Thu, 21 Aug 2008 17:25:11 BST CiteULike: pseudopharm Allen http://www.citeulike.org/user/pseudopharm/author/Allen CiteULike.org en-gb Copyright © 2004-2008 citeulike.org http://www.citeulike.org/user/pseudopharm/article/2708117 <i>Drug safety : an international journal of medical toxicology and drug experience, Vol. 31, No. 4. (2008), pp. 345-354.</i><br /><br />OBJECTIVE: This study describes and assesses potential hepatobiliary events related to atomoxetine therapy, as reported in clinical trials and as spontaneous adverse event reports post-launch in 2002. METHODS: Case reports that contained potential hepatobiliary events were identified by a computerized search of the Eli Lilly and Company atomoxetine spontaneous adverse events and clinical trials databases. All cases were reviewed by at least two company physicians, one with expertise in hepatology, to determine the relevance of the information in respect of potential liver toxicity. RESULTS: Of 7961 paediatric and adult patients treated with atomoxetine in clinical trials, 41 were identified as having hepatobiliary events requiring additional analysis. Most of these events were mild increases in ALT and AST levels. None of these cases met Hy's rule criteria or progressed to liver failure. During the 4 years after market launch, 351 spontaneous reports of adverse events were related to the liver, of which 69 had other explanations unrelated to atomoxetine. Of the remaining 282 cases, 133 contained possible confounding factors (and were deemed to be possibly related), 146 presented too little information to assess, and three suggested atomoxetine as a probable cause of liver injuries. One of the three had a positive rechallenge. All three patients recovered after discontinuation of the drug. CONCLUSIONS: Since the launch of atomoxetine therapy, three spontaneously reported cases of reversible drug-induced liver injury were deemed probably related to it. Atomoxetine should be discontinued in patients with jaundice or laboratory evidence of liver injury and should not be restarted. Hepatic events associated with atomoxetine treatment for attention-deficit hyperactivity disorder. ME Bangs L Jin S Zhang D Desaiah AJ Allen HA Read A Regev JF Wernicke Drug safety : an international journal of medical toxicology and drug experience, Vol. 31, No. 4. (2008), pp. 345-354. 2008-04-23T16:26:01-00:00 2008 Drug safety : an international journal of medical toxicology and drug experience 0114-5916 31 4 345 354 adhd anti_depressant gi side_effect http://www.citeulike.org/user/pseudopharm/article/1198973 <i>N Engl J Med (28 March 2007)</i><br /><br />BACKGROUND: Episodes of depression are the most frequent cause of disability among patients with bipolar disorder. The effectiveness and safety of standard antidepressant agents for depressive episodes associated with bipolar disorder (bipolar depression) have not been well studied. Our study was designed to determine whether adjunctive antidepressant therapy reduces symptoms of bipolar depression without increasing the risk of mania. METHODS: In this double-blind, placebo-controlled study, we randomly assigned subjects with bipolar depression to receive up to 26 weeks of treatment with a mood stabilizer plus adjunctive antidepressant therapy or a mood stabilizer plus a matching placebo, under conditions generalizable to routine clinical care. A standardized clinical monitoring form adapted from the mood-disorder modules of the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, was used at all follow-up visits. The primary outcome was the percentage of subjects in each treatment group meeting the criterion for a durable recovery (8 consecutive weeks of euthymia). Secondary effectiveness outcomes and rates of treatment-emergent affective switch (a switch to mania or hypomania early in the course of treatment) were also examined. RESULTS: Forty-two of the 179 subjects (23.5%) receiving a mood stabilizer plus adjunctive antidepressant therapy had a durable recovery, as did 51 of the 187 subjects (27.3%) receiving a mood stabilizer plus a matching placebo (P=0.40). Modest nonsignificant trends favoring the group receiving a mood stabilizer plus placebo were observed across the secondary outcomes. Rates of treatment-emergent affective switch were similar in the two groups. CONCLUSIONS: The use of adjunctive, standard antidepressant medication, as compared with the use of mood stabilizers, was not associated with increased efficacy or with increased risk of treatment-emergent affective switch. Longer-term outcome studies are needed to fully assess the benefits and risks of antidepressant therapy for bipolar disorder. (ClinicalTrials.gov number, NCT00012558.) Copyright 2007 Massachusetts Medical Society. Effectiveness of Adjunctive Antidepressant Treatment for Bipolar Depression. Gary S Sachs Andrew A Nierenberg Joseph R Calabrese Lauren B Marangell Stephen R Wisniewski Laszlo Gyulai Edward S Friedman Charles L Bowden Mark D Fossey Michael J Ostacher Terence A Ketter Jayendra Patel Peter Hauser Daniel Rapport James M Martinez Michael H Allen David J Miklowitz Michael W Otto Ellen B Dennehy Michael E Thase doi:10.1056/NEJMoa064135 N Engl J Med (28 March 2007) 2007-03-30T21:32:13-00:00 2007 N Engl J Med 1533-4406 anti_depressant bipolar clinical_trial mood_stabilizer