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Biomedical subjects

F M Quitkin

Publications and source records attributed to F M Quitkin.

At least 73 records · Page 4Linked to original sources
PubMed1993

Chronic depression: response to placebo, imipramine, and phenelzine.

We reanalyzed data from a larger, previously published study in order to directly address whether very chronically depressed patients could benefit from antidepressant medications. This study entered 598 depressed patients into a study randomizing patients to 6 weeks of double-blind treatment with imipramine, phenelzine, or placebo. Patients were assessed for chronicity on a four-point scale from "mostly well" to "virtually always depressed." The current analyses include only the 153 study completers who were rated as "virtually always depressed." In these patients, imipramine was effective for significantly more patients than was placebo (22 [46%] of 48 responding to imipramine vs. 9 [17%] of 52 responding to placebo; chi 2 = 9.50; p = 0.002), whereas phenelzine was significantly more effective than imipramine (37 [70%] of 53 responding to phenelzine; chi 2 = 5.96; p = .015). Patients with mild depression, early onset, or histories of panic attacks did not have substantially different outcomes than patients without these characteristics. These findings suggest that some chronically depressed patients may be good candidates for treatment with antidepressant medication. Because the majority (80%) of the sample met Columbia criteria for definite or probable atypical depression, too few chronic depressives were available to evaluate separately antidepressant efficacy in chronically depressed outpatients who did not have atypical depression. Hence, these results may be applicable only to patients with atypical depression.

Adult↗
PubMed1993

Columbia atypical depression. A subgroup of depressives with better response to MAOI than to tricyclic antidepressants or placebo.

We summarise a series of studies using a MAOI to help establish the validity of a subgroup of depressives referred to as atypical depressives. Patients with reactive mood meeting DSM-III criteria for depressive illness who had associated atypical features (which include hyperphagia, hypersomnolence, leaden paralysis, and rejection sensitivity) were randomised to imipramine, phenelzine and placebo. Non-responders were crossed over, and in all there were over 400 patient trials. Phenelzine consistently was found to be superior to imipramine. Only in trials which included patients lacking atypical, vegetative symptoms was imipramine found to equal phenelzine. We conclude that the researcher and the clinician should consider the relevance of the atypical depressive syndrome.

Antidepressive Agents, Tricyclic↗
PubMed1993

[Impact of personality factors in depression].

Patients meeting criteria for borderline personality disorder are heterogeneous. Our studies suggest that at least two sub-types exist which benefit from specific treatments. Data will be presented which suggests that some patients who meet borderline criteria and have atypical depression (patients meeting DSM III-R criteria for major depression or dysthymia reactive wills mood and any vegetative atypical symptoms, i.e. overeating, oversleeping, rejection sensitivity, leaden paralysis) clearly benefit from treatment with antidepressant medication. Although some patients with atypical depression who meet borderline criteria will improve with tricyclic therapy, a significantly greater proportion will improve with the monoamine oxidase inhibitor (MAOI) phenelzine if they suffer from atypical depression. The validity of emotionally unstable character disorder (EUCD) will also be examined. Patients with this disorder frequently meet criteria for borderline character disorder. The validity of this sub-group is supported by the presence of neurological soft signs, their negative response to anti-depressants, and their positive response to chlorpromazine and lithium.

Antidepressive Agents↗
PubMed1993

Atypical depression. A valid clinical entity?

The history of atypical depression is summarized, and the results of several treatment outcome studies are reviewed. A number of clinical course, family, and biologic variables in patients with atypical depression are investigated, and these patients are compared with patients with other depressive conditions. The Atypical Depression Diagnostic Scale Question Book also is presented.

Antidepressive Agents↗
PubMed1993

Imipramine is effective after unsuccessful cognitive therapy: sequential use of cognitive therapy and imipramine in depressed outpatients.

As a partial test of whether the same or different patients benefit from cognitive therapy and tricyclic antidepressant agents, depressed outpatients first received cognitive therapy, then nonresponders were treated with either imipramine or placebo. If the two treatments were effective for the same subgroup of patients, imipramine should not be more effective than placebo because potential responders should already have been removed by treatment with cognitive therapy. Alternatively, if cognitive therapy and imipramine are effective for different subtypes of depressive disorder, then imipramine ought to be more effective than placebo for patients failing to benefit from cognitive therapy because some potential imipramine failures would already have been removed. Thirty-six depressed outpatients were treated with weekly cognitive therapy for 16 weeks with 17 (47%) responding. Nonresponders were then randomly assigned to imipramine or placebo for 6 weeks to a maximum dose of 300 mg of imipramine per day. Of 12 patients completing the double-blind medication trial, all 5 assigned to imipramine had a clear-cut response, whereas none of the other seven benefited from placebo (chi 2 = 12.00; p = 0.001). Although the numbers are small, these results suggest rejection of the hypothesis that imipramine is effective for the same subpopulation of depressed patients as is cognitive therapy.

Adult↗
PubMed1992

Abnormal cerebral laterality in bipolar depression: convergence of behavioral and brain event-related potential findings.

Cerebral laterality in bipolar and unipolar major depression was compared using visual half-field and dichotic listening measures of perceptual asymmetry. The results replicate our prior finding of abnormal laterality in bipolar depressed patients on a visuospatial test. Bipolar patients (n = 11) failed to show the left visual field (right hemisphere) advantage for dot enumeration seen for both unipolar patients (n = 43) and normal controls (n = 24). Bipolar patients performed significantly poorer than unipolar patients on normal controls for left visual field, but not right visual field stimuli. An electrophysiological correlate of abnormal visual field asymmetry in bipolar depression was found in brain event-related potentials recorded during audiospatial and temporal discrimination tasks. Bipolar patients had smaller N100 amplitudes for test stimuli in the left than right hemifield, whereas unipolar patients and normals did not. The origins of left hemifield deficits in bipolar depression are discussed in terms of right-sided dysfunction of an arousal/attentional system involving temporoparietal and possibly frontal regions.

Adolescent↗
PubMed1992

Methodology of measuring the efficacy of antidepressants.

Evaluation of the efficacy of antidepressant agents needs to take into account factors which increase the "effect size", such as dosage, treatment duration, the use of two-phase trials, and pattern analysis of responders. Although many patients are thought to receive inadequate doses of antidepressants, relatively few dose-response studies have been performed. However, trials of both tricyclic antidepressants and phenelzine have shown that statistically significant improvements in outcome result from the use of higher dosages; the length of treatment may also affect results. In some studies, the proportion of patients showing a clear-cut response increased significantly among patients treated with active drug instead of placebo when the treatment period was extended from 4 to 6 weeks, independent of the dose used. There may thus be a distinct advantage in extending trials of antidepressants for a minimum of 6 weeks. Two-phase drug trials can be used to extend the trial period still further in responding patients, to emphasize the contrast between treatment and placebo effects and to eliminate type-2 errors. Twelve-week trials might increase the statistical power of the evaluation by 10-20%, in studies where the drug effect size is small. Pattern analysis of the timing and duration of patients' responses has been shown to aid the distinction of true responses from non-specific or placebo effects, and may be useful for evaluating data from studies of antidepressant agents which yield ambiguous results.

Antidepressive Agents↗
PubMed1992

Review of the use of pattern analysis to differentiate true drug and placebo responses.

Placebo response in patients assigned active drug is a troubling source of variance in antidepressant studies. This paper summarizes a series of studies utilizing pattern analysis to distinguish between placebo and true drug responses. Analysis of the persistence, speed, and timing of onset of patients' improvement during antidepressant therapy reveals distinct patterns of response which are likely to be attributable to placebo and true drug effects. While true drug effects seem to be characterized by a 2-week delay in onset followed by persistent improvement, placebo effects seem to be characterized by abrupt, transient improvement. Gradual responses on placebo may be due to spontaneous remission. The heuristic and clinical implications of pattern analysis are discussed.

Adolescent↗
PubMed1992

Can mildly depressed outpatients with atypical depression benefit from antidepressants?

OBJECTIVE: The authors' goal was to explore the efficacy of antidepressant medications in outpatients with mild depression. METHOD: Four hundred one outpatients were diagnosed as depressed by DSM-III criteria. Atypical Depression Diagnostic Scale criteria were also applied to these patients; these criteria require reactivity of mood plus two of four associated features, including hypersomnia, hyperphagia, leaden paralysis, and pathological sensitivity to rejection. All patients were then randomly treated for 6 weeks with up to 300 mg/day of imipramine, up to 90 mg/day of phenelzine, or placebo. Outcome at 6 weeks was determined by clinical global improvement ratings. The outcomes of patients with entry Hamilton Rating Scale for Depression scores in the low (scores of 12 or lower), medium (scores of 13-15), and high (scores above 16) range were compared. RESULTS: The majority (N = 332, 83%) of the 401 depressed patients had definite or probable atypical depression. Among the 140 patients who had low pretreatment Hamilton scale scores, 19 (33%) of 57 given placebo, 25 (60%) of 42 given imipramine, and 34 (83%) of 41 given phenelzine responded. Each of the antidepressants was superior to placebo. Similar findings applied to the patients with medium and high Hamilton scale scores, except that the rates of placebo response were lower (29% and 10%, respectively). CONCLUSIONS: These data support the use of antidepressant medication for some mildly depressed patients, at least if they have atypical depression. Too few patients were included who did not have atypical depression to draw conclusions about such patients.

Adolescent↗
PubMed1992

The pharmacotherapy of minor depression.

Although the literature appears to demonstrate the efficacy of standard antidepressant medications for the short-term treatment of patients with minor depression, they are not widely prescribed. In comparison, psychotherapy is generally recommended, but without convincing data to support this conviction. We, therefore, advocate successive trials with antidepressants in any depressed patient, particularly if they have failed to benefit from psychotherapy or other supportive measures for three months.

Antidepressive Agents, Tricyclic↗
PubMed1992

A pilot sequential study of cognitive therapy and pharmacotherapy of atypical depression.

BACKGROUND: Parallel comparison studies of cognitive therapy and antidepressant medication have suggested that both treatments are effective. However, we cannot determine from these studies whether cognitive therapy and antidepressant medication are effective for the same populations of depressives. A sequential study in which nonresponders to the first treatment are then treated with the second can address this issue. METHOD: Twenty-seven patients meeting DSM-III criteria for major depression or dysthymic disorder and Columbia criteria for atypical depression received cognitive therapy followed by antidepressant medication for cognitive therapy nonresponders. A response rate with the second treatment equal to that expected with placebo would suggest both treatments target the same depressive population. RESULTS: Of the 25 completers of the study, 14 (56%) were judged responders to cognitive therapy alone. Sixty-nine percent (9/13) of the responders maintained their benefits for 6 months or more. Seven of the 11 cognitive therapy nonresponders (63%) responded to antidepressant medication. These results were compared with those of a concurrent double-blind medication study; both its sample and ours were drawn from the same population at the same time: cognitive therapy and antidepressant medication response rates were higher than expected with placebo (28%). CONCLUSION: The results suggest that (1) cognitive therapy and antidepressant medication are effective treatments for differing populations of depressed patients, as the antidepressant medication response of cognitive therapy nonresponders was greater than expected with placebo, and (2) cognitive therapy has a lasting effect.

Adult↗
PubMed1992

Predictive value of symptoms of atypical depression for differential drug treatment outcome.

Data for 401 depressed outpatients with mood reactivity who participated in a randomized trial comparing placebo, imipramine, and phenelzine were analyzed for predictors of differential response by stepwise multiple regression techniques. Features of the Columbia criteria for atypical depression including oversleeping, overeating, severe anergy, and pathologic rejection sensitivity were each predictive of a poorer response to imipramine than to phenelzine only when compared to those patients with none of the features. These features were not additive in their contribution to differential outcome. Lack of endogenous features was not predictive of a differential drug treatment response. Compared with patients who have no symptoms of atypical depression, patients with any of the four features had an inferior imipramine response rather than a superior phenelzine response. These analyses indicate that the clear differential responsivity to medication treatment in atypical depression is not simply related to any one defining symptom and that further correlates of this apparent biological heterogeneity need to be explored.

Adult↗
PubMed1991

Event-related potentials in depression: influence of task, stimulus hemifield and clinical features on P3 latency.

P3 latency, a brain event-related potential (ERP) correlate of stimulus evaluation time, was measured in 25 unmedicated depressed patients and 27 normal controls during auditory temporal and spatial discrimination tasks. Patients were divided into two subgroups, one having a typical major depression (melancholia or simple mood reactive depression) and one having an atypical depression. Typical depressives had abnormally long P3 latency for the spatial task but not the temporal task. They also showed an abnormal lateral asymmetry, with longer P3 latency for stimuli in the right hemifield than the left. In contrast, atypical depressives did not differ from normals in either respect. Longer P3 latency correlated with ratings of insomnia, while abnormal lateral asymmetry correlated with reduced right visual field advantage for syllables. The P3 latency findings point to a task-related slowing of perceptual decisions in a subgroup of depression.

Adjustment Disorders↗
PubMed1991

Response to phenelzine and imipramine in placebo nonresponders with atypical depression. A new application of the crossover design.

We employed a study design that permitted a double-blind 12-week contrast of imipramine hydrochloride and phenelzine sulfate therapies in patients who met Columbia University criteria for atypical depression and were unresponsive to 7 weeks of treatment with placebo. These patients were found to benefit selectively from therapy with monoamine oxidase inhibitors compared with tricyclic drug therapy. This supports our observation about treatment response in depressed patients with reversed vegetative features. The design we utilized in this study has not previously been reported, to our knowledge. It was hypothesized that it would offer the advantage of the removal of a portion of placebo responders and serve to replicate our original findings. Treatment response to therapy with both imipramine and pheneizine in placebo nonresponders was uniformly lower (roughly 20% less than corresponding rates for patients who did not participate in the initial 6-week placebo trial). This is consistent with the view that the lower response rates were a result of the removal of some "placebo" responders in the drug groups. We think this is a useful design that should be considered in all studies of placebo and two active treatment regimens.

Adult↗
PubMed1991

Life satisfaction and psychosocial functioning in chronic depression: effect of acute treatment with antidepressants.

Social functioning was evaluated in 61 chronically depressed adults with early onset. Patients were treated for 6 weeks in a double-blind trial of phenelzine, imipramine, L-deprenyl, or placebo and functioning was reassessed. The posttreatment social functioning of patients who received drug treatment was superior to the placebo group in the following areas: work functioning, house functioning, relationship with relatives, sex frequency and life satisfaction. These results suggest that psychosocial impairment in some chronic depressives may be a sequaela of depression, rather than a global manifestation of characterological pathology.

Activities of Daily Living↗
PubMed1991

Heterogeneity of clinical response during placebo treatment.

OBJECTIVE: The authors attempted to identify different patterns of improvement among patients receiving placebo during clinical trials. It was hypothesized that patients who improved abruptly would differ from patients whose improvement was gradual in that they would tend to improve earlier and would tend to have less persistent improvement. METHOD: The subjects were 144 patients who met the DSM-III criteria for depressive illness and were randomly assigned to placebo medication in four double-blind antidepressant drug trials. All studies lasted 6 weeks. Mood change was rated each week on a 7-point scale; a rating of 1 or 2 was considered an indication of improvement. Improvement was judged to be abrupt if the first score of 1 or 2 was immediately preceded by a score of 4 or worse, and it was classified as gradual if the first score of 1 or 2 was preceded by a score of 3 in at least 1 week. Improvement was considered persistent if a score of 1 or 2 was not followed by a score of 3 or worse in any subsequent week. RESULTS: Of the 144 patients, 72 showed clinical improvement during at least one weekly visit; 33 improved abruptly and 39 improved gradually. The abrupt improvements occurred significantly earlier in the trial and were less likely to persist than the gradual improvements regardless of when they occurred. CONCLUSIONS: These data suggest that among patients receiving placebo abrupt improvements are a form of placebo response and gradual responses may be the result of spontaneous remission. These preliminary observations require validation.

Adolescent↗
PubMed1991

Different types of placebo response in patients receiving antidepressants.

OBJECTIVE: The authors studied the responses of drug-treated patients in an attempt to validate observations about abrupt and gradual improvements in patients receiving placebo. Since previous data suggested that in the first 2 weeks of antidepressant treatment specific drug effects are unlikely, the authors hypothesized that this improvement is a placebo effect. Therefore, in the first 2 weeks of antidepressant treatment abrupt and gradual improvements should have the characteristics of their placebo counterparts. METHOD: The subjects were 263 patients in controlled antidepressant trials lasting 6 weeks. RESULTS: The percentage of abrupt improvements that occurred in the first 2 weeks was higher than that for gradual improvements. Abrupt improvements during the first 2 weeks of drug treatment were also less persistent than gradual improvements with drug and no more persistent than improvements with placebo during the same period. However, in weeks 3, 4, and 5, abrupt and gradual improvements with drug were equally persistent and both were more persistent than abrupt improvements with placebo. CONCLUSIONS: These data support the authors' findings about placebo. Abrupt improvements during treatment with both drug and placebo are more likely during the first 2 weeks of treatment and are less likely to persist than gradual improvements. The fact that persistence of abrupt improvements with drug in weeks 1 and 2 appears different from that of gradual improvements but appears no different after week 3 suggests that the mechanism of action of abrupt improvement with drug changes after week 2.

Adolescent↗