<?xml version='1.0'?>
<!DOCTYPE art SYSTEM 'http://www.biomedcentral.com/xml/article.dtd'>
<art>
   <ui>1471-227X-5-5</ui>
   <ji>1471-227X</ji>
   <fm>
      <dochead>Case report</dochead>
      <bibl>
         <title>
            <p>QT interval prolongation after sertraline overdose: a case report</p>
         </title>
         <aug>
            <au id="A1" ca="yes">
               <snm>de Boer</snm>
               <mi>A</mi>
               <fnm>Rudolf</fnm>
               <insr iid="I1"/>
               <insr iid="I2"/>
               <email>rudolfdeboer@wanadoo.nl</email>
            </au>
            <au id="A2">
               <snm>van Dijk</snm>
               <mi>H</mi>
               <fnm>Tonnis</fnm>
               <insr iid="I1"/>
               <email>th.van.dijk@mzh.nl</email>
            </au>
            <au id="A3">
               <snm>Holman</snm>
               <mi>D</mi>
               <fnm>Nicole</fnm>
               <insr iid="I1"/>
               <email>n.holman@mzh.nl</email>
            </au>
            <au id="A4">
               <snm>van Melle</snm>
               <mi>P</mi>
               <fnm>Joost</fnm>
               <insr iid="I2"/>
               <insr iid="I1"/>
               <email>j.p.van.melle@thorax.umcg.nl</email>
            </au>
         </aug>
         <insg>
            <ins id="I1">
               <p>Department of Internal Medicine, Intensive Care Unit, Martini Hospital, Groningen, The Netherlands</p>
            </ins>
            <ins id="I2">
               <p>Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands</p>
            </ins>
         </insg>
         <source>BMC Emergency Medicine</source>
         <issn>1471-227X</issn>
         <pubdate>2005</pubdate>
         <volume>5</volume>
         <issue>1</issue>
         <fpage>5</fpage>
         <url>http://www.biomedcentral.com/1471-227X/5/5</url>
         <xrefbib>
            <pubidlist>
               <pubid idtype="pmpid">16029494</pubid>
               <pubid idtype="doi">10.1186/1471-227X-5-5</pubid>
            </pubidlist>
         </xrefbib>
      </bibl>
      <history>
         <rec>
            <date>
               <day>26</day>
               <month>4</month>
               <year>2005</year>
            </date>
         </rec>
         <acc>
            <date>
               <day>19</day>
               <month>7</month>
               <year>2005</year>
            </date>
         </acc>
         <pub>
            <date>
               <day>19</day>
               <month>7</month>
               <year>2005</year>
            </date>
         </pub>
      </history>
      <cpyrt>
         <year>2005</year>
         <collab>de Boer et al; licensee BioMed Central Ltd.</collab>
         <note>This is an Open Access article distributed under the terms of the Creative Commons Attribution License (<url>http://creativecommons.org/licenses/by/2.0</url>), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</note>
      </cpyrt>
      <abs>
         <sec>
            <st>
               <p>Abstract</p>
            </st>
            <sec>
               <st>
                  <p>Background</p>
               </st>
               <p>Selective serotonin reuptake inhibitors (SSRIs) are the most common antidepressants used in first-world countries and are generally well tolerated. Specifically, less cardiovascular toxicity has been reported in comparison with tricyclic antidepressants. Here we report QT interval prolongation after an overdose of the SSRI sertraline.</p>
            </sec>
            <sec>
               <st>
                  <p>Case presentation</p>
               </st>
               <p>A previously healthy female patient presented with an attempted suicide with overdoses sertraline (2250 mg), diazepam (200 mg), and temazepam (400 mg). Routine laboratory studies were normal and her ECG upon admission showed a normal QT interval. The next day, her ECG showed prolongation of the QT<sub>c </sub>interval up to 525 ms. After discontinuation of sertraline the QT interval normalized. Echocardiography and exercise electrocardiography were normal. After hospitalization, the patient resumed sertraline in the normally recommended dose and QT interval remained within normal ranges.</p>
            </sec>
            <sec>
               <st>
                  <p>Conclusion</p>
               </st>
               <p>It seems that the SSRI sertraline in overdose may cause QT interval prolongation.</p>
            </sec>
         </sec>
      </abs>
   </fm>
   <bdy>
      <sec>
         <st>
            <p>Background</p>
         </st>
         <p>Since their introduction in 1987, the use of Selective Serotonin Reuptake Inhibitors (SSRIs) has increased dramatically <abbrgrp><abbr bid="B1">1</abbr></abbrgrp>. They clearly have a more favorable safety profile compared to tricyclic antidepressants <abbrgrp><abbr bid="B2">2</abbr></abbrgrp>, although prolongation of the QT interval has been reported as a side effect <abbrgrp><abbr bid="B3">3</abbr></abbrgrp>. This is an important side effect since prolongation of the QT interval is strongly associated with life-threatening arrhythmias, most notably torsades de pointes. Although sertraline belongs to the same class of antidepressants, controversy persists whether this holds true for the SSRI sertraline <abbrgrp><abbr bid="B4">4</abbr></abbrgrp>. Here we here present a patient with prolonged QT interval after sertraline overdose.</p>
      </sec>
      <sec>
         <st>
            <p>Case presentation</p>
         </st>
         <p>A 40-year old female patient was referred to our emergency department because of an intended overdose with 200 mg diazepam, 400 mg temazepam, and 2250 mg sertraline.</p>
         <p>Her main complaints were fatigue and drowsiness. Blood pressure, pulse rate, and auscultation of the heart and lungs were normal. The patient was treated with sodiumsulfate and charcoal and was admitted to the intensive care unit for continuous control of vital signs. Routine laboratory studies (hematology, chemistry) were normal. Plasma levels of diazepam and temazepam were elevated, 1155 ugr/l (normal: 125 &#8211; 750 ugr/l) and 1710 ugr/l (normal: 300&#8211;900 ugr/l, respectively). Plasma levels of sertraline and desmethylsertraline were 174 ug/l (normal 20&#8211;55 ug/l <abbrgrp><abbr bid="B5">5</abbr></abbrgrp>) and 276 ng/l, respectively.</p>
         <p>Her ECG upon admission (upper panel of the figure) shows a sinus rhythm (77 b.p.m.) without conduction disturbances. QT interval in lead V2 was 370 ms. We used the Bazett method (QT time divided by the square root of the RR interval) to calculate the corrected QT (QT<sub>c</sub>). QT<sub>c </sub>at admission was 420 ms and negative T-waves were found in leads V1&#8211;V3. A second ECG, taken one day after admission (lower panel of the figure), showed a markedly prolonged QT interval with deepened negative T waves in leads V1&#8211;V3. QT interval was 520 ms in V2, at a heart rate (HR) of 63 b.p.m (QT<sub>c </sub>525 ms). An old ECG (august 2002) showed a sinus rhythm with a HR of 63 b.p.m and a QT interval in lead V2 of 370 ms (QT<sub>c </sub>373 ms; ECG not shown).</p>
         <p>After 4 days the patient was discharged to a psychiatric hospital because the risk for another suicide attempt was deemed high by the psychiatric consultant. After discharge, the patient underwent further out-patient cardiac evaluation. Echocardiography revealed no structural heart disease. On exercise electrocardiography, patient reached 88% of her maximum HR &#8211; no abnormal ST-segment changes were observed. Hereafter, the use of sertraline was resumed in a dose of 50 mg twice daily under guidance of her psychiatrist. Control ECG revealed a normal QT interval (not shown).</p>
      </sec>
      <sec>
         <st>
            <p>Discussion</p>
         </st>
         <p>We here present a patient with prolonged QT interval associated with sertraline overdose. An acquired cause of QT prolongation was suspected since QT intervals had been normal on admission, about 3 hours after ingestion of 2250 mg of sertraline (11 times the maximum maximum recommended dose of 200 mg/day), and were markedly prolonged after one day in hospital. The QT interval normalized after sertraline withdrawal. Therefore, a temporal relation existed between the overdose of sertraline and the development of QT prolongation. However, other causes for QT prolongation, both acquired and inherited, must be considered. For example, combinations of psychoactive drugs have been shown to cause prolongation of the QT interval <abbrgrp><abbr bid="B6">6</abbr></abbrgrp>, and our patient ingested temazepam as well as nitrazepam in overdose.</p>
         <p>Whereas previous clinical studies <abbrgrp><abbr bid="B7">7</abbr><abbr bid="B8">8</abbr><abbr bid="B9">9</abbr><abbr bid="B10">10</abbr></abbrgrp> did not reveal any QT prolongation as a side-effect of sertraline, this case report suggests it may have this potential. We are aware of 1 additional report by Amin et al <abbrgrp><abbr bid="B11">11</abbr></abbrgrp> who described 'a clinically significant' increase in QT interval after treatment with 200 mg of sertraline, however the magnitude of QT prolongation was not specified.</p>
         <p>Naturally, implications of this finding are limited because it is only a single case. Two other limitations deserve comment. First, we did not perform a rechallenge with high dosage of sertraline, since this would be unethical. Second, only one blood sample was taken to assess plasma concentration of sertraline &#8211; the sertraline plasma level was found clearly increased according to other reports <abbrgrp><abbr bid="B5">5</abbr><abbr bid="B12">12</abbr></abbrgrp>. It was therefore not possible to investigate the relation between the course of QT interval prolongation and their paralleled serum levels of sertraline</p>
      </sec>
      <sec>
         <st>
            <p>Conclusion</p>
         </st>
         <p>Our observation suggests that the SSRI sertraline may have the potential to prolong QT interval in rare cases. This case underscores the need for continuous post marketing surveillance.</p>
      </sec>
      <sec>
         <st>
            <p>List of abbreviations</p>
         </st>
         <p>HR heart rate</p>
         <p>LV left ventricular</p>
         <p>QT<sub>c </sub>Corrected QT interval</p>
         <p>SSRI selective serotonin reuptake inhibitor</p>
      </sec>
      <sec>
         <st>
            <p>Competing interests</p>
         </st>
         <p>The author(s) declare that they have no competing interests.</p>
      </sec>
      <sec>
         <st>
            <p>Authors' contributions</p>
         </st>
         <p>RADB, THVD, and NDH cared for the patient in the intensive care unit, conducted QT analyses, and arranged laboratory samples. RADB and JPVM noticed that QT interval prolongation had not been discussed previously in the case of sertraline overdose. RADB, THVD, NDH wrote the paper, whereas JPVM critically revised the discussion for important intellectual content. All authors read and approved the final manuscript.</p>
         <fig id="F1">
            <title>
               <p>Figure 1</p>
            </title>
            <caption>
               <p>ECGs of the patient</p>
            </caption>
            <text>
               <p>ECGs of the patient. ECG of the patient upon admission (upper panel) shows a normal sinus rhythm with a QT interval in lead V2 of 370 ms (QT<sub>c </sub>420 ms). There were negative T-waves in leads V1&#8211;V3. A second ECG was obtained one day after admission (lower panel) shows a markedly prolonged QT interval of 520 ms in V2 (QT<sub>c </sub>525 ms).</p>
            </text>
            <graphic file="1471-227X-5-5-1"/>
         </fig>
      </sec>
   </bdy>
   <bm>
      <ack>
         <sec>
            <st>
               <p>Acknowledgements</p>
            </st>
            <p>Written consent was obtained from the patient for publication of the patient's details.</p>
         </sec>
      </ack>
      <refgrp>
         <bibl id="B1">
            <title>
               <p>Incidence and determinants of long-term use of antidepressants</p>
            </title>
            <aug>
               <au>
                  <snm>Meijer</snm>
                  <fnm>WE</fnm>
               </au>
               <au>
                  <snm>Heerdink</snm>
                  <fnm>ER</fnm>
               </au>
               <au>
                  <snm>Leufkens</snm>
                  <fnm>HG</fnm>
               </au>
               <au>
                  <snm>Herings</snm>
                  <fnm>RMC</fnm>
               </au>
               <au>
                  <snm>Egberts</snm>
                  <fnm>ACG</fnm>
               </au>
               <au>
                  <snm>Nolen</snm>
                  <fnm>WA</fnm>
               </au>
            </aug>
            <source>Eur J Clin Pharmacol</source>
            <pubdate>2004</pubdate>
            <volume>60</volume>
            <fpage>57</fpage>
            <lpage>61</lpage>
            <xrefbib>
               <pubidlist>
                  <pubid idtype="doi">10.1007/s00228-004-0726-3</pubid>
                  <pubid idtype="pmpid" link="fulltext">14985889</pubid>
               </pubidlist>
            </xrefbib>
         </bibl>
         <bibl id="B2">
            <title>
               <p>Selective serotonin reuptake inhibitors: introduction and overview</p>
            </title>
            <aug>
               <au>
                  <snm>Kelsey</snm>
                  <fnm>JE</fnm>
               </au>
               <au>
                  <snm>Nemeroff</snm>
                  <fnm>CB</fnm>
               </au>
            </aug>
            <source>Kaplan and Sadock's Comprehensive Textbook of Psychiatry</source>
            <publisher>Philadelphia: Lippincott Williams &amp; Wilkins</publisher>
            <editor>Sadock BJ, Sadock VA</editor>
            <edition>7</edition>
            <pubdate>2000</pubdate>
            <fpage>2432</fpage>
            <lpage>2435</lpage>
         </bibl>
         <bibl id="B3">
            <title>
               <p>What clinicians should know about the QT interval</p>
            </title>
            <aug>
               <au>
                  <snm>Al-Khatib</snm>
                  <fnm>SM</fnm>
               </au>
               <au>
                  <snm>LaPointe</snm>
                  <fnm>NM</fnm>
               </au>
               <au>
                  <snm>Kramer</snm>
                  <fnm>JM</fnm>
               </au>
               <au>
                  <snm>Califf</snm>
                  <fnm>RM</fnm>
               </au>
            </aug>
            <source>JAMA</source>
            <pubdate>2003</pubdate>
            <volume>289</volume>
            <fpage>2120</fpage>
            <lpage>2127</lpage>
            <xrefbib>
               <pubidlist>
                  <pubid idtype="doi">10.1001/jama.289.16.2120</pubid>
                  <pubid idtype="pmpid" link="fulltext">12709470</pubid>
               </pubidlist>
            </xrefbib>
         </bibl>
         <bibl id="B4">
            <title>
               <p>Medications that prolong the QT interval</p>
            </title>
            <aug>
               <au>
                  <snm>Gillespie</snm>
                  <fnm>JA</fnm>
               </au>
               <au>
                  <snm>Clary</snm>
                  <fnm>CM</fnm>
               </au>
            </aug>
            <source>JAMA</source>
            <pubdate>2003</pubdate>
            <volume>290</volume>
            <fpage>1025</fpage>
            <note>(letter)</note>
            <xrefbib>
               <pubidlist>
                  <pubid idtype="pmpid" link="fulltext">12941667</pubid>
                  <pubid idtype="doi">10.1001/jama.290.8.1025-b</pubid>
               </pubidlist>
            </xrefbib>
         </bibl>
         <bibl id="B5">
            <url>http://www.mdbrowse.com/Druginf/S/sertraline.htm#Sertraline</url>
         </bibl>
         <bibl id="B6">
            <title>
               <p>QT interval prolongation related to psychoactive drug treatment: a comparison of monotherapy versus polytherapy</p>
            </title>
            <aug>
               <au>
                  <snm>Sala</snm>
                  <fnm>M</fnm>
               </au>
               <au>
                  <snm>Vicentini</snm>
                  <fnm>A</fnm>
               </au>
               <au>
                  <snm>Brambilla</snm>
                  <fnm>P</fnm>
               </au>
               <au>
                  <snm>Montomoli</snm>
                  <fnm>C</fnm>
               </au>
               <au>
                  <snm>Jogia</snm>
                  <fnm>JR</fnm>
               </au>
               <au>
                  <snm>Caverzasi</snm>
                  <fnm>E</fnm>
               </au>
               <au>
                  <snm>Bonzano</snm>
                  <fnm>A</fnm>
               </au>
               <au>
                  <snm>Piccinelli</snm>
                  <fnm>M</fnm>
               </au>
               <au>
                  <snm>Barale</snm>
                  <fnm>F</fnm>
               </au>
               <au>
                  <snm>De Ferrari</snm>
                  <fnm>GM</fnm>
               </au>
            </aug>
            <source>Ann Gen Psychiatry</source>
            <pubdate>2005</pubdate>
            <volume>4</volume>
            <fpage>1</fpage>
            <xrefbib>
               <pubidlist>
                  <pubid idtype="doi">10.1186/1744-859X-4-1</pubid>
                  <pubid idtype="pmpid" link="fulltext">15845138</pubid>
               </pubidlist>
            </xrefbib>
         </bibl>
         <bibl id="B7">
            <title>
               <p>Relative toxicity of selective serotonin reuptake inhibitors (SSRIs) in overdose</p>
            </title>
            <aug>
               <au>
                  <snm>Isbister</snm>
                  <fnm>GK</fnm>
               </au>
               <au>
                  <snm>Bowe</snm>
                  <fnm>SJ</fnm>
               </au>
               <au>
                  <snm>Dawson</snm>
                  <fnm>A</fnm>
               </au>
               <au>
                  <snm>Whyte</snm>
                  <fnm>IM</fnm>
               </au>
            </aug>
            <source>J Toxicol Clin Toxicol</source>
            <pubdate>2004</pubdate>
            <volume>42</volume>
            <fpage>277</fpage>
            <lpage>285</lpage>
            <xrefbib>
               <pubidlist>
                  <pubid idtype="doi">10.1081/CLT-120037428</pubid>
                  <pubid idtype="pmpid">15362595</pubid>
               </pubidlist>
            </xrefbib>
         </bibl>
         <bibl id="B8">
            <title>
               <p>Electrocardiographic findings in sertraline depression trials</p>
            </title>
            <aug>
               <au>
                  <snm>Fisch</snm>
                  <fnm>C</fnm>
               </au>
               <au>
                  <snm>Knoebel</snm>
                  <fnm>SB</fnm>
               </au>
            </aug>
            <source>Drug Invest</source>
            <pubdate>1992</pubdate>
            <volume>4</volume>
            <fpage>305</fpage>
            <lpage>312</lpage>
         </bibl>
         <bibl id="B9">
            <title>
               <p>Sertraline safety and efficacy in major depression: a double-blind fixed-dose comparison with placebo</p>
            </title>
            <aug>
               <au>
                  <snm>Fabre</snm>
                  <fnm>LF</fnm>
               </au>
               <au>
                  <snm>Abuzzahab</snm>
                  <fnm>FS</fnm>
               </au>
               <au>
                  <snm>Amin</snm>
                  <fnm>M</fnm>
               </au>
               <au>
                  <snm>Claghorn</snm>
                  <fnm>JL</fnm>
               </au>
               <au>
                  <snm>Mendels</snm>
                  <fnm>J</fnm>
               </au>
               <au>
                  <snm>Petrie</snm>
                  <fnm>WM</fnm>
               </au>
               <au>
                  <snm>Dube</snm>
                  <fnm>S</fnm>
               </au>
               <au>
                  <snm>Small</snm>
                  <fnm>JG</fnm>
               </au>
            </aug>
            <source>Biol Psychiatry</source>
            <pubdate>1995</pubdate>
            <volume>38</volume>
            <fpage>592</fpage>
            <lpage>602</lpage>
            <xrefbib>
               <pubidlist>
                  <pubid idtype="doi">10.1016/0006-3223(95)00178-8</pubid>
                  <pubid idtype="pmpid" link="fulltext">8573661</pubid>
               </pubidlist>
            </xrefbib>
         </bibl>
         <bibl id="B10">
            <title>
               <p>Sertraline treatment of major depression in patients with acute MI or unstable angina</p>
            </title>
            <aug>
               <au>
                  <snm>Glassman</snm>
                  <fnm>AH</fnm>
               </au>
               <au>
                  <snm>O'Connor</snm>
                  <fnm>CM</fnm>
               </au>
               <au>
                  <snm>Califf</snm>
                  <fnm>RM</fnm>
               </au>
               <au>
                  <snm>Swedberg</snm>
                  <fnm>K</fnm>
               </au>
               <au>
                  <snm>Schwartz</snm>
                  <fnm>P</fnm>
               </au>
               <au>
                  <snm>Bigger</snm>
                  <fnm>JT</fnm>
                  <suf>Jr</suf>
               </au>
               <au>
                  <snm>Krishnan</snm>
                  <fnm>KR</fnm>
               </au>
               <au>
                  <snm>van Zyl</snm>
                  <fnm>LT</fnm>
               </au>
               <au>
                  <snm>Swenson</snm>
                  <fnm>JR</fnm>
               </au>
               <au>
                  <snm>Finkel</snm>
                  <fnm>MS</fnm>
               </au>
               <au>
                  <snm>Landau</snm>
                  <fnm>C</fnm>
               </au>
               <au>
                  <snm>Shapiro</snm>
                  <fnm>PA</fnm>
               </au>
               <au>
                  <snm>Pepine</snm>
                  <fnm>CJ</fnm>
               </au>
               <au>
                  <snm>Mardekian</snm>
                  <fnm>J</fnm>
               </au>
               <au>
                  <snm>Harrison</snm>
                  <fnm>WM</fnm>
               </au>
               <au>
                  <snm>Barton</snm>
                  <fnm>D</fnm>
               </au>
               <au>
                  <snm>Mclvor</snm>
                  <fnm>M</fnm>
               </au>
               <au>
                  <cnm>Sertraline Antidepressant Heart Attack Randomized Trial (SADHEART) Group</cnm>
               </au>
            </aug>
            <source>JAMA</source>
            <pubdate>2002</pubdate>
            <volume>288</volume>
            <fpage>701</fpage>
            <lpage>709</lpage>
            <xrefbib>
               <pubidlist>
                  <pubid idtype="doi">10.1001/jama.288.6.701</pubid>
                  <pubid idtype="pmpid" link="fulltext">12169073</pubid>
               </pubidlist>
            </xrefbib>
         </bibl>
         <bibl id="B11">
            <title>
               <p>A double-blind, placebo-controlled dose-finding study with sertraline</p>
            </title>
            <aug>
               <au>
                  <snm>Amin</snm>
                  <fnm>M</fnm>
               </au>
               <au>
                  <snm>Lehmann</snm>
                  <fnm>H</fnm>
               </au>
               <au>
                  <snm>Mirmiran</snm>
                  <fnm>J</fnm>
               </au>
            </aug>
            <source>Psychopharmacol Bull</source>
            <pubdate>1989</pubdate>
            <volume>25</volume>
            <fpage>164</fpage>
            <lpage>167</lpage>
            <xrefbib>
               <pubid idtype="pmpid">2690162</pubid>
            </xrefbib>
         </bibl>
         <bibl id="B12">
            <title>
               <p>A tale of two patients</p>
            </title>
            <aug>
               <au>
                  <snm>Preskorn</snm>
                  <fnm>SH</fnm>
               </au>
            </aug>
            <source>J Pract Psych Behav Health</source>
            <pubdate>1999</pubdate>
            <fpage>160</fpage>
            <lpage>164</lpage>
            <url>http://www.preskorn.com/columns/9905.html.</url>
         </bibl>
      </refgrp>
      <sec>
         <st>
            <p>Pre-publication history</p>
         </st>
         <p>The pre-publication history for this paper can be accessed here:</p>
         <p>
            <url>http://www.biomedcentral.com/1471-227X/5/5/prepub</url>
         </p>
      </sec>
   </bm>
</art>

