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ABSTRACT: 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.
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.
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.
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.
American Journal of Psychiatry 03/1991; 148(2):193-6. · 12.54 Impact Factor
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ABSTRACT: 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.
The subjects were 263 patients in controlled antidepressant trials lasting 6 weeks.
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.
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.
American Journal of Psychiatry 03/1991; 148(2):197-203. · 12.54 Impact Factor
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ABSTRACT: One hundred ninety-four nonmelancholic depressed outpatients with features of atypical depression took part in a 6-week randomized trial of imipramine hydrochloride, phenelzine sulfate, and placebo. Their courses of illness were also rated for chronicity. Significantly more patients responded to phenelzine (71%) than to imipramine (48%), which benefited significantly more patients than placebo (26%). Both chronicity and DMS-III diagnosis predicted response on several outcome measures. For example, patients with dysthymic disorder responded better to treatment than did those with major depression, suggesting that dysthymic disorder can be treated with medication. Placebo response correlated inversely with chronicity, regardless of DMS-III diagnosis. Atypical depression and longitudinal course of illness may add to the usefulness of DMS-III depressive diagnosis as a predictor of antidepressant response.
Archives of General Psychiatry 01/1990; 46(12):1080-7. · 12.02 Impact Factor
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ABSTRACT: Sixty patients who met Research Diagnostic Criteria for major, intermittent, or minor depressive disorder and had reactive mood without atypical symptoms were treated with imipramine hydrochloride, phenelzine sulfate, or a placebo. These patients, referred to as simple mood reactive depressives, were contrasted with previously published data from 180 atypical depressives. Atypical depressives had the presence of at least one vegetative atypical sign (hypersomnia, hyperphagia, leaden feeling, or rejection sensitivity) but were otherwise indistinguishable from simple mood reactive depressives. In contrast to the atypical depressives for whom phenelzine was effective and imipramine was relatively ineffective, both medications were equivalently good in simple mood reactive depressives. Since all groups did poorly when given a placebo and well when given phenelzine, the salient feature of atypical symptoms may be that they predict poor response to imipramine. Since the difference between imipramine and placebo depends on the diagnostic group, pharmacologic dissection suggests that atypical symptoms in patients with nonautonomous mood may delineate a qualitatively distinct subgroup.
Archives of General Psychiatry 10/1989; 46(9):787-93. · 12.02 Impact Factor
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ABSTRACT: The charts of 80 outpatients who responded to antidepressants were reviewed to determine if there was a higher rate of premature medication discontinuation with phenelzine than with imipramine. The phenelzine responders had a significantly (p less than .01) higher rate of drug discontinuation, mainly because of side effects. Controlled studies of long-term use are needed to better explain the problem of attrition.
The Journal of Clinical Psychiatry 06/1988; 49(5):196-8. · 5.80 Impact Factor
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ABSTRACT: Although the electrocardiographic effects of the tricyclic antidepressants have been extensively investigated, there are fewer data on the effects of monoamine oxidase inhibitors and tetracyclics on cardiac conduction. This study used high speed recordings of the electrocardiogram to investigate the cardiographic effects of phenelzine and mianserin and to compare these to the effects of imipramine, amitriptyline, and placebo. Phenelzine caused significant slowing of the heart rate, while mianserin showed little effect on heart rate compared to the increases in rate seen with tricyclics. In clinically effective doses, neither phenelzine nor mianserin caused changes in conduction, while both tricyclics studied caused the expected prolongation of conduction. These data suggest that phenelzine and mianserin deserve further study in patients with disease of the cardiac system as they may be less likely to cause heart block in these patients.
Journal of Clinical Psychopharmacology 11/1987; 7(5):335-9. · 4.10 Impact Factor
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ABSTRACT: Ninety-two outpatients with depressive disorders which met Research Diagnostic Criteria were treated either with mianserin or placebo in a 6-week controlled trial. Twenty-four of 42 (57%) mianserin-treated patients were rated responders to mianserin treatment while 15 of 50 (30%) were rated responders to placebo treatment (chi 2 = 6.89, p less than 0.01). This rate of drug response was comparable to that achieved with a tricyclic antidepressant in a similar study done in our clinic, supporting the use of mianserin in mildly depressed outpatients.
Neuropsychobiology 02/1985; 14(3):128-32. · 2.67 Impact Factor
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ABSTRACT: We investigated the antidepressant efficacy of l-deprenyl (selegiline), a selective monoamine oxidase B inhibitor (MAOI), in a six-week open trial of 17 patients with atypical depression. Such patients have previously been shown to benefit from nonselective MAOIs such as phenelzine sulfate. Ten patients (59%) responded to l-deprenyl, but nine required dosages above the 10 to 20 mg/day used in previous investigations. l-Deprenyl was superior to six weeks of placebo administered to diagnostically similar patients in a separate double-blind study. In contrast with previous findings with pheneizine, responders to l-deprenyl differed from nonresponders by having lower baseline anxiety ratings. Even at high dosages, there appeared to be fewer side effects with l-deprenyl than with nonselective MAOIs.
Archives of General Psychiatry 09/1984; 41(8):777-81. · 12.02 Impact Factor
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ABSTRACT: Psychopharacologist have had a longstanding interest in identifying a depressive subtype which selectively benefits from monoamine oxidase inhibitors (MAOIs). A superior rate of improvement with MAOI treatment might help delineate a depressive subgroup with pathophysiology different from other depressive syndromes. Research is described which indicates that patients with reactivity of mood, as well as two of four associated features (hypersomnia, overeating, lethargy, and rejection sensitivity), may have a preferential response to phenelzine as compared with imipramine or placebo. Preliminary data are presented to suggest that patients with reactive mood and only one associated feature may have a preferential response rate to phenelzine compared to imipramine and placebo. Data on patients with reactive mood but no associated features are insufficient at this point to draw any conclusions.
The Journal of Clinical Psychiatry 08/1984; 45(7 Pt 2):19-21. · 5.80 Impact Factor
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ABSTRACT: 34 patients who met the research diagnostic criteria for major depressive disorder as defined by Spitzer et al. [Archs gen. Psychiat. 35: 773-782, 1978] completed a double-blind 6-week trial of mianserin versus amitriptyline following 1 week of single-blind placebo washout. After 2 weeks of dose build-up, patients took 150 mg/day of mianserin or 300 mg/day of amitriptyline throughout the next 4 weeks. At week 6, 63% of mianserin patients and 73% of amitriptyline patients were rated as responders; this difference is not statistically significant. No clinically meaningful differences between drugs were observed with respect to number or severity of side effects as reported by either patient or physician. Overall, mianserin was found to be equivalent to amitriptyline in terms of efficacy, patient tolerance and ease of administration.
Neuropsychobiology 02/1984; 12(4):224-8. · 2.67 Impact Factor
