Perceptual and conceptual information processing in schizophrenia and depression.

Schizophrenic patients (n = 20), depressive patients (n = 20), and normal adults (n = 20) were compared on global vs local analyses of perceptual information using tachistoscopic tasks and on top-down vs bottom-up conceptual processing using card-sort tasks. The schizophrenic group performed more poorly on tasks requiring either global analyses (counting lines when distracting circles were present) or top-down conceptual processing (rule learning) than they did on tasks requiring local analyses (counting heterogeneous lines) or bottom-up processing (attribute identification). The schizophrenic group appeared not to use conceptually guided processing. Normal adults showed the reverse pattern. The depressive group performed similarly to the schizophrenic group on perceptual tasks but closer to the normal group on conceptual tasks, thereby appearing to be less dependent on a particular information-processing strategy. These deficits in organizational strategy may be related to the use of available processing resources as well as the allocation of attention.

Panic disorder: review of the empirical and rational basis of pharmacological treatment.

The increasing interest in and clinical research on the nature and treatment of panic disorder and agoraphobia have produced and should continue to produce rapid progress in the accumulation of scientific knowledge in this field. This article reviews some basic aspects of the effective pharmacotherapeutic management of panic-agoraphobic patients. Research results with different drug classes are reviewed and their implications for effective treatment discussed. The final section deals with special issues of case management, such as choice of specific drug, length of treatment, and probability and frequency of relapse.

Differential changes in areas of social adjustment from depressive episodes through recovery.

The findings of the present short-term prospective study of 99 depressed outpatients further support previous cross-sectional observations to the effect that the course of depressive illness is often complicated by fluctuating social disturbances manifested by uneasiness in the work area, by disagreements with colleagues, and by difficulty in maintaining conflict-free relationships with significant others. By contrast, the incapacity to enjoy and use leisure time appeared less related to the symptomatologic variation in depression. Although we favor the hypothesis that impairment in leisure activity may represent a trait marker of depression, the hypothesis of it being a residual complication of repeated depressive episodes cannot be ruled out in view of short follow-up.

Clomipramine for panic disorder: I. The first 10 weeks of a long-term comparison with imipramine.

Clomipramine and imipramine treatments were compared in a sample of 152 panic disorders. Diagnosis was according to the positive criteria of DSM-III-R, but without exclusion of comorbid affective or personality disorders. The 2-year design provides non-blind treatment under typical clinical practice conditions, and it includes random assignment, periodic assessment with standardized measures, and comparable, flexible drug dosages. Findings on six outcome measures in the first 59 cases to complete 10 weeks showed both tricyclics to be markedly and equally effective for blocking panic attacks, alleviating phobic avoidance, and reducing nonspecific aspects of anxiety. Clomipramine's predominantly serotonergic action seemed not to determine a different action spectrum. During the first 2 weeks, clomipramine was significantly and unexpectedly superior to imipramine in both antipanic and antiphobic actions. These results require replication under double-blind conditions.

A proposed new approach to the clinical subclassification of depressive illness.

This paper focuses on the classification of mood disorders. Data are reported from 227 outpatients who met DSM-III-R criteria for Major Depressive Episode. Each patient was evaluated by the Semistructured Interview for Depression (SID), which was developed and organized according to a decision tree model. The SID was used both to identify the sample with major depressive disorders and, then, to subclassify them into five subtypes. Three bipolar types (I, II, III) and two unipolar types (recurrent and single episode) were distinguished, and comparisons among the subtypes are presented. Therapeutic implications of the classification are discussed in relation to recent advances in targeting short and long-term treatments for specific subtypes.

Tricyclic treatment of generalized anxiety disorder.

While tricyclic antidepressants (TCAs) have now long been used in treatment for depressive and panic-phobic disorders, we reviewed and reported on their efficacy in generalized anxiety states. These ill-defined states usually have admixtures of anxiety and depression. While there is no neat diagnostic categorization to fit this wasteland of yet-to-be-defined disorders, they show surprising responsiveness to imipramine. The onset of efficacy appears to begin at about 2 weeks or later and is probably superior to at least one well-known benzodiazepine, chlordiazepoxide, well beyond that time. It is not possible to dismiss these observed antianxiety effects as secondary to antidepressant effects or as attributable to the unintended inclusion of a peculiarly sensitive subset of individuals such as panic-phobic patients. These findings indicate that affect regulation by TCAs applies to so-called generalized anxiety as well as to depression and panic-phobic disorder. Brief reminders and guidelines are outlined for the possible clinical use of TCAs in anxiety disorders, but there remain more questions than answers. Several replication studies concerning the results reviewed here are now under way.

Imipramine and chlordiazepoxide in depressive and anxiety disorders. I. Efficacy in depressed outpatients.

We randomly assigned 425 outpatients, independently classified as primarily depressed by two trained psychiatrists, to double-blind treatment with Imipramine hydrochloride, chlordiazepoxide hydrochloride, or placebo. Those patients who remained at least moderately depressed (following a two-week placebo washout period) were treated for an additional eight weeks. An endpoint analysis of 387 patients who completed two or more weeks of medication disclosed early therapeutic advantages of chlordiazepoxide. By week 4 of treatment, however, imipramine produced more improvement than did placebo and chlordiazepoxide. By six and eight weeks a general, marked therapeutic advantage was found for imipramine relative to placebo and to chlordiazepoxide on measures of depression, anxiety, anger-hostility, interpersonal sensitivity, and global improvement. Chlordiazepoxide-treated patients generally did significantly better on sleep difficulty but significantly worse on anger-hostility and interpersonal sensitivity than did imipramine- or placebo-treated patients.

Imipramine and chlordiazepoxide in depressive and anxiety disorders. II. Efficacy in anxious outpatients.

A double-blind, placebo-controlled comparison at three collaborating university sites included 242 patients diagnosed as having anxiety disorders. A two-week placebo washout period preceded random assignment to eight weeks of imipramine hydrochloride, chlordiazepoxide hydrochloride, or placebo treatment. Antianxiety effects of imipramine were superior to those of the other two agents by the second treatment week; these effects became more clearly significant thereafter and were independent of degree of both baseline depression and anxiety. Excluding patients with possible panic-phobic syndromes from the analyses removed most significant antiphobic and antidepressant effects of imipramine but left intact imipramine's significantly superior antianxiety effects.

Amoxapine and amitriptyline. I. Relative speed of antidepressant action.

Speed of onset of antidepressant effect was studied in 20 depressed outpatients assigned double-blind to equipotent doses of amoxapine or amitriptyline. In counter-balanced order, each patient had 2 periods of 3 weeks on active agent interspersed with 2 similar periods of placebo control. On daily and weekly self-ratings, amoxapine was found to reduce symptoms significantly more rapidly than amitriptyline. Psychiatrist-ratings were consonant with self-reports.

Amoxapine and amitriptyline. II. Specificity of cognitive effects during brief treatment of depression.

Cognitive effects of brief antidepressant treatments were studied in depressed outpatients assigned double-blind to equipotent doses of amoxapine or amitriptyline in a 12-week double-crossover of 3-week periods of active agent and placebo. The two drugs had different profiles of effects: amitriptyline was associated with faster reaction time on tests of attention and immediate memory, reduced accuracy on an attention task, and impaired long-term memory (after 1 but not 3 weeks); amoxapine slowed performance and increased intraperson variability on a psychomotor coordination task. Amitriptyline facilitated performance in the more depressed patients, and amoxapine in the older patients. Both agents also increased pulse rate and reduced palmar sweating.

Evidence for bipolar mood states.

Currently, the mood states are regarded as monopolar. This study tested in psychiatric subjects for the presence of five bipolar mood states after the influence of extreme response bias had been removed. The affective states hypothesized were: composed vs anxious, agreeable vs hostile, energetic vs fatigued, elated vs depressed, and clear-thinking vs confused. The sample of 303 cases included anxious, depressed and agoraphobic cases. Ratings of the 72 adjectives of the Profile of Mood States were intercorrelated. After extreme response bias score was partialled out the resulting correlations were analyzed by the method of principal components. The five factors isolated clearly support the bipolar nature of mood states postulated.

Simulated public speaking as a model of clinical anxiety.

Normal male volunteers took single acute doses of either diazepam or placebo under double-blind conditions in three simulated public speaking experiments. Measures of palmar sweating and subjective anxiety showed that anticipation of speaking in public increased anxiety relative to baseline and prestress conditions, and performance of public speaking further increased anxiety. A dose-related anxiolytic effect of diazepam on subjective anxiety supported the model's clinical relevance. Moreover, the intensity of the subject's public speaking phobia predicted both degree of prestress anxiety relief from 10 mg diazepam and overall anxiety level, regardless of medication, throughout the experimental session. A measure of traditionalism predicted placebo and 5 mg diazepam response during prestress: As in previous clinical trials, high traditionalism scorers reported more relief from placebo, whereas low scorers showed more relief from diazepam.

Tricyclic antidepressants and peripheral anticholinergic activity.

Peripheral anticholinergic activity of single acute doses of three tricyclic antidepressants (amitriptyline 50 mg, desipramine 50 mg, doxepin 100 mg) and placebo was assessed by several physiologic measures in normal male volunteers. Amitriptyline and doxepin produced similar significant depressions in salivary flow and finger sweating compared to placebo, while desipramine produced no change. Supine and standing blood pressures and standing pulse yielded significant differences among the drugs. Measures in at least three areas (salivation, perspiration, and pulse-blood pressure) offer a simple and reliable battery of tests for the peripheral autonomic effects of tricyclic antidepressants.

Two Bass Scale factors and response to placebo and anxiolytic drugs.

Two principal oblique factors are identified in the Bass Social Acquiescence Scale, a measure previously shown to correlate positively with placebo response and negatively with anxiolytic drug response. The two factors appeared very similar in separate analyses of data from samples of 941 psychiatric outpatients and 1,837 college students. Also, results are presented which indicate that one factor, tentatively labeled "traditionalism", accounted for the empirically observed relationships to placebo and drug response in two clinical trials.

Placebo response, placebo effect, and two attributes.

Two putative predictors of placebo response were studied in three samples of psychiatric outpatients. Two groups, 73 university medical center patients and 56 college health service patients, underwent 1 week of placebo treatment. A quasi-control group of 112 patients receiving no medication waited about 1 week before beginning psychotherapy. One attribute, acquiescence or traditionalism, predicted placebo response, thereby replicating prior findings. Acquiescence was unrelated to change in controls indicating that it may represent a correlate of true placebo effect under some conditions. Additional findings suggested qualifications as to the generality of the relationship. The second attribute, autonomic awareness, was associated with change in all three samples. It appeared to predict nonspecific improvement unrelated to placebo probably due to its relationship to intensity of somatization.

Symptomatic volunteers in multicenter drug trials.

1. Symptomatic volunteers were recruited at two collaborating institutions for anti-anxiety and antidepressant drug trials. Advertisements were placed for volunteers with significant symptoms of anxiety, depression, or both, and who were not currently in treatment. 2. It was possible to recruit adequate numbers of volunteers who met the numerous criteria for severity of distress; and who were not ruled out by various exclusion criteria, such as medical contraindications, etc. 3. Acceptable homogeneity across the samples at the collaborating institutions was found for demographic characteristics, level of distress, duration of symptoms, etc. 4. Attrition rates for these volunteers were lower than for the typical anxiolytic and antidepressant trials using outpatients. 5. Symptomatic volunteers appear to present a feasible alternative to the increasingly diminishing pool of outpatients.