Serotonin or 5-hydroxytryptamine (5-HT) is a neurotransmitter that's of integral physiological importance for our body's systems as it regulates most of our (behaviors, mood, memory, etc.). It is utilized as the main treatment for many psychiatric and neurological cases as a class of 5-HT elevating drugs called antidepressants which work on disorders such as Major depressive disorder, dysthymia, post-traumatic stress disorder, bulimia nervosa, obsessive-compulsive disorder, anxiety, aggressive behavior, premenstrual dysphoric disorder, panic disorders, social phobia, bipolar disorder, atypical depression and migraines.
There was a noticed pattern of disrupted 5-HT levels in the areas of concentration in the CNS and peripherally in the plasma, which might have contributed to pathogenesis in most cases. There is no consensus over the fact that 5-HT is the only main neurotransmitter involved in initiating the pathophysiological mechanism of neuropsychiatric disorders. However, the potency of antidepressants which effect 5-HT levels has been proven, leading to elevation centrally and peripherally. Consequently, restoring the homeostatic balance of 5-HT levels will increase the chances of good prognosis.
The serotonergic pathway's pre-synaptic axons terminals will start the formation of 5-HT through tryptophan hydroxylase utilizing tryptophan. Although, it is thought to be mainly in the CNS (raphe nuclei), maintaining cortical functions such as perception, memory, mood. It's also found in different sites (e.g., enterochromaffin cells, platelets, etc.), regulating its tone, functionality, and blood supply. Then the release of 5-HT in the synaptic cleft, where it majorly has a receptor-dependent effect as through one pathway will cause adrenergic responses (e.g., mydriasis, increased heart, and respiratory rates, etc.), which in observation are adrenergic outcomes. Thus, different serotonergic and adrenergic receptor subtypes might show distinctive molecular affinities and actions.
In the post-synaptic end, metabotropic G-protein receptors with high 5-HT affinity will initiate second messenger cascades. The cascades' visceral effect differs based on the receptor subtype. The metabotropic receptors (HTR1/2) alongside its different subtypes, has an effect of decreasing cyclic-AMP (CAMP), through the coupling of Gi/o protein alpha subunit (GNAI) in which the activity of adenylate cyclase (ADCY) will be inhibited. On the other hand, (HTR4/6/7) cascades work on a coupling of Gs protein alpha (GNAS) which stimulates ADCY, and that leads to increased CAMP. The only Ionotropic receptors (HTR3) will maintain electrolytic gradients. The electrolytes gradient difference between sodium influx and potassium efflux will depolarize the membrane and facilitate the need for a physiological outcome. Therefore, the outcome has its basis on the visceral function in response to such induced gradient of CAMP.
Moreover, as 5-HT plays a role in increasing CAMP concentration a partial function will be the downregulation of the innate immune system. That plays a role in preventing symptoms from occurring in some hypersensitive pathologies such as asthma.
Additionally, as 5-HT is a neurotransmitter there are few things to note down in regulating its function.
Similarly, there is also a range of different legal and illegal drug groups (e.g. SNRIs or ecstasy) that will work on elevating 5-HT concentration.
Most patients would prefer to take the drug orally taken as a pill (PO). The other methods can be by applying dermal patches, through nasal route, intraperitoneal (IP) not clinically used, intramuscularly (IM) and intravenously (IV), each route has a different half-life, efficacy, and potency of the type of drug administered. Furthermore, in IV administration, one needs to be careful and monitor BP alongside vital signs and cardiac activity to prevent sudden deterioration. Also, in (IM) injections applied for local vasoconstricting effect would cause the induction of pain in patients rather than alleviating it. Intraperitoneal (IP) frequent administration has shown a correlation with disrupting thyroidal hormones function and concentration and other physiological functions, which is why it is not used clinically, only on experimental rats. Although we have different forms of delivering 5-HT related drugs, we need to understand which route the patient is more comfortable with, which shows the needed efficacy to tackle the pathology.
5-HT has known and undiscovered functions; moreover, the adverse effects might range from mostly they are mild symptoms but can increase in severity. These adverse effects can present as hyperhidrosis, mydriasis, hypertension, nausea, dry mouth, constipation, rash, paranesthesia, akathisia, headaches, orthostatic hypotension, increased bleeding time, hyponatremia, insomnia, agitation, anxiety, extrapyramidal side effects, and sexual dysfunction. The underaged patients might experience abnormal and/or suicidal thoughts; however, treatment continuation in neuropsychiatric disorders is of necessity. Also, long term administration may induce the pathogenesis of carcinoid heart disease.
The effects are further triaged based on hospitals' coding system to either minor, mild, or major (toxicity), has been made to elaborate more on how to approach and treat it. There has been increasing evidence that most patients are not adherent with their drug course, due to the evolving side effects that are relieved mostly by abstinence.
Utilization of any drugs elevating or depleting 5-HT concentration peripherally or centrally need to be dosed appropriately and patient-oriented not fixed-doses administration. A room for dose changing while checking for tolerance is of therapeutic benefit. The maintenance of serum-serotonin-level (SSL) at a range in between 101 to 283 nanograms per milliliter (ng/mL) is within normal levels. On the one hand, an increase in SSL above normal ranges can lead to cardiac arrhythmias. Abrupt bone metabolic regulation by causing a decrease in the bone mineral density and abnormal regulation of metabolic processes such as lipolysis and gluconeogenesis. On the other hand, a decrease in SSL generally correlates with depressive disorders and many neuropsychiatric disorders. Thus, the true nature of pathogenesis is still not fully understood. Clinically, frequent checks of vital signs, cardiac rhythm, blood analysis, and the continuous checkups on patients for the appearance of any signs of toxicity or minor side effects. Contrarily, if the patient after the drug's onset of action time has passed and there are no signs of the patient's evaluation improving, that might suggest an increase in dose to reach the needed concentration. Additionally, tryptophan plasma levels have shown to play a major indicator of decreased or increased SSL and its concentration centrally.
Serotonin syndrome or toxicity (ST) is a combination of hyper-serotonergic visceral presentation. Toxicity can present when a patient receives a combination of 5-HT elevating drugs or in an overdose. The spectrum of clinical manifestations can be life-threating, thus manageable signs and symptoms appear first, which help in early recognition. The signs and symptoms may develop 24-hours after administration as the drug's pharmacokinetic and pharmacodynamic processes take place. The diagnostic mechanism of ST is mostly dependent on a thorough history and physical examination while having increased emphasis on integrating Sternbach, Radomski, and Hunter's criteria of diagnosis. The predominant diagnostic mechanism is having the presentation dependent on three parts, which are the neuromuscular, autonomic, and mental manifestations:
Consequently, a presence in abnormalities within these three domain will confirm the diagnosis of ST.
The an interprofessional approach to deal with serotonin toxicity (ST) is crucial. The confirmation of the diagnosis also requires the combination of nurses, doctors, and toxicologists' investigatory methods. Nonetheless, blood analysis must be done to check for the appropriate plan of care to understand where the patient is standing and to alleviate patient's toxicity. Furthermore, health practitioners should be updated with the new edits to the diagnostic criterion of ST as the integration of Sternbach, Radomski, and Hunter's methods have shown optimum results so far. The presentation will require the triage nurse or doctor to understand the level of severity at which the patient's manifestations has reached. The next step is to manage to symptoms and try to get some history either from the patient if alert or family if possible. There is a need to contact the psychiatric ward for consultation if the patient has a file within the hospital and getting their feedback on whether it is a suicidal attempt or a part of a specific neuropsychiatric disorder the patient is facing. Therefore, formulating patient's data between nurses, doctors, toxicologists, pharmacists, and psychiatrists is the optimal path to early recognize ST and to treat it accordingly.
The treatment of serotonin toxicity is mainly dependent on decreasing the dosages of the serotonergic agonist(s) taken by the patient. The maintenance of the patient's vital sign, continuous cardiac monitoring, and sedation by benzodiazepines are required; moreover, controlling the patient's hyperthermia by IV cold fluid and antipyretics is essential to prevent further autonomic and neuromuscular disruption. Eventually, a serotonin antagonist might be necessary. Cyproheptadine is the first-line choice and is considered as an antidote, though caution is advisable as there are reports of prolonged sedation and transient hypotension. The resolution of mild to moderate cases can be within 24 hours, as early recognition and management is key to improved prognosis.
|||Berger M,Gray JA,Roth BL, The expanded biology of serotonin. Annual review of medicine. 2009; [PubMed PMID: 19630576]|
|||Masand PS,Gupta S, Selective serotonin-reuptake inhibitors: an update. Harvard review of psychiatry. 1999 Jul-Aug; [PubMed PMID: 10471245]|
|||Boyer WF, Potential indications for the selective serotonin reuptake inhibitors. International clinical psychopharmacology. 1992 Jun; [PubMed PMID: 1431022]|
|||van Praag HM,Kahn R,Asnis GM,Lemus CZ,Brown SL, Therapeutic indications for serotonin-potentiating compounds: a hypothesis. Biological psychiatry. 1987 Feb; [PubMed PMID: 2434148]|
|||Owens MJ,Nemeroff CB, Role of serotonin in the pathophysiology of depression: focus on the serotonin transporter. Clinical chemistry. 1994 Feb; [PubMed PMID: 7508830]|
|||Young SN,Smith SE,Pihl RO,Ervin FR, Tryptophan depletion causes a rapid lowering of mood in normal males. Psychopharmacology. 1985; [PubMed PMID: 3931142]|
|||Potter WZ,Manji HK, Catecholamines in depression: an update. Clinical chemistry. 1994 Feb; [PubMed PMID: 8313609]|
|||Zangen A,Overstreet DH,Yadid G, Increased catecholamine levels in specific brain regions of a rat model of depression: normalization by chronic antidepressant treatment. Brain research. 1999 Apr 10; [PubMed PMID: 10196455]|
|||Fournier JC,DeRubeis RJ,Hollon SD,Dimidjian S,Amsterdam JD,Shelton RC,Fawcett J, Antidepressant drug effects and depression severity: a patient-level meta-analysis. JAMA. 2010 Jan 6; [PubMed PMID: 20051569]|
|||Lane R,Baldwin D,Preskorn S, The SSRIs: advantages, disadvantages and differences. Journal of psychopharmacology (Oxford, England). 1995 Jan; [PubMed PMID: 22297235]|
|||Gibbons RD,Hur K,Brown CH,Davis JM,Mann JJ, Benefits from antidepressants: synthesis of 6-week patient-level outcomes from double-blind placebo-controlled randomized trials of fluoxetine and venlafaxine. Archives of general psychiatry. 2012 Jun; [PubMed PMID: 22393205]|
|||Bellono NW,Bayrer JR,Leitch DB,Castro J,Zhang C,O'Donnell TA,Brierley SM,Ingraham HA,Julius D, Enterochromaffin Cells Are Gut Chemosensors that Couple to Sensory Neural Pathways. Cell. 2017 Jun 29; [PubMed PMID: 28648659]|
|||Mohammad-Zadeh LF,Moses L,Gwaltney-Brant SM, Serotonin: a review. Journal of veterinary pharmacology and therapeutics. 2008 Jun; [PubMed PMID: 18471139]|
|||Brenner B,Harney JT,Ahmed BA,Jeffus BC,Unal R,Mehta JL,Kilic F, Plasma serotonin levels and the platelet serotonin transporter. Journal of neurochemistry. 2007 Jul; [PubMed PMID: 17506858]|
|||Leysen JE,Van Gompel P,Gommeren W, Distinction between adrenergic and serotonergic receptor subtypes: specificity of drugs and absence of cooperative interactions between adrenergic and serotonergic receptor binding sites. Journal of cardiovascular pharmacology. 1988; [PubMed PMID: 2459521]|
|||Bockaert J,Claeysen S,Bécamel C,Dumuis A,Marin P, Neuronal 5-HT metabotropic receptors: fine-tuning of their structure, signaling, and roles in synaptic modulation. Cell and tissue research. 2006 Nov; [PubMed PMID: 16896947]|
|||Raymond JR,Mukhin YV,Gelasco A,Turner J,Collinsworth G,Gettys TW,Grewal JS,Garnovskaya MN, Multiplicity of mechanisms of serotonin receptor signal transduction. Pharmacology [PubMed PMID: 11916537]|
|||Niesler B,Kapeller J,Hammer C,Rappold G, Serotonin type 3 receptor genes: HTR3A, B, C, D, E. Pharmacogenomics. 2008 May; [PubMed PMID: 18466097]|
|||Strüder HK,Weicker H, Physiology and pathophysiology of the serotonergic system and its implications on mental and physical performance. Part I. International journal of sports medicine. 2001 Oct; [PubMed PMID: 11590474]|
|||Sangkuhl K,Klein TE,Altman RB, Selective serotonin reuptake inhibitors pathway. Pharmacogenetics and genomics. 2009 Nov; [PubMed PMID: 19741567]|
|||Serezani CH,Ballinger MN,Aronoff DM,Peters-Golden M, Cyclic AMP: master regulator of innate immune cell function. American journal of respiratory cell and molecular biology. 2008 Aug; [PubMed PMID: 18323530]|
|||Young MR,Kut JL,Coogan MP,Wright MA,Young ME,Matthews J, Stimulation of splenic T-lymphocyte function by endogenous serotonin and by low-dose exogenous serotonin. Immunology. 1993 Nov; [PubMed PMID: 8288316]|
|||Ménard G,Turmel V,Bissonnette EY, Serotonin modulates the cytokine network in the lung: involvement of prostaglandin E2. Clinical and experimental immunology. 2007 Nov; [PubMed PMID: 17822443]|
|||Nau F Jr,Miller J,Saravia J,Ahlert T,Yu B,Happel KI,Cormier SA,Nichols CD, Serotonin 5-HT₂ receptor activation prevents allergic asthma in a mouse model. American journal of physiology. Lung cellular and molecular physiology. 2015 Jan 15; [PubMed PMID: 25416380]|
|||Peterlin BL,Rapoport AM, Clinical pharmacology of the serotonin receptor agonist, zolmitriptan. Expert opinion on drug metabolism [PubMed PMID: 18028032]|
|||Lucki I,Singh A,Kreiss DS, Antidepressant-like behavioral effects of serotonin receptor agonists. Neuroscience and biobehavioral reviews. 1994 Spring; [PubMed PMID: 8170624]|
|||Hurley LM, Different serotonin receptor agonists have distinct effects on sound-evoked responses in inferior colliculus. Journal of neurophysiology. 2006 Nov; [PubMed PMID: 16870843]|
|||Mace S,Taylor D, Selective serotonin reuptake inhibitors: a review of efficacy and tolerability in depression. Expert opinion on pharmacotherapy. 2000 Jul; [PubMed PMID: 11249500]|
|||Fiedorowicz JG,Swartz KL, The role of monoamine oxidase inhibitors in current psychiatric practice. Journal of psychiatric practice. 2004 Jul; [PubMed PMID: 15552546]|
|||Gillman PK, Tricyclic antidepressant pharmacology and therapeutic drug interactions updated. British journal of pharmacology. 2007 Jul; [PubMed PMID: 17471183]|
|||Watts SW,Morrison SF,Davis RP,Barman SM, Serotonin and blood pressure regulation. Pharmacological reviews. 2012 Apr; [PubMed PMID: 22407614]|
|||Henderson LA,Yu PL,Frysinger RC,Galons JP,Bandler R,Harper RM, Neural responses to intravenous serotonin revealed by functional magnetic resonance imaging. Journal of applied physiology (Bethesda, Md. : 1985). 2002 Jan; [PubMed PMID: 11744676]|
|||Ernberg M,Hedenberg-Magnusson B,Kurita H,Kopp S, Effects of local serotonin administration on pain and microcirculation in the human masseter muscle. Journal of orofacial pain. 2006 Summer; [PubMed PMID: 16913434]|
|||Sullo A,Brizzi G,Maffulli N, Chronic peripheral administration of serotonin inhibits thyroid function in the rat. Muscles, ligaments and tendons journal. 2011 Apr; [PubMed PMID: 23738246]|
|||Brizzi G,Foglia M,Acunzo S,Manganiello C, [Time course of blood glucose levels in rats after intraperitoneal injection of a dose of serotonin]. Bollettino della Societa italiana di biologia sperimentale. 1981 Apr 15; [PubMed PMID: 7272048]|
|||Trindade E,Menon D,Topfer LA,Coloma C, Adverse effects associated with selective serotonin reuptake inhibitors and tricyclic antidepressants: a meta-analysis. CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne. 1998 Nov 17; [PubMed PMID: 9861221]|
|||Ferguson JM, SSRI Antidepressant Medications: Adverse Effects and Tolerability. Primary care companion to the Journal of clinical psychiatry. 2001 Feb; [PubMed PMID: 15014625]|
|||Spigset O, Adverse reactions of selective serotonin reuptake inhibitors: reports from a spontaneous reporting system. Drug safety. 1999 Mar; [PubMed PMID: 10221856]|
|||Serebruany VL, Selective serotonin reuptake inhibitors and increased bleeding risk: are we missing something? The American journal of medicine. 2006 Feb; [PubMed PMID: 16443409]|
|||Hu XH,Bull SA,Hunkeler EM,Ming E,Lee JY,Fireman B,Markson LE, Incidence and duration of side effects and those rated as bothersome with selective serotonin reuptake inhibitor treatment for depression: patient report versus physician estimate. The Journal of clinical psychiatry. 2004 Jul; [PubMed PMID: 15291685]|
|||Holtkamp K,Herpertz-Dahlmann B, [SSRI and SNRI treatment in children and adolescents. Current views of the benefits and risks]. Der Nervenarzt. 2008 Nov; [PubMed PMID: 18958442]|
|||Gustafsson BI,Tømmerås K,Nordrum I,Loennechen JP,Brunsvik A,Solligård E,Fossmark R,Bakke I,Syversen U,Waldum H, Long-term serotonin administration induces heart valve disease in rats. Circulation. 2005 Mar 29; [PubMed PMID: 15781732]|
|||Yuan SM, Valvular Disorders in Carcinoid Heart Disease. Brazilian journal of cardiovascular surgery. 2016 Sep-Oct; [PubMed PMID: 27982350]|
|||Demyttenaere K,Enzlin P,Dewé W,Boulanger B,De Bie J,De Troyer W,Mesters P, Compliance with antidepressants in a primary care setting, 1: Beyond lack of efficacy and adverse events. The Journal of clinical psychiatry. 2001; [PubMed PMID: 11599645]|
|||Crawford AA,Lewis S,Nutt D,Peters TJ,Cowen P,O'Donovan MC,Wiles N,Lewis G, Adverse effects from antidepressant treatment: randomised controlled trial of 601 depressed individuals. Psychopharmacology. 2014 Aug; [PubMed PMID: 24525810]|
|||Löppönen P,Tetri S,Juvela S,Huhtakangas J,Saloheimo P,Bode MK,Hillbom M, Association between warfarin combined with serotonin-modulating antidepressants and increased case fatality in primary intracerebral hemorrhage: a population-based study. Journal of neurosurgery. 2014 Jun; [PubMed PMID: 24506245]|
|||Parry BL,Rush AJ, Oral contraceptives and depressive symptomatology: biologic mechanisms. Comprehensive psychiatry. 1979 Jul-Aug; [PubMed PMID: 37042]|
|||Faryal U,Rashid S,Hajra B,Hassan M,Saqib J,Ali MA, EFFECT OF HORMONAL CONTRACEPTIVES ON SERUM SEROTONIN IN FEMALES OF REPRODUCTIVE AGE GROUP. Journal of Ayub Medical College, Abbottabad : JAMC. 2016 Jan-Mar; [PubMed PMID: 27323563]|
|||Christ T,Rozmaritsa N,Engel A,Berk E,Knaut M,Metzner K,Canteras M,Ravens U,Kaumann A, Arrhythmias, elicited by catecholamines and serotonin, vanish in human chronic atrial fibrillation. Proceedings of the National Academy of Sciences of the United States of America. 2014 Jul 29; [PubMed PMID: 25024212]|
|||el-Mahdy SA, 5-Hydroxytryptamine (serotonin) enhances ventricular arrhythmias induced by acute coronary artery ligation in rats. Research communications in chemical pathology and pharmacology. 1990 Jun; [PubMed PMID: 2117299]|
|||Weissman AM,Levy BT,Hartz AJ,Bentler S,Donohue M,Ellingrod VL,Wisner KL, Pooled analysis of antidepressant levels in lactating mothers, breast milk, and nursing infants. The American journal of psychiatry. 2004 Jun; [PubMed PMID: 15169695]|
|||Eberhard-Gran M,Eskild A,Opjordsmoen S, Use of psychotropic medications in treating mood disorders during lactation : practical recommendations. CNS drugs. 2006; [PubMed PMID: 16529525]|
|||Lanza di Scalea T,Wisner KL, Antidepressant medication use during breastfeeding. Clinical obstetrics and gynecology. 2009 Sep; [PubMed PMID: 19661763]|
|||Theodore WH, Does Serotonin Play a Role in Epilepsy? Epilepsy currents. 2003 Sep; [PubMed PMID: 15346169]|
|||Braitberg G,Curry SC, Seizure after isolated fluoxetine overdose. Annals of emergency medicine. 1995 Aug; [PubMed PMID: 7618791]|
|||Bagdy G,Kecskemeti V,Riba P,Jakus R, Serotonin and epilepsy. Journal of neurochemistry. 2007 Feb; [PubMed PMID: 17212700]|
|||Davis RP,Szasz T,Garver H,Burnett R,Tykocki NR,Watts SW, One-month serotonin infusion results in a prolonged fall in blood pressure in the deoxycorticosterone acetate (DOCA) salt hypertensive rat. ACS chemical neuroscience. 2013 Jan 16; [PubMed PMID: 23336053]|
|||Fraer M,Kilic F, Serotonin: a different player in hypertension-associated thrombosis. Hypertension (Dallas, Tex. : 1979). 2015 May; [PubMed PMID: 25753975]|
|||Chen VC,Ng MH,Chiu WC,McIntyre RS,Lee Y,Lin TY,Weng JC,Chen PC,Hsu CY, Effects of selective serotonin reuptake inhibitors on glaucoma: A nationwide population-based study. PloS one. 2017; [PubMed PMID: 28257449]|
|||Razeghinejad MR,Myers JS,Katz LJ, Iatrogenic glaucoma secondary to medications. The American journal of medicine. 2011 Jan; [PubMed PMID: 21092926]|
|||Richa S,Yazbek JC, Ocular adverse effects of common psychotropic agents: a review. CNS drugs. 2010 Jun; [PubMed PMID: 20443647]|
|||Chung H, Dosing of Selective Serotonin Reuptake Inhibitors. Primary care companion to the Journal of clinical psychiatry. 2001 Oct; [PubMed PMID: 15014578]|
|||Papakostas GI,Charles D,Fava M, Are typical starting doses of the selective serotonin reuptake inhibitors sub-optimal? A meta-analysis of randomized, double-blind, placebo-controlled, dose-finding studies in major depressive disorder. The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry. 2010 Mar; [PubMed PMID: 20218793]|
|||Mödder UI,Achenbach SJ,Amin S,Riggs BL,Melton LJ 3rd,Khosla S, Relation of serum serotonin levels to bone density and structural parameters in women. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2010 Feb; [PubMed PMID: 19594297]|
|||Sumara G,Sumara O,Kim JK,Karsenty G, Gut-derived serotonin is a multifunctional determinant to fasting adaptation. Cell metabolism. 2012 Nov 7; [PubMed PMID: 23085101]|
|||Crane JD,Palanivel R,Mottillo EP,Bujak AL,Wang H,Ford RJ,Collins A,Blümer RM,Fullerton MD,Yabut JM,Kim JJ,Ghia JE,Hamza SM,Morrison KM,Schertzer JD,Dyck JR,Khan WI,Steinberg GR, Inhibiting peripheral serotonin synthesis reduces obesity and metabolic dysfunction by promoting brown adipose tissue thermogenesis. Nature medicine. 2015 Feb; [PubMed PMID: 25485911]|
|||Levada OA,Cherednichenko NV,Rybak IR, [Serum serotonin level in patients with depression and panic attacks]. Likars'ka sprava. 2006 Jul-Sep; [PubMed PMID: 17380868]|
|||Saldanha D,Kumar N,Ryali V,Srivastava K,Pawar AA, Serum Serotonin Abnormality in Depression. Medical journal, Armed Forces India. 2009 Apr; [PubMed PMID: 27408213]|
|||Fabre LF,Abuzzahab FS,Amin M,Claghorn JL,Mendels J,Petrie WM,Dubé S,Small JG, Sertraline safety and efficacy in major depression: a double-blind fixed-dose comparison with placebo. Biological psychiatry. 1995 Nov 1; [PubMed PMID: 8573661]|
|||Volpi-Abadie J,Kaye AM,Kaye AD, Serotonin syndrome. The Ochsner journal. 2013 Winter; [PubMed PMID: 24358002]|
|||Smith KA,Fairburn CG,Cowen PJ, Relapse of depression after rapid depletion of tryptophan. Lancet (London, England). 1997 Mar 29; [PubMed PMID: 9093253]|
|||Anderson IM,Parry-Billings M,Newsholme EA,Poortmans JR,Cowen PJ, Decreased plasma tryptophan concentration in major depression: relationship to melancholia and weight loss. Journal of affective disorders. 1990 Nov; [PubMed PMID: 2148339]|
|||Gillman PK, A review of serotonin toxicity data: implications for the mechanisms of antidepressant drug action. Biological psychiatry. 2006 Jun 1; [PubMed PMID: 16460699]|
|||Dunkley EJ,Isbister GK,Sibbritt D,Dawson AH,Whyte IM, The Hunter Serotonin Toxicity Criteria: simple and accurate diagnostic decision rules for serotonin toxicity. QJM : monthly journal of the Association of Physicians. 2003 Sep; [PubMed PMID: 12925718]|
|||Boyer EW,Shannon M, The serotonin syndrome. The New England journal of medicine. 2005 Mar 17; [PubMed PMID: 15784664]|
|||Gillman PK, Advances pertaining to the pharmacology and interactions of irreversible nonselective monoamine oxidase inhibitors. Journal of clinical psychopharmacology. 2011 Feb; [PubMed PMID: 21192146]|
|||Foong AL,Patel T,Kellar J,Grindrod KA, The scoop on serotonin syndrome. Canadian pharmacists journal : CPJ = Revue des pharmaciens du Canada : RPC. 2018 Jul-Aug; [PubMed PMID: 30237838]|
|||Uddin MF,Alweis R,Shah SR,Lateef N,Shahnawaz W,Ochani RK,Dharani AM,Shah SA, Controversies in Serotonin Syndrome Diagnosis and Management: A Review. Journal of clinical and diagnostic research : JCDR. 2017 Sep; [PubMed PMID: 29207768]|
|||Simon LV,Keenaghan M, Serotonin Syndrome 2019 Jan; [PubMed PMID: 29493999]|
|||Gillman PK, The serotonin syndrome and its treatment. Journal of psychopharmacology (Oxford, England). 1999; [PubMed PMID: 10221364]|
|||Mason PJ,Morris VA,Balcezak TJ, Serotonin syndrome. Presentation of 2 cases and review of the literature. Medicine. 2000 Jul; [PubMed PMID: 10941349]|