Predictors and moderators of time to remission of major depression with interpersonal psychotherapy and SSRI pharmacotherapy.

BACKGROUND: Although many studies suggest that, on average, depression-specific psychotherapy and antidepressant pharmacotherapy are efficacious, we know relatively little about which patients are more likely to respond to one versus the other. We sought to determine whether measures of spectrum psychopathology are useful in deciding which patients with unipolar depression should receive pharmacotherapy versus depression-specific psychotherapy. METHOD: A total of 318 adult out-patients with major depression were randomly assigned to escitalopram pharmacotherapy or interpersonal psychotherapy (IPT) at academic medical centers at Pittsburgh, Pennsylvania and Pisa, Italy. Our main focus was on predictors and moderators of time to remission on monotherapy at 12 weeks. RESULTS: Participants with higher scores on the need for medical reassurance factor of the Panic-Agoraphobic Spectrum Self-Report (PAS-SR) had more rapid remission with IPT and those with lower scores on the psychomotor activation factor of the Mood Spectrum Self-Report (MOODS-SR) experienced more rapid remission with selective serotonin reuptake inhibitor (SSRI) pharmacotherapy. Non-specific predictors of longer time to remission with monotherapy included several panic spectrum and mood spectrum factors and the Social Phobia Spectrum (SHY) total score. Higher baseline scores on the 17- and 25-item Hamilton Depression Rating Scales (HAMD-17 and HAMD-25) and the Work and Social Adjustment Scale (WSAS) also predicted a longer time to remission, whereas being married predicted a shorter time to remission. CONCLUSIONS: This exploratory study identified several non-specific predictors but few moderators of psychotherapy versus pharmacotherapy outcome. It offers useful indicators of the characteristics of patients that are generally difficult to treat, but only limited guidance as to who benefits from IPT versus SSRI pharmacotherapy.

Self-reported binge eating in severe pediatric obesity: impact on weight change in a randomized controlled trial of family-based treatment.

OBJECTIVE: This study sought to document self-reported binge eating in a large sample of severely obese children and to examine the impact of binge eating on changes in percent overweight among children randomized to family-based behavioral treatment (intervention) versus control (usual care). PARTICIPANTS AND METHODS: As part of a larger randomized controlled trial, 192 children aged 8-12 years (M=10.2, s.d.=1.2) with a mean body mass index (BMI) percentile of 99.2 (s.d.=0.7) completed assessments at baseline and 6-, 12-, and 18 months post-randomization. A parent or guardian also participated. Child psychological symptoms, including binge eating, were measured before randomization using self-report questionnaires. Child height and weight were measured at baseline, 6-, 12-, and 18 months. The primary study outcome was percent overweight (that is, percent over median BMI for age and sex). RESULTS: Twenty-two children (11.5%) endorsed binge eating at baseline (Binge Eating Group). Children in the Binge Eating Group were younger and had more depressive, anxiety, and eating disorder symptoms, and lower self-esteem than children in the rest of the sample (No Binge Eating Group). There also were differences between the Binge Eating and No Binge Eating groups with respect to the short-term effects of treatment group assignment on change in percent overweight during the study. Specifically, improvements in percent overweight in the intervention condition relative to usual care were documented in the No Binge Eating Group only. Among children in the Binge Eating Group, those assigned to intervention showed a 2.6% increase in percent overweight, on average, at the completion of acute treatment as compared to an 8.5% decrease among children without binge eating. However, these effects were not maintained during follow-up. CONCLUSION: Results of this study suggest the importance of considering binge eating in the development of weight management programs for severely obese youth.

Comparative outcomes among the problem areas of interpersonal psychotherapy for depression.

BACKGROUND: Although interpersonal psychotherapy (IPT) is an efficacious treatment for acute depression, the relative efficacy of treatment in each of the four IPT problem areas (grief, role transitions, role disputes, interpersonal deficits) has received little attention. We evaluated the specificity of IPT by comparing treatment success among patients whose psychotherapy focused on each problem area. Moreover, we sought to understand how the patient characteristics and interpersonal problems most closely linked to the onset of a patient's current depression contributed to IPT success. METHODS: Patients meeting DSM-IV criteria for an episode of major depressive disorder (n=182) were treated with weekly IPT. Remission was defined as an average Hamilton Rating Scale for Depression 17-item score of 7 or below over 3 weeks. Personality disorders were diagnosed using the Structured Clinical Interview for DSM-IV Personality Disorders. RESULTS: Contrary to our prediction that patients whose treatment was focused on interpersonal deficits would take longer to remit, survival analyses indicated that patients receiving treatment focused on each of the four problem areas did not differ in their times to remission. Nor were patients in the interpersonal deficits group more likely to have an Axis II diagnosis. Patients whose treatment focused on role transitions remitted faster than those whose treatment focused on role disputes, after controlling for covariates. CONCLUSION: With skillful use of IPT strategies and tactics and with careful medication management where appropriate, patients in this study whose treatment focused on each problem area were treated with equal success by trained IPT clinicians.

Self-reported cognitive problems predict employment trajectory in patients with bipolar I disorder.

BACKGROUND: Cognitive impairment in bipolar disorder has been associated with poor functional outcomes. We examined the relation of self-reported cognitive problems to employment trajectory in patients diagnosed with bipolar I disorder. METHODS: 154 bipolar I disorder patients were followed for 15-43months at the Bipolar Disorders Center for Pennsylvanians. Using a multinomial logistic regression we examined predictors of employment group including self-reported cognitive problems, mood symptoms, education and age. Cognitive functioning was measured via 4 self-report items assessing memory/concentration at baseline and termination. Employment status was recorded at baseline and termination. Employment was categorized as working (full-time, part-time, homemaker, volunteer) or not working (leave of absence, disability, unemployed, no longer volunteering) at each time point. Patients were categorized as good stable, improving, worsening and poor stable. RESULTS: Baseline self-reported concentration problems and years of education significantly predicted employment trajectory. LIMITATIONS: Post-hoc analyses of existing clinical data. CONCLUSIONS: Self-reported concentration problems assessed in the context of specific areas of functioning may serve as a sensitive predictor of functional outcome in patients diagnosed with bipolar I disorder.

Serum anticholinergic activity, white matter hyperintensities, and cognitive performance.

The authors investigated whether the cognitive impairments associated with white matter hyperintensities (WMH) in normal elderly subjects are exacerbated by any anticholinergic medications being taken by the subjects. Results showed serum anticholinergic activity (SAA) and WMH volume to have a synergistic interaction such that the cognitive decrements associated with increasing WMH volume were greatest in those older individuals in the highest quartile of the SAA distribution.

Personality pathology and outcome in recurrently depressed women over 2 years of maintenance interpersonal psychotherapy.

BACKGROUND: Empirical data on the impact of personality pathology on acute treatment outcome for depression are mixed, in part because of challenges posed by assessing trait-like personality patterns while patients are in an active mood episode. To our knowledge, no previous study has examined the effect of personality pathology on maintenance treatment outcome. By maintenance treatment we refer to long-term treatment provided to prevent depression recurrence among remitted patients. METHOD: Structured Clinical Interviews for the DSM-III-R Personality Disorders (SCID-II) were obtained on a sample of 125 recurrently depressed women following sustained remission of the acute mood episode and prior to entering maintenance treatment. SCID-II interviews were then repeated following 1 and 2 years of maintenance interpersonal psychotherapy. RESULTS: At the pre-maintenance assessment, 21.6% of the sample met SCID-II personality disorder criteria. Co-morbid personality pathology was related to an earlier age of onset, more previous depressive episodes, and a greater need for adjunctive pharmacotherapy to achieve remission of the acute mood episode. Co-morbid personality pathology predicted both higher rates of depression recurrence and a shorter time to recurrence over the 2-year course of maintenance treatment. Notably, among those patients who remained depression-free, continuous levels of personality pathology steadily declined over the 2-year course of maintenance therapy. CONCLUSIONS: Results highlight the need for early and effective intervention of both episodic mood disorder and inter-episode interpersonal dysfunction inherent to the personality disorders. Future maintenance treatment trials are needed to clarify the relationship between episodic mood disorder and personality function over time.

Clinical indicators for the use of antidepressants in the treatment of bipolar I depression.

OBJECTIVES: Current guidelines provide little practical information on the clinical characteristics of bipolar I patients who are likely to benefit from the combination of a mood stabilizer and an antidepressant. Rather, guidelines simply state that an adjunctive antidepressant is recommended in cases of 'severe' depression. Our objective was to evaluate the clinical and demographic differences between patients who remitted on a mood stabilizer alone and patients who subsequently required an adjunctive antidepressant to achieve stabilization. METHODS: We retrospectively compared the pharmacological treatment strategies of 39 patients with bipolar I disorder who were in a current depressive episode. Patients who did not respond to mood stabilizer monotherapy were prescribed an adjunctive antidepressant. We evaluated the clinical differences at baseline and week 1, 2 and 3 of treatment between patients stabilizing on a mood stabilizer alone and patients that did not remit until they subsequently received an adjunctive antidepressant. RESULTS: Patients who required an adjunctive antidepressant had significantly higher total Hamilton Depression Rating (HRS-D) scores at week 1, 2 and 3 of treatment, but not at baseline. Patients who remitted on mood stabilizer monotherapy were more likely to be married, achieved stabilization in less time, presented with higher Young Mania Rating Scale (YMRS) scores, and experienced the previous episode of depression more recently than patients who required an antidepressant. CONCLUSIONS: Our findings suggest that rapid improvement after achieving a therapeutic dose of a mood stabilizer is clinically significant and represents a surrogate endpoint in the treatment of bipolar I depression. Larger, prospective, and controlled studies are needed to verify our results and to identify additional indicators for a mood stabilizer and antidepressant combination treatment strategy.

The relation of White Matter Hyperintensities to implicit learning in healthy older adults.

OBJECTIVE: This study examined whether MRI evidence of cerebrovascular disease in the form of white matter hyperintensities (WMH) was associated with decreased implicit sequence learning performance in a high-functioning group of normal elderly volunteers. METHOD: One hundred and eight community-dwelling elderly individuals received an MRI and performed an implicit sequence learning task, the serial reaction time (SRT) task. RESULTS: Hyperintensities present in the white matter were associated with a decreased learning effect. This association was found with both deep white matter and periventricular changes. Other factors affecting SRT performance (i.e., baseline reaction time and switch-cost) were not significantly related to the presence of WMH. CONCLUSIONS: The results indicate that in addition to previously identified generalized cognitive deficits, WMH are also associated with a specific decrease in the implicit learning of sequences.

The establishment of a brain bank for the study of late-life depression: a feasibility study of factors facilitating consent.

BACKGROUND: Studies of postmortem brain tissue are advancing the understanding of the pathophysiology of major depressive disorder (MDD). The nature and quality of subject samples, however, limit their applicability to late-life MDD. OBJECTIVE: To examine the feasibility of establishing a brain bank for late-life MDD, and identify clinical, demographic, and procedural factors that might facilitate subject enrollment. METHODS: Elderly subjects participating in clinical trials associated with the Mental Health Intervention Research Center for Late-Life Mood Disorders (MHIRC/LLMD) at the University of Pittsburgh were approached by clinical research staff for consent to future brain-only autopsy. Subjects who consented to participation were compared with those who refused participation on demographic and clinical variables. MHIRC/LLMD clinical research staff were interviewed to determine factors that may have facilitated or hindered the consent process and reasons for subject consent or refusal. RESULTS: Eighty out of 242 subjects (33%) subjects approached for participation in the brain bank provided consent. Consent to participate was associated with higher level of education and with lower Mini-Mental State Examination score. Several factors facilitating and hindering the consent process were identified. CONCLUSION: We provide preliminary evidence for the feasibility of establishing a brain bank for the study of late-life MDD. Future efforts may be guided by the factors identified as facilitating the consent process, especially the inclusion of family in the consent process.

Emotion-focused psychotherapy for patients with panic disorder.

OBJECTIVE: Recent studies have suggested that most patients treated for panic disorder receive forms of psychotherapy other than cognitive behavior therapy, even though there is little information about the efficacy of such treatments or how they compare to proven active treatments. The authors compared one of these other forms, emotion-focused psychotherapy (given to 30 patients with panic disorder), to results obtained with recommended standard treatment (either cognitive behavior therapy [N=36] or imipramine [N=22]). The authors also compared emotion-focused psychotherapy to results obtained in subjects given pill placebo (N=24). METHOD: Subjects met DSM-IV criteria for panic disorder with no more than mild agoraphobia. Treatment consisted of approximately 3 months of weekly visits followed by 6 monthly maintenance visits. Assessments were conducted after each treatment phase and at a follow-up visit after 6 months of no treatment. RESULTS: Emotion-focused psychotherapy was less effective for symptoms of panic disorder than treatment with either cognitive behavior therapy or imipramine; results obtained with emotion-focused psychotherapy after the acute and maintenance phases were similar to those seen with placebo. Treatment expectations were not different among the different groups. Patients receiving emotion-focused psychotherapy had the highest completion rate. CONCLUSIONS: The results suggest that emotion-focused psychotherapy (a supportive form of psychotherapy) has low efficacy for the treatment of panic disorder. However, emotion-focused psychotherapy may be superior to medical management in helping patients stay in treatment.

A twelve-week, double-blind, randomized comparison of nortriptyline and paroxetine in older depressed inpatients and outpatients.

Selective serotonin reuptake inhibitors may be less efficacious than tricyclic antidepressants in the treatment of severe depression in older patients. The authors compared the 12-week clinical outcome of older depressed patients treated with nortriptyline or paroxetine in a double-blind randomized comparison in 116 psychiatric inpatients and outpatients (mean age: 72+/-8 years) who presented with a major depressive episode or melancholic depression. Discontinuation and response rates were compared in patients who began or who completed treatment. The discontinuation rate due to side effects was significantly higher with nortriptyline than with paroxetine (33% vs. 16%). There were no significant differences between the rates of response in the Intent-to-Treat analysis (nortriptyline: 57% vs. paroxetine: 55% ), or the Completer analysis (nortriptyline: 78% vs. paroxetine: 84%). Although paroxetine appears to be better tolerated than nortriptyline, the efficacy of these two drugs does not appear to differ in the acute treatment of older depressed patients, including hospitalized patients and those with melancholic features.

The effect of a combined influenza/pneumococcal immunization reminder letter.

BACKGROUND: The effect of a combined influenza and pneumococcal immunization reminder letter on increasing influenza and pneumococcal immunization rates, and the timeliness of receiving immunizations after receipt of a reminder letter, have not been examined. This study addresses these issues using a sample of new Medicare beneficiaries residing in Hawaii. METHODS: Newly enrolled Medicare beneficiaries in Hawaii from 25 September 1995 through 31 August 1996 were randomly assigned to one of three groups: Group 1, no letter (n=2144); Group 2, influenza immunization reminder letter only (n=2213); or Group 3, pneumococcal and influenza immunization reminder letter (n=2171). Health Care Financing Administration claims data were compared among groups. RESULTS: In Group 3, the influenza immunization rate increased 3.8 percentage points (n=87; p=0.017) compared with Group 1. The Group 3 pneumococcal immunization rate increased 3.5 percentage points (n=78; p<0.001) compared to Group 1 and 4.0 percentage points (n=86; p<0.001) compared to Group 2. Sixty-six beneficiaries in Group 3 received simultaneous pneumococcal and influenza immunizations, a significant difference compared to Group 1 or Group 2. Increases in immunizations were observed immediately following the reminder letters and the effect persisted for 5 to 7 weeks. CONCLUSIONS: The combination letter increased both influenza and pneumococcal immunization rates and the simultaneous administration of immunizations without detrimental effect to influenza immunization rates. A combined reminder letter is inexpensive and recommended as part of a multicomponent campaign for adult immunization.

Tolerability of combined treatment with lithium and paroxetine in patients with bipolar disorder and depression.

Patients with bipolar disorder are often prescribed lithium in combination with a selective serotonin reuptake inhibitor. Doubts still remain, however, about the safety of the combination, particularly with regard to the risk of developing a serotonin syndrome. The authors retrospectively evaluated the safety of the combination of lithium and paroxetine when the two medications were sequentially prescribed in patients with bipolar disorder. The authors examined a sample of 17 patients with bipolar disorder who were treated with lithium during a depressive episode and who required paroxetine as an adjunctive antidepressant to ongoing lithium treatment. Averaging across all subjects, no statistically significant increase was found for any of the somatic symptoms that were assessed before and after paroxetine was added to ongoing lithium therapy. Examining the clinical records of each patient in detail; however, four patients who developed significant adverse events, possibly related to an emerging serotonin syndrome were identified. Clinicians should be aware of the possible development of a serotonin syndrome among patients in whom paroxetine is added to ongoing lithium treatment.

Reliability and validity of the Panic Disorder Severity Scale: replication and extension.

UNLABELLED: The Panic Disorder Severity Scale (PDSS) is a recently developed seven-item instrument to rate overall severity of Panic Disorder. The scale has previously shown good psychometric properties in a sample of Panic Disorder patients with no more than mild agoraphobia. The purpose of this paper is to confirm reliability and validity, to provide an estimate of a cut-score discriminating the presence or absence of current DSM-IV Panic Disorder, and to determine the factor structure of the instrument. PROCEDURES: 104 psychiatric outpatients, including 54 with current Panic Disorder, underwent structured diagnostic assessment and the PDSS interview. The PDSS was repeated within 3-17 days. RESULTS: we confirmed reliability and validity of the instrument and found a one-factor solution fit the data. A cut-off score of eight identifies patients with current panic with a sensitivity of 83.3%, and a specificity of 64%. CONCLUSION: the PDSS is a simple, reliable instrument for use in Panic Disorder studies. A cut-score of eight may be useful as a tool to screen patients in settings such as primary care, for diagnosis-level symptoms.

Treatment outcome in suicidal vs. non-suicidal elderly patients.

The authors investigated treatment outcome in elderly suicidal and non-suicidal patients with recurrent major depression. Patients without suicidal ideation in the current episode (Non-Ideators; n=150) were compared with 30 patients who expressed suicidal ideation (Ideators). Patients received combined pharmacotherapy and psychotherapy during acute and continuation treatment. Ideators had higher numbers of lifetime suicide attempts and reported significantly higher levels of depression, anxiety, and hopelessness before starting treatment. Ideators and Non-Ideators had almost identical remission rates (77% vs. 78%), but Ideators had higher relapse rates during continuation treatment (26% vs. 13%) and were more likely to receive augmentation pharmacotherapy. Anxiety and use of adjunctive medication, but not suicidal ideation, were negatively related to both remission and relapse. Our data suggest that elderly suicidal patients have an overall favorable treatment outcome. However, treatment response may be more brittle and may require the continuing use of adjunctive medications to prevent early relapse.

Accounting for covariate measurement error in a Cox model analysis of recurrence of depression.

When a covariate measured with error is used as a predictor in a survival analysis using the Cox model, the parameter estimate is usually biased. In clinical research, covariates measured without error such as treatment procedure or sex are often used in conjunction with a covariate measured with error. In a randomized clinical trial of two types of treatments, we account for the measurement error in the covariate, log-transformed total rapid eye movement (REM) activity counts, in a Cox model analysis of the time to recurrence of major depression in an elderly population. Regression calibration and two variants of a likelihood-based approach are used to account for measurement error. The likelihood-based approach is extended to account for the correlation between replicate measures of the covariate. Using the replicate data decreases the standard error of the parameter estimate for log(total REM) counts while maintaining the bias reduction of the estimate. We conclude that covariate measurement error and the correlation between replicates can affect results in a Cox model analysis and should be accounted for. In the depression data, these methods render comparable results that have less bias than the results when measurement error is ignored.

The development of study exit criteria for evaluating antimanic compounds.

BACKGROUND: There is increasing interest on the part of investigators and the public at large in finding ways to study and improve treatments for the seriously mentally ill without exposing such individuals to unnecessary risks. One group of particular interest in this regard are patients suffering from acute mania. We set out to define "exit" criteria or novel clinical endpoints that might help to assess the efficacy of antimanic compounds. We sought a method that would be safer, more economical, and less sensitive to nonspecific factors in the clinical environment while still allowing unambiguous assessment of efficacy. METHOD: From a pool of subjects being screened for or already participating in intervention studies, we retrospectively identified 76 admissions of patients with a manic or mixed episode according to DSM-IV. We fit a mixed-effects regression model to all available data obtained using the Bech-Rafaelsen Mania Scale from admission to day 28 of treatment. Using the estimated model coefficients, we obtained empirical Bayes (EB) estimates of each subject's trend coefficients based on (1) all available data and (2) data through day 11 of treatment for mania. RESULTS: We found a high correlation (r = .67) between EB estimates of final response at day 28 and actual day 28 scores on the Bech-Rafaelsen scale based on scores through day 11. When subjects were categorized as full, partial, or nonresponders according to their final Bech-Rafaelsen score, we were able to show that only 2 of the 23 predicted nonresponders became full responders, 27 of the 31 predicted full responders became full responders, and 16 of the 22 predicted partial responders became partial or full responders. CONCLUSION: We conclude on the basis of this chart review study that it should be possible to define exit criteria for trials assessing the efficacy of antimanic compounds on the basis of relatively short duration exposure to experimental treatment.

Sleep and treatment response in depression: new findings using power spectral analysis.

This study examined quantitative measures of sleep electroencephalogram (EEG) and phasic rapid eye movements (REM) as correlates of remission and recovery in depressed patients. To address correlates of remission, pre-treatment EEG sleep studies were examined in 130 women outpatients with major depressive disorder treated with interpersonal psychotherapy (IPT). To address correlates of recovery, baseline and post-treatment EEG sleep studies were examined in 23 women who recovered with IPT alone and 23 women who recovered with IPT+fluoxetine. Outcomes included EEG power spectra during non-rapid eye movement (NREM) sleep and REM sleep and quantitative REMs. IPT non-remitters had increased phasic REM compared with remitters, but no significant differences in EEG power spectra. IPT+fluoxetine recoverers, but not IPT recoverers, showed increases in phasic REM and REM percentage from baseline to recovery. In NREM sleep, the IPT+fluoxetine group showed a decrease in alpha power from baseline to recovery, while the IPT group showed a slight increase. The number of REMs was a more robust correlate of remission and recovery than modeled quantitative EEG spectra during NREM or REM sleep. Quantitative REMs may provide a more direct measure of brainstem function and dysfunction during REM sleep than quantitative sleep EEG measures.

Dual-task performance in depressed geriatric patients.

Older patients suffering from a major depression are often impaired on tasks that require executive control processes. However, a wide variety of executive abilities exist in humans, and it is not clear that all are impaired in depression or that such impairments persist beyond remission of the depression. One executive process that plays a central role in mental operations such as working memory is the ability to co-ordinate the simultaneous performance of multiple tasks. Dual-task performance has been extensively studied in normal subjects but there is little work with depressed patients. The present study examined the performance of depressed (M age=71.0, S.D.=7.1) and control subjects (M age=69.3, S.D.=7.0) on two tasks (visual tracking and backward digit span), both when each task was carried out by itself and when the two tasks were carried out simultaneously. Dual-task performance was impaired in depressed patients prior to antidepressant treatment and this impairment persisted even after remission of the depression. These results suggest that, like other executive abilities, the ability to schedule and co-ordinate the conflicting processing demands present in a dual-task situation is impaired in depressed geriatric patients and that this impairment may be a trait effect.

Using medicare databases for outcomes research in rehabilitation medicine.

With the advent of computerized billing for healthcare services, claims data have become useful in academic medicine. One of the largest suppliers of these types of data is Medicare, the US Government's healthcare insurance organization for the elderly and disabled. Because Medicare patients often require rehabilitation, this type of data can be useful in rehabilitation outcomes studies. Despite several significant limitations to Medicare billing data, Medicare claims data are powerful tools with which to analyze concepts in physical medicine and rehabilitation.