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
Corresponding author
Intensive Care Medicine Unit, Hospital Son Llàtzer, Carretera de Manacor, Km 4, 07198 Palma de Mallorca, Spain
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"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"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Case presentation</span><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><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:7 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Case presentation" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Availability of data and material" ] 2 => array:2 [ "identificador" => "sec0015" "titulo" => "Authors’ contributions" ] 3 => array:2 [ "identificador" => "sec0020" "titulo" => "Funding" ] 4 => array:2 [ "identificador" => "sec0025" "titulo" => "Competing interests" ] 5 => array:2 [ "identificador" => "xack435446" "titulo" => "Acknowledgements" ] 6 => 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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| 2023 December | 166 | 32 | 198 |
| 2023 November | 153 | 36 | 189 |
| 2023 October | 166 | 30 | 196 |
| 2023 September | 99 | 32 | 131 |
| 2023 August | 100 | 18 | 118 |
| 2023 July | 120 | 32 | 152 |
| 2023 June | 156 | 28 | 184 |
| 2023 May | 103 | 36 | 139 |
| 2023 April | 95 | 15 | 110 |
| 2023 March | 148 | 29 | 177 |
| 2023 February | 82 | 16 | 98 |
| 2023 January | 72 | 12 | 84 |
| 2022 December | 66 | 26 | 92 |
| 2022 November | 69 | 45 | 114 |
| 2022 October | 77 | 30 | 107 |
| 2022 September | 60 | 35 | 95 |
| 2022 August | 56 | 50 | 106 |
| 2022 July | 44 | 33 | 77 |
| 2022 June | 47 | 15 | 62 |
| 2022 May | 50 | 31 | 81 |
| 2022 April | 48 | 35 | 83 |
| 2022 March | 70 | 44 | 114 |
| 2022 February | 92 | 32 | 124 |
| 2022 January | 68 | 31 | 99 |
| 2021 December | 78 | 42 | 120 |
| 2021 November | 49 | 35 | 84 |
| 2021 October | 106 | 63 | 169 |
| 2021 September | 86 | 29 | 115 |
| 2021 August | 43 | 23 | 66 |
| 2021 July | 44 | 13 | 57 |
| 2021 June | 50 | 21 | 71 |
| 2021 May | 49 | 41 | 90 |
| 2021 April | 94 | 41 | 135 |
| 2021 March | 71 | 27 | 98 |
| 2021 February | 54 | 35 | 89 |
| 2021 January | 29 | 18 | 47 |
| 2020 December | 35 | 12 | 47 |
| 2020 November | 19 | 8 | 27 |
| 2020 October | 16 | 10 | 26 |
| 2020 August | 4 | 0 | 4 |
| 2020 July | 10 | 4 | 14 |
| 2020 June | 13 | 10 | 23 |
| 2020 May | 17 | 5 | 22 |
| 2020 April | 9 | 10 | 19 |
| 2020 March | 1 | 0 | 1 |
| 2020 February | 1 | 0 | 1 |
| 2020 January | 1 | 2 | 3 |
Show all
