title: Lithium augmentation increases the ACTH and cortisol response in the combined DEX/CRH test in unipolar major depression.
abstract: Lithium augmentation is a well established strategy for treatment-resistant depression. The exact mode of its action is unknown, but an enhancement of serotonergic transmission is hypothesized. The authors investigated changes in the hypothalamic-pituitary-adrenocortical (HPA) system during lithium augmentation and their correlation to clinical response by means of the combined dexamethasone/CRH test (DEX/CRH test). Thirty patients with unipolar major depressive episodes (DSM IV) who had not responded to an adequate trial with an antidepressant were assessed on the day before lithium augmentation (baseline) with the DEX/CRH test (pretreatment with 1.5 mg dexamethasone p.o. at 11 P.M. and CRH stimulation at 3 P.M. on the next day). Twenty-four patients were re-assessed after response was determined or, in cases of non-response, four weeks after initiation of lithium augmentation. Response to lithium augmentation was measured by weekly ratings on the Hamilton Depression Rating Scale (HDRS 17-item version). Response was defined as a DeltaHDRS of > or =50% and an endpoint score of < 10. Patients had a significantly higher ACTH and cortisol response to CRH stimulation during lithium augmentation compared with the values at baseline. There was no difference in ACTH and cortisol reaction between responders and non-responders to lithium augmentation. This increase is in contrast to the known normalization of HPA-axis overdrive after treatment with a tricyclic antidepressant like amitriptyline. Because the effect was independent of response status we suggest that this increase reflects an effect of lithium that is independent from the psychopathological state or its change. This effect might be explained by the serotonergic effects of lithium.
authors.affiliation: Department of Psychiatry, Technische Universität Dresden, Dresden, Germany. bschor@mailbox.tu-dresden.de
authors.forename: Tom
authors.initials: T
authors.lastname: Bschor
authors.forename: Mazda
authors.initials: M
authors.lastname: Adli
authors.forename: Christopher
authors.initials: C
authors.lastname: Baethge
authors.forename: Uta
authors.initials: U
authors.lastname: Eichmann
authors.forename: Marcus
authors.initials: M
authors.lastname: Ising
authors.forename: Manfred
authors.initials: M
authors.lastname: Uhr
authors.forename: Sieglinde
authors.initials: S
authors.lastname: Modell
authors.forename: Heike
authors.initials: H
authors.lastname: Künzel
authors.forename: Bruno
authors.initials: B
authors.lastname: Müller-Oerlinghausen
authors.forename: Michael
authors.initials: M
authors.lastname: Bauer
mesh_terms: D000293:Adolescent; D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000328:Adult; D000368:Aged; D003346:Corticotropin-Releasing Hormone / Q000627:therapeutic use*; D003866:Depressive Disorder / Q000097:blood / Q000188:drug therapy*; D003907:Dexamethasone / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000503:physiopathology; D008094:Lithium / Q000627:therapeutic use*; D008297:Male; D016555:Matched-Pair Analysis; D008875:Middle Aged; D018709:Statistics, Nonparametric; D016896:Treatment Outcome
chemical_list: D005938:Glucocorticoids; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D008094:Lithium; D006854:Hydrocortisone