Maintaining reliability in a long-term psychiatric study: an ongoing inter-rater reliability monitoring program using the longitudinal interval follow-up evaluation.

The Longitudinal Interval Follow-up Evaluation (LIFE), has been shown to be a valid and reliable instrument for characterizing the week-by-week course of anxiety disorders examined retrospectively over the period of 1 year. Due to the chronic nature of these disorders, there is a need for reliable, valid instruments for measuring course over periods of several years if we are to learn more about the natural history of these disorders. This paper describes a rater-monitoring program designed to ensure long-term inter-rater reliability and prevent "rater drift". In this program, clinical interviewers score taped interviews and are required to maintain a median intra-class correlation coefficient (ICC) of at least 0.80 with the other raters. Raters also assess tapes from previous years, to ensure that they are using the same diagnostic criteria as earlier generations of interviewers. A reliability study was conducted to compare psychiatric status ratings (PSRs) collected using biweekly telephone interviews with the semi-annual interviews. The ICCs for panic, agoraphobia, social phobia, and generalized anxiety disorder were very good to excellent. Another reliability study examined the PSRs of subjects who had been previously lost to follow-up. ICCs for panic, agoraphobia, generalized anxiety disorder and depression were good to excellent. These results show that the LIFE, when used in conjunction with an intensive training and rater monitoring system, is a reliable instrument for use in longitudinal studies of the course of anxiety disorders.

The relationship between comorbid personality disorders and treatment received in patients with anxiety disorders.

Few studies have addressed the relationship between the presence of a comorbid personality disorder and the amount of psychiatric treatment received by patients with an Axis I disorder. This issue has not been studied in patients with anxiety disorders. In a prospective, naturalistic, longitudinal study of anxiety disorders, 526 subjects were assessed with the Personality Disorder Examination, and types of treatment received in 1991 and 1996 were identified. In 1991, compared to subjects without a personality disorder, subjects with a personality disorder were as likely to receive medication and they received a greater number of medications. Subjects with borderline personality disorder were more likely to receive heterocyclic antidepressants and interventions characteristic of psychodynamic psychotherapy and cognitive therapy; they also reported receiving a greater number of medications and types of psychosocial treatment than other subjects. In 1996, subjects with borderline personality disorder were more likely to receive psychodynamic interventions. These findings suggest that in patients with an anxiety disorder, the presence of a comorbid personality disorder is associated with receiving a greater number of medications but not with a greater likelihood of receiving pharmacologic or psychosocial treatment. However, the presence of borderline personality disorder is associated with a greater likelihood of receiving, and receiving a greater number of, certain types of somatic and psychosocial treatments.

Patterns of personality pathology in patients with generalized anxiety disorder, panic disorder with and without agoraphobia, and social phobia.

The relationship between co-occurring personality disorders and anxiety disorders (panic disorder with or without agoraphobia, social phobia, and generalized anxiety disorder) was examined, taking into account the effect of major depression. This article describes findings for 622 participants in the Harvard/Brown Anxiety Research Project, a longitudinal follow-up study of DSM-III-R-defined anxiety disorders. A total of 24% of participants had at least one personality disorder, with avoidant, obsessive compulsive, dependent, and borderline most common. Generalized anxiety disorder, social phobia, and major depression were positively associated with the occurrence of one or more personality disorders, whereas panic disorder with agoraphobia was not associated. Major depression was associated in particular with dependent, borderline, histrionic, and obsessive compulsive personality disorders and social phobia was associated with avoidant personality disorder. Whereas some of our findings confirm results from earlier studies, others are somewhat inconsistent with previous results and indicate the need for further investigation.

Suicidal behavior in patients with current or past panic disorder: five years of prospective data from the Harvard/Brown Anxiety Research Program.

OBJECTIVE: The authors' goals were to examine predictors of suicidal behavior and provide guidelines for assessing suicide risk in patients with panic disorder. METHOD: Four hundred ninety-eight patients with panic disorder were followed for 5 years. Survival analysis was used to examine variables correlated with prospectively observed suicidal behavior. RESULTS: Subjects had a 0.06 probability of suicidal behavior during follow-up. Affective disorders, substance abuse, eating disorders, personality disorders, and being female were risk factors. Two subjects were suicidal in the absence of risk factors; both developed depression during follow-up. CONCLUSIONS: Panic disorder is not associated with suicidal behavior in the absence of other risk factors.

Factors predicting the clinical course of generalised anxiety disorder.

BACKGROUND: Cross-sectional data show that generalised anxiety disorder (GAD) is a chronic condition with episodes lasting much longer than the six-month minimum required by DSM-III-R and DSM-IV. Although GAD is chronic, little is known about factors influencing illness duration. AIMS: To investigate variables that influence the clinical course of GAD. METHOD: A total of 167 patients with GAD participated in the Harvard-Brown Anxiety Research Program. Patients were assessed at intake and re-examined at six- to twelve-month intervals for five years. Kaplan-Meier curves were constructed to assess the likelihood of remission. Regression analysis was used to investigate factors predicting full or partial remission. RESULTS: The rate of remission was 0.38 after five years. Diminished likelihood of remission was associated with low overall life satisfaction, poor spousal or family relationships, a concurrent cluster B or C personality disorder and a low global assessment score. CONCLUSIONS: Full or partial remissions were less likely to occur in patients with poor relationships and personality disorders. These patients should be given more intensive and possibly multi-modal therapy.

Personality disorders, history of trauma, and posttraumatic stress disorder in subjects with anxiety disorders.

The purpose of the study was to examine the association of personality disorders, history of trauma, and posttraumatic stress disorder (PTSD) in a large sample of subjects with anxiety disorders. Categorical and continuous indices of personality disorders were compared in three groups from the Harvard/Brown Anxiety Disorders Research Project (HARP): subjects with no history of trauma (n = 403), subjects with a history of trauma but no history of PTSD (n = 151), and subjects with a current or past diagnosis of PTSD (n = 68). Subjects with PTSD were more likely to meet criteria for borderline or self-defeating personality disorder than subjects in the other two groups. PTSD subjects also had higher scores on the continuous measures (total number of criteria met) for borderline and self-defeating personality disorder than the other two groups. The findings suggest that a diagnosis of PTSD rather than a history of trauma is associated with borderline and self-defeating personality disorder features. Alternative conceptualizations of axis II features in individuals with PTSD are discussed.

Multiple recurrences of major depressive disorder.

OBJECTIVE: The authors of this study examined multiple recurrences of unipolar major depressive disorder. METHOD: A total of 318 subjects with unipolar major depressive disorder were prospectively followed for 10 years within a multicenter naturalistic study. Survival analytic techniques were used to examine the probability of recurrence after recovery from the index episode. RESULTS: The mean number of episodes of major depression per year of follow-up was 0. 21, and nearly two-thirds of the subjects suffered at least one recurrence. The number of lifetime episodes of major depression was significantly associated with the probability of recurrence, such that the risk of recurrence increased by 16% with each successive recurrence. The risk of recurrence progressively decreased as the duration of recovery increased. Within subjects, there was very little consistency in the time to recurrence. CONCLUSIONS: Major depressive disorder is a highly recurrent illness. The risk of the recurrence of major depressive disorder progressively increases with each successive episode and decreases as the duration of recovery increases.

Psychosocial treatment prescriptions for generalized anxiety disorder, panic disorder, and social phobia, 1991-1996.

OBJECTIVE: Pharmacologic prescriptions for anxiety disorders have changed significantly in the last decade. This article investigates whether psychosocial treatments, as reported by 362 subjects in the Harvard/Brown Anxiety Disorders Research Program from 1991 to 1996, changed as well. METHOD: Subjects were interviewed in 1991 and 1995-1996 to determine which psychosocial treatments (behavioral, cognitive, dynamic, or relaxation or meditation) they had received. RESULTS: The percentage of subjects who received each type of psychosocial treatment either declined or remained the same from 1991 to 1995-1996. Dynamic psychotherapy remained the most frequently used method of these four. The percentage of subjects receiving any such method declined. CONCLUSIONS: Behavioral and cognitive treatment, two empirically validated forms of psychotherapy, were less frequently used than dynamic psychotherapy, which lacks such validation. All use of verbal treatment methods declined from 1991 to 1995-1996.

Comparing primary and secondary generalized anxiety disorder in a long-term naturalistic study of anxiety disorders.

This study explores the potential differences in comorbidity and course between primary generalized anxiety disorder (GAD), which develops before other anxiety disorders, and secondary GAD. As part of the Harvard/Brown Anxiety Research Project (HARP), a naturalistic, long-term, longitudinal study of 711 subjects from a variety of clinic settings with DSM III-R defined anxiety disorders, 210 subjects with GAD were identified. Of these, 78 (37%) had primary GAD, and 84 (40%) had secondary GAD; of the remainder, 28 (13%) had no other anxiety disorder and 20 (10%) developed GAD within a month of another anxiety disorder and were excluded from the analysis. All subjects were comorbid for at least one other anxiety disorder. Primary GAD subjects were more likely to be in episode at intake (90% vs. 77%, P = .04) and less likely than secondary GAD subjects to have current or past agoraphobia without panic disorder (3% vs. 11%, P = .04), social phobia (19% v. 52%, P = .001), simple phobia (14% v. 30%, P = .02), or post traumatic stress disorder (5% vs. 20%, P = .01). Subjects with primary GAD were also less likely to have current or past alcohol use disorders (17% vs. 37%, P = .004) or major depressive disorder (60% vs. 76%, P = .03). There were no significant differences in either treatment approaches or remission rates for primary compared to secondary GAD. Whether GAD first occurs before or after another anxiety disorder, it is similar in terms of prevalence, treatment, and course. The only significant differences between primary and secondary GAD lie in the rates of comorbidity of both other anxiety disorders and non-anxiety disorders, including major depression and substance abuse. These results support the concept of GAD as a valid, separate and distinct entity, whether it occurs primarily or secondarily.

Recurrence after recovery from major depressive disorder during 15 years of observational follow-up.

OBJECTIVE: The recurrence of an affective disorder in people who initially recover from major depressive disorder was characterized by using the unique longitudinal prospective follow-up data from the National Institute of Mental Health Collaborative Program on the Psychobiology of Depression-Clinical Studies. METHOD: Up to 15 years of prospective follow-up data on the course of major depressive disorder were available for 380 subjects who recovered from an index episode of major depressive disorder and for 105 subjects who subsequently remained well for at least 5 years after recovery. Baseline demographic and clinical characteristics were examined as predictors of recurrence of an affective disorder. The authors also examined naturalistically applied antidepressant therapy. RESULTS: A cumulative proportion of 85% (Kaplan-Meier estimate) of the 380 recovered subjects experienced a recurrence, as did 58% (Kaplan-Meier estimate) of those who remained well for at least 5 years. Female sex, a longer depressive episode before intake, more prior episodes, and never marrying were significant predictors of a recurrence. None of these or any other characteristic persisted as a predictor of recurrence in subjects who recovered and were subsequently well for at least 5 years. Subjects reported receiving low levels of antidepressant treatment during the index episode, which further decreased in amount and extent during the well interval. CONCLUSIONS: Few baseline demographic or clinical characteristics predict who will or will not experience a recurrence of an affective disorder after recovery from an index episode of major depressive disorder, even in persons with lengthy well intervals. Naturalistically applied levels of antidepressant treatment are well below those shown effective in maintenance pharmacotherapy studies.

National Academy of Clinical Biochemistry Standards of Laboratory Practice: recommendations for the use of cardiac markers in coronary artery diseases.

The Sixth Conference on the "Standards of Laboratory Practice Series", sponsored by the National Academy of Clinical Biochemistry (NACB), was held on August 4-5, 1998, at the Annual Meeting of the American Association for Clinical Chemistry, in Chicago, IL. An expert committee was assembled to write recommendations on the use of cardiac markers in coronary artery diseases. The NACB Committee prepared a preliminary draft of the guidelines, made them available on the World Wide Web (www.nacb.org), and distributed them before the presentations. The recommendations were divided into four areas: the use of markers in the triage of patients with chest pain, acute coronary syndromes, clinical applications other than acute myocardial infarction and research, and assay platforms and markers of acute myocardial infarction. The recommendations were revised and subsequently re-presented in part at the "Biomarkers in Acute Cardiac Syndromes Conference", sponsored by the Jewish Hospital Heart and Lung Institute, Louisville KY, on October 16-17, 1998. This report lists each recommendation, its scientific justification, and a summary of discussions from conference participants and reviewers. Approximately 100 individuals responded to various versions of these recommendations via direct correspondences, telephone calls to Committee members, electronic mail correspondence to the Committee Chairman, or oral questions and comments raised during one of the two conference presentations. Some of the recommendations were changed to reflect the consensus opinion. In cases in which there was no consensus, the Committee included pertinent discussion without necessarily changing the original recommendations. At times, the Committee members felt that although a particular recommendation might not be the current standard of care today, they anticipate that it likely will be adopted in the near future.

Patterns of remission and relapse in obsessive-compulsive disorder: a 2-year prospective study.

OBJECTIVE: This study examined the course of illness in patients with obsessive-compulsive disorder (OCD) over a 2-year period. METHOD: Sixty-six patients with a primary diagnosis of DSM-III-R OCD were followed prospectively for 2 years. Baseline information was collected on demographic characteristics, Axis I and II diagnoses, and severity of OCD symptoms. Follow-up measures obtained at 3, 6, 12, and 24 months after baseline assessment included information on symptomatic and diagnostic status as well as behavioral and somatic treatments received. RESULTS: The probability of full remission from OCD over the 2-year period was 12%. The probability of partial remission was 47%. After achieving remission from OCD, the probability of relapse was 48%. No factors were identified that significantly predicted full or partial remission. Seventy-seven percent (N = 51) of the subjects received a serotonin reuptake inhibitor (SRI) for > or =12 weeks, and 68% (N = 45) received medium-to-high doses of SRIs for > or =12 weeks. Only 18% received a full trial of behavior therapy. CONCLUSION: Despite exposure to at least 1 adequate trial of an SRI, the likelihood of full remission of OCD in this study was low. Results of this study also suggest that behavior therapy may be under-utilized.

Chronicity in posttraumatic stress disorder (PTSD) and predictors of course of comorbid PTSD in patients with anxiety disorders.

The purpose of this study was to examine the course of comorbid posttraumatic stress disorder (PTSD) in 54 patients with another anxiety disorder. Using a prospective longitudinal design, the present study found that during the first 5 years of follow-up the probability of full remission from a chronic episode of PTSD was .18. Findings from this and other research confirm clinical impressions that a substantial number of people never fully remit from their PTSD even after many years. Variables associated with a longer time to remit from an episode of chronic PTSD were a history of alcohol abuse and a history of childhood trauma.

Prospective study of fluoxetine treatment and suicidal behavior in affectively ill subjects.

OBJECTIVE: There has been speculation in the literature about a link between fluoxetine use and suicidal behavior. The authors of this study hypothesized that there is no elevation in risk of suicidal behavior associated with use of fluoxetine. METHOD: The data come from the National Institute of Mental Health Collaborative Depression Study, a prospective, naturalistic follow-up of persons who presented for treatment of affective disorders. The analyses included data on 643 subjects who were followed up after fluoxetine was approved by the Food and Drug Administration in December 1987 for the treatment of depression. RESULTS: Nearly 30% (N = 185) of the study group was treated with fluoxetine at some point during the follow-up period. Relative to the other subjects, those who were subsequently treated with fluoxetine had onset of affective illness at a younger age and, after intake into the study and before 1988, had elevated rates of suicide attempts before fluoxetine treatment. A mixed-effects survival analysis that incorporated treatment exposure time, multiple treatment trials, and multiple suicide attempts per subject showed that relative to no treatment, use of fluoxetine and use of other somatic antidepressants were associated with nonsignificant reductions in the likelihood of suicide attempts or completions. Severity of psychopathology was strongly associated with elevated risk, and each suicide attempt after intake into the Collaborative Depression Study was associated with a marginally significant increase in risk of suicidal behavior. CONCLUSIONS: The results do not support the speculation that fluoxetine increases the risk of suicide. Rather, there was a nonsignificant reduction in risk of suicidal behavior among patients treated with fluoxetine, even though those subjects were more severely ill before treatment with fluoxetine.

Predictors of course in obsessive-compulsive disorder.

Systematic studies of course of illness in obsessive-compulsive disorder (OCD) using standardized diagnostic criteria are relatively rare. In the present study, 100 patients diagnosed with OCD were prospectively followed for up to 5 years. Other comorbid conditions included anxiety disorders (76%), major depressive disorder (33%), and at least one personality disorder (33%), mainly in the anxious cluster. Approximately 20% of patients had full remission and 50% had partial remission during follow-up. Significant predictors of partial remission included being married and having lower global severity scores at intake; the presence of major depression was marginally predictive of poorer course. Adequate serotonergic medication was associated with worse course, but findings are likely spurious. Only marital status and global severity were retained as predictors in a final regression model. Findings are discussed with regard to sample characteristics and similarity to other reports on predictors of course and of treatment outcome.

Simple phobia as a comorbid anxiety disorder.

This study sought to describe clinical and demographic characteristics differentiating patients with DSM-III-R simple phobias comorbid with one or more of five DSM-III-R index anxiety disorders as compared with those with the index diagnoses alone. From 711 subjects participating in a multicenter, longitudinal, naturalistic study of anxiety disorders, 115 subjects with comorbid simple phobias were compared with 596 subjects without simple phobias in terms of demographic data, comorbidity with other disorders, somatic and psychosocial treatment received, and quality of life. In addition, episode characteristics, types of simple phobias found, and course of illness were specified. Subjects with simple phobias had more additional comorbid anxiety disorders by history than did those without. Mean length of intake episode was 22.43 years and severity was typically moderate. Fears of heights and animals were the most commonly represented simple phobias. Subjects with uncomplicated panic disorder were less likely to have comorbid simple phobias than were subjects with other index diagnoses, and subjects with simple phobia were more likely to have comorbid posttraumatic stress disorder than were these without simple phobia. Subjects with and without simple phobias did not differ by somatic or psychosocial treatment received or in terms of quality of life. Simple phobia appeared in this study to be a chronic illness of moderate severity for which behavioral treatment methods of recognized efficacy were not being frequently utilized. Uncomplicated panic disorder may reflect some type of resistance to phobia development.

Is the course of panic disorder the same in women and men?

OBJECTIVE: Panic disorder with or without agoraphobia has a chronic relapsing course. Factors associated with poor outcome include early onset of illness and phobic avoidance. Several, but not all, authors have found a worse clinical course for women. Using observational, longitudinal data from the Harvard/Brown Anxiety Disorders Research Program, the authors analyzed remission and symptom recurrence rates in panic patients with respect to sex. METHOD: Male and female patients (N = 412) in an episode of panic with or without agoraphobia were assessed by structured interview and prospectively followed for up to 5 years. Data on remission, symptom recurrence, and comorbid psychiatric conditions for each sex were compared. RESULTS: There were no significant differences between men and women in panic symptoms or level of severity at baseline. Women were more likely to have panic with agoraphobia (85% versus 75%), while men were more likely to have uncomplicated panic (25% versus 15%). The rates of remission for panic with or without agoraphobia at 5 years were equivalent in men and women (39%). Of the subjects who achieved remission, 25% of the women and 15% of the men reexperienced symptoms by 6 months. Recurrence of panic symptoms continued to be higher in women (82%) than men (51%) during the follow-up period and was not influenced by concurrent agoraphobia. CONCLUSIONS: This study extends previous findings by showing that not only are women more likely to have panic with concurrent agoraphobia, but they are more likely than men to suffer a recurrence of panic symptoms after remission of panic.

Recovery from major depression. A 10-year prospective follow-up across multiple episodes.

BACKGROUND: Major depressive disorder is often marked by repeated episodes of depression. We describe recovery from major depression across multiple mood episodes in patients with unipolar major depression at intake and examine the association of sociodemographic and clinical variables with duration of illness. METHODS: A cohort of 258 subjects treated for unipolar major depressive disorder was followed up prospectively for 10 years as part of the Collaborative Depression Study, a multicenter naturalistic study of the mood disorders. Diagnoses were made according to the Research Diagnostic Criteria, and the course of illness was assessed with the Longitudinal Interval Follow-up Evaluation. Survival analyses were used to calculate the duration of illness for the first 5 recurrent mood episodes after recovery from the index episode. RESULTS: Diagnosis remained unipolar major depressive disorder for 235 subjects (91%). The median duration of illness was 22 weeks for the first recurrent mood episode, 20 weeks for the second, 21 weeks for the third, and 19 weeks for the fourth and fifth recurrent mood episodes; the 95% confidence intervals were highly consistent. From one episode to the next, the proportion of subjects who recovered by any one time point was similar. For subjects with 2 or more recoveries, the consistency of duration of illness from one recovery to the next was low to moderate. None of the sociodemographic or clinical variables consistently predicted duration of illness. CONCLUSION: In this sample of patients treated at tertiary care centers for major depressive disorder, the duration of recurrent mood episodes was relatively uniform and averaged approximately 20 weeks.