A placebo-controlled study of sertraline in the treatment of outpatients with seasonal affective disorder

Moscovitch, Adam; Blashko, Carl A.; Eagles, John M.; Darcourt, G; Thompson, Christopher; Kasper, Siegfried; Lane, Roger

doi:10.1007/s00213-003-1594-8

Cited by 68 publications

(21 citation statements)

References 35 publications

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“…Enhanced 5-HTT function as suggested by the present data may be an important mechanism contributing to low synaptic serotonin levels during depression, since it presumably leads to enhanced synaptic serotonin clearance. This mechanism is compatible with the known antidepressant effects of 5-HTT blockade in seasonal (Lam et al, 2006;Moscovitch et al, 2004) and nonseasonal (Axelrod and Inscoe, 1963) depression. Our data suggest that changes in 5-HTT efficiency are a meaningful and naturally occurring physiological process that is altered in patients with SAD, and they show that changes in 5-HTT efficiency occur parallel to changes in depressive symptoms.…”

Section: Resultssupporting

confidence: 84%

Enhanced Serotonin Transporter Function during Depression in Seasonal Affective Disorder

Willeit

Sitte

Thierry

et al. 2007

Neuropsychopharmacol

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Decreased synaptic serotonin during depressive episodes is a central element of the monoamine hypothesis of depression. The serotonin transporter (5-HTT, SERT) is a key molecule for the control of synaptic serotonin levels. Here we aimed to detect state-related alterations in the efficiency of 5-HTT-mediated inward and outward transport in platelets of drug-free depressed patients suffering from seasonal affective disorder (SAD). 5-HTT turnover rate, a measure for the number of inward transport events per minute, and tyramineinduced, 5-HTT-mediated outward transport were assessed at baseline, after 4 weeks of bright light therapy, and in summer using a case-control design in a consecutive sample of 73 drug-free depressed patients with SAD and 70 nonseasonal healthy controls. Patients were drug-naive or medication-free for at least 6 months prior to study inclusion, females patients were studied in the follicular phase of the menstrual cycle. All participants were genotyped for a 5-HTT-promoter polymorphism (5-HTTLPR) to assess the influence of this polymorphism on 5-HTT parameters. Efficiency of 5-HTT-mediated inward (p ¼ 0.014) and outward (p ¼ 0.003) transport was enhanced in depressed patients. Both measures normalized toward control levels after therapy and in natural summer remission. Changes in outward transport showed a clear correlation with treatment response (r ¼ 0.421, p ¼ 0.001). Changes in inward transport were mediated by changes in 5-HTT transport efficiency rather than affinity or density. 5-HTTLPR was not associated with any of the 5-HTT parameters. In sum, we conclude that the 5-HTT is in a hyperfunctional state during depression in SAD and normalizes after light therapy and in natural summer remission.

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Section: Resultssupporting

confidence: 84%

Enhanced Serotonin Transporter Function during Depression in Seasonal Affective Disorder

Willeit

Sitte

Thierry

et al. 2007

Neuropsychopharmacol

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“…Antidepressant medication is a second effective treatment for SAD (see Lam et al, 1995;Moscovitch et al, 2004), and it is appropriate to consider whether the predictions of the PSH are also confirmed with this intervention. Two hypotheses were therefore tested.…”

Section: Introductionmentioning

confidence: 98%

Therapeutic Mechanism in Seasonal Affective Disorder: Do Fluoxetine and Light Operate Through Advancing Circadian Phase?

Murray

Michalak

Levitt

et al. 2005

Chronobiology International

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In the context of Lewy's phase delay hypothesis, the present study tested whether effective treatment of winter Seasonal Affective Disorder (SAD) is mediated by advancing of circadian phase. Following a baseline week, 78 outpatients with SAD were randomized into 8 weeks of treatment with either fluoxetine and placebo light treatment or light treatment and placebo pill. Depression levels were measured on the Ham17+7 and the BDI-II, and circadian phase was estimated on the basis of daily sleep logs and self-reported morningness-eveningness. Among the 61 outpatients with complete data, both treatments were associated with significant antidepressant effect and phase advance. However, pre- and post-treatment comparisons found that the degree of symptom change did not correlate with the degree of phase change associated with treatment. The study therefore provides no evidence that circadian phase advance mediates the therapeutic mechanism in patients with SAD. Findings are discussed in terms of the limitations of the circadian measures employed.

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“…Serotonergic agents working via different mechanisms to enhance 5-HT neurotransmission, including d-fenfluramine (O'Rourke et al, 1987) and selective serotonin reuptake inhibitors (Moscovitch et al, 2004), have been found to be effective in the treatment of SAD. Moreover, circadian and 5-HT-related polymorphisms have been reported in people with SAD (Johansson et al, 2003).…”

Section: The 5-ht 1b Ko Mouse As a Model For Seasonal Affective Disormentioning

confidence: 99%

Photic Entrainment Is Altered in the 5-HT_1B Receptor Knockout Mouse

et al. 2006

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The hypothalamic suprachiasmatic nucleus (SCN) is a circadian oscillator that receives glutamatergic afferents from the retina and serotonergic afferents from the midbrain. Activation of presynaptic serotonin 1B (5-HT1B) receptors on retinal terminals in the SCN inhibits retinohypothalamic neurotransmission and light-induced behavioral phase shifts. To assess the role of 5-HT1B receptors in photic entrainment, 5-HT1B receptor knockout (5-HT1B KO) and wild-type (WT) mice were maintained in non-24 h L:D cycles (T cycles). WT mice entrained to T = 21 h and T = 22 h cycles, whereas 5-HT1B KO animals did not. 5-HT1B KO animals did entrain to T = 23 h and T = 26 h cycles, although their phase angle of entrainment was altered compared to WT animals. 5-HT1BKO mice were significantly more phase delayed under T = 23 h conditions and significantly more phase advanced under T = 26 h conditions compared to WT mice. When 5-HT1B KO mice were housed in a T = 23 h short-day photoperiod (9.5L:13.5D), the delayed phase angle of entrainment was more pronounced. Light-induced phase shifts were reduced in 5-HT1B KO mice, consistent with their behavior in T cycles, suggesting an attenuated response to light. Based on previous work, this attenuated response to light might not have been predicted but can be explained by consideration of GABAergic mechanisms within the SCN. Phase-delayed circadian rhythms during the short days of winter are characteristic of patients suffering from seasonal affective disorder, and 5-HT has been implicated in its pathophysiology. The 5-HT1B KO mouse may be useful for investigating the altered entrainment evident during this serious mood disorder.

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A placebo-controlled study of sertraline in the treatment of outpatients with seasonal affective disorder

Abstract: Sertraline pharmacotherapy has been demonstrated to be an effective and well-tolerated therapy for out patients with SAD. As such, sertraline offers an important pharmacological option in the clinical management of this condition.

Cited by 68 publications

References 35 publications

Enhanced Serotonin Transporter Function during Depression in Seasonal Affective Disorder

Enhanced Serotonin Transporter Function during Depression in Seasonal Affective Disorder

Therapeutic Mechanism in Seasonal Affective Disorder: Do Fluoxetine and Light Operate Through Advancing Circadian Phase?

Photic Entrainment Is Altered in the 5-HT_1B Receptor Knockout Mouse

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A placebo-controlled study of sertraline in the treatment of outpatients with seasonal affective disorder

Abstract: Sertraline pharmacotherapy has been demonstrated to be an effective and well-tolerated therapy for out patients with SAD. As such, sertraline offers an important pharmacological option in the clinical management of this condition.

Cited by 68 publications

References 35 publications

Enhanced Serotonin Transporter Function during Depression in Seasonal Affective Disorder

Enhanced Serotonin Transporter Function during Depression in Seasonal Affective Disorder

Therapeutic Mechanism in Seasonal Affective Disorder: Do Fluoxetine and Light Operate Through Advancing Circadian Phase?

Photic Entrainment Is Altered in the 5-HT1B Receptor Knockout Mouse

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Photic Entrainment Is Altered in the 5-HT_1B Receptor Knockout Mouse