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F M Quitkin

Publications and source records attributed to F M Quitkin.

At least 19 recordsLinked to original sources
PubMed2001

Strengthening clinical effectiveness trials: equipoise-stratified randomization.

As psychiatric practice patterns evolve to take advantage of the growing list of treatments with proven efficacy, research studies with broader aims will become increasingly important. Randomized trials may need to accommodate multiple treatment options. In completely randomized designs, patients are assigned at random to one of the options, requiring that patients and clinicians find each of the options acceptable. In "clinician's choice" designs, patients are randomized to a small number of broad strategies and the choice of specific option within the broad strategy is left up to the clinician. The clinician's choice design permits some scope to patient and clinician preferences, but sacrifices the ability to make randomization-based comparisons of specific options. We describe a new approach, which we call the "equipoise stratified" design, that merges the advantages and avoids the disadvantages of the other two designs for clinical trials. The three designs are contrasted, using the National Institute of Mental Health Sequenced Treatment Alternatives to Relieve Depression trial as an example.

Antidepressive Agents↗
PubMed2001

Electroencephalographic and perceptual asymmetry differences between responders and nonresponders to an SSRI antidepressant.

BACKGROUND: Recent reports suggest the value of electroencephalographic and dichotic listening measures as predictors of response to antidepressants. This study examines the potential of electroencephalographic alpha asymmetry and dichotic measures of perceptual asymmetry as predictors of clinical response to 12 weeks of treatment with fluoxetine (Prozac). METHODS: Resting electroencephalography (eyes open and eyes closed) and dichotic listening with word or complex tone stimuli were assessed in depressed outpatients during a pretreatment period. RESULTS: Fluoxetine responders (n = 34) differed from nonresponders (n = 19) in favoring left over right hemisphere processing of dichotic stimuli. They also differed in their resting electroencephalographic alpha asymmetry, particularly in the eyes open condition. Nonresponders showed an alpha asymmetry indicative of overall greater activation of the right hemisphere than the left, whereas responders did not. The relationship between hemispheric asymmetry and treatment response interacted with gender, being evident among depressed women but not men. CONCLUSIONS: The results are consistent with the hypothesis that a characteristic tendency toward greater left than right hemisphere activation is associated with favorable response to fluoxetine, whereas the opposite hemispheric asymmetry predicts poor response.

Adolescent↗
PubMed2001

Does mirtazapine have a more rapid onset than SSRIs?

BACKGROUND: A single study utilizing a cross-sectional analysis of scores on the Hamilton Rating Scale for Depression (HAM-D) suggested that mirtazapine has a more rapid onset than selective serotonin reuptake inhibitors (SSRIs). Analysis based on the HAM-D may favor drugs with sleep-producing effects. The purpose of the present study was to determine if a review of all studies comparing an SSRI with mirtazapine, utilizing persistent improvement as the dependent variable, would suggest that mirtazapine had a more rapid onset than SSRIs. METHOD: All double-blind studies comparing mirtazapine with SSRIs were analyzed. Included in the analysis to determine speed of onset were 298 patients taking mirtazapine and 285 taking an SSRI. Pattern analysis, which has been described and used by other researchers, was employed to study speed of onset. RESULTS: At the end of each of the 3 studies, the total number of responders for each of the drugs did not differ. However, the proportion of responders with onset of persistent improvement in week 1 was greater for mirtazapine (13%, 38/298) than for the SSRIs (6%, 18/285; chi2 = 6.95, df = 1, p = .008). CONCLUSION: These data support the possibility that mirtazapine may have a more rapid onset than SSRIs. This observation should be considered preliminary because of the retrospective nature of the analysis and the absence of a placebo group.

Antidepressive Agents, Tricyclic↗
PubMed2000

Event-related potentials (ERPs) to hemifield presentations of emotional stimuli: differences between depressed patients and healthy adults in P3 amplitude and asymmetry.

Depression may involve dysfunction of right parietotemporal cortex, a region activated during perception of affective stimuli. To further test this hypothesis, event-related brain potentials (ERPs) were measured in a paradigm previously shown to produce ERP asymmetries to affective stimuli over parietal sites in healthy adults. Pictures of patients with dermatological diseases showing disordered or healed facial areas before (negative) or after (neutral) surgical treatment were briefly exposed for 250 ms to either the left or right hemifield. ERPs of 30 unmedicated, unipolar depressed patients and 16 healthy adults, all right-handed, were recorded from 30 electrodes. A principal components analysis extracted factors which closely corresponded to distinctive ERP components previously reported for this task (N1, N2, early P3, late P3, slow wave). Significant effects of emotional content, i.e. enhanced amplitudes to negative than neutral stimuli, were found for early and late P3. Control subjects showed significant hemispheric asymmetries of emotional processing for late P3 (peak latency 460 ms), with the largest emotional content effects over the right parietal region. In striking contrast to control subjects, depressed patients did not show an increase in late P3 for negative compared to neutral stimuli over either hemisphere and had smaller late P3 amplitude than control subjects. Patients did, however, show larger early P3 (peak latency 330 ms) to negative than neutral stimuli. Results suggest intact early discrimination but abnormal late appraisal of affective content in depression, which may arise from selective inhibition of right parietal regions integral for perceiving and evaluating emotional stimuli.

Adult↗
PubMed2000

Current concepts in the treatment of depression in alcohol-dependent patients.

This article addresses the comorbidity of depression and alcoholism, including an overview of the epidemiologic evidence available, reasons for the association between depression and alcoholism, and basic mechanisms common to both disorders. Practical evidence and experience-based advice on the management of these patients also are provided.

Alcoholism↗
PubMed2000

A method to quantify rater bias in antidepressant trials.

Some studies indicate that the blind in clinical trials of the efficacy of antidepressant drugs is less than perfect. It has been suggested that, as a consequence of this incomplete blind, biased raters inflate efficacy and that, in fact, these drugs are relatively ineffective. However, in the literature, we could find no prior attempt to quantify rater bias and, thus, measure its contribution to claims of antidepressant efficacy. We used the distribution of SCL-90 (Symptom Check List) depression scale scores to derive a patient-based effect size, and contrasted this with the clinician-based effect size. We propose the difference between these two effect sizes (patient self-rating and clinician-derived) to be an indirect measure of bias. If patients had a prodrug bias, this method would be invalid. However the response rate from studies with active placebo suggest a patient prodrug bias is unlikely. The effect sizes derived from patient self-ratings are smaller than those derived from clinician ratings. This allows for the possibility that some clinician ratings were biased. However, quantifying the effect of bias suggests that it was insufficient to invalidate the original study conclusions based on clinician ratings, because the proportion of responders, based on patient self-ratings, differed significantly between the two drugs and placebo. Their 95% confidence intervals (CI) did not overlap. This analysis allows that some clinician ratings may be biased. However, the extent of bias appears insufficient to alter conclusions based on clinician ratings regarding efficacy of antidepressant drugs in this trial. Application of our approach in other trials is necessary to establish generalizability.

Antidepressive Agents↗
PubMed2000

Validity of clinical trials of antidepressants.

OBJECTIVE: Recent reports have criticized the design of antidepressant studies and have questioned their validity. These critics have concluded that antidepressants are no better than placebo treatment and that their illusory superiority depends on methodologically flawed studies and biased clinical evaluations. It has been suggested that the blind in randomized trials is penetrable-since clinician's guesses exceed chance-and that only active placebo can appropriately camouflage the difference between drug and placebo response. Furthermore, evidence has been cited to suggest that psychotherapy is as effective as antidepressants in both the acute and maintenance treatment of depression. These positions are often accepted as valid and have been broadly discussed in both the lay press and scientific literature. The purpose of this review is to reassess the cited data that support these assertions. METHOD: The authors examined the specific studies that were cited in these reports, evaluated their methodology, and conducted aggregate analyses. RESULTS: Analyses of the original sources failed to substantiate 1) that standard antidepressants are no more effective than placebo, 2) that active placebo offers an advantage over inactive placebo, or 3) that substantial evidence of a medication bias is suggested by raters' treatment guesses exceeding chance. The authors also note that some researchers have suggested that the interpretation of psychotherapy trials can be complicated by "allegiance effects." CONCLUSIONS: The issue of bias or allegiance effects for both antidepressant and psychotherapy research is real. Investigators of all orientations must guard against potential bias. However, studies cited as supporting the questionable validity of antidepressant trials fail upon closer examination to support assertions that these trials are invalid.

Antidepressive Agents↗
PubMed2000

A placebo-controlled study of fluoxetine versus imipramine in the acute treatment of atypical depression.

OBJECTIVE: The atypical subtype of depression appears to be both well validated and common. Although monoamine oxidase inhibitors are effective in treating atypical depression, their side effects and prescription-associated dietary restrictions reduce their suitability as a first-line treatment. The objective of this study was to estimate the efficacy of the selective serotonin reuptake inhibitor (SSRI) fluoxetine in the treatment of major depression with atypical features. METHOD: One hundred fifty-four subjects with DSM-IV major depression who met the Columbia criteria for atypical depression were randomly assigned to receive fluoxetine, imipramine, or placebo for a 10-week clinical trial. Imipramine was included because its known efficacy for treatment of atypical depression helped to calibrate the appropriateness of the study group. RESULTS: In both intention-to-treat and completer groups, the effectiveness of both fluoxetine and imipramine was significantly better than that of placebo. The two medications did not differ from each other in effectiveness. Significantly more patients dropped out of treatment with imipramine than with fluoxetine. Before treatment, patients on average rated themselves as very impaired on psychological dimensions of general health and moderately impaired on physical dimensions, compared with population norms. The self-ratings of patients who responded to treatment essentially normalized on these measures. CONCLUSIONS: Despite earlier data that SSRIs might be the treatment of choice, fluoxetine appeared to be no better than imipramine in the treatment of atypical depression, although fluoxetine was better tolerated than imipramine.

Adolescent↗
PubMed2000

Divalproex treatment for youth with explosive temper and mood lability: a double-blind, placebo-controlled crossover design.

OBJECTIVE: The authors sought to replicate open-label findings showing that specific criteria for explosive temper and mood lability identify disruptive youth who improve while receiving the anticonvulsant divalproex sodium. METHOD: Twenty outpatient children and adolescents (ages 10-18) with a disruptive behavior disorder (oppositional defiant disorder or conduct disorder) met the specific criteria for explosive temper and mood lability. They received 6 weeks of divalproex treatment and 6 weeks of placebo by random assignment. Independent evaluators blind to group assignment assessed response at the end of each phase. RESULTS: At the end of phase 1, eight of 10 subjects had responded to divalproex; zero of 10 had responded to placebo. Of the 15 subjects who completed both phases, 12 has superior response taking divalproex. CONCLUSIONS: This preliminary study replicates open-label findings showing that divalproex is an efficacious treatment for explosive temper and mood lability in disruptive children and adolescents.

Adolescent↗
PubMed2000

Predictors of relapse during fluoxetine continuation or maintenance treatment of major depression.

BACKGROUND: The goal was to examine predictors of relapse during continuation/maintenance treatment of major depression that had remitted following 12 to 14 weeks of fluoxetine therapy. METHOD: The study utilizes data collected in a collaborative clinical trial including patients with DSM-III-R major depression at 5 university-affiliated outpatient psychiatry clinics. Three hundred ninety-five patients who remitted with fluoxetine therapy were randomly assigned to 1 of 4 treatments: fluoxetine for 14 weeks followed by placebo for 36 weeks, fluoxetine for 38 weeks followed by placebo for 12 weeks, fluoxetine for 50 weeks, or placebo for 50 weeks. Cox proportional hazard models were used to identify predictors of time to relapse. RESULTS: In addition to the previously reported longitudinal pattern of response during acute treatment, neurovegetative symptom pattern was a predictor of fluoxetine benefit compared with placebo. Greater chronicity predicted poorer survival, which was not differential by treatment. The most robust advantage of fluoxetine was seen for patients with endogenous vegetative symptoms, chronic depression, and acute treatment response characterized by onset in the third week or later and persistence of response once attained. CONCLUSION: Both nonspecific pattern of response and neurovegetative symptoms characteristic of atypical depression were predictive of lack of fluoxetine efficacy in continuation/ maintenance treatment. These findings have importance for both clinical management and analyses of future maintenance trials.

Adult↗
PubMed1999

Perceptual asymmetry differences between major depression with or without a comorbid anxiety disorder: a dichotic listening study.

Predictions that anxious and nonanxious depression would differ in perceptual asymmetry (PA), as well as in sensitivity for perceiving emotional words, were evaluated using dichotic listening tasks. A total of 149 patients having a major depressive disorder (51 with and 98 without an anxiety disorder) and 57 healthy controls were tested on fused-word and complex tone tasks. The anxious and nonanxious depression groups showed a consistent difference in PA across tasks; that is, the anxious group had a larger left-ear advantage for tones and a smaller right-ear advantage for words when compared with the nonanxious group. There was no group difference in sensitivity for perceiving emotional words. Patients having an anxious depression appear to have a greater propensity to activate right than left-hemisphere regions during auditory tasks, whereas those having a nonanxious depression have the opposite hemispheric asymmetry.

Adult↗
PubMed1999

Do tricyclic responders have different brain laterality?

A previous study showed that depressed patients who improved with tricyclic antidepressant medication had dichotic complex tones test results suggesting right-hemisphere dysfunction relative to nonresponders and controls (G. E. Bruder et al., 1990). A new sample of 68 depressed patients completed dichotic consonant-vowel (CV) and complex tones (CT) tests and then were treated with imipramine or placebo. A significant Ear x Test x Treatment x Response interaction was accounted for by significantly poorer left-ear accuracy for CVs among imipramine responders compared with nonresponders, placebo responders, and controls. CV left-ear accuracy was also significantly greater among placebo responders than placebo nonresponders and controls. The results only partially replicate the prior study in that evidence of right-hemisphere dysfunction in tricyclic responders was seen for the CV test but not the CT test.

Antidepressive Agents, Tricyclic↗
PubMed1999

Blood pressure changes during short-term fluoxetine treatment.

Recent reports of sustained hypertension in some patients receiving venlafaxine have rekindled concerns about antidepressant-induced hypertension. This study examined sitting and standing systolic and diastolic blood pressure, pulse rate, and rate of sustained hypertension in 796 depressed patients (mean +/- SD age, 40 +/- 11 years) taking fluoxetine 20 mg daily for up to 12 weeks. A modest reduction in sitting and standing systolic (p < 0.001) and diastolic (p < 0.001) blood pressure measures were observed in the entire patient sample. Patients with pretreatment diastolic blood pressure < 60 mmHg (N = 32) showed a modest increase in mean diastolic blood pressure (p < 0.001), whereas patients with pretreatment diastolic blood pressure > or = 90 mmHg and < or = 95 mmHg (N = 57) had a modest reduction in mean diastolic blood pressure (p < 0.001). Patients with preexisting, stable cardiovascular disease (including hypertension) (N = 35) showed no significant blood pressure change (p = not significant). Of the patients receiving fluoxetine, 1.7% had sustained hypertension for > or = 3 consecutive clinic visits-a rate significantly lower than that previously reported with venlafaxine (4.8%) (chi2 = 13.3, p < 0.001) and similar to that previously seen with placebo (2.1%). In conclusion, these data demonstrate a low rate of sustained hypertension (1.7%) during short-term fluoxetine treatment.

Adolescent↗
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↗