Cianopramine and amitriptyline in the treatment of depressed patients ? a placebo-controlled study

Hormazabal, L.; Omer, L. M. O.; Ismail, Shajahan

doi:10.1007/bf00431710

Cited by 13 publications

(9 citation statements)

References 5 publications

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“…Forty-seven trials that met these inclusion criteria were included in our original meta-analysis. Of these, we excluded six studies (Claghorn et al , 1983; Dominguez et al , 1985; Hormazabal et al , 1985; Amsterdam et al , 1986; Ferguson et al , 1994; Khan, 1995) for the present meta-analysis because they did not conduct outcome assessments at week 6.…”

Section: Methodsmentioning

confidence: 99%

Therapeutic effect of follow-up assessments on antidepressant and placebo response rates in antidepressant efficacy trials

2007

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BackgroundIt remains unclear how much various factors contribute to the placebo response.AimsTo estimate the therapeutic impact of follow-up assessments on placebo response in antidepressant trials.MethodDouble-blind, placebo-controlled antidepressant trials that reported weekly changes in Hamilton Rating Scale for Depression (HRSD) scores over 6 weeks were selected. Included studies (n=41) were divided into those that conducted four, five or six follow-up assessments. Reductions in HRSD scores as a function of the different follow-up schedules were compared.ResultsAn extra follow-up visit at week 3 was associated with a 0.86 further reduction in HRSD score; an extra visit at week 5 was associated with a 0.67 further reduction. These effects represented approximately 34–44% of the placebo response that occurred over these time frames. Two additional visits were associated with twice the reduction in HRSD score than one, suggesting that the therapeutic impact of assessment visits is cumulative and proportional. A comparable therapeutic effect was also found in participants receiving active medication.ConclusionsFollow-up assessments in antidepressant treatment trials incur a significant therapeutic effect for participants on placebo, and this represents about 40% of the placebo response.

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Section: Methodsmentioning

confidence: 99%

Therapeutic effect of follow-up assessments on antidepressant and placebo response rates in antidepressant efficacy trials

2007

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“…11, NO. 1 Placebo Run-in for Antidepressant Trials 35 Feighner et al 1979;Goldberg and Finnerty 1980;Reimherr et al 1990;Rickels and Case 1982; Rowen et al 1982; Claghorn et al 1983;Hormazabal et al 1985; Irnlah 1985;Rickels et al 1985;Amsterdam et al 1986; Kleiser and Lehmann 1988;Spiker and Kupfer 1988Stewart et al 1981, 1985Veith et al 1982Jarvik et al 1983;Rickels et al 1985Agnew et al 1961Rothman et al 1962;Greenblatt et al 1964;Schildkraut et al 1964; British Medical Research Council 1965;Raskin et al 1978;Kellams et al 1979; Escobar et al 1980; Feighner 1980;Gerner et al 1980;Mann et al 1981;Rickels et al 1981; van der Velde 1981; Rickels et al 1982a,b;Veith et al 1982; Feighner et al 1983a,b; !til et al 1983;Jarvik et al 1983;Meredith and Feighner 1983a;Meredith et al 1984;Reimherr et al 1984; Liebowitz et al 1984a,b; Cohn and Wilcox 1985; Dominguez et al 1985;Kocsis et al 1985;Stark and Hardison 1985;Lipman et al 1986;Mendels and SchIess 1986; Wakelin 1986;Lapierre et al 1987;Rickels et al 1987; Byerley et al 1988;Liebowitz et al 1988;Quitkin et al 1988; Cohn et al. 1989; Conti and dell'Osso 1989; Elkin et al 1989; Feighner and Boyer 1989;Kocsis et al 1989;Lydiard et al 1989;Peselow et al 1989;…”

Section: Methods Of Metaanalysismentioning

confidence: 99%

Does a Placebo Run-In or a Placebo Treatment Cell Affect the Efficacy of Antidepressant Medications?

Trivedi

Rush

1994

Neuropsychopharmacol

167

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During the last decade, there has been an increasing use of a placebo run-in period prior to randomization to active treatments, or placebo in randomized controlled trials aimed at establishing acute phase antidepressant drug efficacy in patients with major depression. This procedure is thought to reduce response rates to placebo treatment after randomization, thereby increasing the drug-placebo difference. Metaanalyses of 101 studies reveal that a placebo run-in does not (1) lower the placebo response KEY WORDS: Depression; Placebo; Metaanalysis; Placebo run-in; Antidepressant medicationThe placebo run-in phase has become virtually stan dard practice in randomized controlled trials (RCTs) to test the efficacy of antidepressant medications in phase III and often phase IV studies. This single-blind phase usually lasts 3-14 days, followed by patients being ran domized to treatment. However, if patients show a meaningful symptomatic reduction (usually deflned as a20% to 25% improvement on a symptom rating scale), subjects are excluded from study. The implications of this practice have rarely been empirically evaluated.The rationale, based largely on intuition, is thought to reduce placebo responders post-randomization, thereby lowering post-randomization placebo response rates, and increasing differences between placebo and active treatments. Prien and Levine (1984) also sug- 655 Avenue of the Americas, New York, NY 10010 rate, (2) increase the drug-placebo difference, or (3) affect the drug response rate post-randomization in either inpatients or outpatients for any antidepressant drug group. If there is a post-randomization placebo treatment cell, drug response rates are unchanged or are slightly lower than if there is no placebo treatment cell for outpatients. These results suggest that a pill placebo run in provides no advantage in acute phase efficacy trials. [Neuropsychopharmacology 11:33-43, 1994J gested that the placebo run-in might eliminate rapid remitters, thereby reducing the need for post-randomiza tion placebo control treatment in some circumstances. The insuffi cient empirical data amassed to test these notions have not strongly supported the practice. Reim herr et al. (1989), in a retrospective reanalysiS, discov ered that the elimination of prerandomization placebo run-in "responders" reduced the drug-placebo differ ence from 30% to 25% in outpatients with major depres sion, and surprisingly, increased the placebo treatment response rates from 13% to 16%.Additional circumstantial data to question the value of this practice is from adult trials that have attempted to clinically characterize placebo responders. Outpa tients who "respond" during the placebo run-in tend to have longer episodes, a more chronic illness, a lower initial level of symptom severity, and are more likely nonendogenous. In comparison, patients who respond to placebo after randomization, tend to have shorter cur rent episodes and higher symptom severity at random ization (Fairchild et al. 1986;Rabkin et al. 1986Rabkin et al...

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“…Numerous structural analogs of 281816 have been tested and shown to be effective in treating a wide variety of neurological diseases (schizophrenia [97], [98], Parkinson and dementia-related psychoses [99], [100]), bipolar disorders [101], [102], and depression [103], [104]. While we have not found experimental studies that report the membrane permeability of 281816, the logP (log of octanol/water partition coefficient) has been calculated to be 4.14, which indicates the compound is likely to exhibit good membrane permeability.…”

Section: Discussionmentioning

confidence: 99%

Identification of a Novel Drug Lead That Inhibits HCV Infection and Cell-to-Cell Transmission by Targeting the HCV E2 Glycoprotein

et al. 2014

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Hepatitis C Virus (HCV) infects 200 million individuals worldwide. Although several FDA approved drugs targeting the HCV serine protease and polymerase have shown promising results, there is a need for better drugs that are effective in treating a broader range of HCV genotypes and subtypes without being used in combination with interferon and/or ribavirin. Recently, two crystal structures of the core of the HCV E2 protein (E2c) have been determined, providing structural information that can now be used to target the E2 protein and develop drugs that disrupt the early stages of HCV infection by blocking E2’s interaction with different host factors. Using the E2c structure as a template, we have created a structural model of the E2 protein core (residues 421–645) that contains the three amino acid segments that are not present in either structure. Computational docking of a diverse library of 1,715 small molecules to this model led to the identification of a set of 34 ligands predicted to bind near conserved amino acid residues involved in the HCV E2: CD81 interaction. Surface plasmon resonance detection was used to screen the ligand set for binding to recombinant E2 protein, and the best binders were subsequently tested to identify compounds that inhibit the infection of Huh-7 cells by HCV. One compound, 281816, blocked E2 binding to CD81 and inhibited HCV infection in a genotype-independent manner with IC50’s ranging from 2.2 µM to 4.6 µM. 281816 blocked the early and late steps of cell-free HCV entry and also abrogated the cell-to-cell transmission of HCV. Collectively the results obtained with this new structural model of E2c suggest the development of small molecule inhibitors such as 281816 that target E2 and disrupt its interaction with CD81 may provide a new paradigm for HCV treatment.

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Cianopramine and amitriptyline in the treatment of depressed patients ? a placebo-controlled study

Cited by 13 publications

References 5 publications

Therapeutic effect of follow-up assessments on antidepressant and placebo response rates in antidepressant efficacy trials

Therapeutic effect of follow-up assessments on antidepressant and placebo response rates in antidepressant efficacy trials

Does a Placebo Run-In or a Placebo Treatment Cell Affect the Efficacy of Antidepressant Medications?

Identification of a Novel Drug Lead That Inhibits HCV Infection and Cell-to-Cell Transmission by Targeting the HCV E2 Glycoprotein

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