RARE DISEASE
Serotonin syndrome
Serotonin syndrome
Serotonin syndrome
Synonyms: Serotonergic syndrome, Serotonin storm, Serotonin toxicity, Serotonin toxidrome
Synonyms: Serotonergic syndrome, Serotonin storm, Serotonin toxicity, Serotonin toxidrome
Synonyms: Serotonergic syndrome, Serotonin storm, Serotonin toxicity, Serotonin toxidrome
Drug discovery
0
drugs
With orphan designations
Overview
Serotonin Syndrome Overview
Serotonin syndrome is a potentially life-threatening condition caused by excess serotonin in the central and peripheral nervous systems, typically due to therapeutic use, overdose, or interactions of serotonergic drugs. It presents as a clinical triad of neuromuscular excitation (e.g., clonus, hyperreflexia), autonomic dysfunction (e.g., tachycardia, hyperthermia), and altered mental status. Diagnosis relies on clinical assessment, primarily the Hunter Serotonin Toxicity Criteria. Management involves discontinuing causative agents, aggressive supportive care (e.g., IV fluids, cooling), and pharmacotherapy (e.g., serotonin antagonists like cyproheptadine, benzodiazepines). Severe cases may require intensive care [1][6][12].
Population
Incidence: 0.07%–0.23% in patients prescribed serotonergic agents, though prevalence is rising with increased antidepressant use [2][14][18].
High-risk groups: Patients on multiple serotonergic medications (e.g., SSRIs/SNRIs with MAOIs), polypharmacy in critically ill populations, and those with impaired drug metabolism [4][9][16].
Burden
Morbidity: Severe cases involve complications like rhabdomyolysis, renal failure, or DIC [12][16].
Mortality: 2%–12% in severe cases, driven by hyperthermia and multi-organ failure [4][8][16].
Economic impact: Median hospitalization costs range from $8,765–$10,792, with inpatient stays accounting for up to 4.35% of cases [2][9].
Therapies
Supportive care: IV hydration, temperature control (external cooling), benzodiazepines for agitation/rigidity [3][6][8].
Pharmacotherapy: Cyproheptadine (12 mg initial dose, then 2 mg every 2 hours) for moderate-severe cases; ICU interventions (e.g., neuromuscular paralysis) for hyperthermia >40°C [1][7][13].
Categories: rare neurological diseases
Research Papers
554 drug discovery papers about Serotonin syndrome, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
554 drug discovery papers about Serotonin syndrome, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-07-01 | Clinical Toxicity and Management of Selective Serotonin Reuptake Inhibitor (SSRI) Poisoning: A Comprehensive Review
Introduction Selective Serotonin Reuptake Inhibitors (SSRIs) are widely prescribed. With the global rise in SSRI prescriptions, the incidence of overdose has increased. SSRI overdose can result in severe toxicity, including serotonin syndrome, seizures, and QT interval prolongation. This review summarizes the clinical features, management, and outcomes associated with SSRI poisoning. Methods A narrative review was conducted using a structured search in PubMed, Web of Science, Embase, and Scopus through January 2025. Fifteen studies, including case reports and cohort studies, were identified. The results of SSRI exposure, clinical symptoms (cardiac, neurologic), treatment, and outcome are summarized. Results SSRI overdose most commonly results in mild symptoms, such as nausea, vomiting, and drowsiness. Serious complications are less frequent and include serotonin syndrome (up to 19.3%), seizures (1-8%), and QT prolongation (3-50.5%), particularly following citalopram overdose. Management is primarily supportive, with activated charcoal and benzodiazepines used when indicated. Intensive care unit admission (2.3-11.4%) and mortality (<0.1%) are uncommon, and most patients recover within 24 h. Discussion Among SSRIs, citalopram is associated with a higher risk of severe neurological and cardiac complications. Variability in diagnostic criteria and dose reporting across studies limits direct comparisons and highlights the need for standardized reporting. Conclusion SSRI poisoning is generally associated with favorable outcomes; however, continuous monitoring is essential for early detection of serious complications. Clinicians should remain vigilant for neurological and cardiac toxicity, particularly in citalopram overdose, where electrocardiographic monitoring is crucial for identifying QTc prolongation.
2026-05-01 | A54-31 Serotonin Syndrome and Adalimumab-Associated Autoimmune Encephalitis: A Dual Diagnostic Challenge in the ICU
Abstract Introduction Acute encephalopathy in critically ill patients requires a broad differential diagnosis, including metabolic, infectious, autoimmune, toxic, and iatrogenic causes. Polypharmacy and supplement use can make evaluation complex particulary when overlapping mechanisms contribute to altered mental status. Our case describes a rare sequential presentation of serotonin syndrome, likely triggered by supratherapeutic ondansetron and supplement interaction, followed by suspected adalimumab-induced autoimmune encephalitis. The case emphasizes the importance of detailed medication and supplements review in the intensive care setting. Case Presentation A 21-year-old man with ankylosing spondylitis treated with adalimumab for one year presented unresponsive after several days of nausea, vomiting, and headache. The day before presentation, he received ketorolac and ondansetron at an urgent care clinic. On arrival, he was febrile (38.9 °C) with leukocytosis (24.9 × 109/L), hyponatremia (Na 113 mmol/L), and creatine kinase 18,000 U/L. Neuroimaging was unremarkable. He was intubated and treated empirically for meningitis. Cerebrospinal fluid analysis revealed lymphocytic pleocytosis (WBC 121 cells/µL, protein 117 mg/dL) with normal glucose. EEG showed no epileptiform activity. On hospital day two, inducible clonus and hyperreflexia raised concern for serotonin syndrome. Collateral history revealed excessive ondansetron ingestion and daily use of creatine and Ashwagandha. Cyproheptadine therapy was initiated, leading to rapid improvement. Re-exposure to ondansetron reproduced the symptoms, confirming serotonin toxicity. Despite resolution, persistent headache and nausea prompted further evaluation. Autoimmune testing demonstrated positive anti-histone antibodies. Adalimumab was discontinued, and high-dose intravenous methylprednisolone (250 mg q6h for 3 days) resulted in complete recovery. Discussion This case demonstrates two uncommon, medication-related causes of encephalopathy occurring sequentially in the same patient. Serotonin syndrome can occur with agents outside the typical antidepressant category, including ondansetron, and may be potentiated by supplements that influence serotonin metabolism and receptor activity. In addition, TNF-α inhibitors such as adalimumab have been associated with autoimmune complications, including lupus-like reactions and antibody-mediated encephalitis. The positive anti-histone antibody and response to corticosteroids support an autoimmune mechanism in this case. Recognition of these overlapping toxic and immune processes requires careful clinical correlation and a high index of suspicion. Conclusion This case highlights the diagnostic complexity of dual drug-induced encephalopathies in critical care. A detailed medication and supplement history is essential when evaluating acute encephalopathy. Early identification and targeted therapy can lead to complete recovery and prevent recurrence in patients with overlapping toxic and autoimmune mechanisms. This abstract is funded by: None
2026-04-16 | Case Report: Pharmacogenetically-triggered fatal serotonin syndrome following sequential serotonergic therapy in Parkinson's disease: a case highlighting the role of CYP2D6*10/*10 genotype and multifactorial drug interactions.
Serotonin syndrome (SS) is a potentially life-threatening condition resulting from excessive serotonergic activity in the central nervous system. We present a fatal case of SS complicated by multiple organ failure in a 72-year-old patient with Parkinson's disease following the sequential administration of two selective serotonin reuptake inhibitors (sertraline and escitalopram) while on a stable regimen of the monoamine oxidase-B inhibitor rasagiline. Pharmacogenomic testing revealed a homozygous CYP2D6*10/*10 genotype, conferring an intermediate metabolizer phenotype, which is postulated to have contributed to serotonergic drug accumulation and resultant toxicity in combination with other significant pharmacodynamic and pharmacokinetic interactions. This case was distinguished by three key features: first, the sequential serotonergic challenge from two different SSRIs in combination with rasagiline; second, the unprecedented severity of clinical manifestations, including rhabdomyolysis, acute hepatic and renal injury, and a disseminated intravascular coagulation-like state; and finally, the pharmacogenetic findings that provide a partial mechanistic explanation for the extreme drug sensitivity. This report underscores the critical importance of pre-emptive pharmacogenomic screening in patients receiving complex polypharmacy, particularly when combining drugs with serotonergic properties. It also serves as a critical warning that even selective MAO-B inhibitors can precipitate life-threatening interactions with SSRIs in genetically susceptible individuals, thereby informing more stringent personalized therapeutic strategies.
2026-03-19 | Chronic tramadol abuse as a cause of serotonin syndrome.
Serotonin syndrome is characterized by autonomic hyperactivity, altered mental status, and neuromuscular abnormalities, ranging from mild to life-threatening manifestations. Tramadol has been associated with serotonin syndrome, predominantly in combination with other serotonergic agents or following acute overdose. Reports describing serotonin syndrome caused by chronic high-dose tramadol use as a single serotonergic agent are scarce. A case of serotonin syndrome in a young adult with chronic high-dose tramadol dependence in the absence of co-ingested serotonergic drugs is presented. A 22-year-old man with tramadol dependence (800 mg daily) presented to the emergency department with anxiety and agitation. Physical examination revealed diaphoresis, mydriasis, tachycardia (130 beats/min), hypertension (140/100 mmHg), hyperreflexia, and inducible ankle clonus. Laboratory investigations, head computed tomography, and urine toxicology screening were unremarkable. Based on the presence of inducible clonus and hyperreflexia in the setting of serotonergic exposure, the Hunter Serotonin Toxicity Criteria were fulfilled. Tramadol was discontinued and replaced with methadone. The patient recovered completely within 48 h. This case illustrates that chronic high-dose tramadol use alone may precipitate serotonin syndrome. Clinicians should remain alert to this potentially life-threatening complication, even in the absence of concomitant serotonergic medication.
2026-03-01 | 4CPS-321 Serotonin syndrome in an elderly patient on dual antidepressant therapy: a case report
Serotonin syndrome (SS) is an uncommon potentially life-threatening adverse drug reaction caused by excessive serotonergic activity, usually related to drug interactions or high-dose antidepressant therapy. In older adults, diagnosis is particularly challenging due to atypical presentations, multiple comorbidities, and polypharmacy. Pharmacists play a key role in identifying drug-related risks and supporting early recognition. To describe the case of an 81-year-old man admitted after traumatic brain injury associated with hypotension, with a history of atrial fibrillation on rivaroxaban and bisoprolol, hypertension, prior ischaemic stroke without sequelae, and depression treated with clomipramine 150 mg/day and venlafaxine 300 mg/day. Relevant comorbidities included benign prostatic hyperplasia and orthostatic hypotension. During hospitalisation, the patient developed fever >39 °C, progressive somnolence, generalised tremor, and rigidity. Laboratory tests showed CK 9100 U/L, AST 883 U/L, ALT 391 U/L, creatinine 1.87 mg/dL, and hypernatraemia. EEG excluded seizures. Considering his medication history, SS was suspected. Neuroleptic malignant syndrome was considered less likely due to the absence of antipsychotics, though CK elevation and rigidity raised diagnostic uncertainty. Empirical therapy with oral cyproheptadine (12 mg initial dose followed by 2 mg every 2 h, maximum 32 mg/day) was started together with supportive measures. Bromocriptine was later added to cover potential diagnostic overlap. Over the following days, the patient showed progressive clinical improvement: fever resolved, myoclonus decreased, consciousness and orientation improved, and CK values declined. After psychiatric consultation, antidepressant therapy was switched to desvenlafaxine due to its lower risk of orthostatic hypotension and serotonergic toxicity. Beta-blocker therapy was also adjusted to minimise hypotensive episodes. The patient continued recovery in a rehabilitation unit. This case highlights the diagnostic complexity of SS in geriatric patients under polypharmacy, particularly when dual antidepressant therapy is involved. Clinical overlap with other syndromes, such as neuroleptic malignant syndrome, can delay recognition. Pharmacist involvement in medication review was crucial to identify the causative agents and propose safer alternatives. Early detection and tailored pharmacological management are essential to reduce morbidity in this vulnerable population. No conflict of interest
proteins
2024-04-03 | The Stable Gastric Pentadecapeptide BPC 157 Pleiotropic Beneficial Activity and Its Possible Relations with Neurotransmitter Activity
We highlight the particular aspects of the stable gastric pentadecapeptide BPC 157 pleiotropic beneficial activity (not destroyed in human gastric juice, native and stable in human gastric juice, as a cytoprotection mediator holds a response specifically related to preventing or recovering damage as such) and its possible relations with neurotransmitter activity. We attempt to resolve the shortage of the pleiotropic beneficial effects of BPC 157, given the general standard neurotransmitter criteria, in classic terms. We substitute the lack of direct conclusive evidence (i.e., production within the neuron or present in it as a precursor molecule, released eliciting a response on the receptor on the target cells on neurons and being removed from the site of action once its signaling role is complete). This can be a network of interconnected evidence, previously envisaged in the implementation of the cytoprotection effects, consistent beneficial particular evidence that BPC 157 therapy counteracts dopamine, serotonin, glutamate, GABA, adrenalin/noradrenalin, acetylcholine, and NO-system disturbances. This specifically includes counteraction of those disturbances related to their receptors, both blockade and over-activity, destruction, depletion, tolerance, sensitization, and channel disturbances counteraction. Likewise, BPC 157 activates particular receptors (i.e., VGEF and growth hormone). Furthermore, close BPC 157/NO-system relations with the gasotransmitters crossing the cell membrane and acting directly on molecules inside the cell may envisage particular interactions with receptors on the plasma membrane of their target cells. Finally, there is nerve-muscle relation in various muscle disturbance counteractions, and nerve-nerve relation in various encephalopathies counteraction, which is also exemplified specifically by the BPC 157 therapy application.
2016-10-31 | Brain-gut Axis and Pentadecapeptide BPC 157: Theoretical and Practical Implications
Brain-gut interaction involves, among others, peptidergic growth factors which are native in GI tract and have strong antiulcer potency and thus could from periphery beneficially affect CNS-disorders. We focused on the stable gastric pentadecapeptide BPC 157, an antiulcer peptidergic agent, safe in inflammatory bowel disease trials and now in multiple sclerosis trial, native and stable in human gastric juice.Review of our research on BPC 157 in terms of brain-gut axis.BPC 157 may serve as a novel mediator of Robert's cytoprotection, involved in maintaining of GI mucosa integrity, with no toxic effect. BPC 157 was successful in the therapy of GI tract, periodontitis, liver and pancreas lesions, and in the healing of various tissues and wounds. Stimulated Egr-1 gene, NAB2, FAK-paxillin and JAK-2 pathways are hitherto implicated. Initially corresponding beneficial central influence was seen when BPC 157 was given peripherally and a serotonin release in particular brain areas, mostly nigrostriatal, was changed. BPC 157 modulates serotonergic and dopaminergic systems, beneficially affects various behavioral disturbances that otherwise appeared due to specifically (over)stimulated/damaged neurotransmitters systems. Besides, BPC 157 has neuroprotective effects: protects somatosensory neurons; peripheral nerve regeneration appearent after transection; after traumatic brain injury counteracts the otherwise progressing course, in rat spinal cord compression with tail paralysis, axonal and neuronal necrosis, demyelination, cyst formation and rescues tail function in both short-terms and long-terms; after NSAIDs or insulin overdose or cuprizone encephalopathies were attenuated along with GI, liver and vascular injuries.BPC 157, a gastric peptide, may serve as remedy in various CNS-disorders.
2012-02-29 | Hypoglycaemia: A little known effect of Venlafaxine overdose
We report the case of a 39-year-old woman who presented with serotonin syndrome and hypoglycaemia likely due to intoxication with a very high dose of venlafaxine. This case of venlafaxine-associated hypoglycaemia was treated first by glucose perfusion, but despite large doses, hypoglycaemia recurred. Blood glucose normalized after injection of octreotide, eliminating the need for hypertonic glucose. Octreotide has been shown to decrease glucose requirements and the number of hypoglycaemic episodes in patients with sulfonylurea-induced hypoglycaemia but, to our knowledge, its ability to resolve hypoglycaemic episodes due to massive venlafaxine overdose has not yet been described.
2005-04-01 | Gastric pentadecapeptide BPC 157 effective against serotonin syndrome in rats
Serotonin syndrome commonly follows irreversible monoamine oxidase (MAO)-inhibition and subsequent serotonin (5-HT) substrate (in rats with fore paw treading, hind limbs abduction, wet dog shake, hypothermia followed by hyperthermia). A stable gastric pentadecapeptide BPC 157 with very safe profile (inflammatory bowel disease clinical phase II, PL-10, PLD-116, PL-14736, Pliva) reduced the duration of immobility to a greater extent than imipramine, and, given peripherally, has region specific influence on brain 5-HT synthesis (α-[14C]methyl-l-tryptophan autoradiographic measurements) in rats, different from any other serotonergic drug. Thereby, we investigate this peptide (10 μg, 10 ng, 10 pg/kg i.p.) in (i) full serotonin syndrome in rat combining pargyline (irreversible MAO-inhibition; 75 mg/kg i.p.) and subsequent l-tryptophan (5-HT precursor; 100 mg/kg i.p.; BPC 157 as a co-treatment), or (ii, iii) using pargyline or l-tryptophan given separately, as a serotonin-substrate with (ii) pargyline (BPC 157 as a 15-min posttreatment) or as a potential serotonin syndrome inductor with (iii) l-tryptophan (BPC 157 as a 15 min-pretreatment). In all experiments, gastric pentadecapeptide BPC 157 contrasts with serotonin-syndrome either (i) presentation (i.e., particularly counteracted) or (ii) initiation (i.e., neither a serotonin substrate (counteraction of pargyline), nor an inductor for serotonin syndrome (no influence on l-tryptophan challenge)). Indicatively, severe serotonin syndrome in pargyline + l-tryptophan rats is considerably inhibited even by lower pentadecapeptide BPC 157 doses regimens (particularly disturbances such as hyperthermia and wet dog shake thought to be related to stimulation of 5-HT2A receptors), while the highest pentadecapeptide dose counteracts mild disturbances present in pargyline rats (mild hypothermia, feeble hind limbs abduction). Thereby, in severe serotonin syndrome, gastric pentadecapeptide BPC 157 (alone, no behavioral or temperature effect) has a beneficial activity, which is likely, particular, and mostly related to a rather specific counteraction of 5-HT2A receptors phenomena.
small molecules
2026-07-01 | Clinical Toxicity and Management of Selective Serotonin Reuptake Inhibitor (SSRI) Poisoning: A Comprehensive Review
Introduction Selective Serotonin Reuptake Inhibitors (SSRIs) are widely prescribed. With the global rise in SSRI prescriptions, the incidence of overdose has increased. SSRI overdose can result in severe toxicity, including serotonin syndrome, seizures, and QT interval prolongation. This review summarizes the clinical features, management, and outcomes associated with SSRI poisoning. Methods A narrative review was conducted using a structured search in PubMed, Web of Science, Embase, and Scopus through January 2025. Fifteen studies, including case reports and cohort studies, were identified. The results of SSRI exposure, clinical symptoms (cardiac, neurologic), treatment, and outcome are summarized. Results SSRI overdose most commonly results in mild symptoms, such as nausea, vomiting, and drowsiness. Serious complications are less frequent and include serotonin syndrome (up to 19.3%), seizures (1-8%), and QT prolongation (3-50.5%), particularly following citalopram overdose. Management is primarily supportive, with activated charcoal and benzodiazepines used when indicated. Intensive care unit admission (2.3-11.4%) and mortality (<0.1%) are uncommon, and most patients recover within 24 h. Discussion Among SSRIs, citalopram is associated with a higher risk of severe neurological and cardiac complications. Variability in diagnostic criteria and dose reporting across studies limits direct comparisons and highlights the need for standardized reporting. Conclusion SSRI poisoning is generally associated with favorable outcomes; however, continuous monitoring is essential for early detection of serious complications. Clinicians should remain vigilant for neurological and cardiac toxicity, particularly in citalopram overdose, where electrocardiographic monitoring is crucial for identifying QTc prolongation.
2026-05-01 | A54-31 Serotonin Syndrome and Adalimumab-Associated Autoimmune Encephalitis: A Dual Diagnostic Challenge in the ICU
Abstract Introduction Acute encephalopathy in critically ill patients requires a broad differential diagnosis, including metabolic, infectious, autoimmune, toxic, and iatrogenic causes. Polypharmacy and supplement use can make evaluation complex particulary when overlapping mechanisms contribute to altered mental status. Our case describes a rare sequential presentation of serotonin syndrome, likely triggered by supratherapeutic ondansetron and supplement interaction, followed by suspected adalimumab-induced autoimmune encephalitis. The case emphasizes the importance of detailed medication and supplements review in the intensive care setting. Case Presentation A 21-year-old man with ankylosing spondylitis treated with adalimumab for one year presented unresponsive after several days of nausea, vomiting, and headache. The day before presentation, he received ketorolac and ondansetron at an urgent care clinic. On arrival, he was febrile (38.9 °C) with leukocytosis (24.9 × 109/L), hyponatremia (Na 113 mmol/L), and creatine kinase 18,000 U/L. Neuroimaging was unremarkable. He was intubated and treated empirically for meningitis. Cerebrospinal fluid analysis revealed lymphocytic pleocytosis (WBC 121 cells/µL, protein 117 mg/dL) with normal glucose. EEG showed no epileptiform activity. On hospital day two, inducible clonus and hyperreflexia raised concern for serotonin syndrome. Collateral history revealed excessive ondansetron ingestion and daily use of creatine and Ashwagandha. Cyproheptadine therapy was initiated, leading to rapid improvement. Re-exposure to ondansetron reproduced the symptoms, confirming serotonin toxicity. Despite resolution, persistent headache and nausea prompted further evaluation. Autoimmune testing demonstrated positive anti-histone antibodies. Adalimumab was discontinued, and high-dose intravenous methylprednisolone (250 mg q6h for 3 days) resulted in complete recovery. Discussion This case demonstrates two uncommon, medication-related causes of encephalopathy occurring sequentially in the same patient. Serotonin syndrome can occur with agents outside the typical antidepressant category, including ondansetron, and may be potentiated by supplements that influence serotonin metabolism and receptor activity. In addition, TNF-α inhibitors such as adalimumab have been associated with autoimmune complications, including lupus-like reactions and antibody-mediated encephalitis. The positive anti-histone antibody and response to corticosteroids support an autoimmune mechanism in this case. Recognition of these overlapping toxic and immune processes requires careful clinical correlation and a high index of suspicion. Conclusion This case highlights the diagnostic complexity of dual drug-induced encephalopathies in critical care. A detailed medication and supplement history is essential when evaluating acute encephalopathy. Early identification and targeted therapy can lead to complete recovery and prevent recurrence in patients with overlapping toxic and autoimmune mechanisms. This abstract is funded by: None
2026-04-16 | Case Report: Pharmacogenetically-triggered fatal serotonin syndrome following sequential serotonergic therapy in Parkinson's disease: a case highlighting the role of CYP2D6*10/*10 genotype and multifactorial drug interactions.
Serotonin syndrome (SS) is a potentially life-threatening condition resulting from excessive serotonergic activity in the central nervous system. We present a fatal case of SS complicated by multiple organ failure in a 72-year-old patient with Parkinson's disease following the sequential administration of two selective serotonin reuptake inhibitors (sertraline and escitalopram) while on a stable regimen of the monoamine oxidase-B inhibitor rasagiline. Pharmacogenomic testing revealed a homozygous CYP2D6*10/*10 genotype, conferring an intermediate metabolizer phenotype, which is postulated to have contributed to serotonergic drug accumulation and resultant toxicity in combination with other significant pharmacodynamic and pharmacokinetic interactions. This case was distinguished by three key features: first, the sequential serotonergic challenge from two different SSRIs in combination with rasagiline; second, the unprecedented severity of clinical manifestations, including rhabdomyolysis, acute hepatic and renal injury, and a disseminated intravascular coagulation-like state; and finally, the pharmacogenetic findings that provide a partial mechanistic explanation for the extreme drug sensitivity. This report underscores the critical importance of pre-emptive pharmacogenomic screening in patients receiving complex polypharmacy, particularly when combining drugs with serotonergic properties. It also serves as a critical warning that even selective MAO-B inhibitors can precipitate life-threatening interactions with SSRIs in genetically susceptible individuals, thereby informing more stringent personalized therapeutic strategies.
2026-03-19 | Chronic tramadol abuse as a cause of serotonin syndrome.
Serotonin syndrome is characterized by autonomic hyperactivity, altered mental status, and neuromuscular abnormalities, ranging from mild to life-threatening manifestations. Tramadol has been associated with serotonin syndrome, predominantly in combination with other serotonergic agents or following acute overdose. Reports describing serotonin syndrome caused by chronic high-dose tramadol use as a single serotonergic agent are scarce. A case of serotonin syndrome in a young adult with chronic high-dose tramadol dependence in the absence of co-ingested serotonergic drugs is presented. A 22-year-old man with tramadol dependence (800 mg daily) presented to the emergency department with anxiety and agitation. Physical examination revealed diaphoresis, mydriasis, tachycardia (130 beats/min), hypertension (140/100 mmHg), hyperreflexia, and inducible ankle clonus. Laboratory investigations, head computed tomography, and urine toxicology screening were unremarkable. Based on the presence of inducible clonus and hyperreflexia in the setting of serotonergic exposure, the Hunter Serotonin Toxicity Criteria were fulfilled. Tramadol was discontinued and replaced with methadone. The patient recovered completely within 48 h. This case illustrates that chronic high-dose tramadol use alone may precipitate serotonin syndrome. Clinicians should remain alert to this potentially life-threatening complication, even in the absence of concomitant serotonergic medication.
2026-03-01 | 4CPS-321 Serotonin syndrome in an elderly patient on dual antidepressant therapy: a case report
Serotonin syndrome (SS) is an uncommon potentially life-threatening adverse drug reaction caused by excessive serotonergic activity, usually related to drug interactions or high-dose antidepressant therapy. In older adults, diagnosis is particularly challenging due to atypical presentations, multiple comorbidities, and polypharmacy. Pharmacists play a key role in identifying drug-related risks and supporting early recognition. To describe the case of an 81-year-old man admitted after traumatic brain injury associated with hypotension, with a history of atrial fibrillation on rivaroxaban and bisoprolol, hypertension, prior ischaemic stroke without sequelae, and depression treated with clomipramine 150 mg/day and venlafaxine 300 mg/day. Relevant comorbidities included benign prostatic hyperplasia and orthostatic hypotension. During hospitalisation, the patient developed fever >39 °C, progressive somnolence, generalised tremor, and rigidity. Laboratory tests showed CK 9100 U/L, AST 883 U/L, ALT 391 U/L, creatinine 1.87 mg/dL, and hypernatraemia. EEG excluded seizures. Considering his medication history, SS was suspected. Neuroleptic malignant syndrome was considered less likely due to the absence of antipsychotics, though CK elevation and rigidity raised diagnostic uncertainty. Empirical therapy with oral cyproheptadine (12 mg initial dose followed by 2 mg every 2 h, maximum 32 mg/day) was started together with supportive measures. Bromocriptine was later added to cover potential diagnostic overlap. Over the following days, the patient showed progressive clinical improvement: fever resolved, myoclonus decreased, consciousness and orientation improved, and CK values declined. After psychiatric consultation, antidepressant therapy was switched to desvenlafaxine due to its lower risk of orthostatic hypotension and serotonergic toxicity. Beta-blocker therapy was also adjusted to minimise hypotensive episodes. The patient continued recovery in a rehabilitation unit. This case highlights the diagnostic complexity of SS in geriatric patients under polypharmacy, particularly when dual antidepressant therapy is involved. Clinical overlap with other syndromes, such as neuroleptic malignant syndrome, can delay recognition. Pharmacist involvement in medication review was crucial to identify the causative agents and propose safer alternatives. Early detection and tailored pharmacological management are essential to reduce morbidity in this vulnerable population. No conflict of interest
proteins
2024-04-03 | The Stable Gastric Pentadecapeptide BPC 157 Pleiotropic Beneficial Activity and Its Possible Relations with Neurotransmitter Activity
We highlight the particular aspects of the stable gastric pentadecapeptide BPC 157 pleiotropic beneficial activity (not destroyed in human gastric juice, native and stable in human gastric juice, as a cytoprotection mediator holds a response specifically related to preventing or recovering damage as such) and its possible relations with neurotransmitter activity. We attempt to resolve the shortage of the pleiotropic beneficial effects of BPC 157, given the general standard neurotransmitter criteria, in classic terms. We substitute the lack of direct conclusive evidence (i.e., production within the neuron or present in it as a precursor molecule, released eliciting a response on the receptor on the target cells on neurons and being removed from the site of action once its signaling role is complete). This can be a network of interconnected evidence, previously envisaged in the implementation of the cytoprotection effects, consistent beneficial particular evidence that BPC 157 therapy counteracts dopamine, serotonin, glutamate, GABA, adrenalin/noradrenalin, acetylcholine, and NO-system disturbances. This specifically includes counteraction of those disturbances related to their receptors, both blockade and over-activity, destruction, depletion, tolerance, sensitization, and channel disturbances counteraction. Likewise, BPC 157 activates particular receptors (i.e., VGEF and growth hormone). Furthermore, close BPC 157/NO-system relations with the gasotransmitters crossing the cell membrane and acting directly on molecules inside the cell may envisage particular interactions with receptors on the plasma membrane of their target cells. Finally, there is nerve-muscle relation in various muscle disturbance counteractions, and nerve-nerve relation in various encephalopathies counteraction, which is also exemplified specifically by the BPC 157 therapy application.
2016-10-31 | Brain-gut Axis and Pentadecapeptide BPC 157: Theoretical and Practical Implications
Brain-gut interaction involves, among others, peptidergic growth factors which are native in GI tract and have strong antiulcer potency and thus could from periphery beneficially affect CNS-disorders. We focused on the stable gastric pentadecapeptide BPC 157, an antiulcer peptidergic agent, safe in inflammatory bowel disease trials and now in multiple sclerosis trial, native and stable in human gastric juice.Review of our research on BPC 157 in terms of brain-gut axis.BPC 157 may serve as a novel mediator of Robert's cytoprotection, involved in maintaining of GI mucosa integrity, with no toxic effect. BPC 157 was successful in the therapy of GI tract, periodontitis, liver and pancreas lesions, and in the healing of various tissues and wounds. Stimulated Egr-1 gene, NAB2, FAK-paxillin and JAK-2 pathways are hitherto implicated. Initially corresponding beneficial central influence was seen when BPC 157 was given peripherally and a serotonin release in particular brain areas, mostly nigrostriatal, was changed. BPC 157 modulates serotonergic and dopaminergic systems, beneficially affects various behavioral disturbances that otherwise appeared due to specifically (over)stimulated/damaged neurotransmitters systems. Besides, BPC 157 has neuroprotective effects: protects somatosensory neurons; peripheral nerve regeneration appearent after transection; after traumatic brain injury counteracts the otherwise progressing course, in rat spinal cord compression with tail paralysis, axonal and neuronal necrosis, demyelination, cyst formation and rescues tail function in both short-terms and long-terms; after NSAIDs or insulin overdose or cuprizone encephalopathies were attenuated along with GI, liver and vascular injuries.BPC 157, a gastric peptide, may serve as remedy in various CNS-disorders.
2012-02-29 | Hypoglycaemia: A little known effect of Venlafaxine overdose
We report the case of a 39-year-old woman who presented with serotonin syndrome and hypoglycaemia likely due to intoxication with a very high dose of venlafaxine. This case of venlafaxine-associated hypoglycaemia was treated first by glucose perfusion, but despite large doses, hypoglycaemia recurred. Blood glucose normalized after injection of octreotide, eliminating the need for hypertonic glucose. Octreotide has been shown to decrease glucose requirements and the number of hypoglycaemic episodes in patients with sulfonylurea-induced hypoglycaemia but, to our knowledge, its ability to resolve hypoglycaemic episodes due to massive venlafaxine overdose has not yet been described.
2005-04-01 | Gastric pentadecapeptide BPC 157 effective against serotonin syndrome in rats
Serotonin syndrome commonly follows irreversible monoamine oxidase (MAO)-inhibition and subsequent serotonin (5-HT) substrate (in rats with fore paw treading, hind limbs abduction, wet dog shake, hypothermia followed by hyperthermia). A stable gastric pentadecapeptide BPC 157 with very safe profile (inflammatory bowel disease clinical phase II, PL-10, PLD-116, PL-14736, Pliva) reduced the duration of immobility to a greater extent than imipramine, and, given peripherally, has region specific influence on brain 5-HT synthesis (α-[14C]methyl-l-tryptophan autoradiographic measurements) in rats, different from any other serotonergic drug. Thereby, we investigate this peptide (10 μg, 10 ng, 10 pg/kg i.p.) in (i) full serotonin syndrome in rat combining pargyline (irreversible MAO-inhibition; 75 mg/kg i.p.) and subsequent l-tryptophan (5-HT precursor; 100 mg/kg i.p.; BPC 157 as a co-treatment), or (ii, iii) using pargyline or l-tryptophan given separately, as a serotonin-substrate with (ii) pargyline (BPC 157 as a 15-min posttreatment) or as a potential serotonin syndrome inductor with (iii) l-tryptophan (BPC 157 as a 15 min-pretreatment). In all experiments, gastric pentadecapeptide BPC 157 contrasts with serotonin-syndrome either (i) presentation (i.e., particularly counteracted) or (ii) initiation (i.e., neither a serotonin substrate (counteraction of pargyline), nor an inductor for serotonin syndrome (no influence on l-tryptophan challenge)). Indicatively, severe serotonin syndrome in pargyline + l-tryptophan rats is considerably inhibited even by lower pentadecapeptide BPC 157 doses regimens (particularly disturbances such as hyperthermia and wet dog shake thought to be related to stimulation of 5-HT2A receptors), while the highest pentadecapeptide dose counteracts mild disturbances present in pargyline rats (mild hypothermia, feeble hind limbs abduction). Thereby, in severe serotonin syndrome, gastric pentadecapeptide BPC 157 (alone, no behavioral or temperature effect) has a beneficial activity, which is likely, particular, and mostly related to a rather specific counteraction of 5-HT2A receptors phenomena.
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0 orphan drug designations.
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Let's accelerate drug discovery
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