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Biomedical subjects

A C Leon

Publications and source records attributed to A C Leon.

At least 19 recordsLinked to original sources
PubMed2006

The association between course of illness and subsequent morbidity in bipolar I disorder.

OBJECTIVE: We examined the relationship between certain bipolar I disorder clinical course variables over 5 years with outcome over the subsequent 5-year period. METHODS: Prospective observational follow-up data of 123 bipolar I subjects were analyzed. Predictive clinical variables included the frequency and direction of switches, and the quantity, polarity and length of affective periods. Outcome variables were an affective burden index (ABI) accounting for week-by-week severity and weeks hospitalized. Bivariate analyses guided the selection of predictors for multivariable analyses against the outcome variables. RESULTS: Affective burden index: while the number and direction of switches, the number of polyphasic episodes, weeks in hypomania/mania/mixed state, weeks in minor/major depression, weeks in at least marked affective syndrome, and weeks in any affective syndrome all had bivariate correlation (p<0.01) with the ABI, only weeks in hypomania/mania/mixed state and weeks in minor/major depression made significant contributions in the multivariable analysis (p<0.01) with the ABI. Weeks hospitalized: weeks in at least marked affective syndrome were significantly correlated with weeks hospitalized in bivariate analysis (p<0.01), and maintained a contribution to weeks hospitalized in the multivariable analysis (p<0.01). CONCLUSIONS: The quantity and severity of weeks in symptomatic affective states are possibly greater predictors of affective burden in bipolar I patients than the quantity and direction of affective switches.

Adult↗
PubMed2005

Executive functioning in depressed patients with suicidal ideation.

OBJECTIVE: Suicidal thinking has been associated with cognitive rigidity, however, not all depressed patients contemplate suicide. Therefore, we hypothesized that compared with depressed subjects without suicidal ideation, depressed individuals with suicidal ideation would display poorer performance on measures of executive functioning that involve mental flexibility. METHOD: In-patients with a current major depressive episode who had no current suicidal ideation (n=28) were compared with those who had current suicidal ideation (n=5) on measures of executive functioning and two neurocognitive tests that predominantly assess non-frontal regions. RESULTS: Compared with non-suicidal depressed patients, depressed suicidal patients performed significantly worse on several measures of executive functioning after controlling for age, IQ, severity of depression and prior suicide attempts. The two groups performed similarly on tests that predominantly assess non-frontal regions. CONCLUSION: Depressed individuals contemplating suicide have cognitive rigidity, which does not appear to be a global brain dysfunction. Suicidal mental states may result from dysfunctional executive decision-making that is associated with the frontal lobe.

Adult↗
PubMed2001

Preliminary evidence of impaired thinking in sick patients.

BACKGROUND: Earlier anecdotal observations suggested to us that certain aspects of judgment in sick adults approximate the thinking of children. OBJECTIVE: To describe changes in judgment associated with serious illness in otherwise competent adults. DESIGN: Cohort study. SETTING: Urban acute-care hospital and senior citizen center. PARTICIPANTS: Sicker (Karnofsky score </= 50; n = 24) and less sick (Karnofsky score > 50; n = 39) hospitalized patients were compared with controls (n = 28). Normal performance on the Mini-Mental State Examination (score >/= 24) was required for study entrance. MEASUREMENTS: Seven Piagetian tasks of judgment designed to study childhood cognitive development. Degree of sickness was determined by using the Karnofsky scale of physical function. RESULTS: Patients with Karnofsky scores of 50 or less responded correctly to fewer Piagetian tasks than controls (mean [+/-SD], 1.8 +/- 2.6 vs. 5.9 +/- 1.6; P < 0.001). Furthermore, a smaller proportion of sicker patients responded correctly to each of the seven tasks. Patients with Karnofsky scores greater than 50 did not perform differently than controls. CONCLUSION: In sicker hospitalized patients, performance on seven Piagetian tasks of judgment was similar to that among children younger than 10 years of age. This evidence of cognitive impairment warrants further investigation.

Case-Control Studies↗
PubMed2001

Can placebo controls reduce the number of nonresponders in clinical trials? A power-analytic perspective.

BACKGROUND: There is ongoing debate regarding the ethics of placebo-controlled clinical trials when a moderately effective standard treatment exists. One aspect of the debate--the number of nonresponders--tends to be overlooked. A larger between-group effect size is expected in placebo-controlled trials than in trials with an active comparator. For that reason, substantially fewer subjects need to be enrolled in placebo-controlled trials; consequently, there tend to be far fewer nonresponders in placebo-controlled trials. OBJECTIVE: This analysis was undertaken to illustrate that the use of placebo as a control can reduce the number of subjects who are unnecessarily exposed to delayed treatment. METHODS: Statistical power analyses were used to estimate the sample size required to detect various population treatment differences and the resulting number of nonresponders for 2-tailed chi-square tests. RESULTS: Empiric evidence of the phenomenon is provided for a wide range of rates of response to placebo, investigational, and comparator treatments. For example, 24 subjects (ie, 12 per group) are needed to detect differences between placebo (10% response rate) and an investigational drug (70% response); 15 of these would not respond. In contrast, if the investigational drug (70% response) is initially compared with a standard therapy (60% response), 752 subjects would be required, 263 of whom would not respond. CONCLUSIONS: This paper shows empirically that placebo controls can reduce the number of nonresponders in a randomized controlled trial. The number of subjects who are exposed to unproven, albeit promising, investigational drugs should be kept to a minimum until placebo-controlled trials support their use.

Clinical Trials as Topic↗
PubMed2001

Maintenance desipramine for dysthymia: a placebo-controlled study.

BACKGROUND: This study examines the efficacy of maintenance pharmacotherapy in dysthymia without concurrent major depression, i.e. 'pure dysthymia'. No published data exist on this topic. METHODS: Responders to a 10-week open trial of desipramine (DMI) whose therapeutic response persisted during a 4-month continuation phase were eligible to begin a 2-year placebo-controlled maintenance phase. We analyzed the subgroup with DSM-III-R pure dysthymia (n=27) that entered maintenance. Time to recurrence during maintenance therapy was compared between the two treatment groups. RESULTS: Six of 13 patients receiving placebo and none of 14 patients receiving ongoing DMI experienced a recurrence. Risk of recurrence was significantly greater for placebo patients. Five of six placebo recurrences occurred within the first 6 months of maintenance. LIMITATIONS: Larger replication studies are needed. CONCLUSION: Desipramine was efficacious as a maintenance treatment in patients with pure dysthymia who responded to 7 months of acute and continuation DMI.

Acute Disease↗
PubMed2001

The significance of psychotic features in manic episodes: a report from the NIMH collaborative study.

BACKGROUND: Psychotic features in the context of major depressive syndromes have correlates in symptom severity, acute treatment response and long-term prognosis. Little is known as to whether psychotic features have similar importance when they occur within manic syndromes. METHODS: These data derive from a multi-center, long-term follow-up of patients with major affective disorder. Raters conducted follow-up interviews at 6-month intervals for the first 5 years and annually thereafter. A sub-set of probands participated in a family study in which all available, adult, first-degree relatives were interviewed as well. RESULTS: Of 139 who entered the study in an episode of mania, 90 patients had psychotic features. Symptom severity ratings at intake were more severe for this group. Though time to first recovery and time to first relapse did not distinguish the groups, psychotic features were associated with a greater number of weeks ill during follow-up and the strength of this association was similar to that seen for psychotic features within depressed patients described in an earlier publication. Patients with psychotic mania at intake did not differ significantly from those with nonpsychotic mania by response to acute lithium treatment, suicidal behavior during follow-up, or risks for affective disorder among first-degree relatives. Psychotic features within manic syndromes were not associated with high psychosis ratings during follow-up. In contrast, when psychotic features accompanied depressive syndromes, they strongly predicted the number of weeks with psychosis during follow-up, particularly among individuals whose episodes at intake were less acute. CONCLUSIONS: As with major depressive syndromes, psychotic features in mania are associated with greater symptom severity and higher morbidity in the long-term. Psychotic features are much less predictive of future psychosis when they occur within a manic syndrome than when they occur within a depressive syndrome.

Activities of Daily Living↗
PubMed2001

Lithium and suicidal behavior in major affective disorder: a case-control study.

OBJECTIVE: A number of studies have suggested that lithium may be particularly effective in reducing suicide risks among patients with major affective disorders. The design of many of these studies left them open to biases associated with treatment compliance, however. METHOD: Subjects were drawn from a naturalistic, long-term follow-up of patients with major affective disorders. Fifteen who committed suicide while receiving somatotherapy where matched to non-suicidal patients who were similarly receiving somatotherapy at the same point in follow-up. The same procedure was followed for 41 patients who made a serious suicide attempt during follow-up. RESULTS: Six (40.0%) of the patients who committed suicide, and eight (53.3%) of their controls, were thought to have been taking lithium in the preceding week. Among attempters and their controls, nine (22.0%) and eight (19.5%), respectively, were taking lithium. CONCLUSION: These results do not support previous suggestions that lithium has uniquely antisuicidal properties. Other existing datasets should be explored with this design to establish whether lithium does, or does not, offer special protection against suicide.

Adult↗
PubMed2001

A placebo-controlled pilot study of the ampakine CX516 added to clozapine in schizophrenia.

CX516, a positive modulator of the glutamatergic alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor, improves performance in tasks requiring learning and memory in animals. CX516 was added to clozapine in 4-week, placebo-controlled, dose-finding (N = 6) and fixed-dose (N = 13) trials. CX516 was tolerated well and was associated with moderate to large, between-group effect sizes compared with placebo, representing improvement in measures of attention and memory. These preliminary results suggest that CX516 and other "ampakines" hold promise for the treatment of schizophrenia.

Adult↗
PubMed2001

Psychiatric symptoms, functional impairment, and receptivity toward mental health treatment among obstetrical patients.

OBJECTIVE: To examine psychiatric symptomatology and associated functional impairment among pregnant women; and to examine the obstetrical patient's receptivity to discussion of and intervention regarding emotional distress. METHODS: Fifty-seven patients 16 weeks or less pregnant presenting for routine obstetrical appointments at a faculty practice at a major medical center participated in this study. Each completed a self-administered assessment packet regarding psychopathology, functional impairment and service utilization attitudes. Statistical analyses were performed using chi-square and Mann-Whitney tests. RESULTS: Seventeen subjects (29.8 percent) screened positive for at least one anxiety disorder. Fourteen of those subjects also screened positive for depression. Those with positive screens for either anxiety and/or depression had significantly higher levels of functional impairment. Only five (29.4 percent) of the 17 subjects with positive screens reported having discussed an emotional issue with their Ob/Gyn, although 14 (82.4 percent) said that they would be willing to do so. All subjects (100 percent) reported that they would see a mental health professional if their Ob/Gyn referred them. CONCLUSION: Routine screens for mental disorders in early pregnancy appear to be a useful adjunct in an obstetrical setting. Although most had never discussed their emotional concerns with their Ob/Gyn, a substantial proportion of our study sample reported psychiatric symptomatology and significant levels of functional impairment that had not been recognized by their Ob/Gyn. All of the patients in our study sample reported a willingness to see a mental health professional if their Ob/Gyn referred them. Further studies investigating the benefits of antenatal diagnosis and treatment of psychiatric disorders are warranted.

Adult↗
PubMed2001

The development and evaluation of the brief depression screen in medically ill disability claimants.

OBJECTIVE: There is literature demonstrating elevated prevalence of depression in primary care. Yet there remains a need for a brief depression screen designed and evaluated specifically for use among medically ill patients. Our objective was to develop and validate a brief, unobtrusive screen for depression among severely medically ill long-term disability claimants. METHODS: The study sample consisted of 480 long-term disability claimants, less than 55 years of age, with one of the following illnesses: cancer, diabetes, myocardial infarction, rheumatoid arthritis, stroke, or multiple sclerosis. Each subject completed a questionnaire that included 26 potential screening items. A subset of subjects was administered the SCID, which served as the gold standard for the DSM-IV depression and dysthymia diagnoses. RESULTS: The Brief Depression Screen, a three-item screen for major depressive disorder and dysthymia, was developed. About 34 percent of the sample met criteria for major depressive disorder or dysthymia. The Brief Depression Screen detected 75 percent of those subjects in this sample. Furthermore, nearly half of the subjects with positive screen results met criteria for depression or dysthymia. These results are comparable to those of the eight-item Burnam screen, but not as sensitive as the more widely used, twenty item CES-D. CONCLUSION: The Brief Depression Screen was developed and evaluated for use with severely ill long-term disability claimants. In practice, a positive screen for depression is to be followed with a comprehensive diagnostic assessment that could be conducted by a trained clinician. Further research is warranted to determine whether the identification and treatment of depression in disability claimants with non-psychiatric medical illnesses will facilitate return to work, even in the presence of comorbid medical illnesses.

Depressive Disorder↗
PubMed2001

Measuring onset of antidepressant action in clinical trials: an overview of definitions and methodology.

This article discusses 4 critical questions that must be addressed in any valid analysis of comparative onset of therapeutic effect among antidepressant drugs: (1) how is onset defined, (2) how is onset measured, (3) how can the treatment groups be compared statistically with regard to onset of effect, and (4) how do these issues affect protocol design? A rigorous study of differential onset of effect should include an estimation of the portion of patients that respond, the timing of the onset of response, and the duration of response and an examination of the dynamic process of the onset of action. Methods for measuring symptom severity changes over time also will be reviewed.

Antidepressive Agents↗
PubMed2001

An ideal trial to test differential onset of antidepressant effect.

Although various published clinical studies have suggested that some antidepressants may have a more rapid onset of therapeutic effect than others, none of these trials was adequately designed to measure differential time to onset of effect. Thus, existing data do not support claims that one drug reduces the symptoms of depression faster than another. In this article, we propose a study that would be ideal for measuring comparative onset of antidepressant effect. The key features of this ideal trial include (1) a prospective definition of early onset of action, (2) increased frequency of assessment, (3) a data-analytic approach capable of capturing the dynamic nature of symptomatic change, and (4) various strategies to minimize bias and heterogeneity of response.

Antidepressive Agents↗
PubMed2001

A pilot open trial of brief psychodynamic psychotherapy for panic disorder.

This is a complete report of an open trial of manualized psychodynamic psychotherapy for treatment of panic disorder, Panic-Focused Psychodynamic Psychotherapy (PFPP). Twenty-one patients with PD were entered into a trial of twice-weekly, 24-session treatment. Sixteen of 21 experienced remission of panic and agoraphobia. Treatment completers with depression also experienced remission of depression. Improvements in symptoms and in quality of life were substantial and consistent across all measured areas. Symptomatic gains were maintained over 6 months. This report was prepared specifically to describe 6-month follow-up on these patients. Psychodynamic psychotherapy appears to be a promising nonpharmacological treatment for panic disorder.

Adult↗
PubMed2000

Family history and symptom levels during treatment for bipolar I affective disorder.

BACKGROUND: Studies of family history and lithium response in patients with bipolar affective disorder have produced mixed results, but the majority have shown relationships between the presence of affective disorder among relatives and positive responses to lithium in probands. The analysis presented here sought to confirm and to further characterize such relationships. METHODS: Subjects described here participated in a long-term, prospective follow-up; had a history of Research Diagnostic Criteria manic disorder or schizoaffective disorder, manic type; and took lithium for periods of 26 weeks or longer. The majority participated in a family study in which first-degree relatives were directly interviewed. Morbidity during lithium and during anticonvulsant trials was quantified in alternative ways, as were the risks among first-degree relatives for bipolar I and nonbipolar affective disorders. RESULTS: Familial loading for bipolar affective disorder was not associated with better outcomes during lithium treatment. Rather, the presence of major depressive disorder (MDD) among relatives was associated with slower improvement during acute treatment and with higher symptom levels during continuing treatment. Findings for morbidity during anticonvulsant treatment were similar. The patients who experienced symptom persistence with lithium did so as well during periods of anticonvulsant treatment and during periods without thymoleptics. CONCLUSIONS: A family history of MDD may have an enduring and negative prognostic significance that manifests across treatment conditions. Though difficult to reconcile with several earlier studies, these findings invite replication and further exploration.

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

A brief assessment of psychosocial functioning of subjects with bipolar I disorder: the LIFE-RIFT. Longitudinal Interval Follow-up Evaluation-Range Impaired Functioning Tool.

Those afflicted with bipolar disorder often suffer from substantial functional impairment both when in episode and when in remission. This study examined the psychometric properties of a brief assessment of psychosocial functioning, the Range of Impaired Functioning Tool (LIFE-RIFT), among subjects with bipolar I disorder. The study sample consisted of 163 subjects who presented with bipolar I disorder at intake into the NIMH Collaborative Depression Study (CDS). All LIFE-RIFT items come from the Longitudinal Interval Follow-up Evaluation (LIFE). Follow-up data that were used to examine the reliability and validity of the scale come from assessments of psychosocial functioning that were conducted 6, 12, 18, and 24 months after intake into the CDS. The results of factor analyses indicate that the scale items are measures of one construct, psychosocial functioning. The interrater agreement on the scale score was very good with an intraclass correlation coefficient was 0.94. The internal consistency reliability among the scale items was uniformly satisfactory over the four assessment periods, with coefficient alpha ranging from 0.78 to 0.84. Mixed-effect regression analyses showed that during mood episodes subjects were significantly more impaired than those in recovery. In conclusion, the psychometric properties of the LIFE-RIFT were examined in subjects with bipolar I disorder. The analyses from this longitudinal, observational study provide empirical support for the reliability and validity of the scale. The LIFE-RIFT provides a brief, inexpensive alternative to scales currently used to assess psychosocial functioning and can be easily added to semistructured assessments that are used in clinical and treatment outcome studies.

Adaptation, Psychological↗
PubMed2000

Open trial of psychodynamic psychotherapy for panic disorder: a pilot study.

OBJECTIVE: This report contains preliminary data from an open trial of brief psychodynamic psychotherapy for panic disorder. METHOD: Fourteen patients with primary DSM-IV panic disorder completed a 24-session, twice-weekly course of psychodynamic psychotherapy. Other psychiatric treatment was not permitted throughout the 12-week treatment period and the 6-month follow-up. Symptoms were assessed at baseline, treatment termination, and 6-month posttermination follow-up (40 weeks). RESULTS: Statistically significant, clinically meaningful improvements appeared in panic, depression, anxiety, and functional impairment both at treatment termination and at 6-month follow-up. CONCLUSIONS: Psychodynamic monotherapy can be used successfully to retain and treat patients with panic disorder. Psychodynamic interventions warrant further study for patients with panic disorder.

Adult↗