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Biomedical subjects

F M Quitkin

Publications and source records attributed to F M Quitkin.

At least 55 records · Page 3Linked to original sources
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

Treating anxiety in patients with alcoholism.

The clinical management of patients who present with anxiety syndromes combined with alcohol abuse or dependence is reviewed. A critical step is to make the differential diagnosis between alcohol-induced anxiety (principally alcohol withdrawal) and anxiety disorders per se. Interview and examination techniques useful in making this differential are presented. Clinical management of and pharmacotherapy for alcohol withdrawal are outlined. Anxiety disorders that can be comorbid with alcoholism include panic disorder, social phobia, obsessive compulsive disorder, generalized anxiety disorder, and posttraumatic stress disorder. Psychotherapeutic and pharmacotherapeutic measures for each of these in the setting of alcoholism are suggested, and various possible interrelationships between anxiety disorders and alcoholism are considered. Although anxiety disorders may contribute to the underlying etiology of alcoholism in some cases, alcohol abuse tends to take on a life of its own. Treatment of an anxiety disorder can rarely, if ever, be expected to cure alcoholism. Therefore, the need to institute simultaneous treatment aimed at establishing and maintaining sobriety is emphasized. Research on anxiety disorders and alcoholism is as yet inadequate to fully answer many clinical questions about their relationship and their appropriate diagnosis and management. More research is needed in this area.

Adolescent↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

Norms for depressed patients for the California verbal learning test: associations with depression severity and self-report of cognitive difficulties.

This study provides norms for depressed subjects for a widely used test of verbal memory, the California Verbal Learning Test (CVLT). Subjects were 156 outpatients with major depression tested during a drug washout period. Mean CVLT memory scores for these patients were generally between one-half and one standard deviation below age- and sex-corrected norms for nondepressed populations. Severity of depression in the patients was not associated with memory performance, but was associated with self-report of cognitive difficulties. A table of age-, sex-, and education-specific norms for the CVLT is provided.

Journal Article↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

Further evidence that a placebo response to antidepressants can be identified.

OBJECTIVE: The authors' goal was to analyze the acute phase of antidepressant drug treatment to identify placebo responses. METHOD: Patients rated as improved after 6 weeks of double-blind treatment with imipramine or phenelzine were followed for an additional 6 weeks of double-blind treatment. Initial responses were classified according to the speed of improvement (abrupt or gradual), the persistence or nonpersistence of improvement, and the timing of improvement (early or late onset). RESULTS: It was predicted that patients with nonpersistent, abrupt responses to the drugs were actually experiencing a placebo response and would have the worst prognosis. In fact, this group accounted for a disproportionate number of the relapses. Nonpersistent responders to a drug had a 23.7% relapse rate, but persistent responders had only a 9.0% relapse rate, a significant difference. CONCLUSIONS: The authors conclude that a significant proportion of relapses within the first 6 weeks of treatment with an active drug are not related to loss of a true drug effect. Rather, some are related to loss of nonspecific placebo effects, and abrupt nonpersistent responses during drug treatment are most likely the result of placebo effects.

Antidepressive Agents↗
PubMed1993

Imipramine treatment of alcoholism with comorbid depression.

Of 60 depressed alcoholics who completed an open trial of imipramine, 27 (45%) responded with improvement in both mood and drinking behavior, and eight (13%) responded after further dosage increases or treatment with disulfiram. In a subsequent 6-month, randomized discontinuation trial, four of 13 subjects (31%) relapsed during imipramine treatment and seven of 10 (70%) relapsed while taking placebo. This suggests a potential treatment approach for a high-risk subgroup of alcoholics.

Adult↗