5) 5 (12.5) F I G U R E   2   Mean caregiver depression and mental health scores
III 14 (32.6) 11 (27.5) over time. CES-­D, Center for Epidemiologic Studies Depression
Scale; SF-­MCS, SF-­36 Mental Component Summary. aHigher
IV or V 6 (14) 24 (60)
scores indicate poorer symptoms/functioning. bHigher scores
Age of onset, mean ± SD 19.7 ± 9.7 indicate better health status [Colour figure can be viewed at
Total psychiatric admissions, 4.4 ± 4.6 wileyonlinelibrary.com]
mean ± SD
Lifetime diagnosis The results of our analytic models for the primary study out-
Bipolar I disorder 0 (0) 34 (85) comes, together with the small and non-­
overlapping confidence
Bipolar II disorder 0 (0) 6 (15) intervals at post-­
treatment and 6-­
month follow-­
up assessments,
Major depressive disorder 14 (32.6) 0 (0) suggest that, despite the relatively small sample size, the results can
Current episode be generalized to the population of persons with bipolar disorder
Major depressive episode 2 (4.6) 18 (45) and their caregivers with 95% confidence (Figures 2 and 3).
Manic episode 0 (0) 6 (15)
Hypomanic episode 0 (0) 2 (5) 3.4 | Mediational hypotheses
No episode 41 (95.4) 14 (35)
Results of the Sobel test suggest that reductions observed on
Began medication after treatmentc 16 (40)
the HAM-­D during follow-­up for patients whose caregivers were
aAll values are n (%) unless otherwise noted. The higher number of car-
treated with FFT-­HPI were significantly mediated by reductions in
egivers reflects participation of both parents for young adults.
b
Based on the Hollingshead & Redlich (1958) two-­point scale.
caregiver depression level during this same time frame (z = −2.74,
c
Refers to the n and % of patients who were not treated with medication P < .01). Similarly, Sobel test results for the YMRS suggest that the
for their bipolar disorder at the beginning of treatment, who began or re- association between assignment to FFT-­HPI (vs HE) and reductions
sumed medication treatment during the course of their caregiver’s treat- in patient manic/hypomanic symptoms observed during follow-­up
ment with Family-­ Focused Treatment-­ Health Promotion Intervention
were significantly mediated by reductions in caregiver depres-
(FFT-­HPI). No patients in the health education (HE) condition began med-
ication treatment during the course of their caregiver’s treatment. sion during this same time frame (z = −1.98, P < .05). Together,
SD, standard deviation. these results suggest that caregiver treatment with FFT-­HPI was
PERLICK et al. |
      629

TA B L E   2   Caregiver outcomes

Treatment condition Analysis

Health promotion Health education Group-­by-­time

intervention (N = 24) (N = 19) Group effect Time effect interaction

Scales Mean SD Mean SD Z P Z P Z P

CES-­D −0.24 .81 −0.79 .43 −2.99 .003

Baseline 19.43 a 1.96 20.16 2.35
Immediately post-treatment 10.12b 1.67 15.58 2.70
6 months post-treatment 7.75b 1.83 18.56 2.97
SF-­MCS 0.12 .91 1.63 .10 2.40 .02
Baseline 49.87a 3.47 49.56 4.08
Immediately post-treatment 70.59b 3.31 60.14 4.57
6 months post-­treatment 78.77c 3.35 59.50 5.47
SF-­PCS 1.003 .32 1.32 .19 1.90 .057
Baseline 77.79 3.63 69.05 3.61
Immediately post-treatment 76.35 4.67 77.15 4.57
6 months post-­treatment 81.33 5.32 74.44 3.99
SBAS 0.71 .48 −1.36 .17 2.64 .008
Baseline 0.76a 0.05 0.70 0.06
Immediately post-treatment 0.39b 0.04 0.64 0.08
6 months post-­treatment 0.26c 0.05 0.41 0.06
HRB 0.78 0.43 −0.30 0.77 −1.84 .065
Baseline 4.71 0.46 3.84 .53
Immediately post-treatment 2.04 0.47 3.73 .59
6 months post-­treatment 2.55 1.21 3.44 .63
BSI Anxiety 1.69 09 −0.17 .89 −2.76 .006
Baseline 5.58 a 3.68 3.68 3.37
Immediately post-­treatment 2.96 b 2.99 3.63 4.61
c
6 months post-­treatment 1.70 1.72 3.50 3.17

Higher scores indicate poorer symptoms/functioning, except for the SF-­36 scales where higher scores indicate better health status. Scores with differ-
ing superscripts(a,b,c) differed at P < .05 based on paired t tests within each condition.
CES-­D, Center for Epidemiologic Studies Depression Scale; SF-­MCS, SF-­36 Mental Component Summary; SF-­PCS, SF-­36 Physical Component
Summary; SBAS, Social Behavior Assessment Scale; HRB, Health Risk Behavior; BSI Anxiety, Brief Symptom Inventory Anxiety subscale; SD, standard
deviation.

associated with improved patient outcomes in this treatment arm,
and that it did so by reducing caregiver depression level. Finally,
Sobel test results indicated that the treatment-­related reductions
in caregiver depressive symptoms observed for FFT-­
HPI dur-
ing follow-­up were mediated by reductions in anxiety symptoms
in caregivers assessed during this same time frame (z = −2.90,
P = .004).
4 | D I S CU S S I O N
This study evaluated the benefits of a 12-­15 session family-­based
intervention targeting management of bipolar symptoms and car-
egivers’ own health and mental health needs over the course of
treatment and 6 months post-­t reatment. Although our prior work
had demonstrated an effect of this treatment assessed immedi-
ately post-­t reatment,19 the important question of whether treat-
ment gains would persist over the course of follow-­up was not
addressed. As part of the FFT-­HPI intervention, family members
identified core beliefs about their relatives’ needs, their own re-
sponsibility for meeting these needs, and the ways in which these
beliefs impeded both effective caregiving and self-­c are. Caregivers
assigned to FFT-­HPI and their relatives with bipolar disorder re-
ported significant reductions in mood symptoms relative to car-
egivers assigned to an HE comparison group, even though the
person with bipolar disorder was not included in the treatment.
Specifically, we found that caregivers in the FFT-­HPI condition
reported a reduction in depressive symptoms nearly six times
higher than the reductions among caregivers in HE. Patients asso-
ciated with FFT-­HPI caregivers reported a reduction in depressive
 |
630       PERLICK et al.

TA B L E   3   Clinical outcomes of persons with bipolar disorder

Treatment Condition Analysis

Health promotion Health education Group-­by-­time

intervention (N = 24) (N = 19) Group effect Time effect interaction

Scales Mean SD Mean SD Z P Z P Z P

HAM-­D 0.19 .85 −1.04 .30 −2.08 .04

Baseline 15.22a 2.16 14.53 1.35
Immediately 5.59b 6.1 11.16 2.09
post-­treatment
6 months 5.85b 1.64 10.11 1.87
post-­treatment
YMRS −0.51 .61 −1.15 .25 8.01 .000
a
Baseline 8.09 2.05 9.32 1.99
Immediately 1.55b 2.40 5.89 2.07
post-­treatment
6 months 2.14 b 1.42 6.94 2.21
post-­treatment

HAM-­D, Hamilton Rating Scale for Depression; YMRS, Young Mania Rating Scale; SD, standard deviation.
For YMRS, the group-­by-­time interaction was stratified by baseline scores above and below the median.
Scores with differing subscripts differed at P < .05 based on paired t tests within each condition.

F I G U R E   3   Mean patient depression and mania scores over
time. HAM-­D, Hamilton Scale for Depression; YMRS, Young Mania
Rating Scale. For both scales, higher scores indicate more severe
symptoms and/or poorer functioning [Colour figure can be viewed
at wileyonlinelibrary.com]
symptoms that was 2.5 times higher than that reported in HE and
a mean reduction in manic symptoms four times higher than that
reported in HE. Results of our mediational analyses suggest that
the reductions in patient bipolar symptoms in FFT-­HPI were in part
accounted for by reductions in caregiver depression observed in
this treatment arm.
Our findings that treating the caregiver alone, without participa-
tion of the patient, can lead to sustained symptomatic improvement
in both depression and mania for the patient, as well as improvement
in depression for the caregiver, are novel. Manualized caregiver-­only
psycho-­educational group interventions (COPGs) for caregivers of
persons with serious mental illness (SMI) have been found to be ef-
fective in reducing caregiver depression and burden, for example
the National Alliance on Mental Illness’s (NAMI’s) Family to Family
program50 and the Support and Family Education (SAFE) program,51
an intervention for caregivers of US veterans with SMI. However,
these interventions have not demonstrated symptomatic or func-
tional improvement for the persons with mental illness. Reinares and
colleagues52 found reduced time to recurrence of mania/hypomania
and a reduced number of total manic episodes, but no effect on pa-
tient depression of a caregiver-­only psychoeducational group model
for bipolar disorder compared to usual care.
Differences between our findings and those reported by Reinares
et al.52 may be attributable to differing treatment targets identified
for each intervention. Reinares’ 12-­session COPG focused on pro-
viding caregivers with knowledge of bipolar disorder and appro-
priate care and coping strategies, resulting in increased knowledge
and reduced subjective burden in the treatment group. FFT-­HPI
additionally targeted caregiver depression through examining and
PERLICK et al.
challenging dysfunctional core beliefs about caregiving that were
depressogenic, contributed to caregiving strain and/or interfered
with self-­care. Examination of such beliefs suggested that caregiver
depressive symptoms were related to anxiety about the patient. For
example, one caregiver said he needed to ‘stay on the alert [to avoid]
being “blindsided”’ if a problem arose. Another experienced caregiv-
ing ‘like a monkey on my back’. Anxiety over the patient’s safety or
well-­being led many caregivers to monitor the patient excessively:
for example, texting the patient over ten times daily or never leav-
ing the patient for more than 2 hours. When these behaviors led to
negative interactions with the patient, caregivers reported feeling
depressed and hopeless. It appeared that anxiety over the patient’s
well-­being was the trigger that initiated a chain of events culminating
in caregiver depression, an observation consistent with our finding
that reductions in caregiver depression in FFT-­HPI were mediated by
reductions in their anxiety.
Two primary strategies were used to reduce caregivers’ anxiety
and its behavioral manifestations. First, concerns and beliefs about
the degree of threat and monitoring or other support needed by the
relatives with bipolar disorder were normalized but also challenged,
and behavioral goals (e.g. to limit texting to one to two times per
week) were set. Second, self-­care goals were set and monitored in
each session. Goals were related both to physical health, as many
caregivers had neglected to seek treatment for physical symptoms
or routine tests, and to engagement in pleasurable activities they
either felt they did not deserve or could not spare time for from
caregiving. By gently challenging these beliefs, while simultaneously
identifying and monitoring progress towards self-­care goals, it ap-
peared that caregivers’ focus shifted from frustrated attempts to
‘cure’ their relative to acceptance of the illness and efforts to bolster
their own health, mental health and coping resources. One caregiver
speculated, ‘Maybe my expectations of [my daughter] are too high,
and when she doesn’t meet them I end up feeling anxious’. She re-
ported telling her daughter, ‘I’m not going to be the general manager
of the world anymore—I am just going to look after myself and hope
the rest of the world does a good job’.
Studies have found that 43% of family members of people
53
with bipolar disorder meet SCID-­P criteria for a mood disorder,
and between 33% and 46% meet criteria for major depression.4,53
Depression erodes close relationships, quality of life, social and oc-
cupational functioning, and coping resilience53 and is associated with
increased health and mental health service use among caregivers.8,16
Depression has also been associated with abnormalities in psycho-­
neuro-­immune functioning among caregivers for family members
with depression.53,54 Among older adults, such abnormalities are
associated with ‘all cause’ mortality.54 Thus, an intervention effec-
tive in reducing symptoms of depression over 4 months of treatment
and 6 months of follow-­up may have important long-­term health as
well as mental health benefits for caregivers and their relatives with
bipolar disorder. Screening of family and other caregivers of clinic
patients for mood or anxiety disorders could help identify those in or
at risk for a mood episode and provide a rationale for implementing
caregiver-­only interventions as secondary prevention strategies.
|
      631
Physical health assessed on the SFPCS did not significantly differ
between treatment groups in this study. Because caregivers were
relatively young, with a mean age of 53 years, scores on the SFPCS
were skewed towards near-­perfect physical health at baseline, lim-
iting the sensitivity of this instrument to detect changes in physical
health within a relatively short time frame.
This study has several limitations, including a relatively small
N, relatively low inclusion of racial and ethnic minorities, male
caregivers and patients treated at mental health care facilities, and
a smaller number of planned sessions in the HE control group than
in the FFT-­HPI treatment group. Although lifetime incidence of
caregiver mood disorders was assessed using a structured clinical
interview at baseline, comorbid conditions were not assessed, and
changes in caregiver depression were evaluated using an interview-­
administered version of a symptom scale, precluding identification
of remission from depressive or other mood episodes, or identifi-
cation of new episodes. Another limitation is lack of more specific
information about patients’ or caregivers’ medications at baseline,
or changes during the study or follow-­up period, an important
factor that might help explain patient outcomes. Because only
20% of consenting caregivers were recruited from mental health
clinics and 80% from a caregiver support group, we lacked access
to provider records for the majority of patients and chose not to
rely on patient self-­report data. We do know from caregiver report
that 58% of patients in the FFT-­HPI condition were receiving no
pharmacotherapy at baseline and began pharmacotherapy during
the treatment or follow-­up, but comparable data are not available
for the HE condition. While we identified caregivers according to
conventional criteria, 22 this method fails to consider the patient’s
perspective. Future work should include more diverse patient and
caregiver samples, utilize clinical measures of depression for care-
givers, assess comorbid diagnoses, systematically evaluate patient
pharmacotherapy, include more sensitive measures of physical
health in a middle-­aged population, assess treatment feasibility
and satisfaction, define the caregiver from the patient as well as
caregiver perspective, and follow participants for > 6 months, in
order to evaluate longer term health and mental health benefits
and costs for patients with mood disorders and their caregivers.
FUNDING
This study was supported by grant R34 MH071396 from the
National Institute of Mental Health to the first author and by the
VISN 2 South Mental Illness, Research Education and Clinical Center.
AC K N OW L E D G E M E N T S
The authors acknowledge and thank the study participants for sup-
porting the development of this intervention.
ORCID
Deborah A. Perlick  http://orcid.org/0000-0001-9331-5105
 |
632       PERLICK et al.
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How to cite this article: Perlick DA, Jackson C, Grier S, et al.
Randomized trial comparing caregiver-only family-focused
treatment to standard health education on the 6-month
outcome of bipolar disorder. Bipolar Disord.
2018;20:622‐633. https://doi.org/10.1111/bdi.12621