title: Clinical and neurobiological effects of tianeptine and paroxetine in major depression.
abstract: Selective serotonin reuptake inhibitors (SSRIs) are widely used as effective pharmacological agents to treat depressive disorders. In contrast to the SSRIs, which block the presynaptic serotonin (5-HT) transporter and by this route increase the concentration of serotonin in the synaptic cleft, the antidepressant tianeptine enhances the presynaptic neuronal reuptake of 5-HT and thus decreases serotonergic neurotransmission. Both SSRIs and tianeptine are clinically effective; however, their opposite modes of action challenge the prevailing concepts on the need of enhancement of serotonergic neurotransmission. To better understand the differences between these two opposite pharmacological modes of action, we compared the changes induced by tianeptine and paroxetine on psychopathology, the hypothalamic-pituitary-adrenocortical (HPA) system, and cognitive functions in a double-blind, randomized, controlled trial including 44 depressed inpatients over a period of 42 days. Depressive symptomatology significantly improved in all efficacy measures, with no significant differences between tianeptine and paroxetine. There was a trend toward better response to the SSRI among women. Assessment of the HPA system showed marked hyperactivity before the beginning of treatment, which then normalized in most of the patients, without significant differences between the two antidepressants. Cognitive assessments showed no significant differences between the two drugs investigated. The results of the current study suggest that the initial effect, i.e., enhancement or decrease of 5-HT release, is only indirectly responsible for antidepressant efficacy, and they support the notion that downstream adaptations within and between nerve cells are crucial. The normalization of the HPA system as a common mode of action of different antidepressants seems to be of special interest.
authors.affiliation: Max Planck Institute of Psychiatry, Munich, Germany. nickel@mpipsykl.mpg.de
authors.forename: Thomas
authors.initials: T
authors.lastname: Nickel
authors.forename: Annette
authors.initials: A
authors.lastname: Sonntag
authors.forename: Julia
authors.initials: J
authors.lastname: Schill
authors.forename: Astrid W
authors.initials: AW
authors.lastname: Zobel
authors.forename: Nibal
authors.initials: N
authors.lastname: Ackl
authors.forename: Alexander
authors.initials: A
authors.lastname: Brunnauer
authors.forename: Harald
authors.initials: H
authors.lastname: Murck
authors.forename: Marcus
authors.initials: M
authors.lastname: Ising
authors.forename: Alexander
authors.initials: A
authors.lastname: Yassouridis
authors.forename: Axel
authors.initials: A
authors.lastname: Steiger
authors.forename: Josef
authors.initials: J
authors.lastname: Zihl
authors.forename: Florian
authors.initials: F
authors.lastname: Holsboer
mesh_terms: D000328:Adult; D000368:Aged; D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use*; D000929:Antidepressive Agents, Tricyclic / Q000627:therapeutic use*; D003071:Cognition / Q000187:drug effects; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D017374:Paroxetine / Q000627:therapeutic use*; D011569:Psychiatric Status Rating Scales; D011594:Psychometrics; D013647:Task Performance and Analysis; D013841:Thiazepines / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D018687:Antidepressive Agents, Second-Generation; D000929:Antidepressive Agents, Tricyclic; D013841:Thiazepines; C050504:tianeptine; D017374:Paroxetine