A 24-week study of 20 mg citalopram, 40 mg citalopram, and placebo in the prevention of relapse of major depression

Montgomery, Stuart; Rasmussen, Jill; Tanghøj, Per

doi:10.1097/00004850-199300830-00008

Cited by 148 publications

(53 citation statements)

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“…In total, the authors had reported in 65 papers on various studies of antidepressant maintenance trials, but 36 of these had not documented suicides or suicide attempts or had not provided data upon request. The following 29 studies were included in our quantitative analysis: Blumenthal et al [30], Cheung et al [31], Doogan and Caillard [32], Emslie et al [33], Feiger et al [34], Goodwin et al [35], Kamijima et al [36], Kishimoto et al [37], Klysner et al [38], Kornstein et al [39], Lepine et al [40], Licht et al [41], Lustman et al [42], McGrath et al [43], Montgomery et al [44], Montgomery and Dunbar [45], Old Age Depression Interest Group [46], Perahia et al [47], Reynolds et al [48], Robinson et al [49], Rosenthal et al [50], Rouillon et al [51], Schmidt et al [52], Shiovitz et al [53], Stewart et al [54], Terra and Montgomery [55], Thase et al [56], Versiani et al [57], Weihs et al [58]. …”

Section: Resultsmentioning

confidence: 99%

Suicides and Suicide Attempts during Long-Term Treatment with Antidepressants: A Meta-Analysis of 29 Placebo-Controlled Studies Including 6,934 Patients with Major Depressive Disorder

Braun¹,

Bschor

Franklin

et al. 2016

Psychother Psychosom

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Background: It is unclear whether antidepressants can prevent suicides or suicide attempts, particularly during long-term use. Methods: We carried out a comprehensive review of long-term studies of antidepressants (relapse prevention). Sources were obtained from 5 review articles and by searches of MEDLINE, PubMed Central and a hand search of bibliographies. We meta-analyzed placebo-controlled antidepressant RCTs of at least 3 months' duration and calculated suicide and suicide attempt incidence rates, incidence rate ratios and Peto odds ratios (ORs). Results: Out of 807 studies screened 29 were included, covering 6,934 patients (5,529 patient-years). In total, 1.45 suicides and 2.76 suicide attempts per 1,000 patient-years were reported. Seven out of 8 suicides and 13 out of 14 suicide attempts occurred in antidepressant arms, resulting in incidence rate ratios of 5.03 (0.78-114.1; p = 0.102) for suicides and of 9.02 (1.58-193.6; p = 0.007) for suicide attempts. Peto ORs were 2.6 (0.6-11.2; nonsignificant) and 3.4 (1.1-11.0; p = 0.04), respectively. Dropouts due to unknown reasons were similar in the antidepressant and placebo arms (9.6 vs. 9.9%). The majority of suicides and suicide attempts originated from 1 study, accounting for a fifth of all patient-years in this meta-analysis. Leaving out this study resulted in a nonsignificant incidence rate ratio for suicide attempts of 3.83 (0.53-91.01). Conclusions: Therapists should be aware of the lack of proof from RCTs that antidepressants prevent suicides and suicide attempts. We cannot conclude with certainty whether antidepressants increase the risk for suicide or suicide attempts. Researchers must report all suicides and suicide attempts in RCTs.

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Section: Resultsmentioning

confidence: 99%

Suicides and Suicide Attempts during Long-Term Treatment with Antidepressants: A Meta-Analysis of 29 Placebo-Controlled Studies Including 6,934 Patients with Major Depressive Disorder

Braun¹,

Bschor

Franklin

et al. 2016

Psychother Psychosom

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“…Twelve trials (13 placebo comparisons) were shorter than 1 year for the randomized followup (18)(19)(20)(21)(22)(23)(24)(25)(26)(27)29,40). These trials provide consistent evidence in favor of active drug over placebo, with the majority representing the efficacy of relapse prevention.…”

Section: Placebo-controlled Trialsmentioning

confidence: 99%

“…Trials shorter than 1 year-Twelve trials were included in our relative risk meta-analysis of trials lasting less than 1 year after randomization ( Figure 1): one on bupropion (18), three on citalopram (19,27,40), one on escitalopram (20), three on fluoxetine (21,22,29), and one each on mirtazapine (23), nefazodone (24), sertraline (25), and venlafaxine (26). The pooled relative risk of relapse was 0.54 (95% CI 0.46 to 0.62) and the NNT to prevent one additional relapse over a mean time of 8 months was 5 (95% CI: 4-6).…”

Section: Meta-analysismentioning

confidence: 99%

Meta-analysis of Major Depressive Disorder Relapse and Recurrence With Second-Generation Antidepressants

Hansen¹,

Gaynes²,

Thieda³

et al. 2008

Psychiatric Services

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Objective-To review data on the efficacy and effectiveness of second-generation antidepressants for preventing major depression relapse and recurrence during continuation and maintenance phase treatment, respectively.Methods-MEDLINE®, EMBASE, and PsychLit; the Cochrane Library; and the International Pharmaceutical Abstracts were searched from January 1980 through April 2007 for reviews, randomized controlled trials, meta-analyses, and observational studies. Two persons independently reviewed abstracts and full text articles using a structured data abstraction form to ensure consistency in appraisal and data extraction.Findings-Four comparative trials and 23 placebo controlled trials that addressed relapse or recurrence prevention were included. Results of comparative trials have not demonstrated statistically significant differences between duloxetine and paroxetine, fluoxetine and sertraline, fluvoxamine and sertraline, and trazodone and venlafaxine. Pooled data for the class of secondgeneration antidepressants compared with placebo suggest a relatively large effect size that persists over time. The number needed to treat to prevent one additional relapse or recurrence is 5 (95% CI 4 to 6). Differences in the length of open-label treatment prior to randomization, drug type, and trial duration did not affect pooled estimates of relapse rates (P = 0.716, P = 0.507, and P = 0.480, aCorresponding author and reprint address:

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“…Indeed, the enhancement of NE neuron firing and release achieved with the ␣ 2 -adrenoceptor antagonist yohimbine can produce anxiety in healthy volunteers and trigger panic attacks in patients with panic disorder (Charney et al, 1984). In contrast to SSRIs, which can decrease the spontaneous firing activity of LC neurons by as much as 50% upon long-term administration (Szabo et al, 2000), YM992 may guard against a lethargic effect sometimes produced by SSRIs (Montgomery et al, 1993), by maintaining a normal NE neuron firing rate (Blier, 2000). Consequently, this normalization of NE neuron firing activity, together with 5-HT 2A receptor antagonism, may also prove beneficial in attenuating sexual dysfunctions which commonly plague SSRI users.…”

Section: -Htmentioning

confidence: 99%

Effects of Serotonin (5-Hydroxytryptamine, 5-HT) Reuptake Inhibition Plus 5-HT_2A Receptor Antagonism on the Firing Activity of Norepinephrine Neurons

Szabo¹,

Blier²

2002

J Pharmacol Exp Ther

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YM992 [(S)-2-[[(7-fluoro-4-indanyl)oxy]methyl]morpholine monohydrochloride] is a selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitor (SSRI) and a potent 5-HT 2A antagonist. The aim of the present study was to assess, using in vivo extracellular unitary recordings, the effect of acute and sustained administration of YM992 (40 mg kg Ϫ1 day Ϫ1 s.c., using osmotic minipumps) on the spontaneous firing activity of locus coeruleus (LC) norepinephrine (NE) neurons. Acute intravenous injection of YM992 (4 mg kg Ϫ1 ) significantly decreased NE neuron firing activity by 29% and blocked the inhibitory effect of a subsequent injection of the 5-HT 2 agonist DOI [1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride]. A 2-day treatment with YM992 decreased the firing rate of NE neurons by 66%, whereas a partial recovery was observed after a 7-day treatment and a complete one after a 21-day treatment. Following the injection of the ␣ 2 -adrenoceptor antagonist idazoxan (1 mg kg -1 i.v.), NE neuron firing was equalized in controls and 2-day YM992-treated rats. This put into evidence an increased degree of activation of ␣ 2 -adrenergic autoreceptors in the treated rats. The suppressant effect of the ␣ 2 -adrenoceptor agonist clonidine was significantly decreased in longterm YM992-treated rats. The recovery of LC firing activity after long-term YM992 administration could thus be explained by a decreased sensitivity of ␣ 2 -adrenergic autoreceptors. Sustained SSRI administration leads to a gradual reduction of the firing activity of NE neurons during long-term administration, whereas YM992 produced opposite effects. The exact basis for the increased synaptic availability of NE by YM992 remains to be elucidated. This NE activity, resulting from 5-HT reuptake inhibition plus 5-HT 2A receptor antagonism, might confer additional benefits in affective and anxiety disorders.The norepinephrine (NE) and the serotonin (5-hydroxytryptamine; 5-HT) systems have both been implicated in anxiety and affective disorders. Although the etiopathology of these two disorders remains enigmatic, greater knowledge exists pertaining to the interactions/alterations of these monoaminergic systems during antidepressant drug treatment. It is well established that locus coeruleus (LC) NE neurons modulate the 5-HT system, and evidence is accumulating for a major influence of 5-HT on the NE system (see Haddjeri et al., 1997;Kaehler et al., 1999). The LC receives dense 5-HT projections coming from dorsal raphe and pericoerulear 5-HT neurons (Aston-Jones et al., 1991;Kaehler et al., 1999), which exert an inhibitory role (Léger and Descarries, 1978;Segal, 1979). This is supported by the observation that lesioning 5-HT neurons with a 5-HT neurotoxin produced a marked elevation of firing rate of NE neurons (Haddjeri et al., 1997). Long-term, but not acute or short-term (2-day) administration of SSRIs decreases the spontaneous firing activity of LC NE neurons in the rat (Béïque et al.,1998;Szabo et al., 2000;Szabo and Blier, 2001a;Grant a...

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A 24-week study of 20 mg citalopram, 40 mg citalopram, and placebo in the prevention of relapse of major depression

Cited by 148 publications

References 0 publications

Suicides and Suicide Attempts during Long-Term Treatment with Antidepressants: A Meta-Analysis of 29 Placebo-Controlled Studies Including 6,934 Patients with Major Depressive Disorder

Suicides and Suicide Attempts during Long-Term Treatment with Antidepressants: A Meta-Analysis of 29 Placebo-Controlled Studies Including 6,934 Patients with Major Depressive Disorder

Meta-analysis of Major Depressive Disorder Relapse and Recurrence With Second-Generation Antidepressants

Effects of Serotonin (5-Hydroxytryptamine, 5-HT) Reuptake Inhibition Plus 5-HT_2A Receptor Antagonism on the Firing Activity of Norepinephrine Neurons

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A 24-week study of 20 mg citalopram, 40 mg citalopram, and placebo in the prevention of relapse of major depression

Cited by 148 publications

References 0 publications

Suicides and Suicide Attempts during Long-Term Treatment with Antidepressants: A Meta-Analysis of 29 Placebo-Controlled Studies Including 6,934 Patients with Major Depressive Disorder

Suicides and Suicide Attempts during Long-Term Treatment with Antidepressants: A Meta-Analysis of 29 Placebo-Controlled Studies Including 6,934 Patients with Major Depressive Disorder

Meta-analysis of Major Depressive Disorder Relapse and Recurrence With Second-Generation Antidepressants

Effects of Serotonin (5-Hydroxytryptamine, 5-HT) Reuptake Inhibition Plus 5-HT2A Receptor Antagonism on the Firing Activity of Norepinephrine Neurons

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Effects of Serotonin (5-Hydroxytryptamine, 5-HT) Reuptake Inhibition Plus 5-HT_2A Receptor Antagonism on the Firing Activity of Norepinephrine Neurons