A double-blind placebo-controlled study of Org 3770 in depressed outpatients

Claghorn, James L.; Lesem, Michael D.

doi:10.1016/0165-0327(95)00014-e

Cited by 56 publications

(33 citation statements)

References 8 publications

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“…Such a difference has not been reported in previous studies (Smith et al 1990;Claghorn and Lesem 1995;Marttila et al 1995;Richou et al 1995;Van Moffaert et al 1995;Zivkov and De Jong 1995). A possible explanation may be found in differences between the present and other trials with mirtazapine.…”

Section: Discussioncontrasting

confidence: 54%

“…In all trials tolerance and safety of mirtazapine were satisfactory. In out-patients efficacy of mirtazapine was reported to be significantly superior to placebo (Smith et al 1990;Claghorn and Lesem 1995) and to trazodon (Van Moffaert et al 1995); no significant differences between mirtazapine and amitriptyline (Smith et al 1990;Zivkov and De Jong 1995), clomipramine (Richou et al 1995) and doxepin (Marttila et al 1995), respectively, have been found.…”

Section: Introductionmentioning

confidence: 99%

“…Mirtazapine has recently been registered as an antidepressant. Efficacy and safety have been explored in controlled clinical trials (Smith et al 1990;Claghorn and Lesem 1995;Marttila et al 1995;Richou et al 1995;Van Moffaert et al 1995;Zivkov and De Jong 1995). In all trials tolerance and safety of mirtazapine were satisfactory.…”

Section: Introductionmentioning

confidence: 99%

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A double-blind, fixed blood-level study comparing mirtazapine with imipramine in depressed in-patients

et al. 1996

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Antidepressant effects of mirtazapine and imipramine were compared in a randomized, double blind, fixed blood-level study with in-patients in a single centre. Patients with a DSM-III-R diagnosis of major depression and a Hamilton (17-item) score of ≥ 18 were selected. After a drug-free and a placebowashout period of 7 days in total, 107 patients still fulfilling the HRSD criterion of ≥ 18, started on active treatment. The dose was adjusted to a predefined fixed blood level to avoid suboptimal dosing of imipramine. Concomitant psychotropic medication was administered only in a few cases because of intolerable anxiety or intolerable psychotic symptoms. Eight patients dropped out and two were excluded from analyses because of non-compliance; 97 completed the study. According to the main response criterion (50% or more reduction on the HRSD score) 11/51 (21.6%) patients responded on mirtazapine and 23 /46 (50 %) on imipramine after 4 weeks' treatment on the predefined blood level. Such a dramatic difference in efficacy between antidepressants has not often been reported before. The selection of (severely ill) in-patients, including those with suicidal or psychotic features, may have significance in this respect. Optimization of treatment with the reference drug imipramine through blood level control, exclusion of non-compliance for both drugs, exclusion of most concomitant medication and a low drop-out rate may also have contributed. It is concluded that imipramine is superior to mirtazapine in the patient population studied.

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Section: Discussioncontrasting

confidence: 54%

Section: Introductionmentioning

confidence: 99%

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A double-blind, fixed blood-level study comparing mirtazapine with imipramine in depressed in-patients

et al. 1996

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“…In this study, 1 mg/kg idazoxan decreased immobility-duration (Figures 1 and 3), supporting the clinical antidepressant efficacy of this drug (Osman et al 1989;Pinder and Sitsen 1987) and of other ␣ 2 -receptor antagonists such as mirtazapine (de Boer 1995(de Boer , 1996 or mianserin (Bremner 1995;Claghorn and Lesem 1995). The concurrent increase in swimming behavior (Figure 3) suggests that the idazoxan-antidepressant-like effect may be mediated through the enhancement of 5-HT-transmission, which is consistent with the drug increasing dorsal-raphe neuronal firing (Garratt et al 1991;Routledge and Marsden 1987).…”

Section: Discussionmentioning

confidence: 67%

“…It is therefore possible that ␣ 2 -receptor an- tagonists, which have already proven to be clinically effective antidepressants in the form of mirtazapine (Bremner 1995;Claghorn and Lesem 1995), may be useful adjuncts to classical antidepressant drugs in augmentation strategies (Maes et al 1999).…”

Section: Discussionmentioning

confidence: 99%

Idazoxan and 8-OH-DPAT Modify the Behavioral Effects Induced by Either NA, or 5-HT, or Dual NA/5-HT Reuptake Inhibition in the Rat Forced Swimming Test

Reneric

Bouvard

Stinus

2001

Neuropsychopharmacology

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The rat forced swimming test (FST) predicts the efficacy of antidepressants, which decrease immobility duration in the test, and can distinguish selective serotonin (5-HT) and noradrenaline (NA) reuptake inhibitors, which, respectively, increase swimming and climbing behaviors. However, dual 5-HT and NA reuptake-inhibition produces climbing behavior solely, thereby suggesting with other data that the NA-system mediates inhibiting interactions on 5-HT-induced swimming in the FST. Since ␣ 2 -adrenoreceptors and 5-HT 1A -receptors have important regulatory functions and are involved in 5-HT/NA interactions, we examined whether the ␣ 2 -receptorantagonist idazoxan and the 5-HT 1A -receptor-agonist 8-hydroxy-2-(di-n -propylamino)-tetralin (8-OH-DPAT) would modify the behavioral pattern induced in the FST by either selective or non-selective antidepressant treatments. The rats were treated subacutely (3 injections IP over 48 h) with: (a) idazoxan (0.5-10 mg/kg) alone, and in combination with desipramine (10 mg/kg), or desipramine ϩ fluoxetine (10/10 mg/kg), or the dual serotonin/ noradrenaline reuptake-inhibitor milnacipran (20 mg/kg). (b) 8-OH- (Porsolt et al. 1977(Porsolt et al. , 1978(Porsolt et al. , 1979, which detects all the major classes of antidepressant treatments (Borsini and Meli 1988) NO . 4 (MAOIs), atypical antidepressants, and electroconvulsive shock. The FST is also used to investigate the mechanisms of action of antidepressant drugs (Borsini 1995) or the functional interactions that occur when antidepressants are administered (Redrobe and Bourin 1999;Rénéric and Lucki 1998). The rat FST consists of placing the animal in a jar filled with water for a pre-test on day 1, and for a five-minute test session 24 hours later, with the drugs being administered sub-acutely (3 injections) between the two sessions. The animal first attempts to escape and then progressively adopts an immobile posture, making only small movements to keep its head above water. Effective antidepressant treatments decrease the duration of immobility in the test session (Porsolt et al. 1978). Other methods of scoring the FST take into account swimming and climbing, two main active behaviors occurring in the test, which contribute to the antidepressant-like decrease in immobility-duration (Detke et al. 1995b). This procedure showed that noradrenaline (NA)-reuptake inhibitors (NRIs) and selective serotonin (5-hydroxytryptamine/ 5-HT)-reuptake inhibitors (SSRIs) increased selectively and respectively climbing and swimming behavior (Detke et al. 1995b). This technique can thus distinguish components to the behavioral response to antidepressants (Lucki 1997), which is in agreement with distinguishable neurochemical and behavioral contributions to the therapeutic effects of antidepressants in humans (Heninger et al. 1996;Katz et al. 1994).Serotonin and noradrenaline systems are directly involved in the pathogenesis and the recovery from depression (Blier et al. 1990;Caldecott Hazard et al. 1991), and there were clinical suggestions that...

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Placebo Response in Studies of Major Depression

Walsh¹,

Seidman

Sysko³

et al. 2002

JAMA

1,040

665

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The response to placebo in published trials of antidepressant medication for MDD is highly variable and often substantial and has increased significantly in recent years, as has the response to medication. These observations support the view that the inclusion of a placebo group has major scientific importance in trials of new antidepressant medications and indicate that efforts should continue to minimize the risks of such studies so that they may be conducted in an ethically acceptable manner.

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A double-blind placebo-controlled study of Org 3770 in depressed outpatients

Cited by 56 publications

References 8 publications

A double-blind, fixed blood-level study comparing mirtazapine with imipramine in depressed in-patients

A double-blind, fixed blood-level study comparing mirtazapine with imipramine in depressed in-patients

Idazoxan and 8-OH-DPAT Modify the Behavioral Effects Induced by Either NA, or 5-HT, or Dual NA/5-HT Reuptake Inhibition in the Rat Forced Swimming Test

Placebo Response in Studies of Major Depression

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