Ellen Frank - US grants

Through the continued systematic, empirical investigation of the response and recovery of female rape victims, the proposed study expects to expand and refine information obtained in our initial investigation. The objectives of the new study are: 1) to evaluate the necessity of formal treatment intervention for subjects reporting psychological symptomatology immediately post-rape, 2) to identify those factors contributing to a positive treatment response in each of the two structured treatment modalities, 3) to compare victims who request treatment (symptomatic subjects) with victims who decline treatment (asymptomatic subjects) especially with respect to coping strategies employed after the assault, 4) to acquire systematic long-term follow-up data on a large group of sexual assault victims in order to provide a better understanding of the factors leading to recovery and the maintenance of good adjustment, and 5) to compare the outcomes for those victims who perceive positive support from their social networks with those who perceive neutral or negative support. Reliable self-report instruments and interview measures will be used to provide data regarding subjects' levels of depression, anxiety, and phobia, social adjustment, coping behavior and social network support. After initial assessment, subjects will be entered into either a formal treatment protocol (Cognitive Therapy or Systematic Desensitization), an informal treatment protocol (Nonscheduled Treatment) or may choose an assessment-only protocol. Measures will be administered mid-way through treatment, at the end of treatment, three months and six months post-assault and every six months thereafter.

Through the continued systematic, empirical investigation of the reaction and recovery of female victims of sexual assault, the proposed study expects to expand and refine current knowledge regarding rape trauma. The objectives are: 1) to test the efficacy of a brief, intensive Psychoeducational Intervention directed specifically toward reducing the intensity of the short-term, intermediate and long-term reactions to rape, 2) to explore the contribution of the victim's personal coping style in determining the nature of her short-term, intermediate and long-term reactions and 3) to explore the contribution of the victim's social support network in determining the nature of her short-term, intermediate and long-term reactions to the assault. Self-report instruments and structured interviews will measure depression, fear, social adjustment, post-traumatic stress, coping behavior and social network support. After initial assessment, all subjects will be randomly assigned to either Group I, a four session Psychoeducational Intervention (PEI), directed at reducing the discomfort associated with the short-term reaction and thereby, inhibiting the development of intermediate and long-term reactions, or to Group II, a course of four sessions of non-directive Psychological Support (PS), conceived as a placebo intervention, in which the clinician engages in supportive listening and refrains from offering direct intervention. Repeated assessments will occur on a biweekly basis for the first 12 weeks after initial assessment. Subjects will be reassessed at 6 and 12 months. A matched control group of non-victims, recruited by the "best friend" method, at the subject's six-month assessment point, will be assessed at five assessment points to provide comparison data.

While even a single episode of depression is disabling and entails considerable economic loss and emotional suffering, recurrent depression represents a major public health problem. Effective treatments are available for the acute episode of depression, but relatively few clinical trials have been conducted on the maintenance treatment or prevention of subsequent episodes. Until now, maintenance treatment for recurrent unipolar depression has focused exclusively on the implementation of somatic therapies with only moderate success. We have over the last four years begun an investigation of psychological and combined treatments in comparison with somatic treatments alone. During the next five years, we expect to achieve the following major research goals: 1) to determine whether active, long-term (3 year) drug treatment (imipramine in combination with psychotherapy (Maintenance Interpersonal Psychotherapy) is superior to active drug treatment alone or psychotherapy alone or in combination with placebo (ongoing Study I); 2) to determine whether patients who do experience a recurrence or illness in a non-medication condition (i.e. no pill or placebo) in Study I, require 100% of their acute treatment dose or can be successfully maintained on 50% of that dose (Study II); 3) to ascertain whether those patients who survive three years of maintenance treatment in Study I without a recurrence can then be withdrawn from medicatIon without experiencing an recurrence in the subsequent two years (Study III); 4) to ascertain whether changes in selected biological, psychosocial, and clinical signs precede or are associated with recurrence of illness in unipolar patients.

DESCRIPTION (Adapted from Applicant's Abstract): Although several forms of treatment have shown promise in ameliorating the course of recurrent depression, a better understanding of the preventative capacity of psychotherapy seems especially critical for women. In light of the potentially adverse implications of antidepressant treatment throughout the childbearing years and the many psychosocial vulnerability factors for depression observed in women, a clearly efficacious maintenance psychotherapy would represent an important addition to the clinical armamentarium. Furthermore, there is increasing evidence that for men and women alike the risk of a new episode of depressive illness in the six months following discontinuation of antidepressant medication is unacceptably high, whether medication had been continued for 12, 18, 36 months or longer following remission. Our earlier study of Maintenance Therapies in Recurrent Depression (MH29618-05-13) pointed to the potential utility of interpersonal psychotherapy as a maintenance treatment (Frank et al., 1990b; 1991), particularly in women. The specific aim of this competing continuation proposal is to complete an investigation that should considerably expand our knowledge regarding the prophylactic capacity of maintenance interpersonal psycotherapy (IPT-M) in women suffering from recurrent depression. In order to determine whether higher "doses" of IPT-M than were employed in our earlier maintenance trial can further extend survival time, depressed women in at least their second episode of unipolar depression are randomly assigned to one of three levels of IPT-M (high dose = weekly; medium dose = biweekly; low dose = monthly) after weekly acute and continuation interpersonal psychotherapy (IPT - Klerman et al., 1984). We hypothesize that increased frequency of IPT-M will be associated with longer time to recurrence and fewer instances of symptomatic exacerbation not meeting criteria for a new episode. We further hypothesize that three variables are likely to moderate this effect: 1) women in patient/therapist dyads rated as low on specificity of IPT during maintenance treatment; 2) women who experience more severely stressful life events during the maintenance phase; and 3) women with reduced delta sleep at pretreatment baseline will all show shorter time to recurrence. By limiting our investigation to those women with recurrent depression who respond to acute IPT, we focus our investigation on the population most likely to benefit from nonpharmacologic maintenance strategies. To our knowledge, no group has yet reported data on maintenance psychotherapy outcome in depression following acute treatment with psychotherapy alone, nor is any other group currently carrying out or planning such an investigation. Thus, when completed, this study will provide unique information regarding the efficacy of psychotherapy alone as a treatment strategy in women with recurrent depression.

The primary goal of this investigation is to examine the additive prophylactic potential of an individual psychotherapy based on interpersonal and social rhythm principles in bipolar I patients maintained on lithium carbonate. An adaptation of maintenance interpersonal psychotherapy, this intervention takes into account the specific vulnerabilities, symptoms, and interpersonal problem areas associated with bipolar disorder. Acutely ill patients in a manic or depressed episode are randomly assigned to either individual psychotherapy or medication clinic visits in addition to appropriate pharmacotherapy. Patients who stabilize (HRSD and Bech- Rafaelsen < 7 for four weeks) are then randomly assigned to preventative treatment with either individual psychotherapy or medication clinic visits in addition to pharmacotherapy. Thus, patients in this study will receive one of four possible treatment strategies: 1) preliminary phase psychotherapy followed by preventative phase psychotherapy; 2) preliminary phase medication clinic visits followed by preventative phase medication clinic visits; 3) preliminary phase psychotherapy followed by preventative phase medication clinic visit; or 4) preliminary phase medication clinic visits followed by preventative phase psychotherapy. Those patients who experience a relapse (during the initial twelve weeks of the preventative phase) or a recurrence (after week 12 of the preventative phase) will be treated with appropriate pharmacotherapy and continued in psychotherapy or medication clinic visits as dictated by their original randomization assignment. These patients will then be followed for the remainder of what would have been their time in the protocol had they remained well.

human therapy evaluation; mood disorders; medical outreach /case finding; diagnosis design /evaluation; mental disorder diagnosis; biomedical facility; social support network; psychometrics; self concept; early experience; relapse /recurrence; child psychology; diagnosis quality /standard; disease /disorder proneness /risk; training; patient /disease registry; anxiety disorders; interpersonal relations; role; personality disorders; human subject;

The primary goal of this investigation is to examine the additive prophylactic potential of an individual psychotherapy based on interpersonal and social rhythm principles in bipolar I patients maintained on lithium carbonate. An adaptation of maintenance interpersonal psychotherapy, this intervention takes into account the specific vulnerabilities, symptoms, and interpersonal problem areas associated with bipolar disorder. Acutely ill patients in a manic or depressed episode are randomly assigned to either individual psychotherapy or medication clinic visits in addition to appropriate pharmacotherapy. Patients who stabilize (HRSD and Bech- Rafaelsen < 7 for four weeks) are then randomly assigned to preventative treatment with either individual psychotherapy or medication clinic visits in addition to pharmacotherapy. Thus, patients in this study will receive one of four possible treatment strategies: 1) preliminary phase psychotherapy followed by preventative phase psychotherapy; 2) preliminary phase medication clinic visits followed by preventative phase medication clinic visits; 3) preliminary phase psychotherapy followed by preventative phase medication clinic visit; or 4) preliminary phase medication clinic visits followed by preventative phase psychotherapy. Those patients who experience a relapse (during the initial twelve weeks of the preventative phase) or a recurrence (after week 12 of the preventative phase) will be treated with appropriate pharmacotherapy and continued in psychotherapy or medication clinic visits as dictated by their original randomization assignment. These patients will then be followed for the remainder of what would have been their time in the protocol had they remained well.

DESCRIPTION: Complication of major depression by the co-occurrence of panic attacks or panic disorder is both common and clinically significant. Patients with this condition show more severe symptom profiles, greater risk of suicidality, poorer psychosocial functioning, and a poorer response to traditional depression treatments. The primary aim of the current proposal is to develop an effective yet efficient psychotherapeutic intervention for patients with major depression complicated by panic symptoms. This new treatment, interpersonal psychotherapy for depression with panic symptoms (I PT-PS), will adapt and integrate components of cognitive behavior therapy (CBT) for panic and anxiety (Barlow & Craske, 1989) into the therapeutic framework of interpersonal psychotherapy for depression (IPT, Kierman et al., 1984) to treat this clinically severe yet treatment-resistant condition. Conceptually, this integrated treatment approach will seek to promote active resolution of interpersonal problems while concurrently addressing symptoms of panic and anxiety that interfere with active interpersonal problem solving. In Phase I of the proposed study, 12 patients with major depression complicated by panic symptoms will be treated with a 16-session course of the newly developed treatment. Specific aims of Phase I include the development, elaboration, and iterative refinement of a treatment manual for IPT-PS; development of therapist training procedures; and the development of measures of treatment adherence, competence, and satisfaction. In Phase II, 24 patients with depression complicated by panic symptoms will be randomly assigned to treatment using IPT-PS, and will be compared with 12 patients randomly assigned to receive standard IPT. Specific aims of this pilot study include: finalizing the treatment manual and measures of treatment adherence, competence, and satisfaction; testing treatment satisfaction with IPT-PS; evaluating characteristics of treatment responders and non-responders; and generating treatment effect size estimates for use in planning a larger efficacy/effectiveness study of IPT-PS.

DESCRIPTION (provided by applicant): Despite decades of clinical trial experience, our understanding of how best to achieve durable recovery from major depression remains very limited. The aim of this study is to define treatment-relevant phenotypes of depression in order to aid practicing clinicians in achieving that goal. We hypothesize that a small, clinically practical set of variables including: 1) dimensional measures of mood disorder and common anxiety comorbidities (embodied in assessment instruments emphasizing a spectrum approach to description of clinical phenotypes); and 2) treatment exposure (embodied in population pharmacokinetic measures for pharmacotherapy and treatment specificity for psychotherapy); will be statistically significant moderators of time to stabilizaton of a major depressive episode. We hypothesize that this same set of variables will be statistically significant mediators of time to relapse and residual functional impairment. Finally we hypothesize that, using signal detection analysis methods to examine the relationship of these variables and traditional correlates of treatment outcome such as baseline severity, residual symptoms and Axis It comorbidity, we can develop clinically useful algorithms to guide clinicians in choosing between pharmacotherapy and psychotherapy as an initial treatment strategy. In order to test these hypotheses, we will randomly assign 288 men and women between 18 and 64 years of age who are seeking treatment for a major depressive episode at local community clinics to begin treatment with either interpersonal psychotherapy (IPT) or SSRI (citalopram) pharmacotherapy. Those who stabilize (Hamilton Rating Scale for Depression score < 7 X 3 weeks) will continue in their initial treatment. Those who do not, will have the other treatment added to their regimen. All stabilizing subjects will enter a continuation treatment phase in which the treatment that brought about the remission (SSRI alone, IPT alone, or the combination) will be continued for 6 months. Our interest is in identifying those subgroups of patients that respond best to specific treatments or treatment sequences, achieve full remission of symptoms and return of functioning, and are able to sustain their recovery and improved functioning through an extended well interval. By using a relatively small set of variables that we believe have high potential for outcome prediction to characterize patients and their treatment, we expect to accomplish this goal in the context of the proposed study. Cox proportional hazard survival regression models and random regression models will be used to analyze the association of time to stabilization and time to relapse and degree of functional impairment) with spectrum assessments and treatment exposure variables. Signal detection analysis will be used to determine which combination of spectrum assessment scores and other clinical variables describe the profile of patients likely to stabilize or relapse with each of the treatments.

DESCRIPTION (provided by applicant): Bipolar disorder is a devastating, chronically recurring condition with significant public health impact, characterized high rates of suicide and high levels of functional and occupational impairment. In the last 15 years, combined psychosocial intervention and medication has been found to speed remission of acute symptoms, delay recurrences, and reduce inter-episode symptoms in a number of controlled trials, yet these effective psychosocial interventions are seldom implemented in community mental health settings. The proposal seeks to address these challenges by developing and piloting a comprehensive approach to implementation that will support the implementation of an evidence-based psychotherapy (EBP) for bipolar disorder in community mental health settings. The proposal builds on approaches developed during a large multi-site bipolar effectiveness trial (STEP-BD). It enhances those approaches through developing a comprehensive approach to implementation that incorporates technology-supported implementation assistance that targets key organizational factors and individual clinician factors associated with effective implementation. The project will then compare this comprehensive approach to implementation designed to improve effective implementation to an implementation-as-usual strategy in terms of feasibility and acceptability. The results will be used to support the development of a larger grant proposal to examine the effectiveness of a comprehensive approach to implementation, as well as provide important information to the field more generally regarding factors associated with effective implementation of interventions in community mental health settings. PUBLIC HEALTH RELEVANCE: Bipolar disorder is a devastating, chronically recurring condition with significant public health impact, characterized high rates of suicide, and high levels of functional and occupational impairment. In the last 15 years, combined psychosocial intervention and medication has been found to speed remission of acute symptoms, delay recurrences, and reduce inter-episode symptoms in a number of controlled trials, yet these effective psychosocial interventions are seldom implemented in community mental health settings. This project seeks to develop and examine the feasibility, acceptability, and preliminary impact of a comprehensive approach to supporting the implementation of an effective psychosocial intervention for bipolar disorder in community mental health settings. If successful, the resulting intervention could substantially lower the public health impact of bipolar disorder.