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P.1.026 Efficacy of sertraline in an anxious subgroupof youths with major depression
PJ, Affective disorders and antidepre~sa~t~
S186
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Efficacy of sertraline in an anxious subgroup of youths with major depression
K.D. Wagner I , P. Ambrosini 2, .T, Qillespie 3 , R. Yang 3 . z University
of Texas Medical Branch, P~ychiatry & Behavioral gcience~, Galveston, U~S,A,; 2©rexel University College of Medicine, Psychiatry, Pf#ladelp~ia, ~SA,," SPfizer Inc,, CNS, New York, US.A.
Background:
In childhood depression, little is known about treatment response in various clinically meaningful subgroups. The goal of this analysis was to evaluate the efficacy of sertraline in depressed youths with above average anxiety. Metllods: This is a secondary analysis of combined data from 2 previously reported 8 week, double-blind studies of sertraline (N=189; 4,S% male; 46% ages 6-11; mean baseline Children's Depression Rating Scale-revised [CDRS-R], 64.3) vs. placebo (N=187; 55% male; 49% ages 6--11; mean baseline CDRSR, 64.6) in MDD. The anxious-depression subtype, based on normative data, by a baseline MASC total score >51 (males) and >58 (females). Primary assessment of efficacy consisted of LOCFendpoint change in the CDRS-R scale and CGI-I responder status (C @1-1 score<2). Results: For depressed patients meeting MASC criteria for above average anxiety wmptoms (N=161; 43% of the total sampie), treatment with sertraline resulted in significantly greater efficacy than placebo on the CDRS-R (-30.0 + 1.6 vs.-25.2 + 1.6; p<0.05). The antidepressant effect size for patients with above average anxiety was somewhat larger than the effect size for the total sample. C o n c i s i o n - " Sertraline demonstrates efficacy in depressed youths with above average symptoms of anxiety. In order to optimize treatment response in childhood depression, more research is needed that evaluates the benefits of antidepressants on clinically meaningful subgroups. References
[i] Wagner KD~ Ambrosini P~ Rynn M, etal. Sertraline Pediatric Depression ~udy Group. Efficacy of sertralinein thetreatment of children and adolescents with major depressive disorder: two randomized controlled trials..IAMA 2003;290:1033-i 041. [2] Varley CK. Psyohopharmacologieal treatment of major depressive disorder in children and adolescents. JAMA 2003;290:i091-i093.
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and/or a greater effect on the 5-ttT system in OCD subjects than Citalopram alone. Methods" 49 patients with OCD (DSIVl IV) without comerbid depression were randomly assigned to a 2-tailed, singleblind, 12-week clinical trial with Citalopram (40-80 mg) plus placebo (CIT+PLC) or Citalopram plus Mirtazapine (CIT+NIR) (15-30 mg). Only patients with OCD symptoms of at leazt 1 year's duration and of at least moderate severity on the Clinical Global Impression Scale (CGI) were included. Assessments were performed weekly with ¥-t)OCS, I-IRSD and CGI. Results: According to Y-t)OCS and CGI, the CIT+MYR group achieved a reduction of at least 35% in Y-BOCS and "much" or "very much improved" in CGI from the 4th week, while the CIT+PLC group obtained these results only from the 8th week. The number of responders was higher in the CIT+MIR group at the 4th week of treatment, while no difference in the re, ponders' rate was noted at the 8th and 12th w e e k of treatment. Conclusions: We found an earlier onset of response action in OCD symptoms and reduced undesired side-effects when Mirtazapine was added to Citalopram. The blocking of alphaadrenergic receptors by Mirtazapine, in addition to SSRI activiW, could be important in order to make the response in ©CD faster28. Specifically, the mechanism could be related to Mirtazapine's specific blocking of alpha-adrenergic hetemreceptors on serotonergic terminals in the prefrontal cortex, which play a role in alterations of hippoeampal 5-t-IT, in combination with SSRI activity. This augmentation strategy deserves clinical and research consideration through further double-blind placebo-controlled studies.
References [1] Nutt DJ'. Tolerability and safety aspects of Mktazapine. Hum Psy&opharmacol 2002, 17 (Suppl. 1): $37-41. [2] Quitkin FM, Taylor BP, Kr~'ner C: Does mirtazapine have a more rapid onset than SSRIs? J Clin Pay&Jetty 2001, May, 62(5): 358-61. [3] Pallanti S, Queroioli L, Koran LM: Citalopram intravenous inNsion in resistant OCD and open trial. J Clin Psychiatry 2002, 63 (9): 796-801.
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Multihormonal correlates of personality dimensions in depression
J.A. Monreal Ortiz I , lq Dural I , M.C. Mokrani 2, G. Pinanlt 3, L. Staner 1 , M.L. Ats61, ;.P. Macher 1. 1Cemre Hospitalier de
Rouffach, Yorenap, Secteur VIII, 8ouffach, France; 2Forenap, Rouffach, France; SForenay, &atistiques, i~ouffach, France Mirtazapine augmentation of citalopram accelerates response in OCD patients without comorbid depression: A pilot study
L. Quercioli 1, Ivf. Bruscoli 1, S. Pallanti 2, 1Institute Di Neuroscienze, Psychiatry, Firenze, Italy," 2 University Of Florence, Psychiatry, Fire~ze, Italy
Background: Therapeutic action of SaRis is delayed from between 8 to 12 weeks in patients with Obsessive-Compulsive Disorder (OCD). Several different agents have been tested to reduce the SSRI therapeutic latency time. Mirtazapine, an antagonist at alpha2-adrenoceptors, does not enhance 5-KT neurotransmission directly but disinhibits the norepinephrine activation of 5-HT neurons and thereby increases 5-t-IT neurotransmission by a mechanism that may not require a time-dependent desensitization of receptors. The present study was undertaken to determine whether the Ivfirtazapine-Citaloprarn combination could induce an exrlier
Bae~round: The aim of this study was to investigate the relationships between Temperament and Character Inventory (TCI) scores and multihormonal responses to a series of neuroendocrine challenges in depressed patients. IVletho& Endocrine responses to 8 AiM and I 1 PM protirelin tests (TRI4, 200I~g . IV), dexametMsone suppression test (DST, 1 mg orally) and apomorphine test (APO, 0.75 rug S.C.)(a dopamin6 (DA) agonist), were examined in 21 drug-free DSM-IV non-psychotic major depressed inpaients. Results: Persistence scores were negatively correlated with APO-stimulated cortisol values (rho = -0.50; p=0.02) and positively with basal oortisol values (rho=0.54; p=0.01). Cooperativen~s scores were negatively correlated with APO-stimulated adrenocorticotropic hormone and cortisol values (rho = - 0 . 5 1 ; p=0.02, and rho = -0.48; p=0.03, respectively) and were correlated positively with basal cortisol values (rho=0.56; p=0.01). Empathy scores were correlated with g-AM and 11-PM ATSI-I
S186
•
Efficacy of sertraline in an anxious subgroup of youths with major depression
K.D. Wagner I , P. Ambrosini 2, .T, Qillespie 3 , R. Yang 3 . z University
of Texas Medical Branch, P~ychiatry & Behavioral gcience~, Galveston, U~S,A,; 2©rexel University College of Medicine, Psychiatry, Pf#ladelp~ia, ~SA,," SPfizer Inc,, CNS, New York, US.A.
Background:
In childhood depression, little is known about treatment response in various clinically meaningful subgroups. The goal of this analysis was to evaluate the efficacy of sertraline in depressed youths with above average anxiety. Metllods: This is a secondary analysis of combined data from 2 previously reported 8 week, double-blind studies of sertraline (N=189; 4,S% male; 46% ages 6-11; mean baseline Children's Depression Rating Scale-revised [CDRS-R], 64.3) vs. placebo (N=187; 55% male; 49% ages 6--11; mean baseline CDRSR, 64.6) in MDD. The anxious-depression subtype, based on normative data, by a baseline MASC total score >51 (males) and >58 (females). Primary assessment of efficacy consisted of LOCFendpoint change in the CDRS-R scale and CGI-I responder status (C @1-1 score<2). Results: For depressed patients meeting MASC criteria for above average anxiety wmptoms (N=161; 43% of the total sampie), treatment with sertraline resulted in significantly greater efficacy than placebo on the CDRS-R (-30.0 + 1.6 vs.-25.2 + 1.6; p<0.05). The antidepressant effect size for patients with above average anxiety was somewhat larger than the effect size for the total sample. C o n c i s i o n - " Sertraline demonstrates efficacy in depressed youths with above average symptoms of anxiety. In order to optimize treatment response in childhood depression, more research is needed that evaluates the benefits of antidepressants on clinically meaningful subgroups. References
[i] Wagner KD~ Ambrosini P~ Rynn M, etal. Sertraline Pediatric Depression ~udy Group. Efficacy of sertralinein thetreatment of children and adolescents with major depressive disorder: two randomized controlled trials..IAMA 2003;290:1033-i 041. [2] Varley CK. Psyohopharmacologieal treatment of major depressive disorder in children and adolescents. JAMA 2003;290:i091-i093.
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and/or a greater effect on the 5-ttT system in OCD subjects than Citalopram alone. Methods" 49 patients with OCD (DSIVl IV) without comerbid depression were randomly assigned to a 2-tailed, singleblind, 12-week clinical trial with Citalopram (40-80 mg) plus placebo (CIT+PLC) or Citalopram plus Mirtazapine (CIT+NIR) (15-30 mg). Only patients with OCD symptoms of at leazt 1 year's duration and of at least moderate severity on the Clinical Global Impression Scale (CGI) were included. Assessments were performed weekly with ¥-t)OCS, I-IRSD and CGI. Results: According to Y-t)OCS and CGI, the CIT+MYR group achieved a reduction of at least 35% in Y-BOCS and "much" or "very much improved" in CGI from the 4th week, while the CIT+PLC group obtained these results only from the 8th week. The number of responders was higher in the CIT+MIR group at the 4th week of treatment, while no difference in the re, ponders' rate was noted at the 8th and 12th w e e k of treatment. Conclusions: We found an earlier onset of response action in OCD symptoms and reduced undesired side-effects when Mirtazapine was added to Citalopram. The blocking of alphaadrenergic receptors by Mirtazapine, in addition to SSRI activiW, could be important in order to make the response in ©CD faster28. Specifically, the mechanism could be related to Mirtazapine's specific blocking of alpha-adrenergic hetemreceptors on serotonergic terminals in the prefrontal cortex, which play a role in alterations of hippoeampal 5-t-IT, in combination with SSRI activity. This augmentation strategy deserves clinical and research consideration through further double-blind placebo-controlled studies.
References [1] Nutt DJ'. Tolerability and safety aspects of Mktazapine. Hum Psy&opharmacol 2002, 17 (Suppl. 1): $37-41. [2] Quitkin FM, Taylor BP, Kr~'ner C: Does mirtazapine have a more rapid onset than SSRIs? J Clin Pay&Jetty 2001, May, 62(5): 358-61. [3] Pallanti S, Queroioli L, Koran LM: Citalopram intravenous inNsion in resistant OCD and open trial. J Clin Psychiatry 2002, 63 (9): 796-801.
•
Multihormonal correlates of personality dimensions in depression
J.A. Monreal Ortiz I , lq Dural I , M.C. Mokrani 2, G. Pinanlt 3, L. Staner 1 , M.L. Ats61, ;.P. Macher 1. 1Cemre Hospitalier de
Rouffach, Yorenap, Secteur VIII, 8ouffach, France; 2Forenap, Rouffach, France; SForenay, &atistiques, i~ouffach, France Mirtazapine augmentation of citalopram accelerates response in OCD patients without comorbid depression: A pilot study
L. Quercioli 1, Ivf. Bruscoli 1, S. Pallanti 2, 1Institute Di Neuroscienze, Psychiatry, Firenze, Italy," 2 University Of Florence, Psychiatry, Fire~ze, Italy
Background: Therapeutic action of SaRis is delayed from between 8 to 12 weeks in patients with Obsessive-Compulsive Disorder (OCD). Several different agents have been tested to reduce the SSRI therapeutic latency time. Mirtazapine, an antagonist at alpha2-adrenoceptors, does not enhance 5-KT neurotransmission directly but disinhibits the norepinephrine activation of 5-HT neurons and thereby increases 5-t-IT neurotransmission by a mechanism that may not require a time-dependent desensitization of receptors. The present study was undertaken to determine whether the Ivfirtazapine-Citaloprarn combination could induce an exrlier
Bae~round: The aim of this study was to investigate the relationships between Temperament and Character Inventory (TCI) scores and multihormonal responses to a series of neuroendocrine challenges in depressed patients. IVletho& Endocrine responses to 8 AiM and I 1 PM protirelin tests (TRI4, 200I~g . IV), dexametMsone suppression test (DST, 1 mg orally) and apomorphine test (APO, 0.75 rug S.C.)(a dopamin6 (DA) agonist), were examined in 21 drug-free DSM-IV non-psychotic major depressed inpaients. Results: Persistence scores were negatively correlated with APO-stimulated cortisol values (rho = -0.50; p=0.02) and positively with basal oortisol values (rho=0.54; p=0.01). Cooperativen~s scores were negatively correlated with APO-stimulated adrenocorticotropic hormone and cortisol values (rho = - 0 . 5 1 ; p=0.02, and rho = -0.48; p=0.03, respectively) and were correlated positively with basal cortisol values (rho=0.56; p=0.01). Empathy scores were correlated with g-AM and 11-PM ATSI-I