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Biomedical subjects

M E Thase

Publications and source records attributed to M E Thase.

At least 19 recordsLinked to original sources

Identifying an abnormal electroencephalographic sleep profile to characterize major depressive disorder.

There is little agreement as to the best definition of a categorically abnormal electroencephalographic (EEG) sleep profile to characterize major depressive disorder. Therefore, a series of classification, replication, and validation analyses were conducted to identify such a profile. The EEG sleep studies of healthy controls (n = 44), depressed inpatients (n = 44), and depressed outpatients (n = 181) were utilized, including subgroups of patients studied both before and after nonpharmacologic treatment with either cognitive behavior therapy (CBT) or interpersonal psychotherapy (IPT). A discriminant index score (based on reduced REM latency, increased REM density, and decreased sleep efficiency) was found to: 1) reliably discriminate between depressed inpatients, depressed outpatients, and controls; 2) show good test-retest reliability; and 3) identify a subset of depressed outpatients who were older, manifested a broader array of EEG sleep disturbances, and were less responsive to CBT or IPT. Posttreatment studies of patients indicated that normal sleep profiles were relatively stable, whereas abnormal profiles tended to normalize. These findings provide an empirically validated method that may improve the applicability, efficiency, and prognostic utility of EEG sleep studies of depressed patients.

Adult

Fluoxetine in depressed alcoholics. A double-blind, placebo-controlled trial.

BACKGROUND: The selective serotonergic medication fluoxetine has demonstrated efficacy in the treatment of major depression and has suggested efficacy in the treatment of alcoholism. However, no completed trials with any selective serotonergic medication have been reported in patients who display both major depression and alcoholism, despite previous observations that both depression and alcoholism are associated with low serotonergic functioning. METHODS: Fifty-one patients diagnosed as having comorbid major depressive disorder and alcohol dependence were randomized to receive fluoxetine (n = 25) or placebo (n = 26) in a 12-week, double-blind, parallel-group trial. Weekly ratings of depression and alcohol consumption were obtained throughout the 12-week course of the study. RESULTS: The improvement in depressive symptoms during the medication trial was significantly greater in the fluoxetine group than in the placebo group. Total alcohol consumption during the trial was significantly lower in the fluoxetine group than in the placebo group. CONCLUSIONS: Fluoxetine is effective in reducing the depressive symptoms and the alcohol consumption of patients with comorbid major depressive disorder and alcohol dependence. It is unknown whether these results generalize to the treatment of less depressed and less suicidal alcoholics.

Adult

The National Institute on Drug Abuse Collaborative Cocaine Treatment Study. Rationale and methods.

The National Institute on Drug Abuse Collaborative Cocaine Treatment Study is a large, multisite psychotherapy clinical trial for outpatients who meet the DSM-IV criteria for cocaine dependence. For 480 randomized patients, the outcomes of 4 treatments are compared for an 18-month period. All treatments include group drug counseling. One treatment also adds cognitive therapy, one adds supportive-expressive psychodynamic therapy, and one adds individual drug counseling; one consists of group drug counseling alone. In addition, 2 specific interaction hypotheses, one involving psychiatric severity and the other involving degree of antisocial personality characteristics, are being tested. This article describes the main aims of the project, the background and rationale for the study design, the rationale for the choice of treatments and patient population, and a brief description of the research plan.

Ambulatory Care

Cognitive therapy with inpatients.

Psychotherapeutic interventions often play a major role in the treatment of patients who are hospitalized for depression. Much of the "therapeutic milieu" of the inpatient unit includes patient participation in group psychotherapy and in one-on-one psychotherapy with staff members. These interventions are designed not only to be primary treatments for depression, but are also used to enhance patients' compliance with pharmacotherapy. Cognitive therapy (CT) has been adapted for use with inpatients and has been used as an organizing theory for the hospital milieu in several inpatient units. Research on inpatient CT suggests that it is a beneficial treatment that enhances continuity of care after discharge from the hospital. This paper describes the general principles of inpatient CT, and discusses the various types of inpatient cognitive therapy units (CTUs) that have been developed. The benefits of such programs are described, and research regarding the effectiveness of inpatient CT is discussed.

Antidepressive Agents

A prospective test of criteria for response, remission, relapse, recovery, and recurrence in depressed patients treated with cognitive behavior therapy.

The definitions that are commonly employed to describe the outcome of the depressive disorders are often used in inconsistent ways and remain largely untested. The lack of a standard and valid set of outcome definitions hinders the study of the naturalistic course and treatment of depressive disorders. In the present study, we operationalized definitions for response, remission, relapse, recovery, and recurrence and examined their validity in a sample of depressed patients treated with cognitive behavior therapy. Validity was evaluated by the ability of the definitions to predict subsequent outcome in acute treatment and during a 3 year follow-up period. All five definitions demonstrated moderate to excellent validity. Moreover, we were able to empirically distinguish response from remission, and relapse from recurrence, despite the frequent confusion of these terms in the literature. Several of the findings suggest that continued refinement of the outcome definitions may enhance validity even further.

Adult

Low rate of membrane lithium transport during treatment correlates with outcome of maintenance pharmacotherapy in bipolar disorder.

Lithium is transported across cell membranes by an exchange diffusion process (Na(+)-Li+ countertransport) that is inhibited during lithium treatment. We hypothesized that low rates of lithium efflux (a potential manifestation of strong transport inhibition) would be associated with better clinical outcome of maintenance pharmacotherapy. We measured the erythrocyte (RBC) apparent rate constant for lithium efflux (kexch) in 22 patients with bipolar disorder who had been euthymic on lithium for 1 month. Subsequently, clinical mood ratings and in vivo RBC: plasma lithium ratios (LiR) were determined monthly. Outcome was categorized according to whether subjects completed 1 year of successful maintenance treatment (n = 10), experienced a recurrent affective episode (n = 8), or dropped out (n = 4). The kexch at the outset of the study was significantly lower (potentially because of greater transport inhibition) in 1-year completers than in patients with recurrences or those who dropped out (median kexch = 0.09, 0.24, and 0.27 h-1, respectively; P < .03). Moreover, 77% of patients with a kexch of 0.11 h-1 or lower were successfully maintained on lithium for 1 year, whereas only 23% of those with a kexch greater than or equal to 0.12 h-1 had a successful treatment outcome. LiR measured during the course of maintenance treatment was significantly higher (suggesting greater transport inhibition) in 1-year completers than in noncompleters (recurrences and dropouts). Measurement of kexch at an early point in treatment may provide a means for prospectively identifying those bipolar patients at greater risk for failure of maintenance lithium therapy.

Adult

Comparison of cognitive models of depression: relationships between cognitive constructs and cognitive diathesis-stress match.

The authors examined the relationship between the cognitive components of the Beckian and Hopelessness models of depression by administering measures of dysfunctional attitudes, attributional style, and life stress to a sample of 59 depressed adults. Confirmatory factor analyses indicated that dysfunctional attitudes and attributional style load on separate factors as opposed to a single factor. Additional analyses revealed that depressed persons conforming to diathesis-stress criteria according to each model were largely independent of one another. Results supported the conclusion that the Beckian and Hopelessness models of depression describe distinct cognitive constructs and refer to distinct subsets of depressed persons.

Adult

Response to cognitive-behavioral therapy in depression: effects of pretreatment cognitive dysfunction and life stress.

Response to cognitive-behavioral therapy (CBT) for depression is variable and the factors that account for differences in response are not yet well established. Level of cognitive dysfunction and the occurrence of negative life stress have been theorized as patient variables, which may account for differences in response to CBT. The relationship between response to CBT and the interaction of cognitive dysfunction with negative life events was examined in a sample of 53 depressed outpatients. Overall, there was little support for the prediction of a difference in acute outcome between patients with or without pretreatment cognitive dysfunction and negative stressors.

Adult

Which depressed patients will respond to interpersonal psychotherapy? The role of abnormal EEG sleep profiles.

OBJECTIVE: The authors tested the hypothesis that patients whose episodes of major depression evidenced more neurobiological disturbance would be less responsive to psychotherapy. METHOD: The study subjects were outpatients who were given a diagnosis of recurrent major depressive disorder (unipolar or bipolar II), according to the Research Diagnostic Criteria, following an interview with the Schedule for Affective Disorders and Schizophrenia. They were classified into a group with normal sleep profiles (N = 50) and a group with abnormal sleep profiles (N = 41) on the basis of a validated index score derived from three EEG sleep variables monitored for 2 nights: sleep efficiency, REM latency, and REM density. The groups' responses to short-term interpersonal psychotherapy were compared by means of chi-square tests and life table and random effects model analyses. Responses to the addition of pharmacotherapy for subjects who did not respond to interpersonal psychotherapy were also compared. RESULTS: The patients with abnormal sleep profiles had significantly poorer clinical outcomes with respect to symptom ratings, attrition rates, and remission rates than the patients with more normal sleep profiles. Seventy-five percent of the patients who did not respond to interpersonal psychotherapy had remissions during subsequent pharmacotherapy. CONCLUSIONS: These findings help to define further a neurobiological "boundary" that may limit response to psychotherapy in depression. An abnormal sleep profile may reflect a more marked disturbance of CNS arousal that warrants pharmacotherapy.

Adult

Low use of neuroleptic drugs in the treatment of psychotic major depression.

OBJECTIVE: The adequacy of pharmacologic treatment received by patients with psychotic major depression was evaluated. METHOD: The authors systematically assessed the pharmacotherapy received by 187 depressed patients before initiation of ECT and compared the medication trials of those with psychotic (N = 53) and nonpsychotic (N = 134) depression. RESULTS: Despite a median of four medication trials and median index episode duration of 20 weeks, only two (4%) of the patients with psychotic depression received at least one adequate pharmacotherapy trial. In contrast, 70 (52%) of the patients with nonpsychotic depression received at least one adequate trial. Twenty-five (47%) of the patients with psychotic depression received either no neuroleptic treatment (N = 11) or treatment for less than 3 weeks (N = 14). Only eight (15%) received a daily neuroleptic dose higher than 200 mg of chlorpromazine equivalents. CONCLUSIONS: These findings suggest that many patients with psychotic major depression referred for ECT receive inadequate pharmacotherapy because of either the absence or the inadequate use of neuroleptic medication.

Antidepressive Agents

Fluoxetine treatment of patients with major depressive disorder who failed initial treatment with sertraline.

BACKGROUND: This study was conducted to determine if patients with major depressive disorder who had previously failed treatment with one serotonin selective reuptake inhibitor (SSRI) would respond to a different SSRI. METHOD: Adult outpatients (N = 106) with DSM-III-R major depressive disorder and a history of either intolerance (N = 34) or nonresponse (N = 72) to treatment with sertraline were treated with fluoxetine (mean dose = 37.2 mg/day) in a standardized, open-label, 6-week clinical trial. Outcome was assessed at each visit using the Hamilton Rating Scale for Depression (HAM-D), the Clinical Global Impressions (CGI-Improvement and CGI-Severity) scales, and the Patient's Global Improvement (PGI) scale. RESULTS: Ninety-one patients (86%) completed the study. Sixty-seven patients (63%) responded to fluoxetine (i.e., experienced > or = 50% reduction in HAM-D28 total score at endpoint versus baseline). In addition, clinically and statistically significant improvements were noted on all measures of depressive symptoms and global functioning. There was a nonsignificant trend for patients with a history of less vigorous sertraline trials to respond more favorably to fluoxetine. Fluoxetine therapy was generally well tolerated, and there were only slight differences in adverse events reported by patients who had been intolerant to sertraline versus those who were nonresponders. CONCLUSION: These findings indicate that fluoxetine and sertraline, two widely used SSRIs, are not interchangeable. Patients who either have had trouble tolerating or have not responded to sertraline may do well on fluoxetine treatment.

1-Naphthylamine

The undertreatment of dysthymia.

BACKGROUND: Dysthymia is a chronic depressive condition that is quite prevalent. This condition can exact a significant toll on the general health and quality of life in the affected individual. Despite the frequency and consequences of dysthymia, however, the condition is often not diagnosed or treated. We present data on prior treatment from 410 patients with DSM-III-R dysthymia, primary type, early onset without concurrent major depression. METHOD: Axis I and II diagnoses were made by using the Structured Clinical Interviews for DSM-III-R, Patient Version (SCID-P) and SCID II for Personality Disorders. The Hamilton Rating Scale for Depression and the Clinical Global Impressions scale were also completed. Prior treatment was assessed, with special attention paid to previous antidepressant drug therapy and psychotherapy. RESULTS: Although the mean duration of dysthymia was about 30 years and almost half of the patients had previous episodes of major depression, only 41.3% had been treated with antidepressants and 56.1% with psychotherapy. A past history of major depression increased the frequency of prior antidepressant pharmacotherapy (45.7%) and psychotherapy (59.4%) compared with no history of major depression (36.8% and 40.9%, respectively). Comorbid personality disorder increased the likelihood of prior psychotherapy (70.7% vs. 49.6%) while having no effect on past pharmacotherapy. A history of substance abuse did not affect the history of antidepressant or psychotherapy treatment. In this study, dysthymia and psychosocial outcomes improved with sertraline and imipramine treatment. CONCLUSION: Dysthymic patients in this sample were significantly undertreated. Newer antidepressant agents may alter the potential for pharmacotherapy interventions in this vulnerable population.

1-Naphthylamine

Double-blind fluoxetine in depressed alcoholic smokers.

Treatment trials involving smoking in alcoholics with major depression are scarce, despite the common co-occurrence of these disorders. In this study, 25 smokers with DSM-III-R diagnoses of both major depressive disorder and alcohol dependence were randomized to fluoxetine or placebo in a 12-week, double-blind, parallel group trial. Almost half (48%) of the patients had made a suicide attempt in the week before hospitalization (where recruitment was performed), and 84 percent reported suicidal ideations during that week. Those in the fluoxetine group demonstrated a significant within-group decrease in smoking during the course of the study, whereas those in the placebo group did not. Those in the fluoxetine group smoked 27 percent fewer cigarettes than those in the placebo group, although this difference was not statistically significant. Cumulative alcohol consumption during the 12 weeks of the pharmacotherapy trial was four times as high in the placebo group as in the fluoxetine group, though this difference was not statistically significant in this limited-sized sample. The change in smoking was significantly associated with a change in drinking. These preliminary findings suggest that fluoxetine has the potential for treating the smoking and drinking behaviors of depressed alcoholic smokers.

Adult

Bipolar depression: an underestimated treatment challenge.

We sought to determine whether depressive and mixed/cycling episodes were as responsive to standardized pharmacotherapeutic interventions as were manic episodes in bipolar 1 patients. As part of the Maintenance Therapies in Bipolar Disorder (MH29618, E. Frank, PI) study, forty-two acutely ill bipolar 1 patients who had been randomly assigned to one of two preliminary phase non-pharmacologic treatment strategies (interpersonal and social rhythm therapy [IPSRT] or a standard medication clinic approach) were treated according to a standardized pharmacotherapeutic protocol. Symptom severity was measured weekly with the Hamilton Depression Rating Scale and the Bech-Rafaelsen Mania Scale in order to assess symptomatic remission. Survival analysis with the proportional hazards model was performed on time to remission. Manic patients were significantly more likely to achieve clinical remission than the depressed patients (100 vs. 59%) and did so significantly more rapidly. The difference in proportion remitting and time to remission between the depressed and mixed/cycling groups was not statistically significant. No significant effect for non-pharmacologic treatment assignment was found. These results point to the need to develop more effective treatments for bipolar depression. They also suggest that psychotherapy has a limited impact in the acute phase treatment of bipolar episodes.

Adult

Integrating psychotherapy and pharmacotherapy for treatment of major depressive disorder. Current status and future considerations.

The treatment of depression with psychotherapy and pharmacotherapy is one of the best-studied areas, yet much controversy exists about the relative merits of these treatments, singly and in combination. The author suggests that a combination of these therapies is not routinely indicated for uncomplicated major depressive disorder and provides some examples in which combined therapy can have a profound and cost-effective impact.

Antidepressive Agents

Abnormal electroencephalographic sleep profiles in major depression: association with response to cognitive behavior therapy.

BACKGROUND: To test the hypothesis that depressed patients with selected neurobiologic disturbances are less responsive to psychotherapy, we examined responses to cognitive behavior therapy in relation to electroencephalographic sleep profiles. METHODS: Under a prospective, case-control design, 90 outpatients with probable or definite endogenous major depression (Schedule for Affective Disorders and Schizophrenia and Research Diagnostic Criteria) were stratified into abnormal and normal sleep subgroups (on the basis of an empirically validated electroencephalographic sleep profile) and more severe and less severe depression subgroups (on the basis of pretreatment Hamilton scores). Response to 16 weeks of treatment was analyzed for both intention-to-treat and completers (n = 82) samples. Outcomes during a 36-month prospective follow-up were assessed with survival analyses. RESULTS: Abnormal sleep profiles and higher pretreatment depression severity were independently associated with poorer outcomes on several analyses. The association between sleep abnormality and cognitive behavior therapy response was not significant in the completers analyses, however, largely because of differential attrition. During follow-up, pretreatment depression severity was predictive of relapse and a lower recovery rate, whereas sleep abnormality was predictive of a lower recovery rate and a higher risk of recurrence. CONCLUSIONS: Depressed patients characterized by higher severity and/or an abnormal electroencephalographic sleep profile were relatively less responsive to cognitive behavior therapy. These associations are hypothesized to result from a constellation of neurophysiologic disturbances that interfere with the acquisition, application, and implementation of the skills emphasized in cognitive behavior therapy.

Adult

The role of psychotherapy in the treatment of depression: review of two practice guidelines.

We review two recent practice guidelines' assessments of the role of psychotherapy in the treatment of major depression in adults. We examine the practice guideline published by the American Psychiatric Association (APA) and that published by the Depression Guideline Panel of the Agency for Health Care Policy and Research. We focus on the guidelines' evaluations of psychotherapies, their statements about the role of psychotherapy in first-line treatment of depression, and the procedures they recommend for choosing among psychotherapies. We argue that the APA guideline understates the value of cognitive, behavioral, brief psychodynamic, and group therapies. Both guidelines understate the value of psychotherapy alone in the treatment of more severely depressed outpatients. The APA guideline overvalues the role of combined psychotherapy-pharmacotherapy regimens, particularly in view of the greater cost of this strategy. The APA guideline also makes recommendations about choosing among psychotherapies that are not well supported by empirical evidence. We conclude with some guidelines for guideline development.

Adult

A placebo-controlled, randomized clinical trial comparing sertraline and imipramine for the treatment of dysthymia.

BACKGROUND: Despite the high prevalence of dysthymia and its associated morbidity, few controlled trials have evaluated the efficacy of antidepressant medication for this disorder. A 12-week, double-blind, placebo-controlled, randomized, multicenter trial was performed to evaluate the safety and efficacy of sertraline hydrochloride and imipramine hydrochloride in treating dysthymia. METHODS: A total of 416 outpatients (271 women and 145 men) aged 25 to 65 years with DSM-III-R-defined, early-onset, primary dysthymia without concurrent major depression were randomized to 12 weeks of treatment with sertraline, imipramine, or placebo. RESULTS: Both active treatments resulted in significantly reduced scores on the 17-item Hamilton Rating Scale for Depression (P = .04 and P = .01 for sertraline and imipramine vs placebo, respectively), the Montgomery-Asberg Depression Rating Scale (P = .01 and P = .003 vs placebo, respectively), Hopkins Symptom Checklist (P < .05), and the self-rated version of the Inventory of Depressive Symptoms (P < .05). With the use of a Clinical Global impressions improvement score of 1 or 2 (very much or much improved) to define response, response rates were 59% for sertraline, 64% for imipramine, and 44% for placebo (P = .02 for sertraline vs placebo and P < .001 for imipramine vs placebo). A significantly greater proportion of patients receiving imipramine than those receiving sertraline or placebo discontinued treatment because of adverse events (P = .001 and P < .001, respectively). CONCLUSIONS: Pharmacotherapy provides considerable relief from the symptoms of dysthymia in patients suffering from this chronic affective disorder, with both sertraline and imipramine being more effective than placebo. The greater tolerability of sertraline is an important consideration because of the chronicity of dysthymia, which may require prolonged treatment with antidepressant medication.

1-Naphthylamine