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
, G. Rialp, S. Franco, M. Romero, M. Ortega, Y. Nieto
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Intensive Care Medicine Unit, Hospital Son Llàtzer, Carretera de Manacor, Km 4, 07198 Palma de Mallorca, Spain
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Hernández, J. Bakker" "autores" => array:2 [ 0 => array:2 [ "nombre" => "G." "apellidos" => "Hernández" ] 1 => array:2 [ "nombre" => "J." "apellidos" => "Bakker" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0210569119302098?idApp=WMIE" "url" => "/02105691/0000004300000009/v1_201911280655/S0210569119302098/v1_201911280655/en/main.assets" ] "en" => array:14 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Scientific Letter</span>" "titulo" => "The role of chronic nutritional supplements consumption in a fulminant serotonin syndrome due to citalopram intoxication" "tieneTextoCompleto" => true "saludo" => "Dear Editor:" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "582" "paginaFinal" => "583" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "I. de Dios, G. Rialp, S. Franco, M. Romero, M. Ortega, Y. Nieto" "autores" => array:6 [ 0 => array:4 [ "nombre" => "I." "apellidos" => "de Dios" "email" => array:1 [ 0 => "inmaculadadadedios@gmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "G." "apellidos" => "Rialp" ] 2 => array:2 [ "nombre" => "S." "apellidos" => "Franco" ] 3 => array:2 [ "nombre" => "M." "apellidos" => "Romero" ] 4 => array:2 [ "nombre" => "M." "apellidos" => "Ortega" ] 5 => array:2 [ "nombre" => "Y." "apellidos" => "Nieto" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Intensive Care Medicine Unit, Hospital Son Llàtzer, Carretera de Manacor, Km 4, 07198 Palma de Mallorca, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "El papel del consumo crónico de suplementos nutricionales en un síndrome serotoninérgico fulminante debido a intoxicación por citalopram" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0010" class="elsevierStylePara elsevierViewall">Selective serotonin reuptake inhibitors (SSRI) are the most frequently prescribed antidepressants and are included among the most frequently found drug in overdose.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> Serotonin syndrome (SS) is an adverse drug reaction caused by excessive activation of postsynaptic serotonin receptors and characterized by altered mental status, autonomic hyperactivity and neuromuscular abnormalities (tremor, myoclonus or hyperreflexia).<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">2–4</span></a> Although SS may result in death, most patients recover completely only with the suppression of the treatment and supportive care. 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, being the association of SSRI with monoaminoxidase inhibitors the most frequent one. Drug combinations involved with SS include SSRI, tricyclic antidepressants, monoamine oxidase inhibitors, serotonin norepinephrine reuptake inhibitors, triptans, trazodone, opioids, buspirone, linezolid, L-tryptophan or methylenedioxymethamphetamine.<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">2–5</span></a> Interestingly, over-the-counter drugs, nutritional supplements or naturopathic treatments together with SSRI may also be involved with the serotonin syndrome.</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. He was treated with a daily dose of 20<span class="elsevierStyleHsp" style=""></span>mg of citalopram for the last four days. 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 (Red Bull®).</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. Initially, he was awake, conscious but showing a marked hyperactivity with diaphoresis, sialorrhea and bilateral and reactive mydriasis. His blood pressure was 168/100<span class="elsevierStyleHsp" style=""></span>mmHg, heart rate 110<span class="elsevierStyleHsp" style=""></span>bpm, respiratory rate 48<span class="elsevierStyleHsp" style=""></span>bpm and axilar temperature of 36<span class="elsevierStyleHsp" style=""></span>°C. Sublingual benzodiazepine treatment was administered without response. Initial haematological and biochemical analysis were normal, blood ethanol was 56<span class="elsevierStyleHsp" style=""></span>mg/dL, and analysis of toxics in urine were negative (cocaine, cannabis, benzodiazepines, opiates, amphetamines and barbiturates).</p><p id="par0025" class="elsevierStylePara elsevierViewall">Patient evolution was fulminant with progressive deterioration of his agitation and increasing muscular rigidity and myoclonus, Babinsky bilateral sign, 39<span class="elsevierStyleHsp" style=""></span>°C temperature, and increasing tachycardia and tachypnea. The patient was admitted to the Intensive Care Unit where he was intubated and connected to mechanical ventilation. A multiorgan failure established itself in a few hours with refractory shock, lactic acidosis, acute renal failure (creatinine 4.5<span class="elsevierStyleHsp" style=""></span>mg/dL) requiring continuous hemodiafiltration, acute respiratory failure and disseminated intravascular coagulation. Analytic evolution showed hypoglycaemia, cytolysis, rhabdomyolysis (LDH 4370<span class="elsevierStyleHsp" style=""></span>U/L, GOT 12,989<span class="elsevierStyleHsp" style=""></span>U/L, GPT 7177<span class="elsevierStyleHsp" style=""></span> U/L, CK 10,935<span class="elsevierStyleHsp" style=""></span>U/L) and leukopenia (1700/cc). All of microbiological cultures were negative. After 72<span class="elsevierStyleHsp" style=""></span>h death was confirmed. The clinical autopsy has not been performed.</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. As a serotonin precursor, tryptophan led to an increase in serotonin production.</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, even in overdose situations. Our patient took a moderated overdose of citalopram (below 30 times the common daily dose) that has been associated with mild or no symptoms.<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">6,7</span></a> Larger pure citalopram overdoses (more than 840<span class="elsevierStyleHsp" style=""></span>mg) and/or with combination with other drugs have been associated with life threatening SS.<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">6–9</span></a> According to the World Health Organization (WHO) tryptophan recommended diet requirements are 4<span class="elsevierStyleHsp" style=""></span>mg/kg/day. In some gym environments it is proposed an additional daily dose of 600<span class="elsevierStyleHsp" style=""></span>mg of tryptophan as nutritional supplement. 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. Moreover, the patient consumed regularly large doses of taurine with the energetic drink (4–8<span class="elsevierStyleHsp" style=""></span>g per day) that could also have serotoninergic activity.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a> All these conditions could predispose the fatal SS, being the citalopram overdose probably the trigger.</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. These substances are not considered drugs but nutrients, and do not need pharmacological or medical control. It is worth remarking the importance of a meticulous anamnesis to detect the consumption of over-the-counter drugs or substances (sportsmen, naturopathy treatments, …) before prescribing SSRI or when SS is suspected, in addition to check pharmacologic interactions with other drugs that the patient could take.</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.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Authors’ contributions</span><p id="par0050" class="elsevierStylePara elsevierViewall">ID and GR analyzed and interpreted the present case, reviewed bibliography and wrote a first draft. SF and MR contributed in writing the manuscript. All authors read and approved the final manuscript.</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.</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.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:6 [ 0 => array:2 [ "identificador" => "sec0010" "titulo" => "Availability of data and material" ] 1 => array:2 [ "identificador" => "sec0015" "titulo" => "Authors’ contributions" ] 2 => array:2 [ "identificador" => "sec0020" "titulo" => "Funding" ] 3 => array:2 [ "identificador" => "sec0025" "titulo" => "Competing interests" ] 4 => array:2 [ "identificador" => "xack435464" "titulo" => "Acknowledgements" ] 5 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0055" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Citalopram in fatal poisoning cases" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "B. 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| 2024 Octubre | 62 | 88 | 150 |
| 2024 Septiembre | 64 | 59 | 123 |
| 2024 Agosto | 69 | 83 | 152 |
| 2024 Julio | 49 | 54 | 103 |
| 2024 Junio | 87 | 114 | 201 |
| 2024 Mayo | 47 | 35 | 82 |
| 2024 Abril | 58 | 47 | 105 |
| 2024 Marzo | 60 | 36 | 96 |
| 2024 Febrero | 29 | 36 | 65 |
| 2024 Enero | 40 | 35 | 75 |
| 2023 Diciembre | 35 | 34 | 69 |
| 2023 Noviembre | 55 | 47 | 102 |
| 2023 Octubre | 37 | 35 | 72 |
| 2023 Septiembre | 34 | 45 | 79 |
| 2023 Agosto | 38 | 25 | 63 |
| 2023 Julio | 38 | 31 | 69 |
| 2023 Junio | 39 | 22 | 61 |
| 2023 Mayo | 48 | 36 | 84 |
| 2023 Abril | 53 | 25 | 78 |
| 2023 Marzo | 55 | 36 | 91 |
| 2023 Febrero | 46 | 43 | 89 |
| 2023 Enero | 33 | 58 | 91 |
| 2022 Diciembre | 52 | 85 | 137 |
| 2022 Noviembre | 60 | 70 | 130 |
| 2022 Octubre | 58 | 48 | 106 |
| 2022 Septiembre | 52 | 60 | 112 |
| 2022 Agosto | 43 | 46 | 89 |
| 2022 Julio | 35 | 45 | 80 |
| 2022 Junio | 53 | 38 | 91 |
| 2022 Mayo | 49 | 40 | 89 |
| 2022 Abril | 70 | 42 | 112 |
| 2022 Marzo | 86 | 60 | 146 |
| 2022 Febrero | 76 | 38 | 114 |
| 2022 Enero | 91 | 44 | 135 |
| 2021 Diciembre | 89 | 52 | 141 |
| 2021 Noviembre | 71 | 49 | 120 |
| 2021 Octubre | 58 | 84 | 142 |
| 2021 Septiembre | 39 | 37 | 76 |
| 2021 Agosto | 27 | 41 | 68 |
| 2021 Julio | 36 | 33 | 69 |
| 2021 Junio | 41 | 30 | 71 |
| 2021 Mayo | 50 | 53 | 103 |
| 2021 Abril | 59 | 82 | 141 |
| 2021 Marzo | 82 | 49 | 131 |
| 2021 Febrero | 70 | 33 | 103 |
| 2021 Enero | 72 | 38 | 110 |
| 2020 Diciembre | 79 | 25 | 104 |
| 2020 Noviembre | 46 | 27 | 73 |
| 2020 Octubre | 36 | 14 | 50 |
| 2020 Agosto | 1 | 4 | 5 |
| 2020 Julio | 23 | 20 | 43 |
| 2020 Junio | 42 | 27 | 69 |
| 2020 Mayo | 52 | 22 | 74 |
| 2020 Abril | 34 | 13 | 47 |
| 2020 Marzo | 58 | 15 | 73 |
| 2020 Febrero | 16 | 5 | 21 |
| 2020 Enero | 11 | 12 | 23 |
| 2019 Diciembre | 17 | 9 | 26 |
| 2019 Noviembre | 4 | 14 | 18 |
| 2019 Octubre | 2 | 2 | 4 |
| 2019 Septiembre | 0 | 0 | 0 |
| 2019 Junio | 0 | 0 | 0 |
| 2019 Mayo | 0 | 1 | 1 |
| 2019 Abril | 0 | 7 | 7 |
| 2019 Marzo | 0 | 5 | 5 |
| 2018 Octubre | 1 | 0 | 1 |
| 2018 Junio | 0 | 1 | 1 |
| 2018 Mayo | 0 | 1 | 1 |
| 2018 Abril | 0 | 1 | 1 |
| 2018 Febrero | 0 | 1 | 1 |
| 2018 Enero | 0 | 2 | 2 |
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