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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0010" class="elsevierStylePara elsevierViewall">Selective serotonin reuptake inhibitors &#40;SSRI&#41; are the most frequently prescribed antidepressants and are included among the most frequently found drug in overdose&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> Serotonin syndrome &#40;SS&#41; is an adverse drug reaction caused by excessive activation of postsynaptic serotonin receptors and characterized by altered mental status&#44; autonomic hyperactivity and neuromuscular abnormalities &#40;tremor&#44; myoclonus or hyperreflexia&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">2&#8211;4</span></a> Although SS may result in death&#44; most patients recover completely only with the suppression of the treatment and supportive care&#46; SS occurs as an idiosyncratic drug reaction<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> or as a result of the interaction of two or more drugs that enhance serotonin transmission&#44; being the association of SSRI with monoaminoxidase inhibitors the most frequent one&#46; Drug combinations involved with SS include SSRI&#44; tricyclic antidepressants&#44; monoamine oxidase inhibitors&#44; serotonin norepinephrine reuptake inhibitors&#44; triptans&#44; trazodone&#44; opioids&#44; buspirone&#44; linezolid&#44; L-tryptophan or methylenedioxymethamphetamine&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">2&#8211;5</span></a> Interestingly&#44; over-the-counter drugs&#44; nutritional supplements or naturopathic treatments together with SSRI may also be involved with the serotonin syndrome&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">We report the case of a previously healthy 42-year-old man with a history of chronic tobacco and alcohol consumption who was recently diagnosed for depression&#46; He was treated with a daily dose of 20<span class="elsevierStyleHsp" style=""></span>mg of citalopram for the last four days&#46; He regularly practiced sport in a gym centre and he routinely consumed tryptophan-rich supplements at a daily dose of 600<span class="elsevierStyleHsp" style=""></span>mg of tryptophan and one or two litres of stimulating taurine-rich drink &#40;Red Bull&#174;&#41;&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">The patient was attended in the emergency department following voluntary ingestion three hours before of 480<span class="elsevierStyleHsp" style=""></span>mg of citalopram and alcohol with autolytic intention&#46; Initially&#44; he was awake&#44; conscious but showing a marked hyperactivity with diaphoresis&#44; sialorrhea and bilateral and reactive mydriasis&#46; His blood pressure was 168&#47;100<span class="elsevierStyleHsp" style=""></span>mmHg&#44; heart rate 110<span class="elsevierStyleHsp" style=""></span>bpm&#44; respiratory rate 48<span class="elsevierStyleHsp" style=""></span>bpm and axilar temperature of 36<span class="elsevierStyleHsp" style=""></span>&#176;C&#46; Sublingual benzodiazepine treatment was administered without response&#46; Initial haematological and biochemical analysis were normal&#44; blood ethanol was 56<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#44; and analysis of toxics in urine were negative &#40;cocaine&#44; cannabis&#44; benzodiazepines&#44; opiates&#44; amphetamines and barbiturates&#41;&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Patient evolution was fulminant with progressive deterioration of his agitation and increasing muscular rigidity and myoclonus&#44; Babinsky bilateral sign&#44; 39<span class="elsevierStyleHsp" style=""></span>&#176;C temperature&#44; and increasing tachycardia and tachypnea&#46; The patient was admitted to the Intensive Care Unit where he was intubated and connected to mechanical ventilation&#46; A multiorgan failure established itself in a few hours with refractory shock&#44; lactic acidosis&#44; acute renal failure &#40;creatinine 4&#46;5<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#41; requiring continuous hemodiafiltration&#44; acute respiratory failure and disseminated intravascular coagulation&#46; Analytic evolution showed hypoglycaemia&#44; cytolysis&#44; rhabdomyolysis &#40;LDH 4370<span class="elsevierStyleHsp" style=""></span>U&#47;L&#44; GOT 12&#44;989<span class="elsevierStyleHsp" style=""></span>U&#47;L&#44; GPT 7177<span class="elsevierStyleHsp" style=""></span> U&#47;L&#44; CK 10&#44;935<span class="elsevierStyleHsp" style=""></span>U&#47;L&#41; and leukopenia &#40;1700&#47;cc&#41;&#46; All of microbiological cultures were negative&#46; After 72<span class="elsevierStyleHsp" style=""></span>h death was confirmed&#46; The clinical autopsy has not been performed&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Our case is of particular interest because chronic tryptophan ingestion by means of non-pharmaceutical substances was probably the unknown predisposing and crucial background factor associated to bad outcome&#46; As a serotonin precursor&#44; tryptophan led to an increase in serotonin production&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Fatality from SS with pure citalopram overdose is rare due to the very safe range of plasmatic levels of SSRI&#44; even in overdose situations&#46; Our patient took a moderated overdose of citalopram &#40;below 30 times the common daily dose&#41; that has been associated with mild or no symptoms&#46;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">6&#44;7</span></a> Larger pure citalopram overdoses &#40;more than 840<span class="elsevierStyleHsp" style=""></span>mg&#41; and&#47;or with combination with other drugs have been associated with life threatening SS&#46;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">6&#8211;9</span></a> According to the World Health Organization &#40;WHO&#41; tryptophan recommended diet requirements are 4<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;day&#46; In some gym environments it is proposed an additional daily dose of 600<span class="elsevierStyleHsp" style=""></span>mg of tryptophan as nutritional supplement&#46; This means that for a subject of 75<span class="elsevierStyleHsp" style=""></span>kg the daily tryptophan intake would be threefold the WHO recommended dose&#46; Moreover&#44; the patient consumed regularly large doses of taurine with the energetic drink &#40;4&#8211;8<span class="elsevierStyleHsp" style=""></span>g per day&#41; that could also have serotoninergic activity&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a> All these conditions could predispose the fatal SS&#44; being the citalopram overdose probably the trigger&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Gym products consumed for its energizing or body building properties generally contain large amounts of tryptophan or derivates&#46; These substances are not considered drugs but nutrients&#44; and do not need pharmacological or medical control&#46; It is worth remarking the importance of a meticulous anamnesis to detect the consumption of over-the-counter drugs or substances &#40;sportsmen&#44; naturopathy treatments&#44; &#8230;&#41; before prescribing SSRI or when SS is suspected&#44; in addition to check pharmacologic interactions with other drugs that the patient could take&#46;</p><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Availability of data and material</span><p id="par0045" class="elsevierStylePara elsevierViewall">The data supporting the findings of this case are included in this manuscript&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Authors&#8217; contributions</span><p id="par0050" class="elsevierStylePara elsevierViewall">ID and GR analyzed and interpreted the present case&#44; reviewed bibliography and wrote a first draft&#46; SF and MR contributed in writing the manuscript&#46; All authors read and approved the final manuscript&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Funding</span><p id="par0055" class="elsevierStylePara elsevierViewall">This report received no research funding&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Competing interests</span><p id="par0060" class="elsevierStylePara elsevierViewall">The authors declare that they have no competing interests&#46;</p></span></span>"
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Scientific Letter
The role of chronic nutritional supplements consumption in a fulminant serotonin syndrome due to citalopram intoxication
El papel del consumo crónico de suplementos nutricionales en un síndrome serotoninérgico fulminante debido a intoxicación por citalopram
I. de Dios
Autor para correspondencia
inmaculadadadedios@gmail.com

Corresponding author.
, G. Rialp, S. Franco, M. Romero, M. Ortega, Y. Nieto
Intensive Care Medicine Unit, Hospital Son Llàtzer, Carretera de Manacor, Km 4, 07198 Palma de Mallorca, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0010" class="elsevierStylePara elsevierViewall">Selective serotonin reuptake inhibitors &#40;SSRI&#41; are the most frequently prescribed antidepressants and are included among the most frequently found drug in overdose&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> Serotonin syndrome &#40;SS&#41; is an adverse drug reaction caused by excessive activation of postsynaptic serotonin receptors and characterized by altered mental status&#44; autonomic hyperactivity and neuromuscular abnormalities &#40;tremor&#44; myoclonus or hyperreflexia&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">2&#8211;4</span></a> Although SS may result in death&#44; most patients recover completely only with the suppression of the treatment and supportive care&#46; SS occurs as an idiosyncratic drug reaction<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> or as a result of the interaction of two or more drugs that enhance serotonin transmission&#44; being the association of SSRI with monoaminoxidase inhibitors the most frequent one&#46; Drug combinations involved with SS include SSRI&#44; tricyclic antidepressants&#44; monoamine oxidase inhibitors&#44; serotonin norepinephrine reuptake inhibitors&#44; triptans&#44; trazodone&#44; opioids&#44; buspirone&#44; linezolid&#44; L-tryptophan or methylenedioxymethamphetamine&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">2&#8211;5</span></a> Interestingly&#44; over-the-counter drugs&#44; nutritional supplements or naturopathic treatments together with SSRI may also be involved with the serotonin syndrome&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">We report the case of a previously healthy 42-year-old man with a history of chronic tobacco and alcohol consumption who was recently diagnosed for depression&#46; He was treated with a daily dose of 20<span class="elsevierStyleHsp" style=""></span>mg of citalopram for the last four days&#46; He regularly practiced sport in a gym centre and he routinely consumed tryptophan-rich supplements at a daily dose of 600<span class="elsevierStyleHsp" style=""></span>mg of tryptophan and one or two litres of stimulating taurine-rich drink &#40;Red Bull&#174;&#41;&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">The patient was attended in the emergency department following voluntary ingestion three hours before of 480<span class="elsevierStyleHsp" style=""></span>mg of citalopram and alcohol with autolytic intention&#46; Initially&#44; he was awake&#44; conscious but showing a marked hyperactivity with diaphoresis&#44; sialorrhea and bilateral and reactive mydriasis&#46; His blood pressure was 168&#47;100<span class="elsevierStyleHsp" style=""></span>mmHg&#44; heart rate 110<span class="elsevierStyleHsp" style=""></span>bpm&#44; respiratory rate 48<span class="elsevierStyleHsp" style=""></span>bpm and axilar temperature of 36<span class="elsevierStyleHsp" style=""></span>&#176;C&#46; Sublingual benzodiazepine treatment was administered without response&#46; Initial haematological and biochemical analysis were normal&#44; blood ethanol was 56<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#44; and analysis of toxics in urine were negative &#40;cocaine&#44; cannabis&#44; benzodiazepines&#44; opiates&#44; amphetamines and barbiturates&#41;&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Patient evolution was fulminant with progressive deterioration of his agitation and increasing muscular rigidity and myoclonus&#44; Babinsky bilateral sign&#44; 39<span class="elsevierStyleHsp" style=""></span>&#176;C temperature&#44; and increasing tachycardia and tachypnea&#46; The patient was admitted to the Intensive Care Unit where he was intubated and connected to mechanical ventilation&#46; A multiorgan failure established itself in a few hours with refractory shock&#44; lactic acidosis&#44; acute renal failure &#40;creatinine 4&#46;5<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#41; requiring continuous hemodiafiltration&#44; acute respiratory failure and disseminated intravascular coagulation&#46; Analytic evolution showed hypoglycaemia&#44; cytolysis&#44; rhabdomyolysis &#40;LDH 4370<span class="elsevierStyleHsp" style=""></span>U&#47;L&#44; GOT 12&#44;989<span class="elsevierStyleHsp" style=""></span>U&#47;L&#44; GPT 7177<span class="elsevierStyleHsp" style=""></span> U&#47;L&#44; CK 10&#44;935<span class="elsevierStyleHsp" style=""></span>U&#47;L&#41; and leukopenia &#40;1700&#47;cc&#41;&#46; All of microbiological cultures were negative&#46; After 72<span class="elsevierStyleHsp" style=""></span>h death was confirmed&#46; The clinical autopsy has not been performed&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Our case is of particular interest because chronic tryptophan ingestion by means of non-pharmaceutical substances was probably the unknown predisposing and crucial background factor associated to bad outcome&#46; As a serotonin precursor&#44; tryptophan led to an increase in serotonin production&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Fatality from SS with pure citalopram overdose is rare due to the very safe range of plasmatic levels of SSRI&#44; even in overdose situations&#46; Our patient took a moderated overdose of citalopram &#40;below 30 times the common daily dose&#41; that has been associated with mild or no symptoms&#46;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">6&#44;7</span></a> Larger pure citalopram overdoses &#40;more than 840<span class="elsevierStyleHsp" style=""></span>mg&#41; and&#47;or with combination with other drugs have been associated with life threatening SS&#46;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">6&#8211;9</span></a> According to the World Health Organization &#40;WHO&#41; tryptophan recommended diet requirements are 4<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;day&#46; In some gym environments it is proposed an additional daily dose of 600<span class="elsevierStyleHsp" style=""></span>mg of tryptophan as nutritional supplement&#46; This means that for a subject of 75<span class="elsevierStyleHsp" style=""></span>kg the daily tryptophan intake would be threefold the WHO recommended dose&#46; Moreover&#44; the patient consumed regularly large doses of taurine with the energetic drink &#40;4&#8211;8<span class="elsevierStyleHsp" style=""></span>g per day&#41; that could also have serotoninergic activity&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a> All these conditions could predispose the fatal SS&#44; being the citalopram overdose probably the trigger&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Gym products consumed for its energizing or body building properties generally contain large amounts of tryptophan or derivates&#46; These substances are not considered drugs but nutrients&#44; and do not need pharmacological or medical control&#46; It is worth remarking the importance of a meticulous anamnesis to detect the consumption of over-the-counter drugs or substances &#40;sportsmen&#44; naturopathy treatments&#44; &#8230;&#41; before prescribing SSRI or when SS is suspected&#44; in addition to check pharmacologic interactions with other drugs that the patient could take&#46;</p><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Availability of data and material</span><p id="par0045" class="elsevierStylePara elsevierViewall">The data supporting the findings of this case are included in this manuscript&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Authors&#8217; contributions</span><p id="par0050" class="elsevierStylePara elsevierViewall">ID and GR analyzed and interpreted the present case&#44; reviewed bibliography and wrote a first draft&#46; SF and MR contributed in writing the manuscript&#46; All authors read and approved the final manuscript&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Funding</span><p id="par0055" class="elsevierStylePara elsevierViewall">This report received no research funding&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Competing interests</span><p id="par0060" class="elsevierStylePara elsevierViewall">The authors declare that they have no competing interests&#46;</p></span></span>"
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