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<meta name="robots" content="INDEX,FOLLOW,NOARCHIVE" /><meta name="citation_inbook_title" content="LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]" /><meta name="citation_title" content="Trazodone" /><meta name="citation_publisher" content="National Institute of Diabetes and Digestive and Kidney Diseases" /><meta name="citation_date" content="2020/02/26" /><meta name="citation_pmid" content="31643874" /><meta name="citation_fulltext_html_url" content="https://www.ncbi.nlm.nih.gov/books/NBK548557/" /><link rel="schema.DC" href="http://purl.org/DC/elements/1.0/" /><meta name="DC.Title" content="Trazodone" /><meta name="DC.Type" content="Text" /><meta name="DC.Publisher" content="National Institute of Diabetes and Digestive and Kidney Diseases" /><meta name="DC.Date" content="2020/02/26" /><meta name="DC.Identifier" content="https://www.ncbi.nlm.nih.gov/books/NBK548557/" /><meta name="description" content="Trazodone is a serotoninergic modulating antidepressant that is used in therapy of depression, aggressive behavior and panic disorder. Trazodone therapy can be associated with transient, usually asymptomatic elevations in serum aminotransferase levels and has been linked to rare instances of clinically apparent acute liver injury." /><meta name="og:title" content="Trazodone" /><meta name="og:type" content="book" /><meta name="og:description" content="Trazodone is a serotoninergic modulating antidepressant that is used in therapy of depression, aggressive behavior and panic disorder. Trazodone therapy can be associated with transient, usually asymptomatic elevations in serum aminotransferase levels and has been linked to rare instances of clinically apparent acute liver injury." /><meta name="og:url" content="https://www.ncbi.nlm.nih.gov/books/NBK548557/" /><meta name="og:site_name" content="NCBI Bookshelf" /><meta name="og:image" content="https://www.ncbi.nlm.nih.gov/corehtml/pmc/pmcgifs/bookshelf/thumbs/th-livertox-lrg.png" /><meta name="twitter:card" content="summary" /><meta name="twitter:site" content="@ncbibooks" /><meta name="bk-non-canon-loc" content="/books/n/livertox/Trazodone/" /><link rel="canonical" href="https://www.ncbi.nlm.nih.gov/books/NBK548557/" /><link rel="stylesheet" href="/corehtml/pmc/css/figpopup.css" type="text/css" media="screen" /><link rel="stylesheet" href="/corehtml/pmc/css/bookshelf/2.26/css/books.min.css" type="text/css" /><link rel="stylesheet" href="/corehtml/pmc/css/bookshelf/2.26/css/books_print.min.css" type="text/css" media="print" /><style type="text/css">p a.figpopup{display:inline !important} .bk_tt {font-family: monospace} .first-line-outdent .bk_ref {display: inline} .body-content h2, .body-content .h2 {border-bottom: 1px solid #97B0C8} .body-content h2.inline {border-bottom: none} a.page-toc-label , .jig-ncbismoothscroll a {text-decoration:none;border:0 !important} .temp-labeled-list .graphic {display:inline-block !important} .temp-labeled-list img{width:100%}</style><script type="text/javascript" src="/corehtml/pmc/js/jquery.hoverIntent.min.js"> </script><script type="text/javascript" src="/corehtml/pmc/js/common.min.js?_=3.18"> </script><script type="text/javascript" src="/corehtml/pmc/js/large-obj-scrollbars.min.js"> </script><script type="text/javascript">window.name="mainwindow";</script><script type="text/javascript" src="/corehtml/pmc/js/bookshelf/2.26/book-toc.min.js"> </script><script type="text/javascript" src="/corehtml/pmc/js/bookshelf/2.26/books.min.js"> </script><meta name="book-collection" content="NONE" />
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<div class="pre-content"><div><div class="bk_prnt"><p class="small">NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.</p><p>LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. </p></div><div class="iconblock clearfix whole_rhythm no_top_margin bk_noprnt"><a class="img_link icnblk_img" title="All Drug Records" href="/books/n/livertox/"><img class="source-thumb" src="/corehtml/pmc/pmcgifs/bookshelf/thumbs/th-livertox-lrg.png" alt="Cover of LiverTox" height="100px" width="80px" /></a><div class="icnblk_cntnt eight_col"><h2>LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet].</h2><a data-jig="ncbitoggler" href="#__NBK548557_dtls__">Show details</a><div style="display:none" class="ui-widget" id="__NBK548557_dtls__"><div>Bethesda (MD): <a href="https://www.niddk.nih.gov/" ref="pagearea=page-banner&targetsite=external&targetcat=link&targettype=publisher">National Institute of Diabetes and Digestive and Kidney Diseases</a>; 2012-.</div></div><div class="half_rhythm"><ul class="inline_list"><li style="margin-right:1em"><a class="bk_cntns" href="/books/n/livertox/">Drug Records</a></li></ul></div><div class="bk_noprnt"><form method="get" action="/books/n/livertox/" id="bk_srch"><div class="bk_search"><label for="bk_term" class="offscreen_noflow">Search term</label><input type="text" title="Search this book" id="bk_term" name="term" value="" data-jig="ncbiclearbutton" /> <input type="submit" class="jig-ncbibutton" value="Search this book" submit="false" style="padding: 0.1em 0.4em;" /></div></form></div></div><div class="icnblk_cntnt two_col"><div class="pagination bk_noprnt"><a class="active page_link prev" href="/books/n/livertox/TrastuzumabEmtansine/" title="Previous page in this title">< Prev</a><a class="active page_link next" href="/books/n/livertox/Tremelimumab/" title="Next page in this title">Next ></a></div></div></div></div></div>
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<div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><h1 id="_NBK548557_"><span class="title" itemprop="name">Trazodone</span></h1><p class="small">Last Update: <span itemprop="dateModified">February 26, 2020</span>.</p></div><div class="body-content whole_rhythm" itemprop="text"><div id="Trazodone.OVERVIEW"><h2 id="_Trazodone_OVERVIEW_">OVERVIEW</h2><div id="Trazodone.Introduction"><h3>Introduction</h3><p>Trazodone is a serotoninergic modulating antidepressant that is used in therapy of depression, aggressive behavior and panic disorder. Trazodone therapy can be associated with transient, usually asymptomatic elevations in serum aminotransferase levels and has been linked to rare instances of clinically apparent acute liver injury.</p></div><div id="Trazodone.Background"><h3>Background</h3><p>Trazodone (traz' oh done) is a triazolopyridine derivative whose mechanism of action is believed to be inhibition of serotonin reuptake and modulation of serotonin receptor activity, which results in increased levels and activity of serotonin. Trazodone was approved for use in major depressive disorder in the United States in 1981 and remains in wide use, with more than 22 million prescriptions being filled yearly. Trazodone is also used off-label for control of aggressive behavior, panic disorder, anxiety, insomnia, substance abuse, bulimia, schizophrenia and dementia. Trazodone has anxiolytic activity and normalizes sleep patterns, effects that have made trazodone one of the most frequently prescribed drugs for insomnia. Trazodone is available in tablets of 50, 75, 100, 150 and 300 mg in several generic forms and formerly under the brand name Desyrel. The recommended dosage for depression in adults is 150 mg in divided doses that can be increased in 50 mg amounts to a maximum of 600 mg daily. An extended release formulation is also available in 150 mg tablets (Oleptro) which is given once daily. It is typically given in single, bedtime lower doses for insomnia. Common side effects of trazodone are drowsiness, fatigue, dizziness, headache, dry mouth, blurred vision, nausea, decreased libido, increased appetite and weight gain. Uncommon but potentially severe adverse events include suicidal thoughts and behaviors, activation of mania, serotonin syndrome, cardiac arrhythmias, orthostatic hypotension, priapism and angle-closure glaucoma.</p></div><div id="Trazodone.Hepatotoxicity"><h3>Hepatotoxicity</h3><p><a class="def" href="/books/n/livertox/glossary/def-item/glossary.liver-test-abnormalities/">Liver test abnormalities</a> occur in a proportion of patients on trazodone, but elevations are usually modest and usually do not require dose modification or discontinuation. At least a dozen instances of acute, clinically apparent episodes of liver injury with marked liver enzyme elevations with or without jaundice have been reported in patients on trazodone. The onset of injury varies from a few days to 6 months and the pattern of serum enzyme elevations is usually hepatocellular, but mixed and cholestatic forms have also been described. Several cases have had immunoallergic features (rash, fever, eosinophilia), but these were not prominent. Autoimmune (autoantibodies) features are uncommon. Rare instances of acute liver failure and death from trazodone have been reported. Nefazodone, an antidepressant similar in structure and mechanism of action to trazodone, was approved for use in 1998, but is currently not commonly used because of multiple reports of acute hepatocellular injury, with a high mortality rate arising 2 weeks to 6 months after starting therapy.</p><p><a class="def" href="/books/n/livertox/glossary/def-item/glossary.likelihood-score/">Likelihood score</a>: B (likely but rare cause of clinically apparent liver injury).</p></div><div id="Trazodone.Mechanism_of_Injury"><h3>Mechanism of Injury</h3><p>The mechanism by which trazodone causes liver injury is not known. Trazodone is extensively metabolized by the liver, mainly via the cytochrome P450 system (CYP3A4), and hepatotoxicity may be mediated by toxic intermediates of its metabolism. Trazodone is susceptible to multiple drug-drug interactions.</p></div><div id="Trazodone.Outcome_and_Management"><h3>Outcome and Management</h3><p>The serum aminotransferase elevations that occur on trazodone therapy are usually self-limited and do not require dose modification or discontinuation of therapy. Rare instances of acute liver failure and chronic hepatitis have been attributed to trazodone therapy. Persons with intolerance to trazodone may have similar reactions to other antidepressants, and careful monitoring is warranted if other such agents are used.</p><p>Drug Class: <a href="/books/n/livertox/Antidepressants/">Antidepressant Agents</a></p><p>Other Drugs in the Subclass: <a href="/books/n/livertox/Nefazodone/">Nefazodone</a></p></div></div><div id="Trazodone.CASE_REPORT"><h2 id="_Trazodone_CASE_REPORT_">CASE REPORT</h2><div id="Trazodone.Case_1_Acute_hepatitis_due_to"><h3>Case 1. Acute hepatitis due to trazodone.(<a class="bk_pop" href="#Trazodone.REF.1">1</a>)</h3><p>A 38 year old woman with rheumatoid arthritis developed itching followed by jaundice approximately 18 months after starting trazodone. She was also receiving prednisone (10 mg daily), methotrexate, hydroxychloroquine, nabumetone, propoxyphene, folate, birth control pills and alendronate, but had been on this regimen for many years. She had no history of liver disease or known risk behaviors for acquiring hepatitis and did not drink alcohol. On examination, she was jaundiced but had no rash, fever or signs of chronic liver disease. Laboratory results showed a bilirubin of 11.0 mg/dL with marked elevations in serum aminotransferase levels (Table). Her liver tests had been normal on routine testing several months previously. Tests for hepatitis A, B and C were negative as were autoantibodies. An abdominal ultrasound showed no evidence of biliary obstruction. A liver biopsy showed intrahepatic cholestasis, modest inflammation, and ballooning degeneration but no fat or fibrosis. Trazodone was stopped, and she began to improve rapidly. She was discharged from the hospital, but one week later restarted trazodone. After two days she had a return of her symptoms and jaundice. Within two weeks of stopping trazodone for the second time, she had no symptoms of liver disease and her liver tests were near-normal.</p><div id="Trazodone.Key_Points"><h4>Key Points</h4><div id="Trazodone.Tc" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK548557/table/Trazodone.Tc/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__Trazodone.Tc_lrgtbl__"><table><tbody><tr><th id="hd_b_Trazodone.Tc_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Medication:</th><td headers="hd_b_Trazodone.Tc_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Trazodone</td></tr><tr><th id="hd_b_Trazodone.Tc_1_1_2_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Pattern:</th><td headers="hd_b_Trazodone.Tc_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Hepatocellular (R=5.8)</td></tr><tr><th id="hd_b_Trazodone.Tc_1_1_3_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Severity:</th><td headers="hd_b_Trazodone.Tc_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">3+ (jaundice, hospitalization)</td></tr><tr><th id="hd_b_Trazodone.Tc_1_1_4_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><a class="def" href="/books/n/livertox/glossary/def-item/glossary.latency/">Latency</a>:</th><td headers="hd_b_Trazodone.Tc_1_1_4_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Initially 18 months, with rechallenge 3 days</td></tr><tr><th id="hd_b_Trazodone.Tc_1_1_5_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Recovery:</th><td headers="hd_b_Trazodone.Tc_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Within 1 month</td></tr><tr><th id="hd_b_Trazodone.Tc_1_1_6_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Other medications:</th><td headers="hd_b_Trazodone.Tc_1_1_6_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Prednisone, methotrexate, hydroxychloroquine, nabumetone, propoxyphene, folate, birth control pills, alendrolate.</td></tr></tbody></table></div></div></div><div id="Trazodone.Laboratory_Values"><h4>Laboratory Values</h4><div id="Trazodone.Td" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK548557/table/Trazodone.Td/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__Trazodone.Td_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_Trazodone.Td_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Time After<br />Starting</th><th id="hd_h_Trazodone.Td_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Time After<br />Stopping</th><th id="hd_h_Trazodone.Td_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><a class="def" href="/books/n/livertox/glossary/def-item/glossary.alanine-aminotransferase-alt-/">ALT</a><br />(U/L)</th><th id="hd_h_Trazodone.Td_1_1_1_4" scope="col" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Alk P<br />(U/L)</th><th id="hd_h_Trazodone.Td_1_1_1_5" scope="col" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><a class="def" href="/books/n/livertox/glossary/def-item/glossary.bilirubin/">Bilirubin</a><br />(mg/dL)</th><th id="hd_h_Trazodone.Td_1_1_1_6" scope="col" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Other</th></tr></thead><tbody><tr><td headers="hd_h_Trazodone.Td_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">12 months</td><td headers="hd_h_Trazodone.Td_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td><td headers="hd_h_Trazodone.Td_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">13</td><td headers="hd_h_Trazodone.Td_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">64</td><td headers="hd_h_Trazodone.Td_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">0.8</td><td headers="hd_h_Trazodone.Td_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Routine testing</td></tr><tr><td headers="hd_h_Trazodone.Td_1_1_1_1 hd_h_Trazodone.Td_1_1_1_2 hd_h_Trazodone.Td_1_1_1_3 hd_h_Trazodone.Td_1_1_1_4 hd_h_Trazodone.Td_1_1_1_5 hd_h_Trazodone.Td_1_1_1_6" colspan="6" scope="col" rowspan="1" style="text-align:center;vertical-align:top;">Onset of pruritus and jaundice 18 months after starting trazodone</td></tr><tr><td headers="hd_h_Trazodone.Td_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">18 months</td><td headers="hd_h_Trazodone.Td_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">0</td><td headers="hd_h_Trazodone.Td_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1092</td><td headers="hd_h_Trazodone.Td_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">206</td><td headers="hd_h_Trazodone.Td_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">11.0</td><td headers="hd_h_Trazodone.Td_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_Trazodone.Td_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td><td headers="hd_h_Trazodone.Td_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">3 days</td><td headers="hd_h_Trazodone.Td_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">786</td><td headers="hd_h_Trazodone.Td_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">191</td><td headers="hd_h_Trazodone.Td_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">8.7</td><td headers="hd_h_Trazodone.Td_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_Trazodone.Td_1_1_1_1 hd_h_Trazodone.Td_1_1_1_2 hd_h_Trazodone.Td_1_1_1_3 hd_h_Trazodone.Td_1_1_1_4 hd_h_Trazodone.Td_1_1_1_5 hd_h_Trazodone.Td_1_1_1_6" colspan="6" scope="col" rowspan="1" style="text-align:center;vertical-align:top;">Discharged from hospital and restarted trazodone shortly thereafter</td></tr><tr><td headers="hd_h_Trazodone.Td_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td><td headers="hd_h_Trazodone.Td_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">10 (0) days</td><td headers="hd_h_Trazodone.Td_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1476</td><td headers="hd_h_Trazodone.Td_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">259</td><td headers="hd_h_Trazodone.Td_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">10.3</td><td headers="hd_h_Trazodone.Td_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_Trazodone.Td_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td><td headers="hd_h_Trazodone.Td_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">15 (5) days</td><td headers="hd_h_Trazodone.Td_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">466</td><td headers="hd_h_Trazodone.Td_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">202</td><td headers="hd_h_Trazodone.Td_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">3.3</td><td headers="hd_h_Trazodone.Td_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_Trazodone.Td_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td><td headers="hd_h_Trazodone.Td_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">19 (9) days</td><td headers="hd_h_Trazodone.Td_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">146</td><td headers="hd_h_Trazodone.Td_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">154</td><td headers="hd_h_Trazodone.Td_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">2.4</td><td headers="hd_h_Trazodone.Td_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_Trazodone.Td_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td><td headers="hd_h_Trazodone.Td_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">23 (13) days</td><td headers="hd_h_Trazodone.Td_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">55</td><td headers="hd_h_Trazodone.Td_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">108</td><td headers="hd_h_Trazodone.Td_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1.6</td><td headers="hd_h_Trazodone.Td_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_Trazodone.Td_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td><td headers="hd_h_Trazodone.Td_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">30 (20) days</td><td headers="hd_h_Trazodone.Td_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">43</td><td headers="hd_h_Trazodone.Td_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">93</td><td headers="hd_h_Trazodone.Td_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1.4</td><td headers="hd_h_Trazodone.Td_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_Trazodone.Td_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td><td headers="hd_h_Trazodone.Td_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">51 (41) days</td><td headers="hd_h_Trazodone.Td_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">17</td><td headers="hd_h_Trazodone.Td_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">71</td><td headers="hd_h_Trazodone.Td_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">0.9</td><td headers="hd_h_Trazodone.Td_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_Trazodone.Td_1_1_1_1 hd_h_Trazodone.Td_1_1_1_2" colspan="2" scope="row" rowspan="1" style="text-align:center;vertical-align:top;">
|
||
<b>Normal Values</b>
|
||
</td><td headers="hd_h_Trazodone.Td_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
||
<b><48</b>
|
||
</td><td headers="hd_h_Trazodone.Td_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
||
<b><125</b>
|
||
</td><td headers="hd_h_Trazodone.Td_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
||
<b><1.2</b>
|
||
</td><td headers="hd_h_Trazodone.Td_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt>* </dt><dd><div id="Trazodone.TF.d.1"><p class="no_margin">Numbers in parentheses indicate the days after stopping the second time.</p></div></dd></dl></div></div></div></div><div id="Trazodone.Comment"><h4>Comment</h4><p>Trazodone has been linked to rare cases of hepatic injury. The onset of injury is generally after several months and is typically hepatocellular, although cases with a shorter latency and with a cholestatic pattern of serum enzyme elevations have been described. In this case, the long latency period was atypical of trazodone and not characteristic of drug induced liver disease in general. Furthermore, the patient was taking other potentially hepatotoxic drugs (methotrexate, nabumetone). What makes the likelihood of trazodone being the cause of the injury was the inadvertent rechallenge that led to a rapid worsening of the injury. Furthermore, the liver biopsy showed no evidence of methotrexate injury and had changes that were considered typical of drug induced liver injury. The hepatic injury rapidly resolved with stopping therapy.</p></div></div></div><div id="Trazodone.PRODUCT_INFORMATION"><h2 id="_Trazodone_PRODUCT_INFORMATION_">PRODUCT INFORMATION</h2><p>
|
||
<b>REPRESENTATIVE TRADE NAMES</b>
|
||
</p><p>Trazodone – Generic, Desyrel®</p><p>
|
||
<b>DRUG CLASS</b>
|
||
</p><p>Antidepressant Agents</p><p>
|
||
<a href="https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=TRAZODONE+HYDROCHLORIDE" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">COMPLETE LABELING</a>
|
||
</p><p>Product labeling at DailyMed, National Library of Medicine, NIH</p></div><div id="Trazodone.CHEMICAL_FORMULA_AND_STRUCTURE"><h2 id="_Trazodone_CHEMICAL_FORMULA_AND_STRUCTURE_">CHEMICAL FORMULA AND STRUCTURE</h2><div id="Trazodone.Te" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK548557/table/Trazodone.Te/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__Trazodone.Te_lrgtbl__"><table><tbody><tr><th id="hd_b_Trazodone.Te_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">DRUG</th><th id="hd_b_Trazodone.Te_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">CAS REGISTRY NUMBER</th><th id="hd_b_Trazodone.Te_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MOLECULAR FORMULA</th><th id="hd_b_Trazodone.Te_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">STRUCTURE</th></tr><tr><td headers="hd_b_Trazodone.Te_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Trazodone</td><td headers="hd_b_Trazodone.Te_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
||
<a href="https://pubchem.ncbi.nlm.nih.gov/substance/134992960" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">19794-93-5</a>
|
||
</td><td headers="hd_b_Trazodone.Te_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">C19-H22-Cl-N5-O</td><td headers="hd_b_Trazodone.Te_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
||
<a href="https://pubchem.ncbi.nlm.nih.gov/substance/134992960" title="View this structure in PubChem" class="img_link" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem"><img src="https://pubchem.ncbi.nlm.nih.gov/image/imgsrv.fcgi?t=l&sid=134992960" alt="image 134992960 in the ncbi pubchem database" /></a>
|
||
</td></tr></tbody></table></div></div></div><div id="Trazodone.CITED_REFERENCES"><h2 id="_Trazodone_CITED_REFERENCES_">CITED REFERENCES</h2><dl class="temp-labeled-list"><dt>1.</dt><dd><div class="bk_ref" id="Trazodone.REF.1">Fernandes NF, Martin RR, Schenker S. Trazodone-induced hepatotoxicity: a case report with comments on drug-induced hepatotoxicity. <span><span class="ref-journal">Am J Gastroenterol. </span>2000;<span class="ref-vol">95</span>:532–5.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/10685763" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10685763</span></a>]</div></dd></dl></div><div id="Trazodone.ANNOTATED_BIBLIOGRAPHY"><h2 id="_Trazodone_ANNOTATED_BIBLIOGRAPHY_">ANNOTATED BIBLIOGRAPHY</h2><p>References updated: 26 February 2020</p><ul class="first-line-outdent"><li><div class="bk_ref" id="Trazodone.REF.zimmerman.1999">Zimmerman HJ. Antidepressants. In, Zimmerman HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott, 1999, pp. 493-8.<div><i>(Expert review of hepatotoxicity published in 1999; trazodone is listed as potentially causing either cholestatic or hepatocellular injury having been implicated in at least 6 cases, including instances of chronic hepatitis).</i></div></div></li><li><div class="bk_ref" id="Trazodone.REF.larrey.2013">Larrey D, Ripault MP. Hepatotoxicity of psychotropic drugs and drugs of abuse. In, Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 3rd ed. Amsterdam: Elsevier, 2013, pp. 443-62.<div><i>(Review of hepatotoxicity of antidepressants mentions that trazodone can cause immunoallergic liver injury with a latency of a few days to 1.5 year and with variable patterns of enzyme elevations).</i></div></div></li><li><div class="bk_ref" id="Trazodone.REF.odonnell.2018">O'Donnell JM, Bies RR, Shelton RC. Drug therapy of depression and anxiety disorders. In, Brunton LL, Hilal-Dandan R, Knollman BC, eds. Goodman & Gilman’s the pharmacological basis of therapeutics. 13th ed. New York: McGraw-Hill, 2018, pp. 267-78.<div><i>(Textbook of pharmacology and therapeutics).</i></div></div></li><li><div class="bk_ref" id="Trazodone.REF.chu.1983.128">Chu AG, Gunsolly BL, Summers RW, Alexander B, McChesney C, Tanna VL. Trazodone and liver toxicity. <span><span class="ref-journal">Ann Intern Med. </span>1983;<span class="ref-vol">99</span>:128–9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/6859716" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 6859716</span></a>]<div>
|
||
<i>(63 year old man developed rash and asymptomatic liver test abnormalities 4 weeks after starting trazodone [bilirubin normal, ALT 55 rising to 211 U/L, Alk P 139 to 535 U/L], serum enzymes worsening for a week after stopping therapy before rapidly falling to normal).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Trazodone.REF.sheikh.1983.274">Sheikh KH, Nies AS. Trazodone and intrahepatic cholestasis. <span><span class="ref-journal">Ann Intern Med. </span>1983;<span class="ref-vol">99</span>:274–5.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/6625402" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 6625402</span></a>]<div>
|
||
<i>(71 year old woman developed jaundice 2 weeks after starting trazodone [bilirubin 12 mg/dL, AST 780 U/L, Alk P 1310 U/L], bilirubin peaking 2 weeks later [29 mg/dL], but injury ultimately resolved within 8 weeks of stopping).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Trazodone.REF.longstreth.1985.149">Longstreth GF, Hershman J. Trazodone-induced hepatotoxicity and leukonychia. <span><span class="ref-journal">J Am Acad Dermatol. </span>1985;<span class="ref-vol">13</span>:149–50.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/4031146" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 4031146</span></a>]<div>
|
||
<i>(57 year old woman developed jaundice 6 months after starting trazodone [bilirubin 14.8 mg/dL, AST 277 U/L, Alk P 161 U/L, protime 29 sec], resolving within 5 weeks of stopping, but minor AST and Alk P elevations persisted for 6 months).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Trazodone.REF.rongioletti.1986.274">Rongioletti F, Rebora A. Drug eruption from trazodone. <span><span class="ref-journal">J Am Acad Dermatol. </span>1986;<span class="ref-vol">14</span>:274–5.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/2936778" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2936778</span></a>]<div>
|
||
<i>(71 year old woman developed fever and rash several months after starting trazodone [bilirubin normal, ALT 81 U/L, Alk P 177 U/L, eosinophils 7%, ANA negative], resolving within 2 weeks of stopping).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Trazodone.REF.beck.1993.791">Beck PL, Bridges RJ, Demetrick DJ, Kelly JK, Lee SS. Chronic active hepatitis associated with trazodone therapy. <span><span class="ref-journal">Ann Intern Med. </span>1993;<span class="ref-vol">118</span>:791–2.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/8470853" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8470853</span></a>]<div>
|
||
<i>(75 year old woman developed jaundice 7 months after starting trazodone [bilirubin 17.9 mg/dL, ALT 933 U/L, Alk P 144 U/L], biopsy showing chronic hepatitis, rapid clinical improvement, but bilirubin was raised for 6 months after stopping).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Trazodone.REF.hull.1994.378">Hull M, Jones R, Bendall M. Fatal hepatic necrosis associated with trazodone and neuroleptic drugs. <span><span class="ref-journal">BMJ. </span>1994;<span class="ref-vol">309</span>:378.</span> [<a href="/pmc/articles/PMC2541185/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2541185</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/7915924" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7915924</span></a>]<div>
|
||
<i>(72 year old woman developed ALT elevations [107 U/L] 10 weeks after starting trazodone, trifluoperazine and lithium, developing jaundice at 18 weeks and dying 2 months later).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Trazodone.REF.robinson.1996.31">Robinson DS, Roberts DL, Smith JM, Stringfellow JC, Kaplita SB, Seminara JA, Marcus RN. The safety profile of nefazodone. <span><span class="ref-journal">J Clin Psychiatry. </span>1996;<span class="ref-vol">97</span> Suppl 2:31–8.</span><div>
|
||
<i>(Pooled analysis of 3500 patients on nefazodone in clinical trials; most common side effects were nausea, somnolence, dry mouth, dizziness, constipation and asthenia; 12% stopped drug for side effects vs 7.5% on placebo, 10.5% fluoxetine and 22% imipramine; no excess weight gain or abnormal laboratory tests vs placebo; no deaths or severe side effects due to liver injury and no mention of ALT elevations).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Trazodone.REF.lucena.1999.2577">Lucena MI, Andrade RJ, Gomez-Outes A, Rubio M, Cabello MR. Acute liver failure after treatment with nefazodone. <span><span class="ref-journal">Dig Dis Sci. </span>1999;<span class="ref-vol">44</span>:2577–9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/10630516" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10630516</span></a>]<div>
|
||
<i>(73 year old woman developed abdominal pain 7 weeks after starting nefazodone [bilirubin 17.1 mg/dL, ALT 834 U/L, Alk P 115 U/L, protime 15 sec], with progressive liver failure and death 4 weeks after presentation).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Trazodone.REF.arandamichel.1999.285">Aranda-Michel J, Koehler A, Bejarano PA, Poulos JE, Luxon BA, Khan CM, Ee LC, et al. Nefazodone-induced liver failure: report of three cases. <span><span class="ref-journal">Ann Intern Med. </span>1999;<span class="ref-vol">130</span>:285–8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/10068386" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10068386</span></a>]<div>
|
||
<i>(Three women, ages 54, 16 and 57 years, developed jaundice 8, 3 and 6 months after starting nefazodone [bilirubin 34.0, 22.5 and 11.8 mg/dL, ALT 2040, 1345 and 1625 U/L, Alk P 97, 206 and 273 U/L], biopsies showing massive and centrilobular necrosis; 1 died, 1 recovered and 1 was transplanted).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Trazodone.REF.van_battum.2000.1964">van Battum PL, van de Vrie W, Metselaar HJ, Verstappen VM, Zondervan PE, de Man RA. <span><span class="ref-journal">Ned Tijdschr Geneeskd. </span>2000;<span class="ref-vol">144</span>:1964–7.</span> [Acute liver failure ascribed to nefazodone: importance of 'postmarketing surveillance' for recently introduced drugs] [<a href="https://pubmed.ncbi.nlm.nih.gov/11048561" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11048561</span></a>]</div></li><li><div class="bk_ref" id="Trazodone.REF.schirren.2000.1596">Schirren CA, Baretton G. Nefazodone-induced acute liver failure. <span><span class="ref-journal">Am J Gastroenterol. </span>2000;<span class="ref-vol">95</span>:1596–7.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/10894614" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10894614</span></a>]<div>
|
||
<i>(52 year old man developed jaundice 5-6 weeks after starting nefazodone with ascites and liver failure requiring liver transplantation 6 weeks after presentation; explant showed massive hepatic necrosis).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Trazodone.REF.eloubeidi.2000.1036">Eloubeidi MA, Gaede JT, Swaim MW. Reversible nefazodone-induced liver failure. <span><span class="ref-journal">Dig Dis Sci. </span>2000;<span class="ref-vol">45</span>:1036–8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/10795773" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10795773</span></a>]<div>
|
||
<i>(46 year old woman developed fatigue followed by jaundice ~4 months after starting nefazodone [bilirubin 14.5 mg/dL, ALT 456 U/L, Alk P 158 U/L], resolving within 4 months of stopping).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Trazodone.REF.fernandes.2000.532">Fernandes NF, Martin RR, Schenker S. Trazodone-induced hepatotoxicity: a case report with comments on drug-induced hepatotoxicity. <span><span class="ref-journal">Am J Gastroenterol. </span>2000;<span class="ref-vol">95</span>:532–5.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/10685763" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10685763</span></a>]<div>
|
||
<i>(39 year old woman developed jaundice 18 months after starting trazodone [bilirubin 11.0 mg/dL, ALT 1092 U/L and Alk P 206 U/L], improving rapidly upon stopping, but recurring with inadvertent rechallenge: Case 1).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Trazodone.REF.rettman.2001.1559">Rettman KS, McClintock C. Hepatotoxicity after short-term trazodone therapy. <span><span class="ref-journal">Ann Pharmacother. </span>2001;<span class="ref-vol">35</span>:1559–61.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/11793619" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11793619</span></a>]<div>
|
||
<i>(46 year old man with HIV-HCV co-infection had onset of symptoms of hepatitis within 5 days of entering cocaine detoxification program and starting trazodone [bilirubin 2.1 mg/dL, ALT 2581 U/L, Alk P 342 U/L], resolving rapidly upon stopping).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Trazodone.REF.ehrentraut.2002.686">Ehrentraut S, Rothenhäusler HB, Gerbes AL, Rau HG, Thiel M, Schirren CA, Kapfhammer HP. <span><span class="ref-journal">Nervenarzt. </span>2002;<span class="ref-vol">73</span>:686–9.</span> [Acute liver failure in nefazodone therapy? A case report] [<a href="https://pubmed.ncbi.nlm.nih.gov/12212533" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12212533</span></a>]<div>
|
||
<i>(52 year old man developed acute liver failure 6 weeks after starting nefazodone [bilirubin 13.9 mg/dL, ALT 1947 U/L, GGT 88 U/L], progressing to hepatic failure requiring liver transplantation, dying of subsequent complications).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Trazodone.REF.stewart.2002.375">Stewart DE. Hepatic adverse reactions associated with nefazodone. <span><span class="ref-journal">Can J Psychiatry. </span>2002;<span class="ref-vol">47</span>:375–7.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/12025437" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12025437</span></a>]<div>
|
||
<i>(Analysis of Canadian Adverse Drug Reaction database found 32 cases of liver injury associated with nefazodone with onset after 1 week to 2 year, mostly within 6 months, 3 with hepatic failure).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Trazodone.REF.carvajal_garc_apando.2002.135">Carvajal García-Pando A, García del Pozo J, Sánchez AS, Velasco MA, Rueda de Castro AM, Lucena MI. Hepatotoxicity associated with the new antidepressants. <span><span class="ref-journal">J Clin Psychiatry. </span>2002;<span class="ref-vol">63</span>:135–7.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/11874214" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11874214</span></a>]<div>
|
||
<i>(Analysis of cases of hepatotoxicity from antidepressants in Spanish Pharmacovigilance System from 1989-1999, identified 99 cases; among SSRIs, 26 due to fluoxetine, 14 paroxetine, 6 fluvoxamine, 5 sertraline, 3 venlafaxine and 2 citalopram; among tricyclics, 16 clomipramine 7 amitriptyline, 6 imipramine; among miscellaneous, 3 nefazodone and 1 trazodone; but all similar in rate ~1-3 per 100,000 patient-years of exposure, except for nefazodone=29/100,000).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Trazodone.REF.lucena.2003.249">Lucena M, Carvajal A, Andrade R, Velasco A. Antidepressant-induced hepatotoxicity. <span><span class="ref-journal">Expert Opin Drug Saf. </span>2003;<span class="ref-vol">2</span>:249–62.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/12904104" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12904104</span></a>]<div>
|
||
<i>(Review of hepatotoxicity of antidepressants; antidepressant use has increased markedly between 1992 and 2002, accounting for 5% of cases of hepatotoxicity; SSRIs are less likely to cause injury than tricyclics and MAO inhibitors; range of presentations, typically self-limited and rapid recovery; no hallmarks of hypersensitivity).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Trazodone.REF.choi.2003.1187">Choi S. Nefazodone (Serzone) withdrawn because of hepatotoxicity. <span><span class="ref-journal">CMAJ. </span>2003;<span class="ref-vol">169</span>:1187.</span> [<a href="/pmc/articles/PMC264962/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC264962</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/14638657" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 14638657</span></a>]<div>
|
||
<i>(Editorial announcing withdrawal of nefazodone in Canada; 51 Canadian reports of adverse hepatic events, 2 requiring transplant).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Trazodone.REF.tzimas.2003.1663">Tzimas GN, Dion B, Deschênes M. Early onset, nefazodone-induced fulminant hepatic failure. <span><span class="ref-journal">Am J Gastroenterol. </span>2003;<span class="ref-vol">98</span>:1663–4.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/12873607" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12873607</span></a>]<div>
|
||
<i>(Two cases of acute liver failure in 61 and 46 year olds, with onset of jaundice 3 and 4 weeks after starting nefazodone with liver failure and encephalopathy, one requiring liver transplant and one with spontaneous survival).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Trazodone.REF.spigset.2003.157">Spigset O, Hägg S, Bate A. Hepatic injury and pancreatitis during treatment with serotonin reuptake inhibitors: data from the World Health Organization (WHO) database of adverse drug reactions. <span><span class="ref-journal">Int Clin Psychopharmacol. </span>2003;<span class="ref-vol">18</span>:157–61.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/12702895" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12702895</span></a>]<div>
|
||
<i>(Among 27,542 reports of hepatic injury in WHO database, 786 were related to SSRIs [3%], including citalopram 42, fluoxetine 222, fluvoxamine 54, paroxetine 191, sertraline 112, nefazodone 91 and venlafaxine 74, only nefazodone has an excess of hepatic reports in relationship to total reports).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Trazodone.REF.s_nchez_ruiz.2004.104">Sánchez Ruiz JC, González López E, Aparicio Tijeras C, Ezquerra Gadea J. <span><span class="ref-journal">Aten Primaria. </span>2004;<span class="ref-vol">34</span>:104.</span> [Hepatotoxicity due to trazodone] [<a href="/pmc/articles/PMC7669174/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7669174</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/15225535" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15225535</span></a>]<div>
|
||
<i>(60 year old was found to have abnormal liver tests without symptoms 6 months after starting trazodone [bilirubin 1.3 mg/dL, ALT 218 U/L, GGT 96 U/L], abnormalities resolving rapidly upon stopping).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Trazodone.REF.conway.2004.353">Conway CR, McGuire JM, Baram VY. Nefazodone-induced liver failure. <span><span class="ref-journal">J Clin Psychopharmacol. </span>2004;<span class="ref-vol">24</span>:353–4.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15118496" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15118496</span></a>]<div>
|
||
<i>(51 year old man developed jaundice and confusion 7 months after starting nefazodone and 1 week after a dose increase [bilirubin 1.7 mg/dL, ALT 1964 U/L, Alk P 96 U/L], resolving rapidly upon stopping).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Trazodone.REF.degner.2004.s39">Degner D, Grohmann R, Kropp S, Rüther E, Bender S, Engel RR, Schmidt LG. Severe adverse drug reactions of antidepressants: results of the German multicenter drug surveillance program AMSP. <span><span class="ref-journal">Pharmacopsychiatry. </span>2004;<span class="ref-vol">37</span> Suppl 1:S39–45.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15052513" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15052513</span></a>]<div>
|
||
<i>(Analysis of adverse drug reactions reported from 1993-2000 in 35 psychiatric hospitals; 0.7% of SSRI recipients had a severe adverse event; hepatic in 0.05%).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Trazodone.REF.andrade.2005.512">Andrade RJ, Lucena MI, Fernández MC, Pelaez G, Pachkoria K, García-Ruiz E, García-Muñoz B, et al. Spanish Group for the Study of Drug-Induced Liver Disease. Drug-induced liver injury: an analysis of 461 incidences submitted to the Spanish registry over a 10-year period. <span><span class="ref-journal">Gastroenterology. </span>2005;<span class="ref-vol">129</span>:512–21.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/16083708" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16083708</span></a>]<div>
|
||
<i>(Reports to a Spanish network found 461 cases of drug induced liver disease, antidepressants accounting for 23 cases [5%]).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Trazodone.REF.bj_rnsson.2006.33">Björnsson E, Olsson R. Suspected drug-induced liver fatalities reported to the WHO database. <span><span class="ref-journal">Dig Liver Dis. </span>2006;<span class="ref-vol">38</span>:33–8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/16054882" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16054882</span></a>]<div>
|
||
<i>(Survey of drug induced liver fatalities reported to WHO database between 1968-2003 revealed 4690 reports; no antidepressant ranked among the top 21 agents that were linked to at least 50 cases each).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Trazodone.REF.kostrubsky.2006.451">Kostrubsky SE, Strom SC, Kalgutkar AS, Kulkarni S, Atherton J, Mireles R, Feng B, et al. Inhibition of hepatobiliary transport as a predictive method for clinical hepatotoxicity of nefazodone. <span><span class="ref-journal">Toxicol Sci. </span>2006;<span class="ref-vol">90</span>:451–9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/16410371" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16410371</span></a>]<div>
|
||
<i>(Nefazodone, unlike trazodone, is a potent inhibitor of the bile salt export protein [BSEP] in cell culture).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Trazodone.REF.sabat_.2007.1401">Sabaté M, Ibáñez L, Pérez E, Vidal X, Buti M, Xiol X, Mas A, et al. Risk of acute liver injury associated with the use of drugs: a multicentre population survey. <span><span class="ref-journal">Aliment Pharmacol Ther. </span>2007;<span class="ref-vol">25</span>:1401–9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/17539979" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17539979</span></a>]<div>
|
||
<i>(Among 126 cases of drug induced liver injury seen in Spain between 1993-2000, 3 were attributed to paroxetine and 3 to fluoxetine, with a relative risk of injury to rate of use in the population of 3.0 and 1.8, respectively).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Trazodone.REF.desanty.2007.1201">DeSanty KP, Amabile CM. Antidepressant-induced liver injury. <span><span class="ref-journal">Ann Pharmacother. </span>2007;<span class="ref-vol">41</span>:1201–11.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/17609231" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17609231</span></a>]<div>
|
||
<i>(Review of drug induced liver injury and reports of injury from MAO inhibitors, SSRIs, tricyclics and atypical agents).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Trazodone.REF.chalasani.2008.1924">Chalasani N, Fontana RJ, Bonkovsky HL, Watkins PB, Davern T, Serrano J, Yang H, Rochon J., Drug Induced Liver Injury Network (DILIN). Causes, clinical features, and outcomes from a prospective study of drug-induced liver injury in the United States. <span><span class="ref-journal">Gastroenterology. </span>2008;<span class="ref-vol">135</span>:1924–34.</span> [<a href="/pmc/articles/PMC3654244/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3654244</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/18955056" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18955056</span></a>]<div>
|
||
<i>(Among 300 cases of drug induced liver disease in the US collected from 2004 to 2008, antidepressants accounted for 12 cases [4%]: duloxetine [6], bupropion [2], fluoxetine [2], amitriptyline [1], sertraline [1]; no mention of trazodone).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Trazodone.REF.detry.2009.3435">Detry O, Delwaide J, De Roover A, Hans MF, Delbouille MH, Monard J, Honore P. Fulminant hepatic failure induced by venlafaxine and trazodone therapy: a case report. <span><span class="ref-journal">Transplant Proc. </span>2009;<span class="ref-vol">41</span>:3435–6.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/19857765" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19857765</span></a>]<div>
|
||
<i>(48 year old woman developed jaundice and liver failure, and underwent liver transplantation, following combined therapy of venlafaxine and trazodone for 4 months).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Trazodone.REF.reuben.2010.2065">Reuben A, Koch DG, Lee WM., Acute Liver Failure Study Group. Drug-induced acute liver failure: results of a U.S. multicenter, prospective study. <span><span class="ref-journal">Hepatology. </span>2010;<span class="ref-vol">52</span>:2065–76.</span> [<a href="/pmc/articles/PMC3992250/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3992250</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/20949552" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20949552</span></a>]<div>
|
||
<i>(Among 1198 patients with acute liver failure enrolled in a US prospective study between 1998 and 2007, 133 were attributed to drug induced liver injury, 3 of which were linked to antidepressants: one each for nefazodone, fluoxetine and venlafaxine).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Trazodone.REF.sedky.2012.53">Sedky K, Nazir R, Joshi A, Kaur G, Lippmann S. Which psychotropic medications induce hepatotoxicity? <span><span class="ref-journal">Gen Hosp Psychiatry. </span>2012;<span class="ref-vol">34</span>:53–61.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/22133982" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22133982</span></a>]<div>
|
||
<i>(Review of the hepatotoxicity of psychotropic drugs in common use, mentions that nefazodone has a “black box” warning and that liver failure occurs at a rate of 1:250,000-300,000 patient-years of exposure; no mention of trazodone).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Trazodone.REF.park.2013.207">Park SH, Ishino R. Liver injury associated with antidepressants. <span><span class="ref-journal">Curr Drug Saf. </span>2013;<span class="ref-vol">8</span>:207–23.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/23914755" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23914755</span></a>]<div>
|
||
<i>(Review of drug induced liver injury due to antidepressants including trazodone and nefazodone).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Trazodone.REF.bj_rnsson.2013.1419">Björnsson ES, Bergmann OM, Björnsson HK, Kvaran RB, Olafsson S. Incidence, presentation and outcomes in patients with drug-induced liver injury in the general population of Iceland. <span><span class="ref-journal">Gastroenterology. </span>2013;<span class="ref-vol">144</span>:1419–25.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/23419359" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23419359</span></a>]<div>
|
||
<i>(In a population based study of drug induced liver injury from Iceland, 96 cases were identified over a 2 year period, none of which were attributed to trazodone).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Trazodone.REF.montastruc.2014.327">Montastruc F, Scotto S, Vaz IR, Guerra LN, Escudero A, Sáinz M, Falomir T, et al. Hepatotoxicity related to agomelatine and other new antidepressants: a case/noncase approach with information from the Portuguese, French, Spanish, and Italian pharmacovigilance systems. <span><span class="ref-journal">J Clin Psychopharmacol. </span>2014;<span class="ref-vol">34</span>:327–30.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/24561328" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24561328</span></a>]<div>
|
||
<i>(Among adverse event reports attributed to antidepressants submitted to 4 European pharmacovigilance databases, 3300 [10%] were for hepatotoxicity, rates being highest for agomelatine [14.6%], but was not above average for trazodone, 1.0% to 4.9%]).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Trazodone.REF.voican.2014.404">Voican CS, Corruble E, Naveau S, Perlemuter G. Antidepressant-induced liver injury: a review for clinicians. <span><span class="ref-journal">Am J Psychiatry. </span>2014;<span class="ref-vol">171</span>:404–15.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/24362450" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24362450</span></a>]<div>
|
||
<i>(Review of the hepatotoxicity of antidepressants mentions that aminotransferase elevations arise in 0.5-3.0% of patients, being highest with MAO inhibitors and lower with SSRIs; all antidepressants have the potential to cause liver injury but is highest with nefazodone, imipramine, amitriptyline, duloxetine, bupropion, trazodone, and agomelatine).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Trazodone.REF.hern_ndez.2014.231">Hernández N, Bessone F, Sánchez A, di Pace M, Brahm J, Zapata R, A, Chirino R, et al. Profile of idiosyncratic drug induced liver injury in Latin America: an analysis of published reports. <span><span class="ref-journal">Ann Hepatol. </span>2014;<span class="ref-vol">13</span>:231–9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/24552865" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24552865</span></a>]<div>
|
||
<i>(Among 176 reports of drug induced liver injury from Latin America published between 1996 and 2012, only one was due to an antidepressant [amitriptyline] and none to trazodone).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Trazodone.REF.chalasani.2015.1340">Chalasani N, Bonkovsky HL, Fontana R, Lee W, Stolz A, Talwalkar J, Reddy KR, et al. United States Drug Induced Liver Injury Network. Features and outcomes of 899 patients with drug-induced liver injury: The DILIN Prospective Study. <span><span class="ref-journal">Gastroenterology. </span>2015;<span class="ref-vol">148</span>:1340–52.e7.</span> [<a href="/pmc/articles/PMC4446235/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4446235</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25754159" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25754159</span></a>]<div>
|
||
<i>(Among 899 cases of drug induced liver injury enrolled in a US prospective study between 2004 and 2013, 20 [15%] were attributed to antidepressants, most frequently to duloxetine [n=7], bupropion [n=4], escitalopram [n=3], and 1 each for imipramine, fluoxetine, nefazodone and trazodone).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Trazodone.REF.gahr.2016.769">Gahr M, Zeiss R, Lang D, Connemann BJ, Hiemke C, Schönfeldt-Lecuona C. Drug-Induced Liver Injury Associated with antidepressive psychopharmacotherapy: an explorative assessment based on quantitative signal detection using different MedDRA terms. <span><span class="ref-journal">J Clin Pharmacol. </span>2016;<span class="ref-vol">56</span>:769–78.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/26470856" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26470856</span></a>]<div>
|
||
<i>(Using data on adverse drug reaction reports from the Uppsala Monitoring Center of WHO, there were higher relative hepatotoxicity reports for nefazodone, agomelatine, many tricyclics and mirtazapine).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Trazodone.REF.friedrich.2016.pyv126">Friedrich ME, Akimova E, Huf W, Konstantinidis A, Papageorgiou K, Winkler D, Toto S, et al. Drug-induced liver injury during antidepressant treatment: results of AMSP, a drug surveillance program. <span><span class="ref-journal">Int J Neuropsychopharmacol. </span>2016;<span class="ref-vol">19</span>:pyv126. </span> pii. [<a href="/pmc/articles/PMC4851269/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4851269</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/26721950" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26721950</span></a>]<div>
|
||
<i>(Among 184,234 psychiatric inpatients from 80 hospitals, 149 cases [0.08%] of drug induced liver injury were reported but only one of them was attributed to trazodone).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Trazodone.REF.chen.2017.30464">Chen VC, Lin CF, Hsieh YH, Liang HY, Huang KY, Chiu WC, Lee Y, McIntyre RS, et al. Hepatocellular carcinoma and antidepressants: a nationwide population-based study. <span><span class="ref-journal">Oncotarget. </span>2017;<span class="ref-vol">8</span>:30464–70.</span> [<a href="/pmc/articles/PMC5444756/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5444756</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/27783998" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27783998</span></a>]<div>
|
||
<i>(Among almost 50,000 cases of hepatocellular carcinoma registered in the Taiwan National Health Insurance Research Database, the rate of antidepressant use was lower than in approximately 250,000 matched controls from the database).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Trazodone.REF.bunchorntavakul.2017.115">Bunchorntavakul C, Reddy KR. Drug hepatotoxicity: newer agents. <span><span class="ref-journal">Clin Liver Dis. </span>2017;<span class="ref-vol">21</span>:115–34.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/27842767" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27842767</span></a>]<div>
|
||
<i>(Review of hepatotoxicity of recently approved medications mentions that liver injury in recently approved agents and only rare instances have been linked to antidepressant use, highest rates associated with duloxetine).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Trazodone.REF.carvalhana.2017.40">Carvalhana S, Oliveira A, Ferreira P, Resende M, Perdigoto R, Barroso E. Acute liver failure due to trazodone and diazepam. <span><span class="ref-journal">GE Port J Gastroenterol. </span>2017;<span class="ref-vol">24</span>:40–2.</span> [<a href="/pmc/articles/PMC5553376/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5553376</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/28848778" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28848778</span></a>]<div>
|
||
<i>(63 year old man developed acute liver failure 3 months after starting trazodone and diazepam [bilirubin 12.0 mg/dL, ALT 4638 U/L, Alk P 122 U/L, INR 1.84], with worsening liver failure and transplant two weeks later).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Trazodone.REF.ferrajolo.2018.95">Ferrajolo C, Scavone C, Donati M, Bortolami O, Stoppa G, Motola D, Vannacci A, et al. DILI-IT Study Group. Antidepressant-induced acute liver injury: a case-control study in an Italian inpatient population. <span><span class="ref-journal">Drug Saf. </span>2018;<span class="ref-vol">41</span>:95–102.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/28770534" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28770534</span></a>]<div>
|
||
<i>(Among 179 cases of hospitalizations for unexplained acute liver injury enrolled in an Italian prospective study between 2010 and 2014, 17 had been exposed to antidepressants including citalopram [n=4], sertraline [n=3], amitriptyline [n=3] and paroxetine [n=2], and trazodone [n=1], and another was exposed to both trazodone and mirtazapine).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Trazodone.REF.billioti_de_gage.2018.673">Billioti de Gage S, Collin C, Le-Tri T, Pariente A, Bégaud B, Verdoux H, Dray-Spira R, et al. Antidepressants and hepatotoxicity: a cohort study among 5 million individuals registered in the French National Health Insurance Database. <span><span class="ref-journal">CNS Drugs. </span>2018;<span class="ref-vol">32</span>:673–84.</span> [<a href="/pmc/articles/PMC6061298/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6061298</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/29959758" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29959758</span></a>]<div>
|
||
<i>(Using the French National Health Insurance Database, 382 serious liver injuries were found in approximately 5 million persons initiating antidepressant therapy, rates being 32.8 per 100,000 with mirtazapine, 22.2 with venlafaxine, 19.2 for SSRIs and 12.6 with duloxetine; trazadone is not specifically discussed).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Trazodone.REF51">Drugs for anxiety disorders. <span><span class="ref-journal">Med Lett Drugs Ther. </span>2019;<span class="ref-vol">61</span>(1578):121–6.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/31386647" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 31386647</span></a>]<div>
|
||
<i>(Concise review of drugs for anxiety including SSRIs, SNRIs and benzodiazepines including mechanism of action, clinical efficacy, safety and costs; does not mention ALT elevations or hepatotoxicity).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Trazodone.REF.pladevallvila.2019.383">Pladevall-Vila M, Pottegård A, Schink T, Reutfors J, Morros R, Poblador-Plou B, Timmer A, et al. Risk of acute liver injury in agomelatine and other antidepressant users in four European countries: a cohort and nested case-control study using automated health data sources. <span><span class="ref-journal">CNS Drugs. </span>2019;<span class="ref-vol">33</span>:383–95.</span> [<a href="/pmc/articles/PMC6441103/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6441103</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/30830574" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30830574</span></a>]<div>
|
||
<i>(Analysis of data sources from 4 European countries identified 3.2 million persons initiating antidepressant therapy among whom there was no increased risk for acute liver injury for agomelatine compared to citalopram, an SSRI with a low rate of hepatotoxicity).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Trazodone.REF.schwasingerschmidt.2019.325">Schwasinger-Schmidt TE, Macaluso M. Other antidepressants. <span><span class="ref-journal">Handb Exp Pharmacol. </span>2019;<span class="ref-vol">250</span>:325–55.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/30194544" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30194544</span></a>]<div>
|
||
<i>(Review of the pharmacology of antidepressants mentions that the common side effects of trazodone are drowsiness, dizziness and dry mouth but does not mention hepatotoxicity or ALT elevations).</i>
|
||
</div></div></li><li><div class="bk_ref" id="Trazodone.REF54">Drugs for depression. <span><span class="ref-journal">Med Lett Drugs Ther. </span>2020;<span class="ref-vol">62</span>(1592):25–32.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/32320387" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32320387</span></a>]<div>
|
||
<i>(Concise review of the mechanism of action, clinical efficacy, safety and costs of drugs for depression; hepatotoxicity is mentioned only for nefazodone [now rarely used because of severe hepatotoxicity] and duloxetine [in heavy drinkers]).</i>
|
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</div></div></li></ul></div><div id="bk_toc_contnr"></div></div></div>
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<div xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Views</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="PDF_download" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li><a href="/books/NBK548557/?report=reader">PubReader</a></li><li><a href="/books/NBK548557/?report=printable">Print View</a></li><li><a data-jig="ncbidialog" href="#_ncbi_dlg_citbx_NBK548557" data-jigconfig="width:400,modal:true">Cite this Page</a><div id="_ncbi_dlg_citbx_NBK548557" style="display:none" title="Cite this Page"><div class="bk_tt">LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Trazodone. 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<a href="https://www.ncbi.nlm.nih.gov/sites/entrez?cmd=search&db=pubmed&pubmedfilters=true&term=trazodone+AND+Human%5BMH%5D+AND+(drug+induced+liver+injury+OR+jaundice/CI+OR+bile+duct+diseases/CI+OR+liver/DE+OR+liver+diseases/CI)+AND+(%221900/1/1%22%5BEDat%5D:%222999/12/31%22%5BEDat%5D)" ref="pagearea=document-links&targetsite=external&targetcat=link&targettype=uri">Recent References on Trazodone: from PubMed.gov</a>
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xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Nefazodone.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. 2012</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/31644143" ref="ordinalpos=1&linkpos=2&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Bupropion.</a><span class="source">[LiverTox: Clinical and Researc...]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Bupropion.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. 2012</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/31643541" ref="ordinalpos=1&linkpos=3&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Mirtazapine.</a><span class="source">[LiverTox: Clinical and Researc...]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Mirtazapine.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. 2012</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/31643342" ref="ordinalpos=1&linkpos=4&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Fluoxetine.</a><span class="source">[LiverTox: Clinical and Researc...]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Fluoxetine.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. 2012</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/31644106" ref="ordinalpos=1&linkpos=5&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Venlafaxine, Desvenlafaxine.</a><span class="source">[LiverTox: Clinical and Researc...]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Venlafaxine, Desvenlafaxine.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. 2012</em></div></div></li></ul><a class="seemore" href="/sites/entrez?db=pubmed&cmd=link&linkname=pubmed_pubmed_reviews&uid=31643874" ref="ordinalpos=1&log$=relatedreviews_seeall&logdbfrom=pubmed">See reviews...</a><a class="seemore" href="/sites/entrez?db=pubmed&cmd=link&linkname=pubmed_pubmed&uid=31643874" ref="ordinalpos=1&log$=relatedarticles_seeall&logdbfrom=pubmed">See all...</a></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Recent Activity</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" 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