Psychotherapy, Symptom Outcomes, and Role ... - Psychiatric Services

Psychotherapy, Symptom Outcomes, and Role Functioning Over One Year Among Patients With Bipolar Disorder David J. Miklowitz, Ph.D. Michael W. Otto, Ph.D. Stephen R. Wisniewski, Ph.D. Mako Araga, M.S. Ellen Frank, Ph.D. Noreen A. Reilly-Harrington, Ph.D. Anna Lembke, M.D. Gary S. Sachs, M.D.

Objective: Randomized trials indicate that psychosocial interventions are effective adjuncts to pharmacotherapy in bipolar disorder (1,2). A oneyear naturalistic-prospective design was used to examine the association between psychotherapy use and the symptomatic and functional outcomes of patients with bipolar disorder. Methods: Patients with bipolar disorder in a depressed phase (N=248) were drawn from the first 1,000 enrollees (November 1999 to April 2002) in the Systematic Treatment Enhancement Program (STEP-BD), a study of patients with bipolar disorder receiving best-practice pharmacotherapy. Patients were seen in clinics and interviewed every three months over one year regarding use of psychotherapy services, symptoms, and role functioning. Mixed-effects regression models were used to examine whether the amount of psychotherapy the patients received during each three-month interval was associated with symptomatic or psychosocial functioning during the same or a subsequent three-month interval. Results: During the study year, 60 percent of the patients had at least one psychotherapy session. Among patients who began an interval with severe depressive symptoms or low functioning, having more frequent sessions of psychotherapy was associated with less severe mood symptoms and better functioning in the same or a subsequent study interval. In contrast, among patients who began an interval with less severe depressive symptoms or higher functioning, fewer psychotherapy sessions were associated with less severe depressive symptoms and greater functioning in the same or a subsequent interval. Conclusions: Intensive psychotherapy may be most applicable to severely ill patients with bipolar disorder, whereas briefer treatments may be adequate for less severely ill patients. (Psychiatric Services 57:959–965, 2006)

Dr. Miklowitz is affiliated with the Department of Psychology, University of Colorado, Muenzinger Building, Boulder, Colorado 80309-0345 (e-mail, [email protected]. edu). Dr. Otto is with the Department of Psychology, Boston University. Dr. Wisniewski and Ms. Araga are with the Graduate School of Public Health and Dr. Frank is with the Department of Psychiatry, University of Pittsburgh. Dr. Reilly-Harrington and Dr. Sachs are with the Department of Psychiatry, Massachusetts General Hospital, Boston. Dr. Lembke is with the Department of Psychiatry, Stanford University, Palo Alto, California. Parts of this article were presented at a meeting of the Association for the Advancement of Behavior Therapy Conference in November 2004 in New Orleans.

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♦ ps.psychiatryonline.org ♦ July 2006 Vol. 57 No. 7

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here is mounting evidence that individual, family, and group psychosocial interventions, when combined with standard pharmacotherapy, delay relapses and enhance the symptomatic outcome of bipolar disorder (1–9). Research on adjunctive psychosocial interventions is based primarily on randomized trials, with carefully selected samples, manual-based psychosocial protocols, and predetermined durations and frequencies of treatment. Although these design features strengthen the internal validity of the trials, they also raise the question of whether psychotherapy as practiced in the community has similar effects on the course of bipolar illness when samples are broadly characterized, psychotherapy methods and intensities vary, and patients elect to receive psychotherapy rather than being randomly assigned to it. No studies have explored the effects of psychosocial interventions on community samples of patients with bipolar disorder followed naturalistically. This study examined whether patients with bipolar disorder who receive regular adjunctive psychosocial intervention in community settings have a lower symptom burden during or after treatment than patients who receive little or no psychosocial intervention. Participants were patients in a depressive phase of bipolar disorder 959

drawn from the first 1,000 enrollees in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) (10), a multicenter research program concerning the nature, course, and long-term outcome of patients with bipolar disorder receiving best-practice pharmacotherapy. Because of its naturalistic design, STEP-BD afforded an opportunity to examine the association between psychotherapy use and outcome among patients who select it because they desire the additional treatment, have the financial means to obtain it, and have access to therapists. An initial cross-sectional study of the first 500 patients in the STEP-BD indicated considerable variability in use of psychotherapy (11). In the three months before entering STEPBD, 54 percent of the eligible patients obtained some form of psychotherapy in addition to medications. Patients who received adjunctive psychotherapy had lower global functioning scores, were less likely to be married, and had greater rates of comorbid disorders than those who did not receive services. This initial study, however, did not address the prospective association between psychotherapy and patients’ longer-term symptomatic or functional outcomes. Using a one-year prospective design, we examined several questions: How frequently did patients with bipolar depression use psychotherapy services during their first year in STEP-BD, and with what kinds of providers? What patient variables were associated with the amount of service use? Did the amount of psychotherapy that patients received in any given study interval predict their concurrent or subsequent levels of depressive or manic symptoms or role functioning once their preinterval levels of symptoms or role functioning were covaried? Was the association between psychotherapy and clinical outcome different for patients who were more severely ill?

November 1999 and April 2002 (12). To qualify for STEP-BD, patients had to be at least 15 years of age and meet DSM-IV (13) criteria for bipolar I or II disorder or a bipolar spectrum disorder (defined below). Patients were excluded if they were unwilling or unable to provide informed consent or did not speak English. All 16 study sites received approval to implement STEP-BD from their respective institutional review boards. All principles of the Declaration of Helsinki were followed. Research staff members fully explained the study protocol to potential participants before obtaining written informed consent (10). Of the first 1,000 patients, 248 (25 percent) entered STEP-BD in a DSM-IV major depressive episode. The number of patients who entered STEP-BD in states of DSM-IV mania, 51, was too small to warrant separate examination. The mean±SD age of the 248 participants with bipolar disorder, depressed phase was 41.1±12.3 years; 137 (58 percent) were women. Participants were predominantly Caucasian (93 percent), and most (95 percent) had graduated from high school. The most common diagnosis was bipolar I disorder (N=166, or 67 percent), followed by bipolar II disorder (N=67, or 27 percent); bipolar disorder not otherwise specified (N=12, or 5 percent); schizoaffective disorder, bipolar subtype (N=2, or 1 percent); or cyclothymic disorder (N=1, which was less than 1 percent). The age at illness onset was 16.6±8.4 years.

Methods

Diagnostic evaluation To validate the bipolar diagnosis at study entry, project clinicians administered the Affective Disorders Evaluation, a semistructured interview adapted from the Structured Clinical Interview for DSM-IV, Patient Version (14,15). Separate clinicians interviewed patients on a different occasion using the Mini-International Neuropsychiatric Interview (MINI Plus, version 5.0) (16). Study diagnoses were assigned once there was consensus between the two interviews.

Participants Individuals with bipolar disorder were drawn from the first 1,000 enrollees in the naturalistic “Standard Care” study of STEP-BD between

Longitudinal follow-up Patients were seen in university- or community-based outpatient clinics, depending on the site. Psychiatrists

960

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treated patients using standardized pharmacological guidelines for bipolar disorder (17). Independent evaluators conducted structured interviews with patients on a quarterly basis for one year (baseline and at three, six, nine, and 12 months), during which they completed service use, role functioning, and symptom severity measures. The instruments for measuring mood symptoms were the Montgomery-Asberg Depression Rating Scale (MADRS) (18) and the Young Mania Rating Scale (YMRS) (19), which yielded estimates of the severity of symptoms in the final week of each three-month study interval. Scores for each range from 0 to 60, with higher scores indicating more severe symptoms. Functional outcomes were measured every three months with the Longitudinal Interval Follow-up Evaluation–Range of Impaired Function Tool (LIFE-RIFT) (20,21) covering the final week of each interval. The LIFE-RIFT is a clinician-rated scale that assigns scores from 1, indicating no impairment, to 5, indicating severe impairment, in each of four areas of functioning—work and role performance, interpersonal relationships, recreation, and satisfaction with activities. Overall role function scores range from 4, indicating good functioning, to 20, indicating poor functioning. Psychosocial service use The measure of psychotherapy use was the interview-based Care Utilization Form (10), which was administered every quarter and covered the prior three-month interval. We narrowed our definition of psychotherapy services to the number of patient contacts during each interval with professionally trained therapists— psychologists, social workers, mental health counselors, or psychiatric nurses—for assistance with emotional problems. We did not include contacts with psychiatrists in these computations because psychiatric sessions within STEP-BD emphasized pharmacological management. Although supportive psychotherapy may have been offered during these visits as well, the amount provided was not standardized or measured within the STEP-BD protocol.


Table 1

Number of psychotherapy sessions among patients with bipolar disorder during consecutive three-month intervals in the Systematic Treatment Enhancement Program for Bipolar Disorder Months 1–3 (N=162)a

Months 4–6 (N=130)a



Therapist

Nb

Mean

SD

Nb

Mean

SD

Nb

Mean

SD

Nb

Mean

SD

Psychologist Social worker Counselor Nurse

41 25 18 7

7.6 7.6 9.3 6.7

5.9 6.7 20.4 6.5

40 15 11 6

6.2 8.6 5.6 10.0

4.1 5.9 4.3 9.5

32 14 3 4

6.2 8.4 30.7 5.0

4.1 6.6 36.0 4.7

28 14 6 2

5.9 8.4 9.7 2.5

4.2 3.9 2.9 .7

a b

Number of patients who completed follow-up interviews during each interval, including those who received no therapy Number of patients who had at least one treatment session with each type of health care provider

Statistical analyses We reasoned that patients who developed symptoms during the course of STEP-BD treatment would seek out or be offered more psychotherapy services. Thus the symptomatic or functional state of patients in the three-month interval before obtaining services needed to be statistically covaried when we examined the association between psychotherapy and symptom outcomes. Second, we reasoned that psychotherapy could be associated with symptomatic or functional outcomes during the same interval in which it was delivered, or it could be associated with future outcomes. When plotting service use (number of sessions received) at each of the four follow-up intervals (months 1–3, 4–6, 7–9, and 10–12), we determined that the distributions were positively skewed and that natural breaks occurred between patients who received no adjunctive psychotherapy sessions, between one and three sessions, between four and 12 sessions, and more than 12 sessions. Accordingly, we conceptualized service use as a four-level categorical variable. With data from each quarterly interval, we used mixed-effects regression models (22) to examine how baseline symptoms (MADRS or YMRS scores measured at the end of the prior interval) and psychotherapy during the interval were related to depression, mania, or role functioning scores during the same or a subsequent interval. The regression models, which were conducted with the PROC MIXED program in the PSYCHIATRIC SERVICES

SAS statistical package (23), enabled us to consider multiple quarterly follow-up intervals simultaneously rather than constructing separate models for each interval. Unlike standard repeated-measures analyses of variance, mixed-effects models with random subjects effects permit the analysis of repeated measurements over time while controlling for the within-subject correlation of the dependent measure—MADRS scores, for example. These methods are valid under the assumption that data are missing at random. For a cogent discussion of the differences between mixed-effects regression models and repeated-measures analysis of variance, see Gueorguieva and Krystal (22). For example, depression recorded at the nine-month assessment point (covering the prior week) was regressed on use of psychotherapy during months 7 through 9, on the level of depression recorded in the final week of interval 3 to 6, and on their statistical interaction. A separate lagged-effects model regressed depression, mania, or role functioning in interval x (for example, at nine months) on use of psychotherapy in the previous interval (months 3 through 6) and on depression in the final week of that interval (months 3 through 6). Because female patients with depression are more likely to seek therapy than male patients (24), and because access to psychotherapy is likely to be influenced by household income, we covaried patients’ sex and income in each regression model. The regression models were under-


powered to examine interactions of treatment and site because of the large number of sites (16); thus we did not include site as a covariate.

Results Patients’ use of psychosocial services at follow-up The mixed-effects regression models included observations from all participants with service use data, even from those who did not complete the full follow-up. Of the 248 patients in a depressive phase of bipolar disorder, data on use of psychotherapy were available during at least one quarterly follow-up interval for 179 (72 percent). A total of 107 of the 179 patients with service use data (60 percent) obtained at least one adjunctive psychotherapy session during the study year. The mean number of psychotherapy contacts for the full sample was 8.04±15.61 (range 0 to 97). Table 1 summarizes the number of contacts that patients had with mental health professionals during each three-month interval. Visits to psychologists were the most common, followed by visits to social workers, counselors, and nurses. Correlates of service use We examined whether patients who received more therapy sessions per interval differed systematically from those who received fewer sessions. A mixed-effects regression model examined the following predictors of service use: age, sex, income, age at illness onset, marital status, bipolar I versus II subtype, comorbid personality disorder (based on the Affective 961

Figure 1

Depression scores as a function of treatment intensity (number of psychotherapy sessions) and prior depression scores for 146 patients in a depressive phase of bipolar disordera

MADRS score in next interval

25 20

No sessions 1–3 sessions

4–12 sessions >12 sessions

15 10 5 0

Low depression

Midlevel depression

High depression

MADRS score in prior interval a

A Montgomery-Asberg Depression Rating Scale (MADRS) score of 15 (low depression) represents the lower 15th percentile of the sample, a score of 23 represents the 50th percentile, and a score of 33 represents the 85th percentile (high depression). MADRS scores in the prior threemonth interval interacted with the amount of therapy received in the next three-month interval in predicting MADRS scores in the next interval (F=2.77, df=3, 138, p=.044).

Disorders Evaluation), past or current anxiety disorder (based on the MINI), past or current substance use disorder, and number of prior episodes of mania or depression. The dependent variables were the fourcategory psychotherapy use variables computed at three, six, nine, or 12 months, with all follow-up points considered simultaneously. Patients with fewer than ten prior depressive episodes used more psychotherapy than patients with more than ten prior episodes (F=3.27, df=3, 110, p=.024). The association between marital status and service use approached but did not reach significance. No other variable predicted service use. To reduce the effects of selection biases in treatment seeking, we included the number of prior depressive episodes and marital status, along with patients’ sex and income as covariates in the mixed-effects regression models. Amount of service use and depression and mania symptoms Concurrent associations. The first mixed-effects model examined predictors of depression severity. In this model, MADRS depression scores recorded in the final week of an interval (three, six, nine, or 12 months) were regressed on psychotherapy use in the same interval, with MADRS and YMRS scores recorded during the final week of the previous interval as predictor variables. Data from 962

146 patients in the sample were available for this analysis. This model (Figure 1) revealed no main effect of amount of therapy use on depression in the same study interval. Depression in the prior threemonth interval predicted depression in the next interval (F=17.04, df=1, 138, p