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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
PubMed2005

Identifying "paradigm failures" contributing to treatment-resistant depression.

BACKGROUND: "Treatment resistant depression" is likely to emerge from a number of factors, including application of the wrong diagnostic and treatment models. METHOD: Current paradigms for managing both depression and treatment resistant depression are considered. We then examine the prevalence of a set of paradigm failures that appeared to contribute to treatment resistant depression in outpatients of a tertiary referral Mood Disorders Unit. RESULTS: Six illustrative paradigm failures are described and their frequencies within the clinical sample reported. Identified paradigm failures were diagnosing and/or managing a non-melancholic condition as if it were melancholic depression, failure to diagnose and manage bipolar disorder, psychotic depression or melancholic depression, misdiagnosing secondary depression and failure to identify organic determinants. CONCLUSION: We suggest that the identification of such "paradigm failures"--and of others that can be assumed to operate--has the potential to enrich the assessment and management of depressed patients, and reduce the prevalence of treatment resistance.

Adolescent↗
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↗
PubMed2002

Does early intervention increase latency to relapse in major depressive disorder? Re-evaluation with cognitive behavior therapy.

BACKGROUND: Major depressive disorder (MDD) has been studied in relation to its propensity for remission and likelihood of relapse. While the general clinical lore suggests that early intervention benefits treatment outcome, the empirical validation of this assumption is inconclusive. Specifically, no studies have been conducted concerning Time to Treatment Entry and long-term clinical course for MDD. METHODS: For the current study, 53 participants received 16-weeks of cognitive behavioral therapy (CBT). Participants who remitted (n=41) from their depression were then inducted into a longitudinal follow-up protocol. RESULTS: Longer Time to Treatment Entry was predictive of longer time to relapse. A greater number of previous depressive episodes was associated with decreased Time to Treatment Entry. LIMITATIONS: A more elaborate protocol could be designed in order to explore the nature of treatment effects and Time to Treatment Entry within one study. CONCLUSIONS: CBT may be the most effective for patients who have delayed seeking treatment. Although the present study adds to the developmental neurobiological assumptions of Post [Severe depressive disorders (1994) 23-65] concerning affective 'kindling,' it also challenges the kindling theory's assumptions concerning early intervention.

Adult↗
PubMed2001

Strengthening clinical effectiveness trials: equipoise-stratified randomization.

As psychiatric practice patterns evolve to take advantage of the growing list of treatments with proven efficacy, research studies with broader aims will become increasingly important. Randomized trials may need to accommodate multiple treatment options. In completely randomized designs, patients are assigned at random to one of the options, requiring that patients and clinicians find each of the options acceptable. In "clinician's choice" designs, patients are randomized to a small number of broad strategies and the choice of specific option within the broad strategy is left up to the clinician. The clinician's choice design permits some scope to patient and clinician preferences, but sacrifices the ability to make randomization-based comparisons of specific options. We describe a new approach, which we call the "equipoise stratified" design, that merges the advantages and avoids the disadvantages of the other two designs for clinical trials. The three designs are contrasted, using the National Institute of Mental Health Sequenced Treatment Alternatives to Relieve Depression trial as an example.

Antidepressive Agents↗
PubMed2001

Cognitive disturbance in outpatient depressed younger adults: evidence of modest impairment.

BACKGROUND: Investigations of cognitive disturbances among patients with mood disorders have yielded inconsistent results. Although marked neuropsychologic deficits have been reported in elderly patients and in midlife patients with severe depression, the severity of cognitive impairments in medically healthy younger ambulatory adults with depression has not been well characterized. METHODS: A comprehensive battery of standard neuropsychologic tests and experimental computerized measures of cognitive functioning were administered to unmedicated ambulatory younger adults with mild to moderate nonbipolar depression and to a group of age- and gender-equated healthy subjects. RESULTS: Patients demonstrated a notable absence of widespread cognitive impairment. Deficits in executive functions were observed on the Wisconsin Card Sort Test but not on several other tests. Despite the absence of significant impairment on tests of attention, memory, and motor performance in the total sample, symptom severity and age of illness onset were correlated with poorer performance on some tests of cognitive functioning even after correction for age. CONCLUSIONS: These findings, derived from a large sample of unmedicated depressed outpatients, indicate that major depressive disorder in healthy younger ambulatory adults does not cause appreciable impairments in cognitive functioning in the absence of clinical and course-of-illness features.

Adult↗
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

Effects of bupropion SR on anterior paralimbic function during waking and REM sleep in depression: preliminary findings using.

This study sought to clarify the effects of bupropion SR on anterior paralimbic function in depressed patients by studying changes in the activation of these structures from waking to REM sleep both before and after treatment. Twelve depressed patients underwent concurrent EEG sleep studies and [18F]fluoro-2-deoxy-D-glucose ([18F]-FDG) positron emission tomography (PET) scans during waking and during their second REM period of sleep before and after treatment with bupropion SR. Nine subjects completed pre- and post-treatment waking PET studies. Five subjects completed pre- and post-treatment waking and REM sleep PET studies. Bupropion SR treatment did not suppress electrophysiologic measures of REM sleep, nor did it alter an indirect measure of global metabolism during either waking or REM sleep. Bupropion SR treatment reversed the previously observed deficit in anterior cingulate, medial prefrontal cortex and right anterior insula activation from waking to REM sleep. In secondary analyses, this effect was related to a reduction in waking relative metabolism in these structures following treatment in the absence of a significant effect on REM sleep relative metabolism. The implications of these findings for the relative importance of anterior paralimbic function in REM sleep in depression and for the differential effects of anti-depressant treatment on brain function during waking vs. REM sleep are discussed.

Adult↗
PubMed2001

Continuation pharmacotherapy in the prevention of relapse following electroconvulsive therapy: a randomized controlled trial.

CONTEXT: Electroconvulsive therapy (ECT) is highly effective for treatment of major depression, but naturalistic studies show a high rate of relapse after discontinuation of ECT. OBJECTIVE: To determine the efficacy of continuation pharmacotherapy with nortriptyline hydrochloride or combination nortriptyline and lithium carbonate in preventing post-ECT relapse. DESIGN: Randomized, double-blind, placebo-controlled trial conducted from 1993 to 1998, stratified by medication resistance or presence of psychotic depression in the index episode. SETTING: Two university-based hospitals and 1 private psychiatric hospital. PATIENTS: Of 290 patients with unipolar major depression recruited through clinical referral who completed an open ECT treatment phase, 159 patients met remitter criteria; 84 remitting patients were eligible and agreed to participate in the continuation study. INTERVENTIONS: Patients were randomly assigned to receive continuation treatment for 24 weeks with placebo (n = 29), nortriptyline (target steady-state level, 75-125 ng/mL) (n = 27), or combination nortriptyline and lithium (target steady-state level, 0.5-0.9 mEq/L) (n = 28). MAIN OUTCOME MEASURE: Relapse of major depressive episode, compared among the 3 continuation groups. RESULTS: Nortriptyline-lithium combination therapy had a marked advantage in time to relapse, superior to both placebo and nortriptyline alone. Over the 24-week trial, the relapse rate for placebo was 84% (95% confidence interval [CI], 70%-99%); for nortriptyline, 60% (95% CI, 41%-79%); and for nortriptyline-lithium, 39% (95% CI, 19%-59%). All but 1 instance of relapse with nortriptyline-lithium occurred within 5 weeks of ECT termination, while relapse continued throughout treatment with placebo or nortriptyline alone. Medication-resistant patients, female patients, and those with more severe depressive symptoms following ECT had more rapid relapse. CONCLUSIONS: Our study indicates that without active treatment, virtually all remitted patients relapse within 6 months of stopping ECT. Monotherapy with nortriptyline has limited efficacy. The combination of nortriptyline and lithium is more effective, but the relapse rate is still high, particularly during the first month of continuation therapy.

Antidepressive Agents↗
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

Variability of erythrocyte and serum lithium levels correlates with therapist treatment adherence efforts and maintenance treatment outcome.

This study investigated the relationship between psychotherapeutic interventions and pharmacologic measures of pharmacotherapy treatment adherence in patients with bipolar I disorder, as well as the relationship between these measures and treatment outcome. Subjects were participating in an ongoing maintenance treatment study. Audiotaped therapy sessions were rated for frequency of psychotherapeutic interventions related to pharmacotherapy treatment adherence. Pharmacologic measures of medication adherence were compared to the tape ratings as well as to treatment outcome. Variability in log erythrocyte (RBC) lithium-a marker of probable nonadherence to the pharmacotherapy regimen-for individual patients correlated significantly with treatment adherence interventions scale ratings. This marker of nonadherence was significantly related to maintenance treatment outcome, as was variability of the serum lithium level/dose (L/D) ratio; however, no relationship was found between treatment adherence interventions scale ratings and outcome.

Adult↗
PubMed2001

Therapeutic alliance as a predictor of outcome and retention in the National Institute on Drug Abuse Collaborative Cocaine Treatment Study.

The authors examined the relation between therapeutic alliance, retention, and outcome for 308 cocaine-dependent outpatients participating in the National Institute on Drug Abuse Collaborative Cocaine Treatment Study. High levels of alliance were observed in supportive-expressive therapy (SE), cognitive therapy (CT), and individual drug counseling (IDC), and alliance levels increased slightly but significantly from Session 2 to Session 5 in all groups. In contrast to other studies, alliance was not a significant predictor of drug outcome. However, alliance did predict patient retention differentially across the 3 treatments. In SE and IDC, either higher levels of alliance were associated with increased retention or no relationship between alliance and retention was found, depending on the time alliance was measured. In CT, higher levels of alliance were associated with decreased retention.

Adult↗
PubMed2001

Impact of psychosocial treatments on associated problems of cocaine-dependent patients.

A previous report from the National Institute on Drug Abuse Collaborative Cocaine Treatment Study (P. Crits-Christoph et al., 1999) found relatively superior cocaine and drug use outcomes for individual drug counseling plus group drug counseling compared with other treatments. Using data from that study, the authors examined the relative efficacy of 4 treatments for cocaine dependence on psychosocial and other addiction-associated problems. The 487 patients were randomly assigned to 6 months of treatment with cognitive therapy, supportive-expressive therapy, or individual drug counseling (each with additional group drug counseling), or to group drug counseling alone. Assessments were made at baseline and monthly for 6 months during the acute treatment phase, with follow-up visits at 9 and 12 months. No significant differences between treatments were found on measures of psychiatric symptoms, employment, medical, legal, family-social, interpersonal, or alcohol use problems. The authors concluded that the superiority of individual drug counseling in modifying cocaine use does not extend broadly to other addiction-associated problems.

Adolescent↗
PubMed2001

Primary care patients' personal illness models for depression: a preliminary investigation.

BACKGROUND: Despite the fact that more than half of depressed persons are treated for this disorder by primary care physicians, depression is often under-recognized or treated inadequately. There is continued emphasis on effective treatment of depression in primary care patients, but little attention has been paid to the role of the depressed person's illness cognitions in coping with this disorder. Given the often recurring and chronic nature of depression, the individual's self-management strategies may be critical to effective treatment, recovery and remaining well. OBJECTIVES: The purpose of this pilot study was to determine whether primary care patients' personal illness cognitions for depression are associated with depression coping strategies and treatment-related behaviour. METHODS: Forty-one primary care patients with depressive symptoms or disorder completed interviews and questionnaires assessing illness cognitions for depression, depression coping strategies and other treatment-related behaviour. Descriptive statistics are used to present patients' illness cognitions for depression. t-tests and correlational analyses were completed to assess the relationship between illness cognitions, depression coping strategies and treatment-related behaviour. RESULTS: Preliminary data describing illness cognitions for depression are presented. Participants' illness cognitions for depression were significantly associated with current and past treatment-seeking behaviour, medication adherence and coping strategies. CONCLUSIONS: Although preliminary, these findings indicate that patients' understanding of depression and its consequences are associated with how they manage this illness. Future research is needed to examine the mediating and moderating effects of illness cognitions for depression on medication adherence and other self-management behaviours of depressed primary care patients. Knowledge about primary care patients' personal illness models will aid in the development of adherence interventions, self-management training and support services appropriate to patients' needs in the primary care setting.

Adaptation, Psychological↗
PubMed2001

Life stress and the symptoms of major depression.

Life stress has been found to be associated with onset of depression and with greater severity of depressive symptoms. It is unclear, though, if life stress is related to particular classes or specific symptoms in depression. The association between severe life events and depressive symptoms was tested in 59 individuals diagnosed by Research Diagnostic Criteria with endogenous primary nonpsychotic major depression. As predicted, life stress was associated principally with cognitive-affective symptoms, not somatic symptoms. There also was a consistent association across different assessment methods between severe events and suicidal ideation. Finally, associations held specifically for severe events occurring before onset, not for severe events occurring after onset. Symptom variation in major depression is related specifically to severe stressors before onset and includes primarily cognitive-affective types of symptoms. There is an especially pronounced association of prior severe stress with suicidal ideation. The implications of stress-symptom associations are addressed for enlarging understanding of symptom heterogeneity and subtype distinctions in major depression.

Adult↗
PubMed2001

Remission rates during treatment with venlafaxine or selective serotonin reuptake inhibitors.

BACKGROUND: It had been suggested that the antidepressant venlafaxine, which inhibits reuptake of both serotonin and (at higher doses) noradrenaline, may result in better outcomes than treatment with selective serotonin reuptake inhibitors (SSRIs). AIMS: To compare remission rates during treatment with SSRIs or venlafaxine. METHOD: Data from eight comparable randomised, double-blind studies of major depressive disorder were pooled to compare remission rates (Hamilton Rating Scale for Depression score < or = 7) during treatment with venlafaxine (n = 851), SSRIs (fluoxetine, paroxetine, fluvoxamine; n = 748) or placebo (four studies; n = 446). RESULTS: Remission rates were: venlafaxine, 45% (382/851); SSRIs, 35% (260/748); placebo, 25% (110/446) (P: < 0.001; odds ratio for remission is 1.50 (1.3-1.9), favouring venlafaxine v. SSRIs). The difference between venlafaxine and the SSRIs was significant at week 2, whereas the difference between SSRIs and placebo reached significance at week 4. Results were not dependent on any one study or the definition of remission. CONCLUSIONS: Remission rates were significantly higher with venlafaxine than with an SSRI.

Adult↗
PubMed2001

Citalopram treatment of fluoxetine nonresponders.

BACKGROUND: We assessed the tolerability and utility of switching fluoxetine nonresponders to citalopram the day that fluoxetine therapy was stopped. METHOD: Fifty-eight outpatients with DSM-IV major depressive episode and prospectively confirmed nonresponse to fluoxetine (mean final dose = 31 mg/day) were switched directly to citalopram (20 mg/day). Of the 58 patients, 44 (76%) had never been successfully treated with antidepressant medication. During a 12-week open-label treatment period, citalopram could be titrated up to a maximum dose of 60 mg/day. Response was evaluated using the Clinical Global Impressions (CGI) scale, the 24-item Hamilton Rating Scale for Depression, and several other measures. RESULTS: Eighty-one percent (N = 47) completed the trial, and citalopram (mean dose = 38.8 mg/day) was well tolerated. The intent-to-treat CGI response rate was 46% (26/57) at week 6 and 63% (36/57) at study endpoint; the completer response rate was 76% among the 47 patients who completed the 12-week trial. Improvement from baseline on all dependent measures was statistically significant after the first week of citalopram treatment. CONCLUSION: Fluoxetine nonresponders can be quickly switched to citalopram, with good tolerability and reasonable chance of therapeutic benefit. Further work is necessary to assess the merits of this treatment strategy relative to other options.

Adult↗