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Background: Crohn's disease (CD) is associated with depression. It is unclear if psychosocial interventions offer benefit for depressive symptoms during active CD. In this secondary analysis of a larger study of treating depression in pediatric inflammatory bowel disease, we assessed whether cognitive behavioral therapy (CBT) would differentiate from supportive nondirective therapy in treating depression and disease activity in youth with CD. We also explored whether somatic depressive symptoms showed a different pattern of response in the overall sample and the subset with active inflammatory bowel disease., Methods: Youth with depression and CD (n = 161) were randomized to 3 months of CBT (teaching coping skills) or supportive nondirective therapy (supportive listening). Depressive severity was measured using the Children's Depression Rating Scale-Revised (CDRS-R) with the somatic depressive subtype consisting of those CDRS-R items, which significantly correlated with CD activity. Disease activity was measured by the Pediatric Crohn's disease Activity Index. Given the potential confound of higher dose steroids, subanalyses excluded subjects on >20 mg/d prednisone equivalent (n = 34)., Results: Total CDRS-R scores in the overall sample significantly decreased over time after both treatments (P < 0.0001). Treatment with CBT was associated with a significantly greater improvement in the Pediatric Crohn's disease Activity Index (P = 0.05) and somatic depressive subtype (P = 0.03) in those with active inflammatory bowel disease (n = 95) compared with supportive nondirective therapy. After excluding those on steroids (n = 34), there was a significant improvement in total CDRS-R (P = 0.03) and in Pediatric Crohn's disease Activity Index (P = 0.03) after CBT., Conclusions: Psychotherapy may be a useful adjunct to treat depression in the context of CD-related inflammation in youth who are not concurrently on higher dose steroids.

Objective: Pediatric inflammatory bowel disease (IBD) is associated with high rates of depression. This study compared the efficacy of cognitive behavioral therapy (CBT) to supportive nondirective therapy (SNDT) in treating youth with comorbid IBD and depression., Method: Youth (51% female and 49% male; age 9-17 years, mean age 14.3 years) with depression and Crohn's disease (n = 161) or ulcerative colitis (n = 56) were randomly assigned to a 3-month course of CBT or SNDT. The primary outcome was comparative reduction in depressive symptom severity; secondary outcomes were depression remission, increase in depression response, and improved health-related adjustment and IBD activity., Results: A total of 178 participants (82%) completed the 3-month intervention. Both psychotherapies resulted in significant reductions in total Children's Depression Rating Scale Revised score (37.3% for CBT and 31.9% for SNDT), but the difference between the 2 treatments was not significant (p = .16). There were large pre-post effect sizes for each treatment (d = 1.31 for CBT and d = 1.30 for SNDT). More than 65% of youth had a complete remission of depression at 3 months, with no difference between CBT and SNDT (67.8% and 63.2%, respectively). Compared to SNDT, CBT was associated with a greater reduction in IBD activity (p = .04) but no greater improvement on the Clinical Global Assessment Scale (p = .06) and health-related quality of life (IMPACT-III scale) (p = .07)., Conclusion: This is the first randomized controlled study to suggest improvements in depression severity, global functioning, quality of life, and disease activity in a physically ill pediatric cohort treated with psychotherapy. Clinical trial registration information-Reducing Depressive Symptoms in Physically Ill Youth; http://clinical trials.gov; NCT00534911., (Copyright © 2014 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

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.

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.

Recent advances in our understanding of both short- and long-term therapeutic interventions for depressive disorders have necessitated greater precision in defining appropriate therapeutic interventions. While these remarkable changes in treatment have been based on the introduction of newer antidepressant agents, the advances have occurred because of more systematic clinical trials and a greater sophistication in defining diagnostic and treatment response criteria. This paper reviews key findings in recurrent depression with respect to long-term treatment. Particular attention is paid to the combination treatment of psychotherapy and antidepressant drugs.

Objective: Although effective treatments for depression exist, under or non-treatment of depression is common. Efforts were made in the early 1990s to improve recognition and treatment of depression, with many of those efforts targeted at groups most vulnerable to under-treatment. The purpose of this study is to assess treatment rates in 1993-1994 and 1996-1997., Method: Using nationally representative surveys of office-based practice covering the years 1993, 1994, 1996, and 1997, we obtained estimates of visits by adults in which depression was diagnosed and a prescription for antidepressant medication and/or psychotherapy was provided or ordered., Results: The proportion of physician office visits in which a depression diagnosis was recorded did not change from 1993-1994 (3.48 percent) to 1996-1997 (3.40 percent). However, the rate of antidepressant prescription or psychotherapy rose from 74.2 percent of visits with a depression diagnosis in 1993-1994 to 82.3 percent of these visits in 1996-1997. Significantly lower rates of treatment for depression during office visits made by African American patients, elderly patients, and patients on Medicaid occurred in 1993-1994, but were not evident in 1996-1997, reflecting improved rates of depression treatment in these populations., Conclusions: Although rates of diagnosis of depression during office visits have not increased, treatment rates for depression are improving among those who are diagnosed, including groups of people who historically were less likely to be offered treatment. Additional efforts to improve recognition and diagnosis of depression in ambulatory medical practice and to improve dissemination of treatment are needed.

Research on life stress has been characterized by inconsistent results, which some researchers attribute to different assessment methodologies. Generally, studies have used either self-report checklists or investigator-based interviews. To test whether different results are derived from these approaches, the authors compared information from a self-report measure of life stress with the additional data available from a follow-up investigator-based measure in prospectively predicting the outcome of treatment for recurrent major depression. The 2 approaches produced different results, with investigator-based life events predicting lower probability of remission and self-report life events either predicting increased likelihood of remission or not predicting at all. The results demonstrated that methodology may account for some of the inconsistencies in the life stress literature.

Interpersonal and social rhythm therapy is an individual psychotherapy designed specifically for the treatment for bipolar disorder. Interpersonal and social rhythm therapy grew from a chronobiological model of bipolar disorder postulating that individuals with bipolar disorder have a genetic predisposition to circadian rhythm and sleep-wake cycle abnormalities that may be responsible, in part, for the symptomatic manifestations of the illness. In our model, life events (both negative and positive) may cause disruptions in patients' social rhythms that, in turn, perturb circadian rhythms and sleep-wake cycles and lead to the development of bipolar symptoms. Administered in concert with medications, interpersonal and social rhythm therapy combines the basic principles of interpersonal psychotherapy with behavioral techniques to help patients regularize their daily routines, diminish interpersonal problems, and adhere to medication regimens. It modulates both biological and psychosocial factors to mitigate patients' circadian and sleep-wake cycle vulnerabilities, improve overall functioning, and better manage the potential chaos of bipolar disorder symptomatology.

Objective: The authors tested the hypothesis that a lifetime history of panic-agoraphobic spectrum symptoms predicts a poorer response to depression treatment., Method: A threshold for clinically meaningful panic-agoraphobic spectrum symptoms was defined by means of receiver operating characteristic curve analysis of total scores on the Structured Clinical Interview for Panic-Agoraphobic Spectrum in a group of 88 outpatients with and without panic disorder. This threshold was then applied to a group of 61 women with recurrent major depression, who completed a self-report version of the same instrument, in order to compare treatment outcomes for patients above and below this clinical threshold., Results: Women with high scores (> or =35) on the Panic-Agoraphobic Spectrum Self-Report were less likely than women with low scores (<35) to respond to interpersonal psychotherapy alone (43.5% versus 68.4%, respectively). Women with high scores also took longer (18.1 versus 10.3 weeks) to respond to a sequential treatment paradigm (adding a selective serotonin reuptake inhibitor when depression did not remit with interpersonal psychotherapy alone). This effect was only partially accounted for by the higher likelihood that patients with high scores required the addition of antidepressants. Although four domains from the Panic-Agoraphobic Spectrum Self-Report were individually associated with a longer time to remission, only stress sensitivity emerged as significant in multivariate regression analyses., Conclusions: A lifetime burden of panic-agoraphobic spectrum symptoms predicted a poorer response to interpersonal psychotherapy and an 8-week delay in sequential treatment response among women with recurrent depression. These results lend clinical validity to the spectrum construct and highlight the need for alternate psychotherapeutic and pharmacologic strategies to treat depressed patients with panic spectrum features.

Background: Few data are available to guide treatment selection in major depression. With increasing pressure to maximize the efficiency and minimize the costs of treatment, it is important to have information that could guide treatment selection or point to treatment strategies that have a high probability of success., Method: We used a successive cohort approach to compare 2 highly similar groups of women with recurrent unipolar disorder (DSM-III-R or DSM-IV): one in which the combination of interpersonal psychotherapy (IPT) and pharmacotherapy was initiated at the outset of treatment and a second in which IPT alone was provided first and only those who did not remit with IPT alone were offered the combination treatment., Results: In the group in which the combination was initiated at the outset of treatment (N = 180), the remission rate was 66%, comparable to the remission rate observed in most outpatient treatment studies of major depression. In contrast, among the women in the second cohort who were first treated with IPT alone and only those who did not remit were given combination therapy (N = 159), the remission rate was 79%, significantly greater than that observed in the group that received combination treatment from the outset (chi2 = 6.55, p = .02)., Conclusion: These results suggest that the strategy of offering IPT to women with recurrent unipolar disorder and, in the absence of remission, adding antidepressant pharmacotherapy can be a highly effective treatment, one that may be particularly attractive to women in the childbearing years. Although slower in its onset of action, this sequential strategy is likely to enable the clear majority of such women to achieve a full remission of depressive symptoms.

The authors compared response rates, by age (60-69 vs. 70+), to acute, continuation, and 1-year maintenance depression treatment. Patients (N = 180) received open combined treatment with nortriptyline (NT)/placebo and interpersonal psychotherapy (IPT). Patients who recovered then entered randomized, double-blind maintenance treatment with NT or placebo or received maintenance monthly IPT (combined with NT or placebo). Comparison of time-to-remission and recovery and absolute rates of remission, relapse, recovery, and recurrence yielded similar times to/rates of remission and recovery; however, older patients had far more recurrence during the first year of maintenance therapy. Although responses to acute and continuation treatment with combined NT and psychotherapy were similar, the older group had more recurrence in the first year of maintenance. Continuation of combined medication and psychotherapy may represent the best long-term treatment.

We examined whether fluoxetine treatment has persistent effects on electroencephalographic sleep after drug discontinuation in patients with recurrent major depression. Age-matched groups of 23 women were treated with interpersonal psychotherapy alone (IPT) or fluoxetine plus interpersonal psychotherapy (IPT + FLU). Sleep studies were conducted when patients were depressed, and again at remission, at least four weeks after fluoxetine discontinuation. The groups did not differ in depression ratings pre- to post-treatment. Significant group*time interaction effects were noted for REM sleep (p = .04) and slow wave sleep (p = .02). REM percentage and phasic REM activity increased in the IPT + FLU group but decreased in the IPT group. The effects of fluoxetine treatment on electroencephalographic sleep can be observed for at least four weeks after drug discontinuation and appear to represent both drug discontinuation and neuroadaptation effects.

Gender-specific responses to pharmacotherapy or psychotherapy for depression are virtually unknown. Early studies rarely examined treatment response by gender, and the small number of males studied has led to inaccurate comparisons between male and female response. This article addresses conceptual issues and reviews what little can be ascertained from earlier studies of the relationship between gender and treatment outcome. It also presents data from a series of studies conducted over the last 15 years at the University of Pittsburgh School of Medicine.

Objective: The authors tested the hypothesis that nortriptyline and interpersonal psychotherapy, alone and in combination, are superior to placebo in achieving remission of bereavement-related major depressive episodes., Method: Eighty subjects, aged 50 years and older, with major depressive episodes that began within 6 months before or 12 months after the loss of a spouse or significant other were randomly assigned to a 16-week doubleblind trial of one of four treatment conditions: nortriptyline plus interpersonal psychotherapy (N = 16), nortriptyline alone in a medication clinic (N = 25), placebo plus interpersonal psychotherapy (N = 17), or placebo alone in a medication clinic (N = 22). The protocol required that the acute-phase double-blind treatment be ended after 8 weeks if Hamilton depression scale ratings had not improved by 50%. Remission was defined as a 17-item Hamilton scale score of 7 or lower for 3 consecutive weeks., Results: The rate of remission for nortriptyline plus interpersonal psychotherapy was 69% (N = 11); for medication clinic, nortriptyline, 56% (N = 14); for placebo plus interpersonal psychotherapy, 29% (N = 5); and for medication clinic, placebo, 45% (N = 10). In a generalized logit model, there was a significant effect of nortriptyline over placebo but no interpersonal psychotherapy effect and no nortriptyline-by-interpersonal psychotherapy interaction. Rates of all-cause attrition were lowest in the nortriptyline plus interpersonal psychotherapy group., Conclusions: Nortriptyline was superior to placebo in achieving remission of bereavement-related major depressive episodes. The combination of medication and psychotherapy was associated with the highest rate of treatment completion. These results support the use of pharmacologic treatment of major depressive episodes in the wake of a serious life stressor such as bereavement.

Background: We compared pretreatment subjective and electroencephalographic sleep measures among depressed patients who remitted with psychotherapy alone and those who did not remit., Methods: Patients were 111 midlife women with recurrent major depressive disorder. Baseline psychiatric ratings and sleep studies were conducted prior to treatment with weekly interpersonal psychotherapy. Remission was defined as a score of < or = 7 for 3 consecutive weeks on the Hamilton Depression Rating Scale. Clinical and sleep measures were compared between remitters (n = 62) and nonremitters (n = 49) using t tests and random regression. Linear discriminant function analyses were used to categorize remitters and nonremitters on the basis of sleep measures., Results: Treatment nonremitters had significantly worse subjective sleep quality and significantly elevated phasic REM sleep as measured by multivariate and univariate analyses. The linear accumulation of REM activity during sleep occurred at a significantly higher rate in nonremitters than in remitters. Linear discriminant function analyses based on subjective sleep quality and REM activity correctly identified 68.3% of nonremitters and 68.5% of remitters., Conclusions: These findings highlight the role of subjective and REM sleep measures as correlates of short-term psychotherapy treatment response in major depressive disorder. Disturbed sleep may be a physiological indicator of increased limbic and brain stem arousal.

Context: Elderly patients with major depression are at high risk for recurrence, increased mortality, and chronic disability., Objective: To determine the efficacy of maintenance nortriptyline hydrochloride and interpersonal psychotherapy (IPT) in preventing recurrence of major depressive episodes in patients older than 59 years., Design: A 2 x 2 randomized, double-blind, placebo-controlled clinical trial, stratified by therapist., Setting: University-based psychiatric research clinic., Patients: Of a total of 187 patients with recurrent nonpsychotic unipolar major depression (average age, 67 years; one third aged > or =70 years) recruited through clinical referral and media announcements, 107 were fully recovered after open acute and treatment continuation with nortriptyline and IPT. These patients were randomly assigned to 1 of 4 maintenance therapy conditions., Interventions: Monthly medication clinic with nortriptyline hydrochloride (80-120 ng/mL steady-state levels) (n = 24); medication clinic with placebo (n = 29); monthly maintenance IPT with placebo (n = 21); and monthly maintenance IPT with nortriptyline (n = 22)., Main Outcome Measure: Recurrence of major depressive episode., Results: The time to recurrence of a major depressive episode for all 3 active treatments was significantly better than for placebo. Recurrence rates over 3 years were as follows: nortriptyline and IPT, 20% (95% confidence interval [CI], 4%-36%); nortriptyline and medication clinic visits, 43 % (95% CI, 25%-61%); IPT and placebo, 64% (95% CI, 45%-83%); and placebo and medication clinic visits, 90% (95% CI, 79%-100%). Combined treatment with nortriptyline and IPT was superior to IPT and placebo and showed a trend to superior efficacy over nortriptyline monotherapy (Wald chi2 = 3.56; P = .06). Subjects aged 70 years and older had a higher and more rapid rate of recurrence than those aged 60 to 69 years., Conclusion: In geriatric patients with recurrent major depression, maintenance treatment with nortriptyline or IPT is superior to placebo in preventing or delaying recurrence. Combined treatment using both appears to be the optimal clinical strategy in preserving recovery.

The aim of this study was to identify elderly depressed patients who can remain well on maintenance Interpersonal Psychotherapy (IPT) alone, after discontinuation of antidepressant medication. Using Cox proportional hazards models, increased severity of depression at pretreatment was associated with increased recurrence rates, to an extent greater in patients maintained on monthly IPT than in those maintained on nortriptyline. The long-term response to maintenance IPT was correctly identified in 20/25 cases by a pretreatment Hamilton score of > or = 20. Fourteen of sixteen patients with pretreatment scores of > or = 20 experienced recurrence of major depression on maintenance IPT, while 6/9 patients with pretreatment scores of less than 20 did not. (Fisher exact P = .01). The same pattern of recurrence in relation to severity was not evident in maintenance placebo, nortriptyline, or combination treatment. In addition, Hamilton scores during continuation treatment were lower (< or = 7) among those who remained well on maintenance IPT than among those who had recurrences. Elderly patients whose depressions are milder at baseline and who show excellent symptomatic remission during acute and continuation therapy may be good candidates for monthly maintenance IPT after initial successful treatment with antidepressant medication and psychotherapy.

Objective: Effective treatments are available for major depressive disorder in later life. The purpose of this study was to elucidate the frequency of treatment resistance among the elderly., Method: Treatment resistance, defined as lack of recovery despite combined pharmacotherapy and psychotherapy, was prospectively examined in 180 elderly patients in an episode of recurrent, nonpsychotic major depression who were referred to a university medical center for treatment. They received open acute and continuation treatment with nortriptyline and interpersonal psychotherapy., Results: Among the 159 patients who completed acute treatment, 19 (11.9%) did not experience a remission of depression. In addition, nine patients who had achieved remission relapsed during continuation therapy and did not recover despite vigorous treatment. Hence, excluding dropouts, 18.4% of the patients met the criteria for treatment resistance by their lack of response to acute treatment or by relapsing during continuation therapy and not recovering subsequently despite further vigorous treatment., Conclusions: The study suggests a relatively low rate of resistance to treatment among depressed geriatric patients referred to a university tertiary care setting.

Major depression and anxiety frequently co-occur, but the implications for psychological treatments have rarely been studied. We examined predictors of acute response to interpersonal psychotherapy in 134 consecutively treated female outpatients with recurrent unipolar depression. Women who failed to remit with interpersonal psychotherapy alone experienced higher levels of somatic anxiety, were more likely to meet criteria for lifetime panic disorder, were more likely to meet criteria for nonendogenous or nonmelancholic depression, and reported greater vocational impairment, higher levels of global severity, a longer duration of the index episode, and, somewhat surprisingly, lower levels of social impairment at pretreatment evaluation. A series of backwards stepping logistic regression analyses showed higher levels of baseline somatic anxiety and social functioning to be the most consistent predictors of nonresponse. Our findings strengthen existing evidence that concomitant anxiety can adversely affect the outcome of interpersonal therapy for depression.

Background: Few reliable correlates of treatment response in depression have emerged despite nearly 40 years of research. We examined the correlates of recovery in a "mega-analysis," or meta-analysis of original data, of 595 patients with major depressive disorder enrolled in 6 standardized treatment protocols., Methods: All patients (mean age, 44 years; 31% male and 69% female) met criteria for nonbipolar, nonpsychotic primary major depressive disorder and were treated for 16 weeks with either cognitive behavior therapy or interpersonal psychotherapy alone (psychotherapy alone; n = 243) or interpersonal psychotherapy plus antidepressant pharmacotherapy (combined therapy; n = 352). The impact of treatment type, severity, study, and other covariates on recovery rates or time to recovery were examined by means of chi 2, log-rank tests, the Cox proportional hazards model, and sensitivity analyses., Results: Whereas combined therapy was not significantly more effective than psychotherapy alone in milder depressions, a highly significant advantage was observed in more severe recurrent depressions. Poorer outcomes were also observed in women and older patients, although these effects were dependent on inclusion of particular studies., Conclusions: Mega-analysis is a powerful method for comparing the efficacy of treatments and examining correlates of response. Using this method, we found new evidence in support of the widespread clinical impression that combined therapy is superior to psychotherapy alone for treatment of more severe, recurrent depressions.

Background: This analysis sought to determine whether lorazepam influences time to response or rate of response in elderly depressed patients receiving nortriptyline and psychotherapy and to examine clinical and polysomnographic correlates of lorazepam treatment., Method: Patients with recurrent major depressive disorder (N = 119; mean +/- SD age = 68.0 +/- 6.1 years; diagnosis defined by Research Diagnostic Criteria) received acute treatment with nortriptyline and interpersonal psychotherapy. Thirty-five patients received open-label adjunctive lorazepam for anxiety or insomnia symptoms (LZ+) and 84 did not. Statistical analyses were conducted between the LZ+ group and a group of 35 patients who received no lorazepam (LZ-) and were matched for anxiety level. Patients had polysomnographic studies prior to treatment and after remission of depressive symptoms., Results: The LZ+ group reported more anxiety on the Brief Symptom Inventory (p = .04) compared with the remaining 84 patients. The LZ+ group had a greater proportion of endogenous depression subtype than the anxiety-matched LZ- group, in addition to more abnormal EEG sleep (higher percentage of REM sleep, shorter REM latency, lower delta sleep ratio). Mean time to initial antidepressant response was no different between groups. However, a significantly greater proportion of LZ+ than LZ- patients responded to acute treatment (91.4% vs. 71.4%; p < .03)., Conclusion: Adjunctive lorazepam does not slow the antidepressant response to combined antidepressant/psychotherapy treatment in elderly depressed patients, and it is associated with a greater likelihood of antidepressant response. A greater percentage of patients treated with lorazepam have endogenous depression subtype and abnormal sleep findings (EEG) than those who are not treated with lorazepam. Adjunctive lorazepam is useful for treating anxiety in elderly depressed patients.

Objective: This study was conducted to identify which elderly patients with remitted recurrent major depression remain well with maintenance interpersonal psychotherapy after discontinuation of active antidepressant medication (nortriptyline)., Method: The authors examined outcomes of maintenance therapy over 1 year for 47 elderly patients who were randomly assigned to monthly maintenance interpersonal psychotherapy with placebo (N = 19) or to placebo and a supportive medication clinic without interpersonal psychotherapy (N = 28). A Kaplan-Meier survival analysis was performed on the basis of treatment assignment and subjective sleep quality assessed by the Pittsburgh Sleep Quality Index, on which good subjective sleep quality is indicated by a score of 5 or lower., Results: Nine (90%) of 10 patients reporting good subjective sleep quality (by 1 month into continuation treatment) remained well for at least 1 year when treated with monthly maintenance interpersonal psychotherapy, versus five (31%) of 16 patients with good sleep quality assigned to a medication clinic, three (33%) of nine patients with impaired sleep quality treated with maintenance interpersonal psychotherapy, and two (17%) of 12 patients with impaired sleep quality assigned to a medication clinic., Conclusions: Recovery of good subjective sleep quality by early continuation treatment is useful in identifying which remitted elderly depressed patients will remain well with monthly maintenance interpersonal psychotherapy, following discontinuation of antidepressant medication, and which patients may be more vulnerable to recurrence of major depressive episodes in the absence of antidepressant medication.

Objective: The authors tested the hypothesis that patients whose episodes of major depression evidenced more neurobiological disturbance would be less responsive to psychotherapy., Method: The study subjects were outpatients who were given a diagnosis of recurrent major depressive disorder (unipolar or bipolar II), according to the Research Diagnostic Criteria, following an interview with the Schedule for Affective Disorders and Schizophrenia. They were classified into a group with normal sleep profiles (N = 50) and a group with abnormal sleep profiles (N = 41) on the basis of a validated index score derived from three EEG sleep variables monitored for 2 nights: sleep efficiency, REM latency, and REM density. The groups' responses to short-term interpersonal psychotherapy were compared by means of chi-square tests and life table and random effects model analyses. Responses to the addition of pharmacotherapy for subjects who did not respond to interpersonal psychotherapy were also compared., Results: The patients with abnormal sleep profiles had significantly poorer clinical outcomes with respect to symptom ratings, attrition rates, and remission rates than the patients with more normal sleep profiles. Seventy-five percent of the patients who did not respond to interpersonal psychotherapy had remissions during subsequent pharmacotherapy., Conclusions: These findings help to define further a neurobiological "boundary" that may limit response to psychotherapy in depression. An abnormal sleep profile may reflect a more marked disturbance of CNS arousal that warrants pharmacotherapy.

We sought to determine whether depressive and mixed/cycling episodes were as responsive to standardized pharmacotherapeutic interventions as were manic episodes in bipolar 1 patients. As part of the Maintenance Therapies in Bipolar Disorder (MH29618, E. Frank, PI) study, forty-two acutely ill bipolar 1 patients who had been randomly assigned to one of two preliminary phase non-pharmacologic treatment strategies (interpersonal and social rhythm therapy [IPSRT] or a standard medication clinic approach) were treated according to a standardized pharmacotherapeutic protocol. Symptom severity was measured weekly with the Hamilton Depression Rating Scale and the Bech-Rafaelsen Mania Scale in order to assess symptomatic remission. Survival analysis with the proportional hazards model was performed on time to remission. Manic patients were significantly more likely to achieve clinical remission than the depressed patients (100 vs. 59%) and did so significantly more rapidly. The difference in proportion remitting and time to remission between the depressed and mixed/cycling groups was not statistically significant. No significant effect for non-pharmacologic treatment assignment was found. These results point to the need to develop more effective treatments for bipolar depression. They also suggest that psychotherapy has a limited impact in the acute phase treatment of bipolar episodes.

Objective: The authors compared response rates, the temporal course of response to acute treatment, and relapse rates during continuation treatment of elderly and midlife patients with recurrent major depression., Method: They analyzed results from two separate controlled studies of maintenance therapies for recurrent major depression, in which 148 elderly patients (mean age = 67.9 years) and 214 midlife patients (mean age = 38.5 years) were treated in open acute and continuation therapy with a combination of interpersonal psychotherapy and a tricyclic antidepressant (nortriptyline for the elderly, imipramine for the midlife patients). In an intent-to-treat analysis, remission rates during acute treatment and relapse rates during continuation treatment were examined. Random regression analysis of weekly Hamilton depression scale ratings was used to compare the temporal course of response., Results: During acute-phase therapy, 78.4% (N = 116) of the elderly patients and 69.6% (N = 149) of the midlife patients had remissions. The midlife patients had a faster reduction of Hamilton depression ratings. Following stabilization, 15.5% of the elderly patients and 6.7% of the midlife patients relapsed. Ultimately, 66.2% of the late-life patients and 57.0% of the midlife patients recovered fully., Conclusions: Older patients appear to benefit as much as, but perhaps more slowly then, midlife patients from treatment of major depression. Continuation treatment should be vigorous and closely monitored, given the apparently higher relapse rates among the elderly. These conclusions should be viewed as preliminary because of the post hoc nature of the analysis reported here.

Life stress was studied in relation to postrecovery attrition, symptom course, and recurrence of depression over 3 years. Participants were 67 individuals with recurrent depression who had responded to treatment. Life stress was assessed for the prior 12 weeks at acute treatment entry (T1), initial recovery (T2), and after 17 weeks of sustained recovery (T3). Severe life events at T1 predicted greater attrition, a more favorable postrecovery symptom course, and a lower likelihood of recurrence over 3 years. Life stress at T2 was not predictive of outcomes. Finally, undesirable life events at T3 tended to predict a worse symptom course and a higher likelihood of recurrence, particularly for individuals on medication. The findings are discussed in terms of (a) different processes influenced by life stress over time and (b) limitations of existing longitudinal research for studying the effects of life stress over prolonged intervals.

Models of long-term treatment in recurrent unipolar illness ideally should integrate both psychological and biological factors. In earlier reports we noted that high treatment specificity (i.e. good-quality maintenance interpersonal psychotherapy) and high delta sleep ratio were each associated with significantly increased wellness intervals in the absence of pharmacotherapy among patients with recurrent unipolar depression. To determine how these specific factors when taken together are related to length of survival time, we examined the concurrent effects of treatment specificity and delta sleep ratio on wellness intervals using survival analysis. We found significant effects of both treatment specificity and delta ratio on survival time. Seventy-three per cent of the patients in the high treatment specificity/high delta ratio group survived the 3-year trial, while 44% of the patients in the low delta ratio but high treatment specificity group survived. None of those rated low on both variables survived. We also found an effect for individual clinicians on treatment specificity and survival time and noted that the prophylactic effect of treatment specificity was maintained even within subsets of therapists grouped by their patients' survival times. Secondary analyses revealed an effect of patient attitudes on treatment specificity and survival time, although, when taken together, treatment specificity was the only variable remaining significantly associated with outcome. We conclude that patients remain well the longest when pre-treatment delta sleep parameters more closely approximate those of non-depressed individuals and when monthly psychotherapy is of higher quality. The key finding is that high specificity is of significant prophylactic benefit even for patients with a biological vulnerability for recurrence. We also conclude that in addition to therapists, patient expectancies contribute to treatment specificity, and high treatment specificity is, in turn, reflected in longer times to recurrence.

Unlabelled: The objectives of this report were (1) to describe residual depressive symptoms in elderly patients during continuation therapy with combined nortriptyline and interpersonal psychotherapy; (2) to determine which symptoms were persistent; (3) to determine the clinical correlates of residual depressive symptoms; and (4) to document distinct response pattern clusters during combined continuation therapy., Method: Box plot analyses of Hamilton depression scores and Global Assessment Scale scores, repeated twice monthly over 4 months, were conducted using data from 105 elderly depressives. Temporal trends in the data were examined via random regression analysis. Individual trajectories for each of the 105 patients were examined for patterns of response during continuation therapy., Results: We observed a low mean Hamilton rating of 7 (SD = 2.3) at the start of continuation therapy and 5 (SD = 3.0) at the end. Both Hamilton and GAS scores showed modest but significant improvement over time. Hamilton variability was most apparent in symptoms of mood lowering, apathy, anxiety (psychological and somatic), feelings of guilt, anergia, insomnia, and loss of libido; other symptoms (retardation, agitation, hypochondriasis, loss of appetite, loss of weight, suicidal ideation, and loss of insight) showed clear resolution. A diagnosis of RDC situational depression was associated with higher levels of residual symptoms, while level of chronic medical burden, personality dysfunction, and social support were not. Examination of response patterns showed that a quarter of patients experienced one or more brief symptomatic exacerbations., Conclusion: On average, an excellent level of symptom resolution was achieved for most patients with Hamilton scores comparable to those seen in healthy elderly controls. These data support a position of therapeutic optimism in late-life depression and underscore full remission as an achievable therapeutic goal.

Research on treatment course and outcome in depression is mixed with respect to the implications of life stress. Several concerns are addressed in a prospective study of 91 individuals treated for recurrent depression. Specific forms of stress occurring before treatment entry predicted a poor clinical response both after 16 weeks and after a more extended intervention period. Specific forms of stress occurring during the 1st 6 weeks of treatment also predicted poor response after 16 weeks and after the extended intervention period. Severe stress occurring early in treatment predicted a longer time to attain relief for treatment responders. Concepts underlying the idea that stress-related disorders have a better clinical outcome are discussed, and it is proposed that life stress has different implications for individuals with and without recurrent depression.

Although the endogenous subtype in depression has long been thought to have prognostic significance, to date no long-term maintenance treatment trial has examined the relative risk of recurrence in patients meeting criteria for this subtype. Following our analysis of the primary hypotheses regarding the relationship between treatment assignment and outcome [Frank et al. (1990) Arch. Gen. Psychiatry 47, 1093-1099], we now examine psychobiologic and maintenance treatment correlates for these recurrent unipolar patients grouped according to melancholic, endogenous but not melancholic, and non-endogenous subtype at index presentation. No differences were observed among the three groups in overall survival time; however, in the 52 patients who received psychotherapy without active medication during the maintenance phase, length of survival was inversely related to endogeneity. Interestingly, no differences were found among the three groups in EEG sleep parameters when studied either at baseline or following recovery.

In earlier reports, we demonstrated that in patients with recurrent unipolar depression, survival time without a new episode of major depression following discontinuation of medication was significantly and positively related to continued interpersonal psychotherapy (IPT). To determine whether the prophylactic benefit of monthly sessions of IPT was a function of specific features of the intervention, we examined the contribution of the quality of IPT sessions to the length of the well interval in this 3-year maintenance trial. Therapy sessions were rated on specificity and purity of interpersonal interventions. Analysis of these ratings indicated that psychotherapy that was more specifically interpersonal was associated with significantly increased survival time. Patients whose therapy sessions were rated above the median on specificity of IPT had a median survival time of almost 2 years, while those below the median had a median survival time of less than 5 months. We concluded that when patient and therapist are able to maintain a high level of interpersonal focus, monthly sessions of IPT have substantial prophylactic benefit.

We conducted a randomized 3-year maintenance trial in 128 patients with recurrent depression who had responded to combined short-term and continuation treatment with imipramine hydrochloride and interpersonal psychotherapy. A five-cell design was used to determine whether a maintenance form of interpersonal psychotherapy alone or in combination with medication could play a significant role in the prevention of recurrence. A second question was whether maintaining antidepressant medication at the dosage used to treat the acute episode rather than decreasing to a "maintenance" dosage would provide prophylaxis superior to that observed in earlier trials in which a maintenance dosage strategy was employed. Survival analysis demonstrated a highly significant prophylactic effect for active imipramine hydrochloride maintained at an average dose of 200 mg and a modest prophylactic effect for monthly interpersonal psychotherapy. We conclude that active imipramine hydrochloride maintained at an average dose of 200 mg is an effective means of preventing recurrence and that monthly interpersonal psychotherapy serves to lengthen the time between episodes in patients not receiving active medication.

Two key questions regarding the treatment of depression remain unanswered: whether early treatment intervention will shorten the length of the episode and whether a previously successful treatment will be associated with a more rapid response when administered during the subsequent episode. A group of 45 patients with recurrent major depression treated with combined pharmacotherapy and psychotherapy in a similar fashion for two consecutive episodes showed comparable mean times to stabilization of between 11 and 12 weeks. However, the early intervention in the second treatment episode significantly shortened the overall length of the depressive episode by approximately 4 to 5 months.

Treatment of the acute phase of recurrent depression has become both routine and successful in the last decade, but the rates of relapse and recurrence remain a problem. In this study a combined psychopharmacologic/psychotherapeutic approach to the acute and continuation treatment of unipolar depressed patients was used. For 59 patients who completed the continuation phase of treatment, the relapse rate after 8 weeks of recovery was 8.5%. Since other recent studies of recurrent depression have reported relapse rates of 15%-22%, these results suggest that there are advantages in combined treatment.

While some advances have occurred in the maintenance treatment of unipolar depression, empirical data on recurrences of illness following the discontinuation of medication are sparse. We examined survival time during the first 18 months after discontinuation of medication in 74 patients with recurrent unipolar depression. Although demographic characteristics, clinical characteristics, and pharmacologic treatment variables failed to predict time to recurrence, continued interpersonal psychotherapy was significantly related to longer survival time.

Electroencephalographic (EEG) sleep and selected hormone measurements were investigated in a group of 34 recurrent depressives receiving both pharmacotherapy and psychotherapy. These biological variables were examined to determine whether such measures could predict the rapidity of treatment response. While the EEG measures of sleep onset difficulty and degree of rapid eye movement (REM) density provided some level of discrimination, the serum cortisol measure, particularly the cortisol nadir, significantly discriminated between normal responders and slow or nonresponders. These data support the notion that biological factors measured before treatment might relate to the rapidity and extent of clinical response achieved by the patient.

Background: Few controlled studies have examined the use of atypical antipsychotic drugs for prevention of relapse in patients with bipolar I disorder. Aims To evaluate whether olanzapine plus either lithium or valproate reduces the rate of relapse, compared with lithium or valproate alone.Method: Patients achieving syndromic remission after 6 weeks'treatment with olanzapine plus either lithium (0.6-1.2 mmol/l) or valproate (50-125 microg/ml) received lithium or valproate plus either olanzapine 5-20 mg/day (combination therapy) or placebo (monotherapy), and were followed in a double-masked trial for 18 months.Results: The treatment difference in time to relapse into either mania or depression was not significant for syndromic relapse (median time to relapse: combination therapy 94 days, monotherapy 40.5 days; P=0.742), but was significant for symptomatic relapse (combination therapy 163 days, monotherapy 42 days; P=0.023).Conclusions: Patients taking olanzapine added to lithium or valproate experienced sustained symptomatic remission, but not syndromic remission, for longer than those receiving lithium or valproate monotherapy. [ABSTRACT FROM AUTHOR]

In a randomized, controlled trial, the authors studied an adjunctive, individual psychotherapy, interpersonal and social rhythm therapy (IPSRT) for bipolar disorder. After stabilizing participants with episode appropriate pharmacotherapy and either IPSRT or intensive clinical management (CM), participants were reassigned to IPSRT or CM in conjunction with pharmacotherapy for 2 years of preventative treatment. Early results (n = 82) suggest that altering participants' treatment assignment at entry to the preventative phase is related to risk of recurrence. Participants remaining in the same treatment for both acute and preventative phases had lower rates of recurrence (< 20% vs. > 40%) and levels of symptomatology over the subsequent 52 weeks than those reassigned to the alternate modality. This finding, consistent with the authors' philosophy that bipolar patients benefit from stable routines, suggests that disruptions in the psychosocial treatment plan contribute to worse outcomes. [ABSTRACT FROM AUTHOR]