The identification and validation of distinct depressive syndromes in a population-based sample of female twins.
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Cross-Over Studies↗
Biomedical subjects
J W Stewart
Publications and source records attributed to J W Stewart.
Outcome of cognitive-behavioral therapy for depression: relation to hemispheric dominance for verbal processing.
Unmedicated depressed outpatients were tested on dichotic syllable and complex tone tests prior to receiving 16 weekly sessions of cognitive therapy (n = 31) or 6-12 weeks of placebo treatment (n = 45). Cognitive-therapy responders had twice the right-ear (left hemisphere) advantage for syllables when compared with nonresponders but did not differ from nonresponders on the nonverbal task. The larger right-ear advantage in cognitive-therapy responders was due to better right-ear accuracy; they did not differ from nonresponders in left-ear accuracy. No differences in perceptual asymmetry or accuracy were found between placebo responders and nonresponders. Right-ear accuracy for syllables was the best predictor of response to cognitive therapy in a logistic regression analysis. The findings suggest that greater left-hemisphere advantage for verbal processing is associated with more favorable outcome of cognitive therapy for depression.
Adult↗
Prophylactic efficacy of phenelzine and imipramine in chronic atypical depression: likelihood of recurrence on discontinuation after 6 months' remission.
OBJECTIVE: Demonstration of antidepressant efficacy beyond 6 months has infrequently been addressed, and no long-term efficacy data exist for patients with chronic atypical depression. METHOD: Sixty patients with atypical depression (according to Columbia University criteria) of at least 2 years' duration and who had improved with imipramine or phenelzine were stabilized for 6 months and then randomly continued the same medication or placebo for 6 months. RESULTS: Several baseline differences suggested that patients who entered the discontinuation trial on a regimen of phenelzine were more chronically depressed than the imipramine-treated patients. Survival analysis showed a marked advantage for phenelzine relative to placebo. In addition, patients switched to placebo from phenelzine experienced a recurrence of depressive symptoms significantly more often than patients switched to placebo from imipramine. Patients maintained with imipramine did not have lower relapse rates than those switched from imipramine to placebo. Recurrence rates were 23% for patients maintained on a regimen of phenelzine, 41% for those maintained on a regimen of imipramine, 47% for those switched from imipramine to placebo, and 87% for placebo-treated patients originally treated with phenelzine. CONCLUSIONS: Patients with chronic atypical depression are at high risk of recurrence if phenelzine is withdrawn 6 months after initial improvement. Similar findings were not demonstrated for imipramine; this replicates acute trials demonstrating imipramine's relative ineffectiveness in patients with atypical depression. Differences in recurrence rates after the switch to placebo from phenelzine and imipramine could be due to the two drugs' different mechanisms of action or to baseline differences in the two populations.
Adult↗
Divalproex treatment of disruptive adolescents: a report of 10 cases.
BACKGROUND: To report an open trial of divalproex sodium in 10 adolescents with chronic temper outbursts and mood lability. METHOD: Ten adolescents meeting screening criteria for chronic temper outbursts and mood lability were followed for 5 consecutive weeks on open divalproex sodium treatment. Temper outburst frequency and mood swings severity at pretreatment and posttreatment were compared by using paired t tests. Subjects continued to be followed to judge persistence of response. RESULTS: All subjects showed clear improvement at 5 weeks and maintained it during follow-up while taking medication. Rapid relapse and recovery occurred in 5 of 6 patients who discontinued and then resumed medication. CONCLUSION: Divalproex sodium may be helpful in teenagers who have explosive tempers and severe mood swings, and benefits may generalize to school and family life.
Adolescent↗
Imipramine treatment of alcoholics with primary depression: A placebo-controlled clinical trial.
BACKGROUND: Depressive disorders are commonly comorbid with alcoholism, particularly in treatment-seeking samples. If antidepressant treatment were safe and improved the treatment outcome in the subset of actively drinking alcoholics with depression, this would be of clinical importance. METHODS: We conducted a randomized, 12-week placebo-controlled trial of imipramine hydrochloride combined with weekly relapse prevention psychotherapy. The subjects were 69 actively drinking alcoholic outpatients with current depressive disorders. The first onset of depression was either antecedent to the abuse of alcohol or occurred during prolonged periods of sobriety. Depression and drinking outcomes at 12 weeks, as well as their relationship, were measured. RESULTS: Imipramine treatment was safe and associated with improvement in depression in both adequately treated and intention-to-treat samples. While there was no overall effect on drinking outcome, patients whose mood improved showed decreased alcohol consumption that was more marked in those treated with imipramine. CONCLUSIONS: Imipramine treatment is effective for primary depression among actively drinking alcoholic outpatients, and may improve alcoholic outcome for those whose depression responds to treatment.
Adult↗
Chronological milestones to guide drug change. When should clinicians switch antidepressants?
BACKGROUND: We attempt to identify the time when patients whose conditions are unimproved while receiving antidepressants are unlikely to respond and should have their treatment changed. METHODS: A total of 593 patients were studied. The course of treatment for patients was examined to determine the weeks at which patients who received drug therapy had a better chance of being rated as responders at the study end (week 6) vs patients who received placebo. RESULTS: At the end of week 3, 19 (32%) of the 59 patients who received drug therapy and 6 (10%) of the 57 patients who received placebo and who never minimally improved were rated as responders at week 6. For those who showed no improvement by week 4, the effects of drug therapy and the placebo were equal. Patients who received drug therapy and whose conditions were unimproved but who had been minimally improved at some point had a superior prognosis with drug therapy vs placebo until week 4. Of those unimproved at week 4 but minimally improved at some point previously, 20 (39%) of the 51 patients who received drug therapy vs 3 (8%) of the 36 patients who received placebo were rated as responders at week 6. Of the 75 patients who minimally improved while receiving drug therapy at the end of week 5, 33 (44%) had a chance of being rated a responder at the end of week 6 vs 9 (26%) of the 35 patients receiving placebo. CONCLUSIONS: Patients tolerant of an adequate dose, whose conditions have never been at least minimally improved by the end of week 4, should have their treatment regimen altered. These patients represented a minority of drug-treated patients in the sample studied (ie, 39/392 [10%]). Patients whose conditions minimally improve at some prior week but not after week 5 should have their treatment changed. Patients whose conditions minimally improve in week 5 should continue treatment until week 6.
Adolescent↗
Six month follow-up of early-onset chronic depression.
BACKGROUND: This study sought to characterize the morbidity and treatment behavior of 49 patients with early-onset chronic depression, 6 months after terminating treatment at a university-based psychopharmacology research clinic. METHOD: Patients with and without early-onset chronic depression were selected to participate in a naturalistic follow-up study. Assessments were conducted blind to patients' histories. Patients' depressive symptoms, psychosocial functioning, and post-discharge treatment histories were assessed. RESULTS: After termination, the mean length of recovery for the sample was 3.6 months. When they left the clinic, 78% (38/49) were euthymic. At follow-up, 37% (14/38) of these had relapsed; while 45% (17/38) remained in remission for 6 months. During the follow-up period, 47% of the patients were on antidepressants. Sixty-three percent of the patients who relapsed, or were depressed when they left the clinic, did not enter treatment, 50% of whom cited insufficient resources as the primary reason for not receiving care. CONCLUSIONS: After leaving a depression research clinic, a substantial portion of patients with early-onset chronic depression remained recovered during a 6-month period, but financial impediments prevented a majority of those who did poorly from entering treatment.
1-Naphthylamine↗
Dichotic listening before and after fluoxetine treatment for major depression: relations of laterality to therapeutic response.
Despite the wide variance in therapeutic response to antidepressants, there are few clinical or biological predictors of treatment outcome. Studies have suggested the possible value of dichotic listening measures of perceptual asymmetry (PA) as predictors of treatment response. This study examined the relation between outcome of fluoxetine treatment and performance on verbal and nonverbal dichotic tests. As part of a multisite study, 86 outpatients with major depression were tested on dichotic fused-words and complex-tones tests both before and during treatment. Fluoxetine responders differed from nonresponders in having greater right-ear (left-hemisphere) advantage for dichotic words and less left-ear (right-hemisphere) advantage for complex tones. There was no change in PA during fluoxetine treatment, which indicates that PA differences between treatment responders and nonresponders are stable (trait) characteristics. An aggregate, characteristic PA measure was the best predictor of responder status in a logistic regression analysis. Findings from two clinical centers support the hypothesis that a characteristic tendency for relatively greater left-than right-hemispheric activation during dichotic listening is associated with better outcome of fluoxetine treatment.
Acoustic Stimulation↗
Can the effects of antidepressants be observed in the first two weeks of treatment?
Recently the claim that there is a lag in the time of onset of antidepressant effects has been questioned. This issue rests on contrasting the time course of ultimate responders versus nonresponders on imipramine and amitriptyline. It is concluded that in 1 week on antidepressants "clinicians were capable of detecting changes in general states between the groups and the specific effects of depressed mood and anxiety and the physical expression of distress" (Katz et al. 1987). To examine this issue, we first used the design in which ultimate responders and ultimate nonresponders to antidepressants were compared at 1 and 2 weeks. Clearly there were statistically significant differences between ultimate responders and nonresponders on drug. However, the same was true on placebo. When the ultimate responders on placebo were contrasted to the ultimate responders on drug at 1 and 2 weeks using the Clinical global Impression (CGI) scale and the Hamilton Depression Rating Scale (HDRS), there was no difference between drug and placebo. This was also true for a subgroup of patients who met the criteria for melancholia. We conclude that, if the effects of nonspecific improvement are partialed out, there is no evidence of a medication effect at 1 and 2 weeks.
Analysis of Variance↗
Imipramine treatment of cocaine abuse: possible boundaries of efficacy.
A 12-week placebo-controlled, randomized clinical trial was undertaken to evaluate imipramine as a treatment for cocaine abuse, and to examine whether its effect may be limited to subgroups defined by route of use or by diagnosis of depression. One-hundred thirteen patients were randomized, stratified by route of use and depression. All patients received weekly individual counseling. Compared to placebo the imipramine group showed greater reductions in cocaine craving, cocaine euphoria, and depression, but the effect of imipramine on cocaine use was less clear. A favorable response, defined as at least 3 consecutive, urine-confirmed, cocaine-free weeks was achieved by 19% (11/59) of patients on imipramine compared to 7% (4/54) on placebo (P < 0.09). The imipramine effect was greater among nasal users--33% (9/27) response on imipramine vs. 5% (1/22) on placebo (P < 0.02). Response was also more frequent, but not significantly so, among depressed users on imipramine (26%, 10/38) than on placebo (13%, 4/31) (P < 0.19). Response rates were low in intravenous and freebase users and those without depression. Considered together with the literature on desipramine, these data suggest tricyclic antidepressants are not promising as a mainstay of treatment for unselected cocaine abusers. However, tricyclics may be useful for selected cocaine abusers with comorbid depression or intranasal use, or in conjunction with a more potent psychosocial intervention.
Adolescent↗
Brain event-related potentials to complex tones in depressed patients: relations to perceptual asymmetry and clinical features.
Brain event-related potentials (ERPs) to probe tones in a dichotic complex tone test were recorded from right-handed depressed patients (n = 44) and normal subjects (n = 19) at homologous sites over left and right hemispheres (F3, F4; C3, C4; P3, P4; O1, O2). There were no differences between groups N1 or P2 amplitude, but patients had smaller P3 amplitude than did normal subjects. Depressed patients failed to show either the left ear advantage or behavior-related hemispheric asymmetry of P3 seen for normal subjects. Depressed patients also showed less difference in hemispheric asymmetry between same and different judgments. These findings indicate that the abnormal behavioral asymmetry for dichotic pitch discrimination in depressed patients reflects a reduction in hemispheric asymmetry and is related to relatively late stages of cognitive processing.
Acoustic Stimulation↗
A double-blind placebo-controlled comparison of phenelzine and imipramine in the treatment of bulimia in atypical depressives.
Although antidepressants have been found to be superior to placebo in 12 of 14 studies, the relationship between improvement in the depressive diathesis and bulimia is unclear. In this study, the efficacy of placebo, imipramine, and phenelzine is examined in patients comorbid for atypical depression and bulimia. Greater improvement was observed for both depressive and bulimic symptoms with phenelzine than with either imipramine or placebo. Consistent with its poor antidepressant effects in atypical depression, imipramine seemed to have minimal efficacy for the bulimic symptoms of atypical depressives. These data suggest that the presence of bulimia does not alter the treatment response of atypically depressed patients. Furthermore, the data may suggest a link between depression and bulimia in atypical depressives. Demonstrating a statistical difference with a small sample suggests the effect size is robust, however conclusions are limited by a small sample size.
Adult↗
Lithium and tricyclic augmentation of fluoxetine treatment for resistant major depression: a double-blind, controlled study.
Forty-one patients who had failed to respond to 8 weeks of treatment with 20 mg of fluoxetine were randomly assigned to one of three treatments for 4 weeks: 40-60 mg/day of fluoxetine, 20 mg/day of fluoxetine plus 25-50 mg/day of desipramine, and 20 mg/day of fluoxetine plus 300-600 mg/day of lithium. Patients treated with high-dose fluoxetine (N = 15) did significantly better than patients treated with fluoxetine plus lithium (N = 14) and those treated with fluoxetine plus desipramine (N = 12). High-dose fluoxetine was the most effective treatment among partial responders to previous treatment, but high-dose fluoxetine and fluoxetine plus lithium were the most effective treatments among nonresponders.
Adult↗
Gepirone treatment of atypical depression: preliminary evidence of serotonergic involvement.
This is a report of a controlled trial of gepirone, a 5-hydroxytryptamine (5-HT1A) partial agonist azapirone related to buspirone, in the treatment of atypical depression. The azapirones are of particular interest because their highly selective actions on the serotonergic system may possibly make them useful pharmacologic probes and potentially selective therapeutic agents. Sixty outpatients meeting Columbia criteria for definite or probable atypical depression were enrolled in a double-blind, randomized, placebo-controlled, 8-week clinical trial at a single site. The dosage schedule was fixed flexible, with 10-mg capsules given on a thrice-daily schedule, with doses of up to 120 mg daily. The response rate at 8 weeks for the intention-to-treat sample analyzed with the last observation carried forward was 62% (18 of 29 patients) for gepirone and 20% (6 of 30 patients) for placebo (chi 2 = 9.1; df = 1; p < 0.001). Robust and consistent drug-placebo differences are seen across virtually all rating scales post-treatment. The effect of gepirone was consistent across the levels of concomitant variables, including duration of episode and presence of dysthymia or panic. Gepirone is a novel antidepressant that holds promise for the treatment of atypical depression and that may be of heuristic value because of its relatively specific actions on the serotonergic system.
Adolescent↗
Treatment response of depressed outpatients unresponsive to both a tricyclic and a monoamine oxidase inhibitor antidepressant.
BACKGROUND: Data regarding effective treatment options for the minority of patients refractory to initial antidepressant trials are essential to guide therapeutic choices and to sustain the hope of patients and perseverance of clinicians. Few such data are available concerning the treatment of patients refractory to treatment with both a tricyclic antidepressant and a monoamine oxidase inhibitor given singly. METHOD: In a study of mood reactive depressed patients, most of whom met Columbia criteria for atypical depression, 20 patients refractory to vigorous 6-week double-blind trials of both imipramine and phenelzine given singly were given clinician's choice open treatment. A chart review of course in open treatment was conducted. RESULTS: Eleven patients (55%) had a full response to subsequent treatments, principally continued phenelzine and the combination of phenelzine with amitriptyline. Another 6 (30%) had at least moderate benefit from a variety of other treatments. CONCLUSION: These data suggest that even among patients who have failed to respond to two vigorous trials of different antidepressants, at least half appear to benefit from other pharmacologic regimens.
Adult↗
Duration of antidepressant trials: clinical and research implications.
The objective of our study was to demonstrate that additional antidepressant benefit occurs between weeks 4 and 6 in adult outpatients, even when dose is not increased. Response between weeks 4 and 6 was studied among depressed outpatients randomly assigned to imipramine, phenelzine, or placebo under double-blind conditions. Patients were selected for analysis only if they did not have a dose increase after the start of the fourth week of treatment (day 22). Eighty-eight patients met this condition. Conditional probability analysis was performed. Nonresponders to 4 weeks (28 days) of treatment had a significantly greater likelihood of responding by week 6 if they were on phenelzine rather than placebo. The same is probably true for patients on imipramine. In research and clinical care, 4 weeks is too short a trial of phenelzine to conclude a lack of efficacy. Four weeks is probably also too short a trial of imipramine.
Adult↗
A double-blind crossover trial of imipramine and phenelzine for outpatients with treatment-refractory depression.
OBJECTIVE: Data from controlled studies concerning the response rates of patients to a second antidepressant medication after they have been unresponsive to a systematic trial of another antidepressant are extremely useful to clinicians for rational prescription of pharmacotherapy. Such information allows making an accurate prognosis, sustaining realistic hope in the patient, and achieving the best possible therapeutic outcome. This study was designed to add to the scanty literature available on this subject. METHOD: Eighty-nine mood-reactive, nonmelancholic, mainly chronically depressed outpatients at a university research clinic who were unresponsive to vigorous double-blind trials of imipramine or phenelzine were crossed over to treatment with the other drug under double-blind conditions. RESULTS: Of 46 patients previously unresponsive to imipramine who completed phenelzine treatment, 31 (67%) responded to phenelzine. Of 22 patients previously unresponsive to phenelzine who completed imipramine treatment, nine (41%) responded to imipramine. The difference in response rates was statistically significant. Even after they had shown no response to 7 weeks of placebo and 6 weeks of imipramine treatment, 10 (83%) of 12 patients who then completed treatment with phenelzine responded. CONCLUSIONS: These data suggest that among chronically ill, mood-reactive depressed patients with many symptoms of atypical depression, phenelzine is strikingly effective in those who have been nonresponders to imipramine and should be tried in such patients.
Adult↗
Loss of drug effects during continuation therapy.
OBJECTIVE: This study sought to determine what proportion of relapses during continuation therapy with antidepressants can be attributed to loss of nonspecific placebo effects while the patients are taking the drugs. METHOD: Depressed patients were studied over a 12-week period. One hundred sixty-four patients were randomly assigned to placebo, 174 to imipramine, and 169 to phenelzine. At 6 weeks 35 were judged to be responders to placebo, 70 to imipramine, and 96 to phenelzine. These patients continued their double-blind treatment for weeks 7-12. RESULTS: Thirty-one percent of the patients who were taking placebo, approximately 12% who were taking imipramine, and approximately 9% who were taking phenelzine relapsed in the 7- to 12-week phase. Two different methods of estimating relapses suggested that during the first 3 months of treatment, a large percentage of the relapses of patients taking drugs was attributable to the loss of nonspecific placebo effects rather than true drug effects. CONCLUSIONS: A considerable proportion of relapses in the first 3 months of treatment with antidepressants appears to be due to loss of placebo effects. These clinically relevant data may be used to encourage patients who relapse during this period, and who erroneously conclude that anti-depressant effects are temporary, to try another medication.
Antidepressive Agents↗