Clinical significance of early non‐response in depressed patients

Boyer, William F.; Feighner, John P.

doi:10.1002/depr.3050020104

Cited by 11 publications

(9 citation statements)

References 17 publications

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“…In our earlier study (Katz et al, 1987), the clinical effects detected within the first 2 weeks were large and were predictive of eventual positive clinical outcome. Findings from a number of other studies (Small et al, 1981;Coryell et al, 1982;Khan et al, 1989;Nagayama et al, 1991;Stassen et al, 1993;Boyer and Feighner, 1994) have also confirmed the positive role of early clinical actions in predicting treatment outcome. The capacity to predict outcome early in treatment would not only shorten the length of a treatment trial but should also decrease morbidity and the risk of suicide from prolonged depressive symptoms (Kiloh et al, 1988).…”

Section: Introductionsupporting

confidence: 62%

“…There have been, however, a number of studies over the years (Small et al, 1981;Coryell et al, 1982;Katz et al, 1987;Khan et al, 1989;Nagayama et al, 1991;Boyer and Feighner, 1994) that have demonstrated a relationship between early response to ADs, mainly tricyclics, and treatment outcome. It is clear from the current study, however, that drug-specific types of behavioral responses in the first 1 or 2 weeks of treatment with DMI or paroxetine are highly predictive of later outcome.…”

Section: Prediction Of Drug Responsementioning

confidence: 99%

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Onset and Early Behavioral Effects of Pharmacologically Different Antidepressants and Placebo in Depression

Katz

Tekell

Bowden

et al. 2003

Neuropsychopharmacol

234

153

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This study was aimed at resolving the time course of clinical action of antidepressants (ADs) and the type of early behavioral changes that precede recovery in treatment-responsive depressed patients. The first goal was to identify, during the first 2 weeks of treatment, the onset of clinical actions of the selective serotonin reuptake inhibitor (SSRI), paroxetine, and the selective noradrenergic reuptake inhibitor, desipramine (DMI). The second aim was to test the hypothesis that the two pharmacologic subtypes would induce different early behavioral changes in treatment-responsive patients. The design was a randomized, parallel group, placebo-controlled, double-blind study for 6 weeks of treatment following a 1-week washout period. The study utilized measures of the major behavioral components of the depressive disorder as well as overall severity. The results indicated that the onset of clinical actions of DMI ranged from 3 to 13 days, averaged 13 days for paroxetine, and was 16-42 days for placebo. Furthermore, as hypothesized, the different types of ADs initially impacted different behavioral aspects of the disorder. After 1 week of treatment, DMI produced greater reductions in motor retardation and depressed mood than did paroxetine and placebo, and this difference persisted at the second week of treatment. Early improvement in depressed mood-motor retardation differentiated patients who responded to DMI after 6 weeks of treatment from those that did not. Paroxetine initially reduced anxiety more in responders than in nonresponders, and by the second week, significantly improved depressed mood and distressed expression in responders to a greater extent. Depressed patients who responded to placebo showed no consistent early pattern of behavior improvement. Early drug-specific behavioral changes were highly predictive of ultimate clinical response to the different ADs, results that could eventually be applied directly to clinical practice.

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Section: Introductionsupporting

confidence: 62%

Section: Prediction Of Drug Responsementioning

confidence: 99%

Onset and Early Behavioral Effects of Pharmacologically Different Antidepressants and Placebo in Depression

Katz

Tekell

Bowden

et al. 2003

Neuropsychopharmacol

234

153

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“…However, 70% of patients who were improved at day 10 were responders after 4 to 6 weeks of therapy (Stassen et al, 1994). Similar results have recently been reported by Boyer and Feighner (1994) in an analysis of paroxetine treatment of depression. Patients who did not respond after 3 weeks of treatment were unlikely to respond to further treatment.…”

Section: What Constitutes An Adequate Antidepressant Trial?supporting

confidence: 90%

Augmentation strategies in patients with refractory depression

Nemeroff

1996

Depress. Anxiety

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In the evaluation of treatment‐resistant or treatment‐refractory depression (TRD), true resistance to antidepressant therapy must be distinguished from inadequate dose, duration, or compliance with past antidepressant therapy. Reassessment of the diagnosis may reveal psychiatric comorbidity, the presence of depressive subtypes, or the possibility of a medical etiology. Management of TRD should consider patient‐specific factors; drug therapy may be directed by depressive subtype or the presence of psychiatric comorbidity. Increasing the dose or duration of current antidepressant therapy is appropriate for patients who have received inadequate therapy in the past. Augmentation of tricyclic antidepressant (TCA) or selective serotonin reuptake inhibitor (SSRI) therapy with thyroid hormone (T3) or lithium has been shown to be effective in open and controlled trials. Efficacy of other strategies such as higher‐dose antidepressant treatment, venlafaxine therapy, combined antidepressant therapy, electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), or augmentation with pindolol or buspirone has been less well established, but emerging data from open studies and case reports are encouraging. Depression and Anxiety 4:169–181, 1996/1997. © 1997 Wiley‐Liss, Inc.

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Section: Onset and Speed Of Action Of Antidepressantsmentioning

confidence: 99%

“…In contrast, survival-analytical methods suggest that among responders, onset of action occurs in more than 70% of cases within the first two weeks of treatment, with an early onset of action being highly predictive of later response. (Angst and Stassen, personal communication;Stassen et al 1993Stassen et al , 1997Coryell et al 1982;Boyer and Feighner 1994).When a new drug designed to increase effectiveness and to act more rapidly is produced, the attempt to evaluate its efficacy and onset in one clinical trial is obviously complicated. Some new drugs have yielded evidence that they act more rapidly than the established ones.…”

mentioning

confidence: 99%

Enhancing the Technology of Clinical Trials and the Trials Model to Evaluate Newly Developed, Targeted Antidepressants

Katz

Halbreich

Bowden

et al. 2002

Neuropsychopharmacology

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Concern about disappointing results from recent multicenter trials of new antidepressants prompted several ACNP workshops on "improving the technology of clinical trials." The workshops focused on technical problems, such as patient screening, reliability of clinical ratings, and the role of the placebo control. They aimed to determine how to 27 , NO . 3 ducing adverse events, and lessening the complexity of dosing regimens. In addition, attention is currently focused on accelerating the onset of drug action to generate more rapidly acting antidepressants. Unfortunately, recently conducted multi-center clinical trials of some of these agents encountered serious technical problems and did not produce the results anticipated from preclinical studies. Although this may be partly due to limitations in extrapolating pre-clinical data to patients, it may also be that there are significant constraints in the current clinical trials model that make it difficult to demonstrate efficacy.The current clinical trials model is now 30 years old. The essential principles of randomization, double blind evaluation, and a placebo control remain sound. But other important aspects of the research design and the methodology are no longer sufficient or well suited to the testing of these new drugs. In effect, such deficiencies in current trial methodologies make it increasingly difficult to demonstrate antidepressant efficacy of these new drugs.One important reason the current model has proved inadequate is that it was initially applied to hospitalized depressed patients. Today new drugs are tested almost exclusively on outpatient samples, many of whom are symptomatic volunteers, responding to advertisements. Depressed outpatients have milder depressive symptomatology than the predominantly inpatient samples used to test the first established drugs. Patients with milder severity provide a narrower range of possible change, and produce a greater number of placebo responders (Fisher et al. 1965;Bowden et al. 2000;Khan et al. 2002).As a consequence of the smaller difference between active treatment and placebo treatment, larger patient samples and/or more sensitive clinical methods are needed to detect differences between drug and placebo. The most commonly utilized scales, the Hamilton Depression Rating Scale (HDRS) (Hamilton 1960) and the Clinical Global Impression Scale (CGI) (Guy 1976), were designed to measure changes in overall severity of the disorder. These scales are not sufficiently sensitive to assess the specific behavioral changes brought about by the newer drugs (Montgomery and Asberg 1979). Further, intensive evaluation of symptomatology and behavioral change are carried out infrequently with outpatients, making evaluation of rapidity of response problematic. Consequently, it appears important to improve the technology applied to assessing the specific actions, onset, and efficacy of the newer drugs.Acknowledging the increased complexity of the goals of clinical trials and the need to improve trial procedures, the desi...

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Clinical significance of early non‐response in depressed patients

Cited by 11 publications

References 17 publications

Onset and Early Behavioral Effects of Pharmacologically Different Antidepressants and Placebo in Depression

Onset and Early Behavioral Effects of Pharmacologically Different Antidepressants and Placebo in Depression

Augmentation strategies in patients with refractory depression

Enhancing the Technology of Clinical Trials and the Trials Model to Evaluate Newly Developed, Targeted Antidepressants

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