Serotonin Syndrome In Patient Research Articles

P524 Etrasimod shows low risk of adverse events following concomitant use with opioids or antidepressants in patients with ulcerative colitis

Abstract Background Etrasimod is an oral, once-daily (QD), selective sphingosine 1-phosphate (S1P)1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). Unlike the other S1P receptor modulator approved for UC, etrasimod and its metabolites do not have a molecular structure to inhibit monoamine oxidase (MAO).1 Coadministration of drugs that inhibit MAO with opioids and antidepressants may increase the risk of adverse events (AEs), including hypertension.2 This post hoc analysis evaluated the incidence of AEs potentially related to serotonin syndrome in patients taking etrasimod and concomitant opioids or antidepressants in the phase 3 ELEVATE UC 52 (NCT03945188) and ELEVATE UC 12 (NCT03996369) trials. Methods Safety data pooled from both trials were analysed in patients receiving etrasimod 2 mg QD (up to 52 weeks of exposure) with/without concomitant opioids or antidepressants. We report the proportions of patients who had ≥1 concurrent AE potentially related to serotonin syndrome, consisting of one standardised MedDRA Query, one query based on the Hunter Criteria and supplemental preferred terms (pyrexia, tachycardia and hypertension-related AEs).3 Results Among 527 patients receiving etrasimod, 77 (14.6%) and 35 (6.6%) patients were taking concomitant opioids or antidepressants, respectively. Most patients on concomitant opioids or antidepressants were White (80.0–88.3%); male (50.6–51.4%); their median age was 35.0 (18.0–70.0) and 41.0 (19.0–74.0) years, respectively. More patients with vs without concomitant opioids or antidepressants, respectively, consumed alcohol (40.3% vs 24.7% and 48.6% vs 25.4%) and used tobacco (40.3% vs 20.9% and 34.3% vs 23.0%). The incidence of other AEs potentially related to serotonin syndrome was low and generally comparable in all subgroups; reported rates of pyrexia and tachycardia were similar in patients with/without concomitant opioids or antidepressants (Table). Hypertension-related AEs were infrequent and generally balanced. No AEs per the Hunter Criteria were reported in patients on concomitant opioids or antidepressants (Table). No reported AEs were serious or led to treatment discontinuation among patients taking these concomitant medications. Conclusion The incidence of AEs was low and comparable in patients receiving etrasimod with or without concomitant opioids or antidepressants. This analysis supports the low likelihood of clinically relevant drug–drug interactions between etrasimod and medications commonly prescribed to patients with UC, such as opioids or antidepressants.

Few cases of serotonin syndrome in patients receiving linezolid and antidepressants

The Brown University Psychopharmacology UpdateVolume 34, Issue 4 p. 7-7 Research Roundup Few cases of serotonin syndrome in patients receiving linezolid and antidepressants First published: 03 March 2023 https://doi.org/10.1002/pu.31000Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume34, Issue4April 2023Pages 7-7 RelatedInformation

Association of Linezolid With Risk of Serotonin Syndrome in Patients Receiving Antidepressants

Linezolid has the potential to interact with some antidepressants, leading to serotonin syndrome. However, few empirical data support warnings for patients taking antidepressants to avoid linezolid. To examine the incidence of serotonin syndrome in patients receiving oral linezolid and how concomitant antidepressant treatment changes this risk. This population-based, retrospective cohort study used linked administrative databases at ICES to collect data from outpatients 66 years or older in Ontario, Canada, who were prescribed oral linezolid for any duration from October 1, 2014, to January 1, 2021, with follow-up to 30 days (January 31, 2021). The use of antidepressants while receiving linezolid therapy vs no antidepressant use while receiving linezolid therapy. The primary outcome was clinically significant serotonin syndrome based on a physician diagnosis, Sternbach criteria, or the Hunter Serotonin Toxicity Criteria within 30 days of starting oral linezolid treatment. Secondary outcomes were altered mental status, hospitalization, or death within 30 days of starting linezolid treatment. The study included 1134 patients (age ranges, 66-69 years for 225 patients [19.8%], 70-79 years for 473 patients [41.7%], and ≥80 years for 436 patients [38.4%]; 595 [52.5%] male) who were prescribed linezolid. Of 1134 patients, 215 (19.0%) were also taking antidepressants. Serotonin syndrome occurred in fewer than 6 patients (<0.5%). The number of serotonin syndrome cases were fewer in the antidepressant group. In a propensity score-matched cohort, the adjusted risk difference for serotonin syndrome between the antidepressant group and the no antidepressant group was -1.2% (95% CI, -2.9% to 0.5%). There were similar rates of altered mental status, hospitalization, and death between the propensity score-matched groups. In this cohort study of older patients who were prescribed linezolid, serotonin syndrome occurred rarely. Concurrent antidepressants did not significantly increase the risk of serotonin syndrome. These findings suggested that linezolid is likely safe for patients receiving antidepressants. Nevertheless, prescribers should remain vigilant for this potential drug interaction.

In Response.

We thank Maguire and Maguire1 for their interest in our review article entitled “Reversal of Vasodilatory Shock: Current Perspectives on Conventional, Rescue, and Emerging Vasoactive Agents for the Treatment of Shock.”2 We aimed to systematically and comprehensively evaluate the vasoconstrictive medications that the anesthesiologist and intensivist may encounter in the perioperative and postoperative period for the treatment of shock. We agree with Maguire and Maguire1 that high-dose hydroxocobalamin can be used as an alternative vasoconstrictor to methylene blue (MB). It utilizes a similar mechanism to MB by targeting the nitric oxide synthase (NOS) pathway, and it also binds to hydrogen sulfide (H2S) to impair H2S-mediated vasodilation.3 One advantage over MB is that hydroxocobalamin does not antagonize monoamine oxidase, and thus, there is less potential for serotonin syndrome in patients taking serotonin reuptake inhibitors. Although hydroxocobalamin has been increasingly used for the treatment of shock that is refractory to conventional vasopressors, Maguire and Maguire1 rightly point out that the use of hydroxocobalamin in this context is off-label and is not supported by robust, high-quality evidence. While hydroxocobalamin is promising because of its unique mechanism of action independent of α1, vasopressin type 1a, and angiotensin type 1 receptor agonism, there are only case reports and 2 case series of 24 and 33 patients that describe its use in the literature.4,5 One case series reported a significant improvement in hemodynamics and vasopressor dosage 30 minutes after administration, while the other found wide variability in response to hydroxocobalamin.4,5 Currently, there are 2 small, ongoing studies examining the use of hydroxocobalamin in septic shock and post cardiopulmonary bypass vasoplegia, and additional high-quality, prospective trials are necessary to examine the efficacy of this drug.6,7 Without these studies, we may not be justified in substituting or prescribing this $650–$1050 drug that is at most supported by anecdotal evidence. Jonathan H. Chow, MDDivision of Critical Care MedicineDepartment of AnesthesiologyUniversity of Maryland School of MedicineBaltimore, Maryland[email protected]Michael A. Mazzeffi, MD, MPHDivisions of Critical Care Medicine and Cardiothoracic AnesthesiologyDepartment of AnesthesiologyUniversity of Maryland School of MedicineBaltimore, MarylandKenichi A. Tanaka, MD, MScDivision of Cardiothoracic AnesthesiologyDepartment of AnesthesiologyUniversity of Maryland School of MedicineBaltimore, Maryland

Serotonin syndrome triggered by postoperative administration of serotonin noradrenaline reuptake inhibitor (SNRI)

BackgroundSerotonin syndrome is a rare but potentially severe disease, which is caused by hyperstimulation of serotonin receptors in the central nervous system. Several antidepressants exert their effect by modulating intrasynaptic serotonin concentration and anesthetics may affect the metabolism of serotonin, implicating to induce serotonin syndrome in patients taking those antidepressants.We present a case which provoked serotonin syndrome immediately after taking serotonin noradrenaline reuptake inhibitor (SNRI) in the postoperative period.Case presentationA 31-year-old female underwent laparoscopic ovarian cystectomy under general anesthesia with propofol, fentanyl, and remifentanil. She has been taking duloxetine, a SNRI for depression. She developed myoclonus seizure with an increase of blood pressure and heart rate after taking duloxetine on the day after the surgery, which was subsided by a non-selective serotonin receptor antagonist.ConclusionsAnesthesiologists should be aware of the risk of perioperative serotonin syndrome in patients taking antidepressants affecting serotonin metabolism.

Incidence of Serotonin Syndrome With Combined Use of Linezolid and Serotonin Reuptake Inhibitors Compared With Linezolid Monotherapy.

Linezolid is a monoamine oxidase inhibitor that may increase the risk of serotonin syndrome in patients receiving combination selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs). The objective of this study was to compare the incidence of serotonin syndrome when linezolid was administered alone and in combination with SSRIs or SNRIs. This was a retrospective case-control study of adult inpatients admitted to the University of Iowa Hospitals and Clinics who received linezolid between January 2010 and December 2014. Patients who received linezolid with or within 14 days of an SSRI or SNRI were eligible for inclusion in the combination therapy group. Patients who received linezolid alone were matched by age and gender to patients in the combination therapy group, and 3 monotherapy patients were included for each combination therapy patient. Clinical features consistent with serotonin syndrome were assessed using the Sternbach and Hunter criteria. A total of 348 patients were included in this study, of which 87 received combination therapy and 261 received linezolid monotherapy. One patient given combination therapy (1.1%) and 1 patient given linezolid monotherapy (0.4%) were determined to have a diagnosis of serotonin syndrome (P = 0.438; relative risk, 3.00; 95% confidence interval, 0.19-47.45). In both cases, signs and symptoms of serotonin syndrome reversed upon discontinuation of linezolid therapy. There was no significant difference in the incidence of serotonin syndrome when linezolid was used alone or in combination with an SSRI or SNRI, and the overall incidence of serotonin syndrome was low.

Serotonin syndrome in patients with headache disorders

Serotonin syndrome (SS) is an iatrogenic, drug-induced syndrome caused by serotoninergic agent. Various serotonergic drugs are used in different headache disorders. Therefore, a possibility of developing SS exists in patients...

Síndrome serotoninérgica associada a uso de sertralina: relato de caso

Relato de caso de síndrome serotoninérgica em paciente que iniciou uso de sertralina em dose maior do que o dobro do recomendado para o tratamento de depressão psicótica. Apresentou contratura de membros, olhar perplexo, mutismo e pressão arterial (PA) de 230 x 110 mmHg. A síndrome é cada vez mais comum, mas não é bem reconhecida. Muitos medicamentos podem causá-la e deve-se considerar essa possibilidade em pacientes em uso de medicamentos serotoninérgicos que se apresentam com distúrbios autonômicos ou mentais e sintomas neurológicos. Os achados de clonus, crise oculógira, hiper-reflexia e hipertonicidade devem levar à revisão da medicação. O tratamento centra-se na cessação de agentes causadores, tratamento da possível hipertermia e uso de benzodiazepínicos para diminuir a hipertonia e a excitabilidade neurológica.

Drug Interaction and Serotonin Toxicity with Opioid Use: Another Reason to Avoid Opioids in Headache and Migraine Treatment.

Treatment of headache, specifically migraine attacks, has always been a challenging subject, especially for neurologist and pain specialists. Triptans are generally underutilized, despite being the gold standard abortive medication for migraine attacks. On the other hand, opioid analgesics are overused as a treatment for headache. One reason for this could be physician unfamiliarity with drug interactions between opioids and other medications, especially the possibility of serotonin toxicity. The general awareness of potential serotonin toxicity with using opioid analgesics is low. In this review, we will conduct a theoretic and evidence-based review of the potential for developing serotonin syndrome in patients who are using opioids analgesics, especially in combination with antidepressants, a common co-prescribed combination. We also review the current diagnostic criteria for serotonin syndrome and identify possible shortcomings of those criteria. Our aim is to increase the awareness of health care providers about potential drug interaction of opioid analgesics with other classes of medication. We place particular emphasis on tramadol since this drug is one of the most commonly used opioid analgesics for headache. The potential for developing serotonin syndrome is relatively high in the patients who are using opioid for pain control. The use of opioids in migraine headache is already discouraged due to the high risk of medication overuse headache and also an increase in headache-related disability (Katsarava et al. Neurology 62:788-790, 2004; Bigal and Lipton. Neurology 71:1821-8, 2008; Casucci and Cevoli. Neurol Sci. 34 Suppl 1:S125-8, 2013). This is another reason that physicians and health care providers should avoid using this class of medication for pain, specifically headache and migraine treatment.

Effects of fentanyl on serotonin syndrome-like behaviors in rats.

Emerging evidence from case reports suggests that fentanyl may precipitate potentially life-threatening serotonin syndrome in patients taking serotonergic drugs. However, the underlying mechanism of the association between serotonin syndrome and fentanyl remains under investigation. We therefore investigated the pharmacological effects of an analgesic dose of fentanyl (0.2mg/kg) injected subcutaneously (s.c.) on serotonergic toxicity-like responses in rats. Rats were s.c. injected with 0.75mg/kg 8-OH-DPAT, a full 5-HT1A agonist, as an animal model of serotonin syndrome. The 8-OH-DPAT-treated rats showed well-characterized serotonin syndrome-like behaviors (low body posture, forepaw treading), hyperlocomotion, and decreased body temperature. Rats injected s.c. with fentanyl alone showed no significant changes in any of the parameters measured, while concomitant administration of fentanyl + 8-OH-DPAT resulted in exaggerated 8-OH-DPAT-induced serototoxic responses. A separate dose-response experiment showed that the serototoxic effect of fentanyl was dose-dependent. Pretreatment with naloxone [2.0mg/kg, intraperitoneal (i.p.) injection], an opioid receptor antagonist, failed to antagonize the fentanyl-induced exaggerated serotonin syndrome-like behaviors. In contrast, pretreatment with WAY-100653, a serotonin 5-HT1A receptor antagonist (0.5mg/kg, i.p. injection) completely inhibited all responses. Our findings provide preclinical proof-of-concept that an analgesic dose of fentanyl enhances serotonin toxicity, likely via its serotonin-reuptake inhibitory activity, independently of interaction with the opioid receptors.

Serotonin syndrome following metaxalone overdose and therapeutic use of a selective serotonin reuptake inhibitor

Metaxalone has only recently been associated with serotonin syndrome. The mechanism of action of this centrally acting muscle relaxant is unknown; however, the observation of serotonin syndrome in patients with metaxalone overdose suggests a role in the serotonergic pathway. Case report. (Case 1) A 29-year-old woman with overdose of metaxalone presented to the emergency department with altered mental status, seizure-like activity, hyperthermia, rigidity in the lower extremities, myoclonus, and hyperreflexia. Vital signs on arrival include blood pressure of 168/80 mmHg, heart rate of 208 beats per minute (bpm), respirations of 20/min, a temperature of 41.6° C rectally, and room air oxygen saturation of 97%. She was intubated and sedated with benzodiazepines, and actively cooled. Serum paroxetine concentration was 23 (therapeutic range: 20–200) ng/mL, and serum metaxalone concentration was 31 mcg/mL (peak plasma concentrations average 0.9 mcg/mL at 3.3 h following a single oral dose of 400 mg). (Case 2) A 27-year-old man presented to the emergency department with altered mental status, rigidity in his lower extremities, myoclonus, and hyperreflexia. Vital signs on arrival include blood pressure of 158/131 mmHg, heart rate of 126 bpm, respiratory rate of 20 breaths per minute, and temperature of 37.2°C, with oxygen saturation of 98% on room air. His medication list included metaxalone and escitalopram. He was managed aggressively with IV boluses of diazepam, in total 80 mg, in the emergency department. Serum escitalopram concentration was 24 ng/mL with a therapeutic range of 21–64 ng/mL, and serum metaxalone concentration was 58 mcg/mL. Conclusion. These two cases suggest that at supratherapeutic concentrations metaxalone has serotonergic effects. Severe serotonin toxicity may result from metaxalone abuse in individuals using a selective serotonin reuptake inhibitor therapeutically.

Serotonin Syndrome Following Methylene Blue Administration During Cardiothoracic Surgery

Introduction: Despite its favorable safety profile, there have been reports of methylene blue-induced encephalopathy and serotonin syndrome in patients undergoing parathyroidectomy. We report a case of serotonin syndrome following methylene blue administration in a cardiothoracic surgery patient. Case Report: A 59-year-old woman taking preoperative venlafaxine and trazodone was given a single dose of 2 mg/kg methylene blue (167 mg) during a planned coronary artery bypass and mitral valve repair. Postoperatively, she was febrile to 38.7°C and developed full-body tremors, rhythmic twitching of the perioral muscles, slow conjugate roving eye movements, and spontaneous movements of the upper extremities. Electroencephalography revealed generalized diffuse slowing consistent with toxic encephalopathy, and a computed tomography scan showed no acute process. The patient’s symptoms were most consistent with a methylene blue-induced serotonin syndrome. Her motor symptoms resolved within 48 hours and she was eventually discharged home. Discussion: Only 2 cases of methylene blue-induced serotonin syndrome during cardiothoracic surgery have been described in the literature, with this report representing the third case. Methylene blue and its metabolite, azure B, are potent, reversible inhibitors of monoamine oxidase A which is responsible for serotonin metabolism. Concomitant administration of methylene blue with serotonin-modulating agents may precipitate serotonin syndrome.

Incidence of Serotonin Syndrome in Patients Treated with Fentanyl on Serotonergic Agents

Background: There has been a recent surge in the literature highlighting the association of fentanyl as precipitating serotonin syndrome in patients on a serotonergic agent. Objective: The purpose of our study was to understand the incidence of serotonin syndrome in patients who receive fentanyl while on serotonergic agents. Study Design: This retrospective analysis was conducted from 2012 to 2013 after approval from the Institutional Review Board. We searched for all patients that had received a serotonergic agent and were admitted to the hospital during the study period. Next, we split these patients into 2 groups by placing all patients who had received fentanyl and a serotonergic agent into one group. We then searched for any of the Hunter Serotonin Toxicity Criteria in the records of patients that had received both fentanyl and a serotonergic agent. Further, we searched for all patients with serotonin syndrome mentioned in their records. Setting: This study was conducted at a 900 bed tertiary care academic center. Results: Over the 2 year study period, 112,045 patients were on a serotonergic agent, and 4,538 of these patients were treated with both fentanyl and a serotonergic agent. A search for Hunter’s Criteria through the records of the patients receiving both fentanyl and a serotonergic agent revealed 23 patients had been documented with some of these symptoms. On detailed chart review, only 4 [95% CI 1 – 10] of these patients truly met Hunter’s Criteria for serotonin syndrome. We then searched all admissions for a diagnosis code of serotonin syndrome during the study period. Five additional cases of serotonin syndrome were found, but none of these patients were treated with fentanyl. Limitations: Some of the limitations of our study include that it represents a single institution, although it is a large academic center. An inherent limitation may be the under diagnosis of serotonin syndrome. Conclusion: The incidence of serotonin syndrome in patients who receive both fentanyl and a serotonergic agent is low. Key words: Fentanyl, serotonin syndrome, serotonergic drugs, opioids, SSRI, antidepressant

Serotonin syndrome: Risk with concurrent use of SSRIs and other serotonergic meds

M depressive disorder affects 14.8 million Americans, with another 3.3 million having mild depression.1 Both conditions are commonly treated with selective serotonin reuptake inhibitors (SSRIs) and other medications that affect serotonin, such as serotonin norepinephrine reuptake inhibitors (SNRIs). Other commonly prescribed medications that affect serotonin include the triptans and tramadol. A rare adverse effect of taking one or multiple serotonin-modulating agents is serotonin syndrome, which ranges from mild to life-threatening symptoms of agitation, restlessness, muscle rigidity, and autonomic hyperactivity.2

Serotonergic and Adrenergic Drug Interactions Associated with Linezolid: A Critical Review and Practical Management Approach

To describe the evidence for serotonergic and adrenergic drug interactions with linezolid and discuss clinical management strategies. A literature search of PubMed (1947-November 2012), MEDLINE (1946-November 2012), EMBASE (1974-November 2012), and International Pharmaceutical Abstracts (1970-November 2012) was conducted using the terms linezolid, drug interaction, serotonin syndrome, serotonin toxicity, sympathomimetic, serotonergic agents, and adrenergic agents. Citations of retrieved articles were also reviewed. English-language articles describing coadministration of serotonergic or adrenergic agents with linezolid to humans were included. Studies published only in abstract form were excluded. One prospective study, 6 retrospective studies, and 24 case reports were identified describing a serotonergic or adrenergic drug interaction. Incidence of serotonin syndrome in patients on linezolid and serotonergic agents ranged between 0.24% and 4%. Serotonergic agents determined to have probable (according to the Horn Drug Interaction Probability Scale) linezolid interactions in case reports included meperidine, citalopram, escitalopram, fluoxetine, paroxetine, sertraline, duloxetine, and venlafaxine. Serotonergic agent dose and duration of coadministration with linezolid did not appear to influence the occurrence of serotonin syndrome. Adrenergic medication coadministration was associated with a possible drug interaction as determined by the Horn Drug Interaction Probability Scale but did not appear to result in clinically significant drug interactions with linezolid. Linezolid-associated serotonergic drug interactions occur more commonly than adrenergic interactions. Serotonergic interactions considered probable according to the Horn Drug Interaction Probability Scale do not appear to correlate with drug dosage; time of onset ranges from <1 to 20 days, and effect resolves in <1 to 5 days after discontinuation of offending agents. If coadministration of linezolid and a serotonergic agent cannot be avoided, clinicians should be aware of the symptoms and management of serotonergic toxicity; close monitoring is recommended and additional serotonergic agents should not be used. While adrenergic drug interactions with linezolid are less common in clinical practice, monitoring for signs of hypertension remains important.

Poster 49 Serotonin Syndrome in Patients with Acquired Brain Injury: A Case Series

Poster 49 Serotonin Syndrome in Patients with Acquired Brain Injury: A Case Series

Serotonin Syndrome Precipitated by Fentanyl During Procedural Sedation

Fentanyl is frequently used for analgesia during emergency procedures. We present the cases of 2 patients who developed agitation and delirium after intravenous fentanyl administration. These patients were chronically taking selective serotonin reuptake inhibitors (SSRIs). Both developed neuromuscular examinations consistent with serotonin syndrome, a diagnosis that must be established on the basis of clinical criteria. Although they required aggressive supportive care, including mechanical ventilation, both patients made a full recovery. Use of fentanyl for procedural sedation may precipitate serotonin syndrome in patients taking SSRIs or other serotonergic drugs.

Linezolid and Serotonergic Drug Interactions: A Retrospective Survey

Linezolid is a reversible, nonselective monoamine oxidase inhibitor. There are currently 11 published case reports of serotonin syndrome being associated with linezolid and selective serotonin reuptake inhibitors (SSRIs). Controversy exists regarding whether linezolid and SSRIs can be given concomitantly. The purpose of this study was to report the incidence of serotonin syndrome in patients receiving linezolid and SSRIs. This study was a retrospective chart review of inpatients at the Mayo Clinic (Rochester, MN) with concomitant orders or therapy within 14 days for linezolid and an SSRI from 2000 to 2004. The Sternbach criteria and Boyer criteria for diagnosis of serotonin syndrome were used to identify clinical features of serotonin syndrome. Seventy-two patients received linezolid and an SSRI or venlafaxine within 14 days of each other. Fifty-two patients (72%) received concomitant therapy with linezolid and an SSRI or venlafaxine, and 20 patients (28%) did not receive concomitant therapy but received linezolid and an SSRI within a 14-day period. Overall, only 2 patients (3%) had a high probability of serotonin syndrome. In both patients with high probability, symptoms reversed rapidly on discontinuation of serotonergic therapy. The Boyer criteria were much more specific than the Sternbach criteria for identification of serotonin syndrome. On the basis of our experience, we suggest that, if the clinical situation warrants use of linezolid in a patient receiving an SSRI, linezolid may be used concomitantly with SSRIs, without a 14-day washout period and with careful monitoring for signs and symptoms of serotonin syndrome. Serotonergic agents should be promptly discontinued if serotonin syndrome is suspected.

Drug Interactions Between Linezolid and Selective Serotonin Reuptake Inhibitors: Case Report Involving Sertraline and Review of the Literature

A 47-year-old woman developed confusion, incoordination, and hypertension after she was given linezolid in addition to sertraline for 5 days. Her symptoms resolved within 4 days of discontinuing linezolid. One and a half months later, she received a second course of linezolid; sertraline was discontinued on day 1 of linezolid therapy. On day 9 of therapy, the patient developed confusion, myoclonus, and incoordination, and cardiopulmonary arrest occurred, leaving the patient in a coma. Diarrhea, hypertension, and tachycardia developed after cardiopulmonary arrest. Linezolid was discontinued on day 10, and cyproheptadine was given. Linezolid is a weak monoamine oxidase inhibitor and has been reported to interact with selective serotonin reuptake inhibitors (SSRIs). Several cases of serotonin syndrome in patients taking linezolid and SSRIs have been reported, including two reports with sertraline, one with paroxetine, four with citalopram, and two with fluoxetine. One abstract of a retrospective analysis reported that serotonin syndrome did not occur in patients who received linezolid and fluoxetine, paroxetine, or sertraline. Because of several limitations, however, no conclusions can be drawn from that retrospective analysis. A drug interaction involving escitalopram and linezolid has not been documented. Caution should be used when linezolid is used in patients receiving an SSRI. Other antibiotic options should be considered first, and linezolid should be reserved as the last resort if possible. If the infection requires linezolid, the SSRI should be discontinued, and the patient should be monitored closely for serotonin syndrome.

Serotonin syndrome and the combined use of deprenyl and an antidepressant in Parkinson's disease. Parkinson Study Group.

The manufacturer of deprenyl (selegeline; Eldepryl) (Somerset Pharmaceuticals, Tampa, FL) recently advised physicians to avoid prescribing the drug in combination with an antidepressant because of potentially serious CNS toxicity that may represent the serotonin syndrome. Manifestations of the serotonin syndrome vary but may include changes in mental status and motor and autonomic function. To better estimate the frequency of the serotonin syndrome in patients with Parkinson's disease (PD) treated with deprenyl and an antidepressant, we surveyed all investigators in the Parkinson Study Group. Based on estimates provided by the 47 investigators (75%) who responded, 4,568 patients were treated with the combination of deprenyl and an antidepressant medication. Eleven patients (0.24%) were reported to have experienced symptoms possibly consistent with the serotonin syndrome. Only two patients (0.04%) experienced symptoms considered to be serious. No deaths were reported. We also reviewed all published case reports and adverse experiences reported to the U.S. Food and Drug Administration and the manufacturer of Eldepryl. Available information indicates that serious adverse experiences resulting from the combined use of deprenyl and an antidepressant medication in patients with PD are quite rare and that the frequency of the true "serotonin syndrome" is even rarer.