Treatment of primary dysthymia with group cognitive therapy and pharmacotherapy: clinical symptoms and functional impairments.

OBJECTIVE: This study assessed the efficacy of antidepressant treatment (sertraline) and group cognitive behavior therapy, alone or in combination, in primary dysthymia. The clinical features of dysthymia, as well as the functional impairments associated with the illness (e.g., quality of life, stress perception, coping styles), were evaluated. METHOD: Patients (N = 97) diagnosed with primary dysthymia, but no other current comorbid disorder, received either sertraline or placebo in a double-blind design over 12 weeks. In addition, a subgroup of the patients (N = 49) received a structured, weekly group cognitive behavior therapy intervention. RESULTS: Treatment with sertraline, with or without group cognitive behavior therapy, reduced the functional impairment of depression. The reductions were similar in the drug-cognitive therapy group and in subjects who received the drug alone. Furthermore, while group cognitive behavior therapy alone reduced the depression scores, this effect was not significantly greater than the effect of the placebo. The drug treatment also induced pronounced improvement in the functional measures, and in some respects these effects were augmented by group cognitive behavior therapy. Among patients who responded favorably to cognitive behavior therapy, the improvements in the functional measures were similar to those who responded to drug treatment, whereas such functional changes were not seen among patients who responded to placebo. CONCLUSIONS: Sertraline treatment effectively reduces the clinical symptoms and functional impairments associated with dysthymia. Although the group cognitive behavior therapy intervention was less effective in alleviating clinical symptoms, it augmented the effects of sertraline with respect to some functional changes, and in a subgroup of patients it attenuated the functional impairments characteristic of dysthymia.

Quantitative EEG in the prediction of antidepressant response to imipramine.

The purpose of this study was to examine the utility of quantitative electroencephalography (QEEG) in the prediction of response to imipramine in depressed patients. Forty patients with a diagnosis of unipolar depression were subjected to a placebo washout and were assessed at pre-drug, 3 h after their first dose of imipramine, and again 2 weeks into treatment. Following 4 weeks of open imipramine treatment, patients were separated into responder (R) and non-responder (NR) groups. Statistical analysis of the 29 patients who completed the study focused on group comparisons of power spectral estimates in four frequency bands from multi-channel recordings. Results showed that theta power differentiated R and NR groups prior to treatment, in response to an acute test dose, as well as after 2 weeks of active drug treatment. Results based on this exploratory study suggest that QEEG may be a useful early predictor of response to imipramine.

Effects of antidepressants on thinking styles in depressed inpatients.

1. Clinical and empirical evidence point to distorted negative thinking during depressive episodes. 2. The present study, utilizing the Cognitions Questionnaire, examined the thinking styles in depressed inpatients prior to antidepressant pharmacotherapy and again 3-4 weeks after treatment. 3. Across the 5 dimensions of thinking assessed, only generalization across situation changed significantly in the drug-respondent group. 4. While clinically, short-term antidepressant treatment was shown to be efficacious, it only changed cognitions in a limited way.

Psychiatric progress. The learned helplessness model of depression.

Attempts have been made to model certain human psychopathological states in the laboratory, with varying degrees of success. The animal model has emerged as an alternative to clinical studies in psychiatry because it is able to provide greater experimental control and allows the exercise of ethical discretion. Although numerous animal models of depression have been proposed in the literature, most, if not all, fail to mimic human depressive symptomatology; their main function is to act as selective screens for antidepressant drugs. The learned helplessness approach has been suggested as an animal analogue of depression because of its similarities to the human depressive state in terms of provocation, manifestation and treatment. Furthermore, the learned helplessness model, which was originally based on animal experimentation, has been shown to be reproducible in human subjects, a finding not observed with other animal models of depression. Although this model has been much criticized in the past, recent reformulation adds credence to it as a more valid analogue of human depression, given the additional cognitive constructs in depressed human subjects.

Time-dependent changes in plasma prolactin level and stress controllability in rats.

1. Numerous studies have shown the importance of controllability factors in the neurochemical, hormonal and behavioural changes associated with presentation of stress stimuli. 2. Previous work from our laboratory revealed that animals exposed to escapable shock had significantly higher prolactin levels than those treated with inescapable shock. 3. The present experiment examined the time-course of plasma prolactin change as a function of shock controllability. 4. Rats were exposed to intermittent escapable, inescapable or no shock for 5, 10, 30 or 60 min and sacrificed for plasma prolactin determination. Additional groups received 60 min shock condition followed by 30 or 60 min rest period prior to sacrifice. 5. Results showed that subjects exposed to 5, 10 or 30 min of escapable shock exhibited higher prolactin levels than inescapable shock or no-shock treated animals. These findings show that the prolactin response to stress is sensitive to controllability factors and is time-dependent.

Effects of nortriptyline treatment on learned helplessness in the rat.

Using an escape delay procedure previously shown to elicit behavioral deficits in mice exposed to uncontrollable shock, rats treated with inescapable but not escapable shock or no shock displayed comparable interference effects when tested in a two-way shuttle box 24 hr later. Treatment with 12.5 mg/kg nortriptyline for 4 or 6 days counteracted the escape deficits produced by inescapable shock while the 0 or 2 day administration regimens were without any appreciable effect. The finding that interference effects produced by inescapable shock were sensitive to sub-acute but not acute drug administration supports the utility of the learned helplessness model in evaluating potential antidepressant agents in experimental animals.

Effects of serotonin content on pain sensitivity in the rat.

In this study the role of serotonin in pain sensitivity was investigated. Brain serotonin was elevated via low and high doses of precursor tryptophan and lowered via parachlorophenylalanine or lesions placed in the dorsal raphe nucleus. The effects on pain sensitivity were then assessed using two psychophysical pain testing procedures: (1) minimum shock intensity (threshold) which produced a conditioned escape response; and (2) total activity elicited by highly aversive inescapable shock. The results showed that only a large elevation of serotonin produced a change in escape thresholds in the direction of hypoalgesia. When total activity to a painful inescapable stimulus was evaluated only lowering of serotonin produced an effect, and this change was in the direction of hyperalgesia. The conclusion was made that serotonin does contribute to the mechanism of pain.

Effects of low and moderate doses of chlorpromazine on discrimination learning in the rat.

The effects of chlorpromazine on the acquisition of a brightness discrimination with food reward were examined. Doses of 0.5, 1.0 or 2.0 mg/kg of CPZ as well as saline were administered intraperitoneally to 4 groups of 7 Sprague-Dawley rats, 1 h prior to testing. After a 3-week period of habituation and pre-training, rats were tested 20 trials a day, 7 days a week. No drug effect was found on the number of trials to reach a criterion of 18/20 successive correct responses, which required an average of 6.2 days of training. Precriterion latencies, however, showed an increase as a function of increasing dose level. Post-choice latencies were not affected, eliminating motor retardation as an explanation for the latency effect.