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Biomedical subjects

F M Quitkin

Publications and source records attributed to F M Quitkin.

At least 37 records · Page 2Linked to original sources
PubMed1999

Placebos, drug effects, and study design: a clinician's guide.

OBJECTIVE: This article examines the role of placebos in evaluating the efficacy of psychiatric drugs. Also addressed are the identification of placebo effects on drugs, the relevance of active placebo, the need for placebo groups in psychotherapy studies, and ethical issues concerning the use of placebo. METHOD: Psychiatric drug treatment trials were reviewed. Emphasis was placed on studies with ambiguous outcomes, studies using an active placebo, and studies attempting to understand the role of placebo effects on patients receiving a drug. The concept of pattern analysis for identifying true drug effect is reviewed. RESULTS: Evidence that placebos are required to prevent a false conclusion about drug efficacy is presented. The public health implications of concluding that an ineffective drug is beneficial are examined. Active placebos do not appear necessary, and there is some evidence that the odds of identifying a patient who has improved as a result of true drug effect (as opposed to placebo effect) exceed chance with pattern analysis. CONCLUSIONS: Psychiatric disorders have a fluctuating course, psychiatry's phenomenologically based nosological system is inexact, and the interaction between these two leads to a large proportion of patients experiencing a placebo effect. It may be possible to identify patients receiving an antidepressant who improved as a result of a placebo effect. This is an educated guess that may be helpful in planning the treatment of patients who have a contraindication to continuing a psychopharmacological regimen.

Anxiety Disorders↗
PubMed1999

Changes in weight during a 1-year trial of fluoxetine.

OBJECTIVE: Fluoxetine has been associated with weight loss during acute treatment, but no controlled studies of weight change during long-term treatment with fluoxetine or other selective serotonin reuptake inhibitors have been reported. Weights were assessed for patients whose depressive symptoms had disappeared with acute fluoxetine treatment. Patients were then randomly assigned to continuation treatment with fluoxetine or placebo. METHOD: Patients whose illness had remitted after 12 weeks of treatment with fluoxetine, 20 mg/day, were randomly assigned to receive up to 38 weeks of treatment with fluoxetine or placebo. Weight was assessed at each visit. Change in weight was analyzed during the initial 12 weeks of acute treatment and after 14, 26, and 38 weeks. Relationships between weight change and body mass index and between weight change and appetite change were assessed. RESULTS: During the initial 4 weeks of therapy, a mean absolute weight decrease of 0.4 kg was observed for all patients. Among patients who completed 50 weeks of therapy, the mean absolute weight increase during continuation treatment was similar for both the placebo- and fluoxetine-treated groups. Weight increase was not related to initial body mass index but was related to both poor appetite at study entry and to improvement in appetite after recovery. No patients discontinued therapy because of weight gain. CONCLUSIONS: Acute therapy with fluoxetine is associated with modest weight loss. After remission of depressive symptoms, weight gain for patients taking fluoxetine for longer periods is not different from that for patients taking placebo and is most likely related to recovery from depression.

Adult↗
PubMed1999

Changes in adverse events reported by patients during 6 months of fluoxetine therapy.

BACKGROUND: Although a period of 6 to 12 months of antidepressant therapy is recommended for most patients with depression, systematic examinations of the course of adverse events over time, the resolution of early-onset events, and the possible emergence of later-onset events are limited. We examined the safety of fluoxetine, 20 mg/day, in a large, prospective, long-term treatment trial, and we report a comparison of early- and late-onset adverse events and the course of adverse events over 26 weeks of treatment. METHOD: Adverse events were recorded at each visit in a uniform format by open-ended questioning, regardless of perceived causality. New or worsened events reported in either the first 4 weeks of treatment (early-reporting interval) or weeks 22 through 26 of treatment (late-reporting interval) were compared. RESULTS: Patients (N = 299) whose depression (DSM-III-R) remitted with 12 weeks of fluoxetine treatment entered continuation therapy, and 174 completed 26 weeks of therapy. All events that occurred in > or =5% of patients early in treatment decreased in frequency over time (p<.05), and no events occurred significantly more frequently during continuation therapy. No previously uncommon adverse events became common during long-term treatment. CONCLUSION: Common adverse events associated with initiating fluoxetine treatment in depressed patients, including nausea, insomnia, nervousness, and somnolence, resolve in the majority of patients and become significantly less frequent with continued treatment over a 6-month period. No adverse events present initially become more frequent late in treatment. Therapy with fluoxetine, 20 mg/day, is well tolerated over 6 months, and most adverse events observed early in treatment resolve.

Anxiety↗
PubMed1998

Imipramine treatment of opiate-dependent patients with depressive disorders. A placebo-controlled trial.

BACKGROUND: The literature is inconclusive on the role of antidepressant medications in treating drug dependence. Studies have either not focused on depressed patients or have selected patients with depressive disorders based on cross-sectional symptoms rather than a syndromal diagnosis. A clinical trial of an antidepressant was, therefore, conducted on drug-dependent patients with syndromal depression. METHODS: Patients receiving methadone hydrochloride maintenance treatment were selected if they met the criteria for a DSM-III-R depressive disorder that was chronologically primary, had persisted during a past abstinent period or was long-standing, and persisted during at least 1 month of stable methadone treatment. Subjects were randomized to a 12-week, double-blind, placebo-controlled trial of imipramine hydrochloride. A favorable response was defined as a Clinical Global Impression scale score for depression of 2 ("much improved") or 1 ("very much improved") and at least a 75% reduction in self-reported drug or alcohol use or abstinence. RESULTS: One hundred thirty-seven patients were randomized, and 84 completed a minimum adequate trial of at least 6 weeks. Among the 84 adequately treated patients, 57% (24/42) receiving imipramine were rated as responders compared with 7% (3/42) receiving placebo (P < .001). On measures of mood, there was a robust effect of imipramine. Imipramine was superior to placebo on some self-reported measures of substance use and craving, and mood improvement was associated with improvement in self-reported substance use. However, few patients achieved urine-confirmed abstinence. CONCLUSIONS: Imipramine was an effective antidepressant in patients receiving methadone who were selected via syndromal criteria for depressive illness. Imipramine may reduce substance abuse among patients whose mood improves; however, this effect was less robust.

Adult↗
PubMed1998

Use of pattern analysis to predict differential relapse of remitted patients with major depression during 1 year of treatment with fluoxetine or placebo.

BACKGROUND: Delayed and persistent ("true drug") improvement characterizes the response to antidepressant medication. Early or nonpersistent ("placebo") benefit is typical of a placebo response. The prediction was that patients with a true drug response would sustain their benefit best if they continued to receive the drug and that patients with a placebo response would have an equivalent prognosis whether they continued to receive the drug or were switched to placebo. METHODS: Patients with major depression who met the study's response criteria (a modified Hamilton Depression Rating Scale score < or =7 and failure to meet major depression criteria after each of the last 3 weeks following 12 to 14 weeks of treatment with fluoxetine hydrochloride, 20 mg/d) were enrolled in a 50-week randomized placebo substitution trial during which the return of depressive symptoms defined relapse. The timing and persistency of response during initial treatment defined true drug or placebo response patterns. RESULTS: Patients with a true drug response pattern relapsed significantly more frequently if they were switched to placebo than if they continued to receive fluoxetine (P<.001 for weeks 12-26, P<.005 for weeks 26-50, and P<.41 for weeks 50-62). Patients with a placebo response pattern had an equivalent outcome whether maintained on fluoxetine therapy or placebo (P< .20 for weeks 12-26, test invalid for weeks 26-50, and P<.67 for weeks 50-62). Patients with a placebo response pattern relapsed more often when they continued to receive fluoxetine than patients with a true drug response pattern (P<.01 for weeks 12-26, P<.10 for weeks 26-50, and P<.36 for weeks 50-62). CONCLUSIONS: These findings confirm that pattern analysis validly differentiates true drug from nonspecific initial responses and extend its use to the continuation and maintenance phases of treatment for depression. Investigations into the mechanisms of antidepressant activity might best be limited to those that can account for delayed efficacy. Fluoxetine's efficacy during the continuation and maintenance phases of treatment may be limited to patients with a true drug pattern of initial response.

Adolescent↗
PubMed1998

Efficacy and safety of fluoxetine in treating bipolar II major depressive episode.

As many as 45% of patients with major depressive episode also meet DSM-IV criteria for bipolar II (BP II) disorder. Although some clinicians advocate using a mood stabilizer in treating BP II depression, antidepressant monotherapy has been less well studied in this disorder. As part of a prospective, placebo-controlled, relapse-prevention study in 839 patients, the efficacy and safety of short- and long-term fluoxetine treatment in patients with BP II major depression compared with patients with unipolar (UP) major depression was retrospectively examined. Eighty-nine BP II patients (mean age, 41+/-11 years) were compared with 89 age- and gender-matched UP patients and with 661 unmatched UP patients (mean age, 39+/-11 years). All received short-term fluoxetine therapy at 20 mg daily for up to 12 weeks. Complete remission was defined as a final Hamilton Rating Scale for Depression score < or = 7 by week 9 that was then maintained for 3 additional weeks. Remitted patients were then randomly assigned to receive double-blind treatment with one of the following: (1) fluoxetine 20 mg daily for 52 weeks; (2) fluoxetine for 38 weeks, then placebo for 14 weeks; (3) fluoxetine for 14 weeks, then placebo for 38 weeks; or (4) placebo for 52 weeks. Antidepressant efficacy was similar in BP and UP patients during short-term therapy. Discontinuation for lack of efficacy was lower in BP II (5%) than in UP (12%) patients (p = not significant [NS]), whereas dropouts for adverse events were similar in BP II (11%) and UP (9%) patients. During long-term relapse-prevention therapy, relapse rates were similar in BP II and UP patients (p = NS). During short-term fluoxetine therapy, three BP II (3.8%) versus no matched UP (p = NS) and 0.3% unmatched UP (p = 0.01) patients had a "manic switch." During long-term fluoxetine therapy, one (2%) BP II and three (1%) unmatched UP patients (one taking placebo) had a manic switch (p = NS). In conclusion, fluoxetine may be a safe and effective antidepressant monotherapy for the short-term treatment of BP II depression with a relatively low manic switch rate. Fluoxetine may also be effective in relapse-prevention therapy in patients with BP II disorder.

Adolescent↗
PubMed1998

Optimal length of continuation therapy in depression: a prospective assessment during long-term fluoxetine treatment.

OBJECTIVE: The purpose of this study was to determine prospectively the optimal length of therapy in a long-term, placebo-controlled continuation study of patients who responded to acute fluoxetine treatment for major depression (defined by DSM-III-R). METHOD: The study was conducted at five outpatient psychiatric clinics in the United States. Patients who met criteria for remission after 12 or 14 weeks of open-label acute fluoxetine therapy, 20 mg/day (N=395 of 839 patients), were randomly assigned to one of four arms of a double-blind treatment study (50 weeks of placebo, 14 weeks of fluoxetine and then 36 weeks of placebo, 38 weeks of fluoxetine and then 12 weeks of placebo, or 50 weeks of fluoxetine). Relapse rate was the primary outcome measure. Both Kaplan-Meier estimates and observed relapse rates were assessed in three fixed 12-week intervals after double-blind transfers from fluoxetine to placebo at the start of the double-blind period and after 14 and 38 weeks of continued fluoxetine treatment. RESULTS: Relapse rates (Kaplan-Meier estimates) were lower among the patients who continued to take fluoxetine compared with those transferred to placebo in both the first interval, after 24 total weeks of treatment (fluoxetine, 26.4%; placebo, 48.6%), and the second interval, after 38 total weeks of treatment (fluoxetine, 9.0%; placebo, 23.2%). In the third interval, after 62 total weeks of treatment, rates were not significantly different between the groups (fluoxetine, 10.7%; placebo, 16.2%). CONCLUSIONS: Patients treated with fluoxetine for 12 weeks whose depressive symptoms remit should continue treatment with fluoxetine for at least an additional 26 weeks to minimize the risk of relapse.

Adult↗
PubMed1998

Placebo run-in period in studies of depressive disorders. Clinical, heuristic and research implications.

BACKGROUND: In spite of the virtually ubiquitous nature of the initial 10-day placebo run-in period (IPR) in drug trials, there is little empirical data establishing its relevance. METHOD: Data from 593 subjects were examined retrospectively to determine whether or not the prognosis of subjects minimally improved during the IPR was different to those who were unimproved. The IPR period was single-blind and was followed by a six-week double-blind phase in all studies. RESULTS: Twenty-six per cent of the subjects were minimally improved and 74% were unimproved. Approximately 10% of the subjects who were much improved were not followed systematically. Across a range of diagnosis, severity and chronicity subjects minimally improved (versus unimproved) after IPR had a more favourable prognosis whether assigned to drug or placebo. CONCLUSIONS: Change during IPR appears to be a meaningful predictor. Stratification should be considered in future antidepressant studies.

Adolescent↗
PubMed1998

Brain ERPs of depressed patients to complex tones in an oddball task: relation of reduced P3 asymmetry to physical anhedonia.

Event-related potentials to binaural complex tones were recorded from 40 depressed outpatients and 22 normal control participants at 30 electrode sites. Patients did not differ from control participants in N1 or P3 amplitude but showed greater N2. N2 was greater over right than over the left hemisphere at lateral sites in patients and control participants. A P3 asymmetry was found for control participants and patients with low scores on a physical anhedonia scale, but not for patients with high anhedonia scores. Topographic (local Laplacian) maps corresponding to P3 showed greater radial current flow over right than over left central regions in control participants. Patients with high anhedonia did not show this asymmetry, whereas patients with low anhedonia showed an intermediate asymmetry. These findings support the hypothesis that anhedonic depression is associated with dysfunction of right hemisphere mechanisms mediating the processing of complex pitch information.

Adult↗
PubMed1997

Regional brain asymmetries in major depression with or without an anxiety disorder: a quantitative electroencephalographic study.

Studies of brain activity in affective disorders need to distinguish between effects of depression and anxiety because of the substantial comorbidity of these disorders. Based on a model of asymmetric hemispheric activity in depression and anxiety, it was predicted that anxious and nonanxious depressed patients would differ on electroencephalographic (EEG) measures of parietotemporal activity. Resting EEG (eyes closed and eyes open) was recorded from 44 unmedicated outpatients having a unipolar major depressive disorder (19 with and 25 without an anxiety disorder), and 26 normal controls using 30 scalp electrodes (13 homologous pairs over the two hemispheres and four midline sites). As predicted, depressed patients with an anxiety disorder differed from those without an anxiety disorder in alpha asymmetry. Nonanxious depressed patients showed an alpha asymmetry indicative of less activation over right than left posterior sites, whereas anxious depressed patients showed evidence of greater activation over right than left anterior and posterior sites. The findings are discussed in terms of a model in which specific symptom features of depression and anxiety are related to different patterns of regional brain activity.

Adult↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

Fluoxetine and norfluoxetine plasma concentrations in major depression: a multicenter study.

OBJECTIVE: Prior studies examining the relationship between fluoxetine plasma concentrations and response in major depression have either found no relationship between plasma concentration and response or suggested a curvilinear relationship with a therapeutic window. To elucidate this relationship, plasma concentrations of fluoxetine, norfluoxetine, fluoxetine plus norfluoxetine, and fluoxetine/norfluoxetine ratio were compared to therapeutic response. METHOD: A total of 839 patients (577 women, 262 men; mean age = 40 [SD = 11] with a DSM-III-R diagnosis of major affective disorder who were in the course of either depression or bipolar disorder not otherwise specified and had a minimum baseline score of 16 on the 17-item Hamilton Depression Rating Scale were initially treated. Response was defined as follows: 1) nonresponders had less that a 50% or more reduction from baseline Hamilton depression score, 2) nonremitting responders had a 50% or more reduction from baseline Hamilton depression score but a final score higher than 7, and 3) remitters had a final Hamilton Depression score of 7 or lower. Plasma fluoxetine and norfluoxetine concentrations were measured after 8 weeks of fixed-dose treatment of 20 mg/day. RESULTS: Plasma concentration data were available from 615 patients. Plasma concentration were similar in responders, both remitting and nonremitting (N = 411), and nonresponders (N = 204) for fluoxetine concentrations, for norfluoxetine concentrations, as well as for the sum of fluoxetine and norfluoxetine and for the ratio of fluoxetine to norfluoxetine. No apparent relationship was observed between plasma drug concentration and clinical response. CONCLUSION: Plasma concentrations of fluoxetine and norfluoxetine do not appear to be related to clinical outcome and should not be used to make treatment decisions.

Adult↗
PubMed1997

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↗
PubMed1997

A preliminary study on the efficacy of sertraline and imipramine on anger attacks in atypical depression and dysthymia.

There is clinical and biological evidence suggesting that patients with anger attacks, sudden spells of anger accompanied by intense autonomic activation, may represent a distinct psychopathological subgroup of patients with depressive disorders. We compared the prevalence of anger attacks in 168 outpatients with atypical depression or primary dysthymia with 38 normal subjects and tested the effect of treatment on anger attacks in a double-blind, placebo-controlled trial of sertraline versus imipramine. Patients were randomly assigned to sertraline (n = 56), imipramine (n = 52), or placebo (n = 60) and were administered the Anger Attacks Questionnaire before and after treatment. Depressed outpatients were significantly more likely to report anger attacks than controls. Anger attacks ceased in 53 percent of the patients receiving sertraline, 57 percent of those receiving imipramine, and 37 percent of those in the placebo group. Our findings support previous studies indicating that anger attacks are more prevalent among depressed outpatients than normals. Our results also suggest that sertraline and imipramine may be more effective than placebo in reducing the number of anger attacks following treatment although the differences were not statistically significant. Larger studies are needed to confirm our findings.

1-Naphthylamine↗