Brief Psychosocial–Behavioral Intervention With Antidepressant Reduces Poststroke Depression Significantly More Than Usual Care With Antidepressant
Living Well With Stroke: Randomized, Controlled Trial
Background and Purpose— Depression after stroke is prevalent, diminishing recovery and quality of life. Brief behavioral intervention, adjunctive to antidepressant therapy, has not been well evaluated for long-term efficacy in those with poststroke depression.
Methods— One hundred one clinically depressed patients with ischemic stroke within 4 months of index stroke were randomly assigned to an 8-week brief psychosocial–behavioral intervention plus antidepressant or usual care, including antidepressant. The primary end point was reduction in depressive symptom severity at 12 months after entry.
Results— Hamilton Rating Scale for Depression raw score in the intervention group was significantly lower immediately posttreatment (P<0.001) and at 12 months (P=0.05) compared with control subjects. Remission (Hamilton Rating Scale for Depression <10) was significantly greater immediately posttreatment and at 12 months in the intervention group compared with the usual care control. The mean percent decrease (47%±26% intervention versus 32%±36% control, P=0.02) and the mean absolute decrease (−9.2±5.7 intervention versus −6.2±6.4 control, P=0.023) in Hamilton Rating Scale for Depression at 12 months were clinically important and statistically significant in the intervention group compared with control.
Conclusion— A brief psychosocial–behavioral intervention is highly effective in reducing depression in both the short and long term.
Depression is a serious sequelae of strokes of all types, affecting at least 33% of stroke survivors.1 Poststroke depression (PSD) has been associated with poor recovery and rehabilitation response,2–6 reduced social functioning and delayed return to work,7–9 greater use of healthcare services,10 and increased risk of subsequent cardiac and stroke events as well as increased mortality from all causes.2,11,12
Antidepressants have demonstrated varying degrees of efficacy when tested over short follow-up periods. A recent Cochrane Review concluded that although mood was improved in many antidepressant drug studies, there was no clear evidence of remission (no longer meeting entry depression criteria) or response (≥50% reduction in depression score) in the short or long term.13 In contrast, a meta-analysis of 16 randomized, controlled trials showed definite overall improvement in PSD in those taking a variety of antidepressants compared with placebo.14 Only recently have there been well-designed trials of nonpharmacologic treatments, both showing important reductions in PSD short term (3 months).15,16 We believe ours is the first to report clinically and statistically important reduction in depression over the long term.
Living Well With Stroke (LWWS) was a randomized treatment efficacy study with usual care control comparing brief psychosocial–behavioral intervention plus antidepressant with usual care and antidepressant.17 The study was approved by the University of Washington Human Subjects Division (Institutional Review Board) for protection of human subjects.
The primary aim was to determine the effect of a nurse-delivered psychosocial–behavioral intervention on depression in community-dwelling poststroke patients. The primary hypothesis was that patients with PSD provided a 9-session problem-solving, pleasant events intervention in addition to antidepressant treatment would have significantly reduced depression severity (Hamilton Rating Scale for Depression [HRSD]) at 12 months poststroke compared with patients with PSD with usual care, including antidepressant treatment.
The secondary aims were to describe the time course for reduction in depressive symptoms and to determine the intervention effect on secondary end points: limitations in ability (physical function), limitation in participation, and overall stroke impact.
Participants were 101 patients within 4 months of an ischemic stroke, verified by CT or MRI, who screened positive for depressive symptoms and whose diagnosis of clinical depression was verified by a diagnostic interview using Diagnostic and Statistical Manual of Mental Disorders, 4th Edition criteria.18 Participants were not excluded for prior or current treatment for depression.
Patients hospitalized in 4 acute care hospitals in Seattle, Wash, were screened for depression with the 30-item Geriatric Depression Scale.19 The diagnosis of depression was validated by the Diagnostic Interview and Structured Hamilton18 in those who scored ≥11 on the Geriatric Depression Scale and consented to the full study.
Psychosocial–Behavioral Intervention and Usual Care
All participants were given written stroke recovery materials from the American Stroke Association, including information about depression. They completed a medication diary each of the first 8 weeks of the trial. These diaries were either mailed to the research coordinator (usual care) with reminder telephone calls or brought to the counseling session (psychosocial–behavioral intervention). All participants saw their stroke care or primary care provider for ongoing medical care, including adjustment of antidepressant medication, as scheduled by that provider.
Those randomized to the psychosocial–behavioral intervention met with a study interventionist 9 times over 8 weeks. Sessions were focused on the individual; however, a participant could opt to have a family member or informal caregiver join these sessions. Fifteen caregivers joined sessions and provided data. The brief psychosocial–behavioral intervention was adapted from the “Seattle Protocols,” shown to reduce disability associated with depression in Alzheimer disease.20
Although antidepressant treatment is often provided to patients with PSD as a community standard, we reasoned that without behavioral change, there would not be a long-lasting change from the initial mood elevation seen with antidepressants. We used language pertinent to stroke and taught participants to view depressive symptoms as observable and modifiable behaviors that are initiated and maintained by person–environment interactions. The treatment goal was to increase the level of pleasant social and physical activity to improve mood. Specific problem-solving approaches were taught and solutions to behavioral challenges were individualized to each person. The content of these sessions is more fully outlined in our design publication17 and in the treatment manual available from the first author.
Usual Care Arm
Participants in the usual care arm saw their stroke care or primary care provider as scheduled by that provider. When used, antidepressant medication was prescribed and adjusted by the usual care provider. Twenty-five caregivers joined the stroke survivor in this arm. We did not design an arm with equivalent time and attention but without the depression content because the Seattle Protocol trials had already demonstrated that an “attention control” as well as a waiting list control had significantly less improvement in depression than did the active intervention, similar to other problem-solving interventions in multiple populations.17,21
Selective serotonin reuptake inhibitor antidepressant treatment was an informal standard of care in this community at the inception of this study. Therefore, the participant’s own provider prescribed the selective serotonin reuptake inhibitor or an alternate antidepressant based on his or her own assessment and recommendation provided through a letter sent to each participant’s provider. The study psychiatrist (R.V.) recommended sertraline as an initial antidepressant choice due to its tolerability in the setting of medical illness and a relatively lower incidence of cardiovascular side effects.
Study Timetable and Assessments
A full baseline data set, including demographics, stroke characteristics, National Institutes of Health Stroke Scale score,22 and Geriatric Depression Scale.19 Diagnostic interview (Diagnostic Interview and Structured Hamilton), including the HRSD,18 Barthel Index,23 Stroke Impact Scale (SIS),24 and percent perceived recovery (Overall Stroke Impact),24 was assessed at entry but before randomization. Measures of depressive symptoms, stroke impact, and perceived recovery were repeated at 9 weeks (immediately postintervention), 21 weeks postentry (roughly 6 months poststroke), and 12 months and 24 months poststroke. Functional and quality-of-life outcomes were conceptualized according to the World Health Organization classification of persisting impairments, disabilities, and handicaps from a variety of chronic illnesses.25 This multidimensional model of illness considers interacting elements of body, person, and social function, replacing the terms disability and handicap with more descriptive terms: limitations in activities and restrictions in participation. We measured limitation in physical ability by the Barthel Index, activities of daily living, strength, and mobility subscales of the SIS; limitation in participation by the communication and work/recreation subscales of the SIS; and overall stroke impact by percent perceived recovery from the SIS.
Randomization and Masking
Randomization status was generated by a computerized adaptive randomization procedure after the method of Pocock and Simon.26 This ensured that the 2 groups remained balanced with respect to important predictors of outcomes: severity of stroke (National Institutes of Health Stroke Scale), severity of depression at baseline (HRSD), age, and gender. All outcome assessors were masked to the participant’s randomization status at each data collection point. We did not detect any breaches in masking.
Sample Size and Statistical Analysis
Over 1000 inpatients with stroke were tracked for potential screening eligibility. The majority was not eligible (comatose, not ischemic stroke, lived out of the region, no evidence of sadness, for example). Two hundred eighty-nine agreed to be screened. One hundred forty-eight of these were found eligible (Geriatric Depression Scale ≥11 and confirmed stroke) and 101 enrolled (see the Figure for details on exclusions). The sample of 101 is adequate to detect a 0.5 SD difference in average HRSD between the 2 groups. The primary end point was HRSD at 12 months. The intent-to-treat analysis controlled for baseline values of the primary outcome variable using analysis of covariance for continuous variables (HRSD) and logistic regression for binary variables (response or remission or not) at 12 months (primary end point) with alpha set at 0.05. Response was defined as ≥50% reduction in HRSD, consistent with prior literature. Remission has been defined variably as HRSD score of ≤9 (no longer meeting depression criterion),13 ≤7 (absence of any depressive symptoms),27 or ≤3 (equivalent to healthy controls).28 We used the more liberal HRSD score of ≤9 for comparison with previous studies of PSD.13,14
Follow-up was achieved on all participants at 9 weeks, except the one person who dropped out of the study after 1 week. Two others in the intervention group dropped out between 9 weeks and 12 months. Two participants in the intervention group died of underlying medical illness before 12 months; none died in the control group. Five dropped out or did not respond to 12-month follow-up in the control group (Figure).
The 2 groups were comparable at baseline in both demographic and stroke variables, except for the prevalence of left hemisphere stroke and diabetes in the control group, as shown in Tables 1 and 2⇓. The participants were predominantly male (59%), had moderate ischemic strokes, ranged in age from 25 to 88 years, and perceived themselves, on average, as approximately half recovered from their strokes (46.3% intervention; 55.3% control). Roughly 70% of both groups had at least one episode of depression before this stroke and 60% of each group was taking antidepressants at entry. This increased to 77% in each randomization group during the 8-week active treatment period. Sertraline, citalopram, and paroxetine were the most commonly prescribed selective serotonin reuptake inhibitor drugs. Tricyclic antidepressants were not commonly prescribed (11% of sample) with amitriptyline being the most common tricyclic antidepressant, prescribed at bedtime.
Primary End Point
The primary hypothesis was supported. Mean decrease in HRSD in the intervention group was significantly greater at 1 year when compared with the control group (−9.2±5.7 intervention versus −6.2±6.4 control, P=0.023). As shown in Table 3, when controlling for baseline HRDS scores, change in HRDS was significantly greater in the intervention group than in the control immediately posttreatment and at 1 year. The effect size is smaller after the first follow-up time but remains stable thereafter, favoring the intervention.
Furthermore, as shown in Table 4, significantly more of the intervention group was in remission (HRSD ≤9) immediately after treatment and at 1 year. The effect was strongest at the first follow-up and favored the intervention group at all time points. By 24 months, the control group remission rate approached the early response of the intervention group, whereas the intervention group continued to increase remission rate. There was no significant interaction effect on treatment response between treatment group and caregiver involvement at 1 year (data not shown). Over three fourths of each randomization group reported taking an antidepressant (selective serotonin reuptake inhibitor, nonselective serotonin reuptake inhibitor antidepressant, or tricyclic) during the 8-week intervention period. There were no significant interactions of reported antidepressant use with either immediate or 1-year remission rates (data not shown).
Secondary End Points
There was no significant main effect for randomization group in examining indicators of limitation in ability (physical function), participation, and percent recovery (overall impact) at 12 months. However, there was an interaction of remission status and scores for these variables with significantly better scores for all indicators except the Barthel Index for those in remission (Table 5). This finding is consistent with the suggestion that poorer rehabilitation and recovery is moderated by depressive symptoms.
This trial is the first to report long-term efficacy (1 and 2 years) of a psychosocial treatment in combination with pharmacotherapy in PSD. It should be emphasized that the recruitment was not aimed at those with first-ever depression manifesting after stroke. Rather, it was a treatment for stroke survivors who manifested a new or recurrent depression consistent with the Activate, Initiate, Monitor (AIM) trial described subsequently.15 Few studies regarding the prevalence of PSD or its treatment describe history of depression, although it is a predictor of future depression.1
This study extends the findings of 2 additional trials in stroke survivors that demonstrated short-term reduction in depression with structured care management15 and with motivational interviewing.16 The intervention in our trial is related to but not the same as those in these recently completed trials. LWWS was behavioral in focus, providing participants with education and skills training to combat their depression. The AIM trial had 3 components to care management: (1) an initial 20-minute structured psychoeducation session with a nurse to activate the participant’s interest and understanding of dealing with PSD and reduce stigma; (2) use of a medication algorithm to initiate a recommendation for an antidepressant to patient’s primary provide; and (3) a bimonthly telephone monitoring of depressive symptoms, medication side effects, and adherence. The timing and focus of sessions with the nurse counselor were substantially shorter than those in our study and more focused on optimizing antidepressant therapy. Although the participants in the treatment arm reduced depression scores significantly over the 12-week follow-up compared with the usual care arm, the drop in HRSD score and percent in remission were smaller than in our more behaviorally oriented study. This latter difference likely reflects the AIM trial’s use of a lower remission score cutoff (HRSD score <8). The AIM trial did not report longer-term outcomes.15
Watkins and colleagues tested a motivational interviewing approach in a randomized, controlled trial of 411 stroke inpatients, not limited to those with depressed mood. The goal was to assist patients still in the hospital to recognize and achieving their own solutions to problems in adjustment to physical and emotional aspects of stroke.16 Components of this intervention are similar to the problem-solving portions of our trial. Therapists supervised by clinical psychologists provided 4 30- to 60-minute individual sessions of motivational interviewing over 4 weeks to patients randomized to the treatment arm. A significantly larger proportion of those who received motivational interviews had a “normal” mood as measured by the General Hospital Questionnaire and did not endorse feeling sad or blue (depression screen) post treatment compared with those with routine hospital care. Longer-term protection from depressive symptoms was not reported.
We postulated that the antidepressant treatment would enable short-term mood elevation, whereas the behavioral treatment would provide cognitive restructuring and specific problem-solving skills for coping with ongoing stressors. Future planned analyses will explore the degree to which attainment of these skills is related to treatment response. Although 77% of each group were prescribed and reported taking antidepressants during the 8-week treatment period, the doses and type of drug were not standardized. This is a limitation of the study but represents the context of everyday practice. Future planned subgroup analyses may help shed light on the role of antidepressants in the rate of remission and overall response to the behavioral treatment.
The findings of the LWWS study are similar to a British series that does not include patients with PSD. They have shown that a 6-session structured problem-solving psychological treatment can be delivered by various members of the primary healthcare team for a variety of emotional disorders, including major depression.29–33 Recent comparison of antidepressant alone with combined problem-solving and antidepressant showed that both were equally effective in reducing depressive symptoms (HRSD) over time with medication alone having a smaller reduction than the psychosocial or combined groups as well as a sustained effect to 1 year.31 Community health nurses and general practitioners were equally effective, although patients were more satisfied with the community nurse treatment.33
Psychosocial therapy combined with antidepressant has been significantly more successful in preventing recurrent depression in older adults than medication alone or psychosocial therapy and placebo.34 More relevant to PSD are the trials of counseling and behavioral tailored problem-solving interventions for depressed medically ill elderly delivered by psychogeriatric teams and psychosocial nurse specialists in the home compared with “standard” care. These have shown a reduction in level of depression, improvement is self-perceived health, and sometimes improved functional status.35,36 Our trial, in combination with the AIM trial and the motivational interviewing previously discussed, add to our knowledge of the range of behavioral interventions effective in the PSD population. Further planned analyses of the LWWS trial will help suggest subgroups most responsive to treatment.
A brief psychosocial–behavioral intervention adjunctive to antidepressant therapy is highly effective in reducing depression and achieving remission in the short term with the effect sustained for up to 2 years. Participants in the usual care control group also reduced their depression over the first year, but more slowly and with a lesser degree of remission. Those who achieved remission in either group had significantly better perceived recovery, lower limitation in ability, and greater social participation at all time points.
Sources of Funding
This study was funded by the National Institute of Nursing Research, National Institutes of Health grant R01NR007755, and registered with the clinical trials identifier NCT00194454 www.clinicaltrials.gov/ct/show/NCT00194454?order=1.
Preliminary results were presented at the 2008 International Stroke Conference with the abstract published in Stroke: Podium presentation ISC published as Mitchell PH, Becker KJ, Buzaitis A, Cain KC, Fruin M, Kohen R, Teri L, Tirschwell D, Veith R. Brief psychosocial/behavioral intervention with antidepressant reduces post-stroke depression significantly more than antidepressant alone. Stroke. 2008;39:543.
- Received February 6, 2009.
- Revision received March 3, 2009.
- Accepted March 11, 2009.
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