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Biomedical subjects

M B Keller

Publications and source records attributed to M B Keller.

At least 19 recordsLinked to original sources
PubMed2003

A double-blind, placebo-controlled trial of fluvoxamine in binge eating disorder: a high placebo response.

Twenty subjects with binge eating disorder were randomly assigned to flexible-dose fluvoxamine or placebo for 12 weeks. A significant reduction in binge frequency, Beck Depression Inventory scores and the eating concern, shape concern and weight concern subscales of the Eating Disorder Examination were noted for both fluvoxamine (n = 9) and placebo (n = 11) groups. There were no significant differences between fluvoxamine and placebo for any treatment outcome variables. The findings from this small trial contribute to the inconsistent results of antidepressant studies in binge eating disorder.

Adult↗
PubMed2003

Patient's therapeutic skill acquisition and response to psychotherapy, alone or in combination with medication.

BACKGROUND: We tested the hypotheses that the addition of medication to psychotherapy enhances participation in the latter by: (1) speeding the acquisition of the psychotherapy's targeted skill; and (2) facilitating higher skill level acquisition. METHOD: Participants were 431 chronically depressed patients who received Cognitive Behavioral Analysis System of Psychotherapy (CBASP), alone (N=214) or in combination with nefazodone (N=217), as part of a randomized chronic depression study (Keller et al. 2000). CBASP, developed specifically to treat chronic depression, uses a specific procedure, 'situational analysis' to help patients engage in more effective goal-oriented interpersonal behaviours. At the end of each session, therapists rated patients on their performance of situational analysis. Outcome on depressive symptoms was assessed with the 24-item Hamilton Rating Scale for Depression. RESULTS: Although reductions in depression were significantly greater in combined treatment compared to CBASP alone, there were no between-group differences in either the rate of skill acquisition or overall skill level at the end of treatment. Proficiency in the use of the main skill taught in psychotherapy at treatment midpoint predicted outcome independently of medication status and of baseline depressive severity. CONCLUSIONS: Effective participation in CBASP, as reflected by proficiency in the compensatory skill taught in psychotherapy, is not enhanced by the addition of medication and does not mediate the between-group difference in depression outcome.

Adolescent↗
PubMed2003

The lifelong course of social anxiety disorder: a clinical perspective.

Social anxiety disorder (SAD) is among the most frequently observed psychiatric disorders, with estimates of approximately 10% of people likely to suffer from the disorder during their lifetime. However, despite causing significant impairment of normal functioning, this disorder is often mistaken as shyness and remains under-recognized and under-treated. Following onset in adolescence, patients with generalized SAD often experience a lifelong and unremitting mental disorder characterized by severe anxiety and disability. Typical duration of the illness is far in excess of that seen in panic disorder, and prospective, long-term, naturalistic studies have indicated that only one-third of individuals attain remission from SAD within 8 years, compared with over two-thirds of those with panic disorder. Comorbidity of other anxiety disorders, depression and personality disorders are common in SAD and associated with more pronounced impairment and a poorer long-term outcome. Effective treatment for SAD is available but use is low and may remain suboptimal, despite the development of pharmacotherapeutic agents with anxiolytic and antidepressant properties and the efficacy of psychotherapeutic approaches. Increased knowledge of the course of SAD highlights the need to examine the role of available treatments, administered individually or in combination, as acute, continuation or maintenance therapy to maximize the chances of remission and long-term benefit for patients.

Adolescent↗
PubMed2002

Optimizing outcomes in depression: focus on antidepressant compliance.

Major depressive disorder is a chronic and recurrent illness that is associated with significant morbidity and mortality. Patients frequently experience recurrent depressive episodes that are of longer duration and increased severity and which are less responsive to treatment than the index episode. Despite the highly prevalent nature of the illness, depression is frequently unrecognized and undertreated. Compliance with antidepressant medication is essential to consolidate treatment response and prevent relapse and recurrence. However, compliance with antidepressant medication is poor. Education of the patient and physician regarding the nature of depression and its treatment is essential for improving patient compliance. Although psychological mechanisms are a major factor affecting patient compliance, speed of onset of action and poor tolerability of antidepressant medication also have a considerable influence on patient compliance. The newer antidepressants, such as selective serotonin reuptake inhibitors, nonselective serotonin-norepinephrine reuptake inhibitors, and the selective norepinephrine reuptake inhibitors, are better tolerated than tricyclic antidepressants, possibly resulting in improved compliance and treatment outcome.

Antidepressive Agents↗
PubMed2001

Effectiveness of St John's wort in major depression: a randomized controlled trial.

CONTEXT: Extracts of St John's wort are widely used to treat depression. Although more than 2 dozen clinical trials have been conducted with St John's wort, most have significant flaws in design and do not enable meaningful interpretation. OBJECTIVE: To compare the efficacy and safety of a standardized extract of St John's wort with placebo in outpatients with major depression. DESIGN AND SETTING: Randomized, double-blind, placebo-controlled clinical trial conducted between November 1998 and January 2000 in 11 academic medical centers in the United States. PARTICIPANTS: Two hundred adult outpatients (mean age, 42.4 years; 67.0% female; 85.9% white) diagnosed as having major depression and having a baseline Hamilton Rating Scale for Depression (HAM-D) score of at least 20. INTERVENTION: Participants completed a 1-week, single-blind run-in of placebo, then were randomly assigned to receive either St John's wort extract (n = 98; 900 mg/d for 4 weeks, increased to 1200 mg/d in the absence of an adequate response thereafter) or placebo (n = 102) for 8 weeks. MAIN OUTCOME MEASURES: The primary outcome measure was rate of change on the HAM-D over the treatment period. Secondary measures included the Beck Depression Inventory (BDI), Hamilton Rating Scale for Anxiety (HAM-A), the Global Assessment of Function (GAF) scale, and the Clinical Global Impression-Severity and -Improvement scales (CGI-S and CGI-I). RESULTS: The random coefficient analyses for the HAM-D, HAM-A, CGI-S, and CGI-I all showed significant effects for time but not for treatment or time-by-treatment interaction (for HAM-D scores, P<.001, P =.16, and P =.58, respectively). Analysis of covariance showed nonsignificant effects for BDI and GAF scores. The proportion of participants achieving an a priori definition of response did not differ between groups. The number reaching remission of illness was significantly higher with St John's wort than with placebo (P =.02), but the rates were very low in the full intention-to-treat analysis (14/98 [14.3%] vs 5/102 [4.9%], respectively). St John's wort was safe and well tolerated. Headache was the only adverse event that occurred with greater frequency with St John's wort than placebo (39/95 [41%] vs 25/100 [25%], respectively). CONCLUSION: In this study, St John's wort was not effective for treatment of major depression.

Adult↗
PubMed2001

Infrequency of "pure" GAD: impact of psychiatric comorbidity on clinical course.

The widespread occurrence of psychiatric comorbidity among patients with generalized anxiety disorder (GAD) has been well documented. However, there is a paucity of studies examining the impact comorbid disorders have on the clinical course of GAD. In this study, 179 patients with GAD at intake, 12 patients with a past history of GAD, and 109 patients who subsequently onset a first episode of GAD during the course of follow-up were followed for 8 years in this naturalistic, prospective study of anxiety disorders. Results indicate that comorbid anxiety, mood, and substance use disorders are very common with GAD and increased during follow-up. For example, 39% of participants with GAD also had a comorbid diagnosis of major depressive disorder at intake and increased to 65% at 4 years and 74% at the 8-year follow-up. Inspection of "pure" cases of GAD indicated that out of 20 patients with GAD alone at intake, all but 1 went on to develop some comorbidity. Results also indicate that being in episode of comorbid MDD or panic disorder with agoraphobia decreased the probability that a subject would remit from their GAD. The findings highlight the need for such long-term, prospective research since results show that patients with GAD at intake had increasing risk for developing other mental disorders during subsequent follow-ups. Additionally, results of such high comorbidity and the impact of these comorbid disorders on the clinical course of GAD should have a notable impact on research into the treatment of GAD.

Adult↗
PubMed2001

Sertraline versus imipramine to prevent relapse in chronic depression.

BACKGROUND: Chronic depressions are common, disabling and under-treated, and long-term treatment is little studied. We report the continuation phase results from a long-term treatment study. METHODS: After 12 weeks of acute phase treatment in a double-blind, randomized, parallel-group, multi-center trial of sertraline or imipramine, patients with chronic depression (> or = 2 years in major depression, or major depression superimposed on dysthymia) continued study drug for 16 weeks. Initially, 635 patients were randomized to sertraline or imipramine in a 2:1 ratio. Nonresponders after 12 weeks entered a 12-week double-blind crossover trial of the alternate medication. Entry into continuation treatment required at least a satisfactory response (partial remission) to initial or crossover treatment. RESULTS: Of 239 acute or crossover responders to sertraline, 60% entered continuation in full remission and 40% with a partial remission. These proportions were identical for imipramine patients (n = 147). For both drug groups, over two-thirds of those entering in full remission retained it. For those entering in partial remission, over 40% achieved full remission. Patients requiring crossover treatment were less likely to maintain or improve their response during continuation treatment. The two drugs did not differ significantly in response distribution, drop out rates or discontinuation due to side effects during continuation treatment. LIMITATIONS: The absence of a placebo group constrains interpretation of our results, but chronic depressions have low placebo response rates. CONCLUSIONS: Most chronic depression patients who remit with 12 weeks of sertraline or imipramine treatment maintain remission during 16 weeks of continuation treatment. Most patients with a satisfactory therapeutic response (partial remission) after 12 weeks of treatment maintain it or further improve. Patients treated with imipramine experienced more side effects, but both drugs were well tolerated.

Adult↗
PubMed2001

The epidemiology of generalized anxiety disorder.

The literature reviewed here is consistent in showing that GAD is a common mental disorder that typically has an early age of onset, a chronic course, and a high degree of comorbidity with other anxiety and mood disorders. Comorbid GAD is often temporally primary, especially in relation to mood disorders, and is associated with an increased risk for the subsequent onset and severity of secondary disorders. The weight of evidence reviewed here argues against the view expressed by early commentators that GAD is better conceptualized as a prodrome, residual, or severity marker of other disorders than as an independent disorder. Focused studies of comorbidity between GAD and major depression, in which comorbidity is high, lead to the same conclusion. The crucial evidence for this conclusion includes the following: 1. Contrary to the findings of clinical studies, GAD in the community does not have a higher comorbidity than do most other anxiety or mood disorders. 2. The symptoms of GAD form an empiric cluster distinct from the symptoms of major depression in studies of symptom profiles. 3. Family studies show distinct aggregation of GAD and major depression. 4. Twin studies show that the environmental determinants of GAD are different from the environmental determinants of major depression. 5. The sociodemographic predictors of GAD in epidemiologic studies are different from the predictors of major depression. 6. The clinical course of GAD is less consistently related to comorbidity than is the course of other anxiety and mood disorders. 7. The impairments associated with GAD are equivalent to, or greater than, those associated with other severely impairing chronic physical and mental disorders. These findings show that the status of GAD as an independent disorder is at least as strongly supported by available evidence as is that of other anxiety or mood disorders. This article also shows that uncertainty remains regarding even the basic epidemiologic characteristics of the GAD syndrome. Lingering concerns about the independence of GAD have conspired to exacerbate this problem by promoting repeated changes in the diagnostic criteria for GAD from the DSM-III to DSM-III-R and to DSM-IV. These successive changes have made it difficult to amass consistent long-term data on the natural history of GAD. Available evidence on the empiric validity of current diagnostic thresholds for GAD raises questions about the requirements, such as whether a 6-month minimum duration and four or more additional psychophysiologic symptoms are optimal for identifying all of the people in the general population who suffer from a clinically significant GAD syndrome. An additional source of potential bias in this regard is that the DSM system requires that anxiety be excessive or unrealistic for a diagnosis of GAD. Interestingly, there is no comparable DSM requirement that dysphoria must be excessive or unrealistic to qualify as major depression. These diagnostic uncertainties make it difficult to gain a clear understanding of the true breadth and depth of the GAD syndrome in the general population. Additional research is needed, ideally from unbiased epidemiologic samples, to resolve these basic uncertainties. The strong comorbidity between GAD and major depression, the fact that most people with this type of comorbidity report that the onset of GAD occurred before the onset of depression, and the fact that temporally primary GAD significantly predicts the subsequent onset of depression and other secondary disorders raise the question of whether early intervention and treatment of primary GAD would effectively prevent the subsequent first onset of secondary anxiety and depression. Unfortunately, little is known about this possibility because, as mentioned earlier, few people with pure GAD seek treatment. Why this is true is unknown. Given the early onset of GAD and its strong effects in predicting the subsequent onset, severity, and persistence of other disorders, efforts are needed to collect epidemiologic data on the reasons for the low rate of help seeking among people with pure GAD and to develop outreach strategies that may correct this situation.

Age of Onset↗
PubMed2001

Efficacy of paroxetine in the treatment of adolescent major depression: a randomized, controlled trial.

OBJECTIVE: To compare paroxetine with placebo and imipramine with placebo for the treatment of adolescent depression. METHOD: After a 7- to 14-day screening period, 275 adolescents with major depression began 8 weeks of double-blind paroxetine (20-40 mg), imipramine (gradual upward titration to 200-300 mg), or placebo. The two primary outcome measures were endpoint response (Hamilton Rating Scale for Depression [HAM-D] score < or = 8 or > or = 50% reduction in baseline HAM-D) and change from baseline HAM-D score. Other depression-related variables were (1) HAM-D depressed mood item; (2) depression item of the Schedule for Affective Disorders and Schizophrenia for Adolescents-Lifetime version (K-SADS-L); (3) Clinical Global Impression (CGI) improvement scores of 1 or 2; (4) nine-item depression subscale of K-SADS-L; and (5) mean CGI improvement scores. RESULTS: Paroxetine demonstrated significantly greater improvement compared with placebo in HAM-D total score < or = 8, HAM-D depressed mood item, K-SADS-L depressed mood item, and CGI score of 1 or 2. The response to imipramine was not significantly different from placebo for any measure. Neither paroxetine nor imipramine differed significantly from placebo on parent- or self-rating measures. Withdrawal rates for adverse effects were 9.7% and 6.9% for paroxetine and placebo, respectively. Of 31.5% of subjects stopping imipramine therapy because of adverse effects, nearly one third did so because of adverse cardiovascular effects. CONCLUSIONS: Paroxetine is generally well tolerated and effective for major depression in adolescents.

Adolescent↗
PubMed2001

An eight-year longitudinal comparison of clinical course and characteristics of social phobia among men and women.

OBJECTIVE: Social phobia is a chronic disorder with a higher prevalence among women than men. Data from an eight-year longitudinal study were analyzed to investigate the course of social phobia and to explore potential sex differences in the course and characteristics of the illness. METHODS: Data were analyzed from the Harvard/Brown Anxiety Research Program, a naturalistic, observational study begun in 1989 in which patients with social phobia are assessed every six to 12 months. Treatment was observed but not prescribed by the program personnel. Data on comorbidity, remission, and health-related quality of life were collected for 176 patients with social phobia. RESULTS: Only 38 percent of women and 32 percent of men experienced a complete remission during the eight-year study period, a difference that was not significant. A larger proportion of women than men had the generalized form of social phobia, although the difference was not significant. Women were more likely to have concurrent agoraphobia, and men had a higher rate of comorbid substance use disorders. Social phobia had a more chronic course among women who had low Global Assessment of Functioning scores and a history of suicide attempts at baseline than among men who had these characteristics. Health-related quality of life was similar for both men and women, except that women were slightly but significantly more impaired in household functioning. CONCLUSIONS: The chronicity of social phobia was striking for both men and women. Although remission rates did not differ significantly between men and women, clinicians should be alert to the fact that women with poor baseline functioning and a history of suicide attempts have the greatest chronicity of illness.

Activities of Daily Living↗
PubMed2001

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.

Adult↗
PubMed2001

Pharmacologic treatment of anxiety disorders in 1989 versus 1996: results from the Harvard/Brown anxiety disorders research program.

OBJECTIVE: This article reports on the pharmacologic treatment of patients diagnosed with generalized anxiety disorder (GAD) enrolled in a naturalistic long-term study of anxiety disorders, with enrollment in 1989 through 1991 and follow-up in 1996. METHOD: 711 patients were enrolled in the study during 1989-1991. At intake, 167 patients met DSM-III-R criteria for GAD; at 1996 follow-up, 103 patients met these criteria. The patients were divided into 3 groups by diagnosis: GAD alone (N = 18 at intake, N =11 at follow-up), GAD comorbid with another anxiety disorder (N = 84 at intake, N = 52 at follow-up), and GAD comorbid with Research Diagnostic Criteria-defined major depressive disorder, with or without another anxiety disorder (N = 65 at intake, N = 40 at follow-up). The groups were evaluated at intake and follow-up on whether they received medication and the types of medication they received. RESULTS: Nearly one third of patients in the 1989-1991 sample were not receiving any medication for treatment of their anxiety disorder; in 1996, 27% of patients still were receiving no medication. There was a decrease in benzodiazepine treatment and an increase in antidepressant treatment in 1996 for GAD patients who did not have comorbid depression or another anxiety disorder. CONCLUSION: The finding of one quarter to one third of patients with GAD receiving no medication is consistent with previous observations of undertreatment of depression. The findings on medication type suggest a shift in the type of medications being prescribed for treatment of GAD from exclusive benzodiazepine treatment to the combination of benzodiazepine and antidepressant treatment.

Ambulatory Care↗
PubMed2001

Efficacy of mirtazapine for prevention of depressive relapse: a placebo-controlled double-blind trial of recently remitted high-risk patients.

BACKGROUND: The necessity of antidepressant continuation-phase therapy following acute-phase response has resulted in the need to characterize the longer-term efficacy and safety of all new medications. Previous studies using "extension" protocols suggest that mirtazapine has sustained antidepressant effects. The current study was performed to evaluate the efficacy and safety of up to 1 year of mirtazapine therapy, using a more rigorous, randomized, placebo-controlled discontinuation design. METHOD: An intent-to-treat sample of 410 patients meeting DSM-IV criteria for moderate-to-severe recurrent or chronic major depressive episodes began 8 to 12 weeks of open-label therapy with mirtazapine (flexibly titrated, 15-45 mg/day). Thereafter, 156 fully remitted patients (according to Hamilton Rating Scale for Depression and Clinical Global Impressions-Improvement scores) were randomly assigned to receive 40 weeks of double-blind continuation-phase therapy with either mirtazapine or placebo. RESULTS: Mirtazapine therapy reduced the rate of depressive relapse by more than half, with 43.8% of patients relapsing on treatment with placebo as compared with 19.7% of the mirtazapine-treated patients. The discontinuation rate due to adverse events was 11.8% for active mirtazapine therapy versus 2.5% for placebo. Although weight gain was significantly greater in the group receiving active medication during the double-blind phase (p = .001), patients taking mirtazapine gained only 1.4 kg (3.1 lb) across the 40 weeks of continuation therapy, and there was no difference in the rates of weight gain as a newonset adverse event. CONCLUSION: Continuation-phase therapy with mirtazapine is effective and well tolerated.

Adult↗
PubMed2001

Long-term treatment of recurrent and chronic depression.

Depression is associated with high rates of impairment and comorbidity with other disorders and has a devastating effect on those who suffer from it. Treatment options are available and can greatly improve functioning; however, undertreatment still persists. Undertreatment may result from incorrect or incomplete diagnoses or inadequate treatment duration. In addition, when treating depression, clinicians must identify underlying conditions, life-span issues, and proper treatment duration to maximize outcome. This article provides an overview of the underlying implications of depression. reviews issues in treating chronic depression that are still unresolved, and recommends standards for maintenance therapy.

Antidepressive Agents↗
PubMed2000

A comparison of nefazodone, the cognitive behavioral-analysis system of psychotherapy, and their combination for the treatment of chronic depression.

BACKGROUND: Patients with chronic forms of major depression are difficult to treat, and the relative efficacy of medications and psychotherapy is uncertain. METHODS: We randomly assigned 681 adults with a chronic nonpsychotic major depressive disorder to 12 weeks of outpatient treatment with nefazodone (maximal dose, 600 mg per day), the cognitive behavioral-analysis system of psychotherapy (16 to 20 sessions), or both. At base line, all patients had scores of at least 20 on the 24-item Hamilton Rating Scale for Depression (indicating clinically significant depression). Remission was defined as a score of 8 or less at weeks 10 and 12. For patients who did not have remission, a satisfactory response was defined as a reduction in the score by at least 50 percent from base line and a score of 15 or less. Raters were unaware of the patients' treatment assignments. RESULTS: Of the 681 patients, 662 attended at least one treatment session and were included in the analysis of response. The overall rate of response (both remission and satisfactory response) was 48 percent in both the nefazodone group and in the psychotherapy group, as compared with 73 percent in the combined-treatment group. (P<0.001 for both comparisons). Among the 519 subjects who completed the study, the rates of response were 55 percent in the nefazodone group and 52 percent in the psychotherapy group, as compared with 85 percent in the combined-treatment group (P<0.001 for both comparisons). The rates of withdrawal were similar in the three groups. Adverse events in the nefazodone group were consistent with the known side effects of the drug (e.g., headache, somnolence, dry mouth, nausea, and dizziness). CONCLUSIONS: Although about half of patients with chronic forms of major depression have a response to short-term treatment with either nefazodone or a cognitive behavioral-analysis system of psychotherapy, the combination of the two is significantly more efficacious than either treatment alone.

Adult↗
PubMed2000

Psychosocial disability during the long-term course of unipolar major depressive disorder.

BACKGROUND: The goal of this study was to investigate psychosocial disability in relation to depressive symptom severity during the long-term course of unipolar major depressive disorder (MDD). METHODS: Monthly ratings of impairment in major life functions and social relationships were obtained during an average of 10 years' systematic follow-up of 371 patients with unipolar MDD in the National Institute of Mental Health Collaborative Depression Study. Random regression models were used to examine variations in psychosocial functioning associated with 3 levels of depressive symptom severity and the asymptomatic status. RESULTS: A progressive gradient of psychosocial impairment was associated with a parallel gradient in the level of depressive symptom severity, which ranges from asymptomatic to subthreshold depressive symptoms to symptoms at the minor depression/dysthymia level to symptoms at the MDD level. Significant increases in disability occurred with each stepwise increment in depressive symptom severity. CONCLUSIONS: During the long-term course, disability is pervasive and chronic but disappears when patients become asymptomatic. Depressive symptoms at levels of subthreshold depressive symptoms, minor depression/ dysthymia, and MDD represent a continuum of depressive symptom severity in unipolar MDD, each level of which is associated with a significant stepwise increment in psychosocial disability.

Adaptation, Psychological↗
PubMed2000

Mortality in eating disorders: a descriptive study.

OBJECTIVE: We report rates and causes of death for a cohort of 246 eating-disordered women and provide descriptive information on their eating disorder and comorbid diagnoses. METHOD: Data on mortality were collected as part of a longitudinal study of anorexia nervosa and bulimia nervosa, now in its 11th year. Other data sources included death certificates, autopsy reports, relative interviews, and a National Death Index search. RESULTS: Seven deaths have occurred during the study, all among anorexic subjects with a history of binging and purging and with comorbid Axis I disorders. The crude mortality rate was 5.1%. The standardized mortality ratios for death (9.6) and suicide (58.1) were significantly elevated (p <. 001). CONCLUSIONS: Anorexia nervosa is associated with a substantial risk of death and suicide. Features correlated with fatal outcome are longer duration of illness, binging and purging, comorbid substance abuse, and comorbid affective disorders.

Adult↗