Therapist competence ratings in relation to clinical outcome in cognitive therapy of depression.

This study reports on the relationship of therapist competence to the outcome of cognitive-behavioral treatment in the National Institute of Mental Health Treatment of Depression Collaborative Research Program. Outpatients suffering from major depressive disorder were treated by cognitive-behavioral therapists at each of 3 U.S. sites using a format of 20 sessions in 16 weeks. Findings provide some support for the relationship of therapist competence (as measured by the Cognitive Therapy Scale) to reduction of depressive symptomatology when controlling for therapist adherence and facilitative conditions. The results are, however, not as strong or consistent as expected. The component of competence that was most highly related to outcome is a factor that reflects the therapist's ability to structure the treatment.

Initial severity and differential treatment outcome in the National Institute of Mental Health Treatment of Depression Collaborative Research Program.

Random regression models (RRMs) were used to investigate the role of initial severity in the outcome of 4 treatments (cognitive-behavior therapy [CBT], interpersonal psychotherapy [IPT], imipramine plus clinical management [IMI-CM], and placebo plus clinical management [PLA-CM]) for outpatients with major depressive disorder seen in the National Institute of Mental Health Treatment of Depression Collaborative Research Program. Initial severity of depression and impairment of functioning significantly predicted differential treatment effects. A larger number of differences than previously reported were found among the active treatments for the more severely ill patients; this was due, in large part, to the greater power of the present statistical analyses.

Temporal course of change of depression.

Two hundred fifty moderately to severely depressed outpatients were randomly assigned to 16 weeks of cognitive-behavioral therapy, interpersonal psychotherapy, imipramine plus clinical management (IMI-CM), or pill placebo plus clinical management. Two hundred thirty-nine patients actually began treatment. The most rapid change in depressive symptoms occurred in the IMI-CM condition, which achieved significantly better results than the other treatments at 8 and 12 weeks on 1 or more variables. Change over the course of treatment on variables hypothesized to be most specifically affected by the respective treatments was found only in the case of pharmacotherapy, in which imipramine produced significantly greater changes on the endogenous measure at 8 and 12 weeks.

Some conceptual and statistical issues in analysis of longitudinal psychiatric data. Application to the NIMH treatment of Depression Collaborative Research Program dataset.

Longitudinal studies have a prominent role in psychiatric research; however, statistical methods for analyzing these data are rarely commensurate with the effort involved in their acquisition. Frequently the majority of data are discarded and a simple end-point analysis is performed. In other cases, so called repeated-measures analysis of variance procedures are used with little regard to their restrictive and often unrealistic assumptions and the effect of missing data on the statistical properties of their estimates. We explored the unique features of longitudinal psychiatric data from both statistical and conceptual perspectives. We used a family of statistical models termed random regression models that provide a more realistic approach to analysis of longitudinal psychiatric data. Random regression models provide solutions to commonly observed problems of missing data, serial correlation, time-varying covariates, and irregular measurement occasions, and they accommodate systematic person-specific deviations from the average time trend. Properties of these models were compared with traditional approaches at a conceptual level. The approach was then illustrated in a new analysis of the National Institute of Mental Health Treatment of Depression Collaborative Research Program dataset, which investigated two forms of psychotherapy, pharmacotherapy with clinical management, and a placebo with clinical management control. Results indicated that both person-specific effects and serial correlation play major roles in the longitudinal psychiatric response process. Ignoring either of these effects produces misleading estimates of uncertainty that form the basis of statistical tests of hypotheses.

Course of depressive symptoms over follow-up. Findings from the National Institute of Mental Health Treatment of Depression Collaborative Research Program.

We studied the course of depressive symptoms during an 18-month naturalistic follow-up period for outpatients with Major Depressive Disorder treated in the National Institute of Mental Health Treatment of Depression Collaborative Research Program. The treatment phase consisted of 16 weeks of randomly assigned treatment with the following: cognitive behavior therapy, interpersonal therapy, imipramine hydrochloride plus clinical management (CM), or placebo plus CM. Follow-up assessments were conducted at 6, 12, and 18 months after treatment. Of all patients entering treatment and having follow-up data, the percent who recovered (8 weeks of minimal or no symptoms following the end of treatment) and remained well during follow-up (no Major Depressive Disorder relapse) did not differ significantly among the four treatments: 30% (14/46) for those in the cognitive behavior therapy group, 26% (14/53) for those in the interpersonal therapy group, 19% (9/48) for those in the imipramine plus CM group, and 20% (10/51) for those in the placebo plus CM group. Among patients who had recovered, rates of Major Depressive Disorder relapse were 36% (8/22) for those in the cognitive behavior therapy group, 33% (7/21) for those in the interpersonal therapy group, 50% (9/18) for those in the imipramine plus CM group, and 33% (5/15) for those in the placebo plus CM group. The major finding of this study is that 16 weeks of these specific forms of treatment is insufficient for most patients to achieve full recovery and lasting remission. Future research should be directed at improving success rates of initial and maintenance treatments for depression.

Lack of early antitoxin response to tetanus booster.

Tetanus immune globulin (TIG) continues to be recommended in persons with tetanus-prone wounds who have incomplete or unknown tetanus immunization status. The aim of this study was to determine whether, following a booster dose of tetanus toxoid in adults who had not been immunized in the previous 10 years, there was an antitoxin response to tetanus toxoid booster within 4 days. Thirty-one adults were investigated, baseline levels for tetanus antitoxin assayed using an ELISA technique, and an injection of adsorbed tetanus toxoid (0.5 ml) given. Blood samples for tetanus antitoxin levels were taken at daily intervals for the 4 days following immunization. Tetanus boosters following the primary course but before the present study did not significantly increase the levels of pre-study tetanus antitoxin and following the study booster there was no difference between the preboost levels and the levels on days 1 to 4. This finding indicates that the present recommendations for the use of TIG in tetanus-prone wounds are appropriate.

Patient predictors of response to psychotherapy and pharmacotherapy: findings in the NIMH Treatment of Depression Collaborative Research Program.

OBJECTIVE: The authors investigated patient characteristics predictive of treatment response in the National Institute of Mental Health (NIMH) Treatment of Depression Collaborative Research Program. METHOD: Two hundred thirty-nine outpatients with major depressive disorder according to the Research Diagnostic Criteria entered a 16-week multicenter clinical trial and were randomly assigned to interpersonal psychotherapy, cognitive-behavior therapy, imipramine with clinical management, or placebo with clinical management. Pretreatment sociodemographic features, diagnosis, course of illness, function, personality, and symptoms were studied to identify patient predictors of depression severity (measured with the Hamilton Rating Scale for Depression) and complete response (measured with the Hamilton scale and the Beck Depression Inventory). RESULTS: One hundred sixty-two patients completed the entire 16-week trial. Six patient characteristics, in addition to depression severity previously reported, predicted outcome across all treatments: social dysfunction, cognitive dysfunction, expectation of improvement, endogenous depression, double depression, and duration of current episode. Significant patient predictors of differential treatment outcome were identified. 1) Low social dysfunction predicted superior response to interpersonal psychotherapy. 2) Low cognitive dysfunction predicted superior response to cognitive-behavior therapy and to imipramine. 3) High work dysfunction predicted superior response to imipramine. 4) High depression severity and impairment of function predicted superior response to imipramine and to interpersonal psychotherapy. CONCLUSIONS: The results demonstrate the relevance of patient characteristics, including social, cognitive, and work function, for prediction of the outcome of major depressive disorder. They provide indirect evidence of treatment specificity by identifying characteristics responsive to different modalities, which may be of value in the selection of patients for alternative treatments.

Mode-specific effects among three treatments for depression.

In the NIMH Treatment of Depression Collaborative Research Program (TDCRP), 250 depressed outpatients were randomly assigned to interpersonal psychotherapy, cognitive-behavioral therapy, imipramine plus clinical management, or pill placebo plus clinical management treatments. Although all treatments demonstrated significant symptom reduction with few differences in general outcomes, an important question concerned possible effects specific to each treatment. The therapies differ in rationale and procedures, suggesting that mode-specific effects may differ among treatments, each of which was precisely specified, applied appropriately, and shown to be discriminable. Outcome measures were selected for presumed sensitivity to the different treatments. Findings provided only scattered and relatively insubstantial support for mode-specific differences. None of the therapies produced consistent effects on measures related to its theoretical origins.

National Institute of Mental Health Treatment of Depression Collaborative Research Program. General effectiveness of treatments.

We investigated the effectiveness of two brief psychotherapies, interpersonal psychotherapy and cognitive behavior therapy, for the treatment of outpatients with major depression disorder diagnosed by Research Diagnostic Criteria. Two hundred fifty patients were randomly assigned to one of four 16-week treatment conditions: interpersonal psychotherapy, cognitive behavior therapy, imipramine hydrochloride plus clinical management (as a standard reference treatment), and placebo plus clinical management. Patients in all treatments showed significant reduction in depressive symptoms and improvement in functioning over the course of treatment. There was a consistent ordering of treatments at termination, with imipramine plus clinical management generally doing best, placebo plus clinical management worst, and the two psychotherapies in between but generally closer to imipramine plus clinical management. In analyses carried out on the total samples without regard to initial severity of illness (the primary analyses), there was no evidence of greater effectiveness of one of the psychotherapies as compared with the other and no evidence that either of the psychotherapies was significantly less effective than the standard reference treatment, imipramine plus clinical management. Comparing each of the psychotherapies with the placebo plus clinical management condition, there was limited evidence of the specific effectiveness of interpersonal psychotherapy and none for cognitive behavior therapy. Superior recovery rates were found for both interpersonal psychotherapy and imipramine plus clinical management, as compared with placebo plus clinical management. On mean scores, however, there were few significant differences in effectiveness among the four treatments in the primary analyses. Secondary analyses, in which patients were dichotomized on initial level of severity of depressive symptoms and impairment of functioning, helped to explain the relative lack of significant findings in the primary analyses. Significant differences among treatments were present only for the subgroup of patients who were more severely depressed and functionally impaired; here, there was some evidence of the effectiveness of interpersonal psychotherapy with these patients and strong evidence of the effectiveness of imipramine plus clinical management. In contrast, there were no significant differences among treatments, including placebo plus clinical management, for the less severely depressed and functionally impaired patients.

Mechanical Resistance of the Seed Coat and Endosperm during Germination of Capsicum annuum at Low Temperature.

Decoated pepper (Capsicum annuum L. cv Early Calwonder) seeds germinated earlier at 25 degrees C, but not at 15 degrees C, compared to coated seeds. The seed coat did not appear to impose a mechanical restriction on pepper seed germination. Scarification of the endosperm material directly in front of the radicle reduced the time to germination at both 15 degrees C and 25 degrees C.The amount of mechanical resistance imposed by the endosperm on radicle emergence before germination was measured using the Instron Universal Testing Machine. Endosperm strength decreased as imbibition time increased. The puncture force decreased faster when seeds were imbibed at 25 degrees C than at 15 degrees C. The reduction in puncture force corresponded with the ability of pepper seeds to germinate. Most radicle emergence occurred at 15 degrees C and 25 degrees C after the puncture force was reduced to between 0.3 and 0.4 newtons.Application of gibberellic acid(4+7) (100 microliters per liter) resulted in earlier germination at 15 degrees C and 25 degrees C and decreased endosperm strength sooner than in untreated seeds. Similarly, high O(2) concentrations had similar effects on germination earliness and endosperm strength decline as did gibberellic acid(4+7), but only at 25 degrees C. At 15 degrees C, high O(2) concentrations slowed germination and endosperm strength decline.

A comparison of enzyme-linked immunosorbent assay (ELISA) with the toxin neutralization test in mice as a method for the estimation of tetanus antitoxin in human sera.

An enzyme-linked immunosorbent assay (ELISA) has been developed for the measurement of tetanus antitoxin in human sera as an alternative to the toxin neutralization test in mice, the currently accepted method of assay. The ELISA was found to be simple and quick to perform and required only small amounts of materials. In addition, the assay was found to give reproducible estimates of antitoxin levels and to measure antitoxin at levels as low as 0.01 IU per ml, a sensitivity similar to that of the neutralization test. Furthermore, a comparison of the results of the ELISA and the neutralization test involving 80 human sera, including sera with both high and low antitoxin levels, showed close agreement in antitoxin levels obtained by the two methods. It was concluded that ELISA was an acceptable alternative to the toxin neutralization test in mice for the measurement of tetanus antitoxin levels in human sera.

The use of psychotherapy with dying patients: an exploratory study.

A group of terminally ill patients received six sessions of psychotherapy. A second group of six patients served as nontreated controls. At the conclusion of the treatment sessions, psychotherapy patients reported a significantly greater increase in death-related anxiety and in their perceived purpose in life than did the nontreated group. Clinical impressions indicated that patients who participated in psychotherapy perceived their treatment experience positively and appreciated the opportunity to explore their feelings about imminent death. These results offer considerable support for the usefulness of psychotherapy to help such patients cope with the emotional stress generated by their limited life expectancy.