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Biomedical subjects

Ellen Frank

Publications and source records attributed to Ellen Frank.

At least 19 recordsLinked to original sources

Report by the ACNP Task Force on response and remission in major depressive disorder.

This report summarizes recommendations from the ACNP Task Force on the conceptualization of remission and its implications for defining recovery, relapse, recurrence, and response for clinical investigators and practicing clinicians. Given the strong implications of remission for better function and a better prognosis, remission is a valid, clinically relevant end point for both practitioners and investigators. Not all depressed patients, however, will reach remission. Response is a less desirable primary outcome in trials because it depends highly on the initial (often single) baseline measure of symptom severity. It is recommended that remission be ascribed after 3 consecutive weeks during which minimal symptom status (absence of both sadness and reduced interest/pleasure along with the presence of fewer than three of the remaining seven DSM-IV-TR diagnostic criterion symptoms) is maintained. Once achieved, remission can only be lost if followed by a relapse. Recovery is ascribed after at least 4 months following the onset of remission, during which a relapse has not occurred. Recovery, once achieved, can only be lost if followed by a recurrence. Day-to-day functioning and quality of life are important secondary end points, but they were not included in the proposed definitions of response, remission, recovery, relapse, or recurrence. These recommendations suggest that symptom ratings that measure all nine criterion symptom domains to define a major depressive episode are preferred as they provide a more certain ascertainment of remission. These recommendations were based largely on logic, the need for internal consistency, and clinical experience owing to the lack of empirical evidence to test these concepts. Research to evaluate these recommendations empirically is needed.

Clinical Trials as Topic↗

Maintenance treatment of major depression in old age.

BACKGROUND: Elderly patients with major depression, including those having a first episode, are at high risk for recurrence of depression, disability, and death. METHODS: We tested the efficacy of maintenance paroxetine and monthly interpersonal psychotherapy in patients 70 years of age or older who had depression (55 percent of whom were having a first episode) in a 2-by-2, randomized, double-blind, placebo-controlled trial. Among patients with a response to treatment with paroxetine and psychotherapy, 116 were randomly assigned to one of four maintenance-treatment programs (either paroxetine or placebo combined with either monthly psychotherapy or clinical-management sessions) for two years or until the recurrence of major depression. Clinical-management sessions, conducted by the same nurses, social workers, and psychologists who provided psychotherapy, involved discussion of symptoms. RESULTS: Major depression recurred within two years in 35 percent of the patients receiving paroxetine and psychotherapy, 37 percent of those receiving paroxetine and clinical-management sessions, 68 percent of those receiving placebo and psychotherapy, and 58 percent of those receiving placebo and clinical-management sessions (P=0.02). After adjustment for the effect of psychotherapy, the relative risk of recurrence among those receiving placebo was 2.4 times (95 percent confidence interval, 1.4 to 4.2) that among those receiving paroxetine. The number of patients needed to be treated with paroxetine to prevent one recurrence was 4 (95 percent confidence interval, 2.3 to 10.9). Patients with fewer and less severe coexisting medical conditions (such as hypertension or cardiac disease) received greater benefit from paroxetine (P=0.03 for the interaction between treatment with paroxetine and baseline severity of medical illness). CONCLUSIONS: Patients 70 years of age or older with major depression who had a response to initial treatment with paroxetine and psychotherapy were less likely to have recurrent depression if they received two years of maintenance therapy with paroxetine. Monthly maintenance psychotherapy did not prevent recurrent depression. (ClinicalTrials.gov number, NCT00178100.).

Aged↗

Smaller cingulate volumes in unipolar depressed patients.

BACKGROUND: The anterior cingulate cortex is a key structure in brain networks involved in mood regulation. Abnormalities in this brain region are possibly implicated in the pathophysiology of depression. This anatomical magnetic resonance imaging (MRI) study compared cingulate cortex volumes in unipolar depressed patients and age- and gender-matched healthy control subjects. METHODS: Thirty-one unmedicated DSM-IV unipolar patients (24 female, aged 39.2 +/- 11.9 years [mean +/- SD]) and 31 healthy control subjects (24 female, aged 36.7 +/- 10.7 years) were studied in a 1.5-T GE Signa magnet (General Electric Medical Systems, Milwaukee, Wisconsin). Cingulate volumes were compared by analysis of covariance with intracranial volume as the covariate. RESULTS: The unipolar patients had significantly smaller anterior and posterior cingulate volumes bilaterally compared with healthy control subjects. When patients were divided into currently depressed (n = 21) and remitted (n = 10) subgroups, currently depressed patients had significantly smaller anterior and posterior cingulate volumes bilaterally compared with healthy control subjects, whereas remitted patients had significantly smaller left anterior cingulate volumes compared with healthy individuals. CONCLUSIONS: Gray matter abnormalities in the cingulate cortex are implicated in the pathophysiology of unipolar depression. Smaller cingulate volumes in currently depressed patients support the hypothesis that cingulate cortex abnormalities are state dependent, whereas changes in left anterior cingulate might be trait related.

Adolescent↗

An open-label trial of enhanced brief interpersonal psychotherapy in depressed mothers whose children are receiving psychiatric treatment.

Major depression affects one out of five women during her lifetime. Depressed mothers with psychiatrically ill children represent an especially vulnerable population. Challenged by the demands of caring for ill children, these mothers often put their own needs last; consequently, their depressions remain untreated. This population is especially difficult to engage in treatment. We have developed a nine-session intervention, an engagement session followed by eight sessions of brief interpersonal psychotherapy designed to increase maternal participation in their own psychotherapy, resolve symptoms of maternal depression, and enhance relationships (IPT-MOMS). This open-label trial assesses the feasibility and acceptability of providing this treatment to depressed mothers. Thirteen mothers meeting DSM-IV criteria for major depression were recruited from a pediatric mental health clinic where their school-age children were receiving psychiatric treatment. Subjects (mothers) were treated openly with IPT-MOMS. Eighty-five percent (11/13) completed the study. Subjects were evaluated with the Hamilton Rating Scale for Depression, and completed self-report measures of quality of life and functioning at three time points: baseline, after treatment completion, and 6-months posttreatment. A signed rank test was used to compare measurement changes between assessment time points. Subjects showed significant improvement from baseline to posttreatment on measures of maternal symptoms and functioning. These gains were maintained at 6-month follow-up. Therapy was well tolerated and accepted by depressed mothers, who are typically difficult to engage in treatment. A high proportion of subjects completed treatment and experienced improvements in functioning. Future randomized clinical trials are needed to establish the efficacy of this approach.

Adolescent↗

Treating complicated grief and substance use disorders: a pilot study.

Empirically supported treatments for co-occurring substance use disorders (SUDs) and grief problems are lacking, despite the salience of grief pathology in substance abusers. Identification of a syndrome of complicated grief, distinct from bereavement-related depression and anxiety, led to the development of a targeted treatment, but this treatment has not been tried with persons with SUDs. We recruited 16 adults with complicated grief and substance dependence or abuse into an open pilot study of a manualized 24-session treatment, incorporating motivational interviewing and emotion coping and communication skills into our efficacious complicated grief treatment. Completer and intent-to-treat analyses showed significant reductions in Inventory of Complicated Grief and Beck Depression Inventory scores, with large effect sizes. Timeline Followback percent days abstinent increased significantly in both analyses, with medium to large effect sizes, and cravings declined significantly. Study limitations notwithstanding, complicated grief and substance use treatment appears to be a promising intervention that merits further research.

Adult↗

Life stress and the long-term treatment course of recurrent depression: III. Nonsevere life events predict recurrence for medicated patients over 3 years.

Research has consistently documented the significance of severe life events for onset of major depression. Theory, however, suggests other forms of stress are relevant for depression's recurrence. Nonsevere life events were tested in relation to depression for 126 patients with recurrent depression in a 3-year randomized maintenance protocol. Life stress was assessed every 12 weeks and rated along dimensions of severity, focus, and independence. A significant interaction between specific types of nonsevere life events and medication was found. For medicated patients, subject-focused independent nonsevere life events predicted recurrence; for unmedicated patients, these events predicted fewer recurrences. Other nonsevere life events did not predict recurrence. The findings underscore the potential importance of specific stressors for triggering recurrences of depression.

Adult↗

Psychotherapy, symptom outcomes, and role functioning over one year among patients with bipolar disorder.

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

Activities of Daily Living↗

Indirect self-destructive behavior and overt suicidality in patients with complicated grief.

BACKGROUND: Complicated grief is associated with increased suicidal ideation in samples of bereaved individuals; however, suicidal behavior has not been assessed in these patients. Additionally, there are no reports of suicidality among help-seeking individuals with complicated grief. Therefore, we examined suicidal behavior and its correlates in 149 patients who signed informed consent statements to participate in a National Institute of Mental Health-funded treatment study of complicated grief. METHOD: All patients met criteria for complicated grief (Inventory of Complicated Grief score>or=25). Suicidality was assessed using a structured clinical interview administered prior to beginning treatment. Participants also completed self-report questionnaires and interview assessment measures rating the presence or absence of DSM-IV Axis I diagnosis and symptom severity. Data were gathered between April 2001 and April 2004. RESULTS: Thoughts of wanting to die following the death of a loved one were reported by 65% of participants. More than half of this group (38% of the study sample) engaged in self-destructive behavior, including 9% who made a suicide attempt and 29% who engaged in indirect suicidal behavior. In a multiple logistic regression model, only the severity of complicated grief symptoms (p<.0001) and history of a suicide attempt (p<.02) were significantly associated with postloss suicidal behavior. DISCUSSION: Consistent with reports of non-help-seeking bereaved people, a high rate of individuals seeking treatment for complicated grief endorsed a wish to die. Notably, 13% of this group made at least 1 suicide attempt, and 44% engaged in indirect self-destructive behavior. Given its frequency, this behavior should be included in assessment of bereaved people.

Attitude to Death↗

Prevalence and clinical correlates of medical comorbidities in patients with bipolar I disorder: analysis of acute-phase data from a randomized controlled trial.

OBJECTIVE: We studied the relationship between number of medical comorbidities in patients with bipolar I disorder and their demographic and clinical characteristics. METHOD: Data were from 174 patients in the acute phase of the Pittsburgh Maintenance Therapies in Bipolar Disorder (MTBD) study, a randomized controlled trial comparing Interpersonal and Social Rhythm Therapy to an intensive clinical management approach for individuals with a lifetime diagnosis of bipolar I disorder or schizoaffective disorder, manic type, according to Research Diagnostic Criteria, who were receiving adjunctive protocol-driven pharmacotherapy. Patients entered the MTBD study from 1991 to 2000. We examined the acute-phase Hamilton Rating Scale for Depression (HAM-D) and Bech-Rafaelsen Mania Scale scores, demographics, clinical history, and medical comorbidities. RESULTS: Patients with a high number of medical comorbidities had longer duration of both lifetime depression (p = .02) and lifetime inpatient depression treatment (p = .04), had higher baseline HAM-D score (p = .01), and were more likely to be treated for a depressed clinical state during the acute phase of the MTBD study (p = .05). Moreover, higher severity of baseline medical comorbidities predicted slower decreases in HAM-D score among depressed (p = .004) and mixed/cycling (p = .003) patients even after controlling for baseline HAM-D score. CONCLUSIONS: Medical illness is correlated with several indicators of poorer prognosis and outcome in bipolar I disorder. Not only do preventing and treating medical comorbidities in bipolar patients decrease the morbidity and mortality related to physical illness, but they could also enhance psychological well-being and possibly improve the course of bipolar illness. Identification of characteristics in bipolar I patients that are correlated to increased risk for medical comorbidities is a fundamental step in understanding the nature of the relationship between bipolar disorder and medical illness.

Adult↗

Treatment of complicated grief: a randomized controlled trial.

CONTEXT: Complicated grief is a debilitating disorder associated with important negative health consequences, but the results of existing treatments for it have been disappointing. OBJECTIVE: To compare the efficacy of a novel approach, complicated grief treatment, with a standard psychotherapy (interpersonal psychotherapy). DESIGN: Two-cell, prospective, randomized controlled clinical trial, stratified by manner of death of loved one and treatment site. SETTING: A university-based psychiatric research clinic as well as a satellite clinic in a low-income African American community between April 2001 and April 2004. PARTICIPANTS: A total of 83 women and 12 men aged 18 to 85 years recruited through professional referral, self-referral, and media announcements who met criteria for complicated grief. INTERVENTIONS: Participants were randomly assigned to receive interpersonal psychotherapy (n = 46) or complicated grief treatment (n = 49); both were administered in 16 sessions during an average interval of 19 weeks per participant. MAIN OUTCOME MEASURE: Treatment response, defined either as independent evaluator-rated Clinical Global Improvement score of 1 or 2 or as time to a 20-point or better improvement in the self-reported Inventory of Complicated Grief. RESULTS: Both treatments produced improvement in complicated grief symptoms. The response rate was greater for complicated grief treatment (51%) than for interpersonal psychotherapy (28%; P = .02) and time to response was faster for complicated grief treatment (P = .02). The number needed to treat was 4.3. CONCLUSION: Complicated grief treatment is an improved treatment over interpersonal psychotherapy, showing higher response rates and faster time to response.

Adaptation, Psychological↗

Structural brain changes in bipolar disorder using deformation field morphometry.

The objective of this study was to investigate anatomical brain abnormalities in adult bipolar patients using a deformation field morphometry technique. Our sample consisted of 32 right-handed bipolar I patients (men/women=16/16) and 32 right-handed, age and gender matched healthy controls. Deformation field morphometry analysis was performed on three-dimensional spoiled gradient recalled acquisition images. We found gender-specific structural differences between bipolar patients and healthy individuals. Bipolar men had significantly larger lateral ventricles (especially pronounced in the left hemisphere) and smaller left dorsolateral prefrontal cortex than healthy male controls. Our results are complementary to the findings of functional imaging and post-mortem studies that demonstrate abnormalities in the dorsolateral prefrontal cortex in bipolar patients.

Adolescent↗

1H Magnetic resonance spectroscopy study of dorsolateral prefrontal cortex in unipolar mood disorder patients.

Neuroimaging and postmortem studies have suggested the involvement of the dorsolateral prefrontal cortex (DLPFC) in the pathophysioloy of unipolar disorder. We examined with in vivo 1H magnetic resonance spectroscopy (MRS) the levels of specific metabolites in the DLPFC of adult unipolar patients and the role of illness chronicity on DLPFC abnormalities. Nineteen unmedicated unipolar mood disorder patients and 19 age- and gender-matched healthy controls underwent a short echo-time 1H MRS examination localized to an 8-cm3 single voxel placed in the left DLPFC. There were no significant differences in metabolite levels, including N-acetylaspartate (NAA), phosphocreatine plus creatine (PCr+Cr) and choline-containing-compounds (GPC+PC), between the two groups. However, NAA/PCr+Cr ratios were significantly lower in the chronic than in the less chronically ill patients and healthy controls. The low levels of NAA/PCr+Cr ratios in the left DLPFC of unipolar patients who had been more chronically ill suggest a potential role for illness chronicity in neuronal abnormalities in the DLPFC in unipolar disorder. This could possibly be accounted for by neurodegenerative processes arising with the progression of the illness. Future 1H MRS investigations should longitudinally examine the role of illness chronicity on DLPFC abnormalities and their relationship with the symptoms of unipolar disorder.

Adult↗

Two-year outcomes for interpersonal and social rhythm therapy in individuals with bipolar I disorder.

CONTEXT: Numerous studies have pointed to the failure of prophylaxis with pharmacotherapy alone in the treatment of bipolar I disorder. Recent investigations have demonstrated benefits from the addition of psychoeducation or psychotherapy to pharmacotherapy in this population. OBJECTIVE: To compare 2 psychosocial interventions: interpersonal and social rhythm therapy (IPSRT) and an intensive clinical management (ICM) approach in the treatment of bipolar I disorder. DESIGN: Randomized controlled trial involving 4 treatment strategies: acute and maintenance IPSRT (IPSRT/IPSRT), acute and maintenance ICM (ICM/ICM), acute IPSRT followed by maintenance ICM (IPSRT/ICM), or acute ICM followed by maintenance IPSRT (ICM/IPSRT). The preventive maintenance phase lasted 2 years. SETTING: Research clinic in a university medical center. PARTICIPANTS: One hundred seventy-five acutely ill individuals with bipolar I disorder recruited from inpatient and outpatient settings, clinical referral, public presentations about bipolar disorder, and other public information activities. INTERVENTIONS: Interpersonal and social rhythm therapy, an adaptation of Klerman and Weissman's interpersonal psychotherapy to which a social rhythm regulation component has been added, and ICM. MAIN OUTCOME MEASURES: Time to stabilization in the acute phase and time to recurrence in the maintenance phase. RESULTS: We observed no difference between the treatment strategies in time to stabilization. After controlling for covariates of survival time, we found that participants assigned to IPSRT in the acute treatment phase survived longer without a new affective episode (P = .01), irrespective of maintenance treatment assignment. Participants in the IPSRT group had higher regularity of social rhythms at the end of acute treatment (P<.001). Ability to increase regularity of social rhythms during acute treatment was associated with reduced likelihood of recurrence during the maintenance phase (P = .05). CONCLUSION: Interpersonal and social rhythm therapy appears to add to the clinical armamentarium for the management of bipolar I disorder, particularly with respect to prophylaxis of new episodes.

Adult↗

Cross-cultural validity of the structured clinical interview for panic-agoraphobic spectrum.

BACKGROUND: We sought to develop a series of assessment measures of psychiatric spectrum conditions associated with major DSM-IV mood and anxiety disorders that might capture the true phenotypes underlying these disorders. The specific objective of this report was to describe the methods we employed to create instruments that could cross linguistic and national boundaries and to evaluate the comparability of results obtained when one of these instruments, the Structured Clinical Interview for Panic-Agoraphobic Spectrum (SCI-PAS), was administered in the United States and in Italy. METHOD: After developing, in parallel, the English and the Italian versions of the SCI-PAS, identical protocols were conducted in patients and control samples at the University of Pittsburgh and the University of Pisa to examine the reliability and validity of the interview. RESULTS: Total and domain scores on the SCI-PAS were strikingly similar in the US and Italian patient groups and in controls. In addition, similarly high levels of inter-rater and test-retest reliability were found at the two sites. Finally, virtually identical patterns of relationships were found between the domains of the SCI-PAS and established measures of the same constructs. CONCLUSIONS: The SCI-PAS displays similar reliability and validity properties in the two versions. This suggests that the instrument taps a phenotype that is consistent in American and Italian patient and control populations.

Adult↗