fluvoxamine and Serotonin-Syndrome

Topics: Adrenergic Uptake Inhibitors; Animals; Cyclopropanes; Cyproheptadine; Diagnosis, Differential; Fluvoxamine; Humans; Milnacipran; Reference Standards; Selective Serotonin Reuptake Inhibitors; Serotonin Antagonists; Serotonin Syndrome

Mood disorders cause much suffering and lost productivity worldwide, compounded by the fact that many patients are not effectively treated by currently available medications. The most commonly prescribed antidepressant drugs are the selective serotonin (5-HT) reuptake inhibitors (SSRIs), which act by blocking the high-affinity 5-HT transporter (SERT). The increase in extracellular 5-HT produced by SSRIs is thought to be critical to initiate downstream events needed for therapeutic effects. A potential explanation for their limited therapeutic efficacy is the recently characterized presence of low-affinity, high-capacity transporters for 5-HT in brain [i.e., organic cation transporters (OCTs) and plasma membrane monoamine transporter], which may limit the ability of SSRIs to increase extracellular 5-HT. Decynium-22 (D-22) is a blocker of these transporters, and using this compound we uncovered a significant role for OCTs in 5-HT uptake in mice genetically modified to have reduced or no SERT expression (Baganz et al., 2008). This raised the possibility that pharmacological inactivation of D-22-sensitive transporters might enhance the neurochemical and behavioral effects of SSRIs. Here we show that in wild-type mice D-22 enhances the effects of the SSRI fluvoxamine to inhibit 5-HT clearance and to produce antidepressant-like activity. This antidepressant-like activity of D-22 was attenuated in OCT3 KO mice, whereas the effect of D-22 to inhibit 5-HT clearance in the CA3 region of hippocampus persisted. Our findings point to OCT3, as well as other D-22-sensitive transporters, as novel targets for new antidepressant drugs with improved therapeutic potential.

Topics: Animals; Antidepressive Agents; Blood-Brain Barrier; Chromatography, High Pressure Liquid; Depression; Dose-Response Relationship, Drug; Drug Synergism; Electrophysiological Phenomena; Fluvoxamine; Hindlimb Suspension; Hippocampus; Mice; Mice, Inbred C57BL; Mice, Knockout; Microinjections; Neurotransmitter Transport Proteins; Octamer Transcription Factor-3; Quinolines; Selective Serotonin Reuptake Inhibitors; Serotonin; Serotonin Syndrome; Spectrophotometry, Ultraviolet

The patient was a 67-year-old male who had been treated for several years with 150 mg fluvoxamine maleate due to depression. He visited our hospital with primary symptoms of swelling of the right upper extremity and dyspnea in August, XXXX. As a result of examinations, he was diagnosed with stage IIIB extended small cell lung cancer(T4N3M0). One course of carboplatin/etoposide(CBDCA/VP-16)therapy was started on October 1. Since the tumor size was reduced, thoracic effusion disappeared, and superior vena cava syndrome was alleviated, the therapy was changed to cisplatin/irinotecan (CDDP/CPT-11)on October 23, and the 3rd course was initiated on November 22. Anxiety and tremor appeared on the 4th day of the 3rd course and because they were exacerbated, and myoclonus appeared, a diagnosis of serotonin syndrome was made on the 38th day, and the administration of fluvoxamine maleate was discontinued. The symptoms were alleviated after the discontinuation, and the 4th course could be implemented. In this patient, serotonin syndrome was considered to have been induced by serotonin secretion promoted by the CDDP administration, and by serotonin in the brain increasing abnormally due to the SSRI.

Topics: Aged; Antineoplastic Agents; Cisplatin; Depression; Fluvoxamine; Humans; Lung Neoplasms; Male; Selective Serotonin Reuptake Inhibitors; Serotonin Syndrome; Small Cell Lung Carcinoma

To report a case of severe serotonergic symptoms following the addition of oxycodone to fluvoxamine.. A 70-year-old woman developed severe serotonergic features, including confusion, nausea, fever, clonus, hyperreflexia, hypertonia, shivering, and tachycardia, following the addition of oxycodone 40 mg twice daily to fluvoxamine 200 mg/day, easily fulfilling diagnostic criteria for serotonin syndrome. Discontinuation of the offending drugs resulted in resolution of her symptoms over 48 hours, and no other cause of the syndrome was identified. Use of the Naranjo probability scale indicated a probable relationship between the serotonergic symptoms and the addition of oxycodone to fluvoxamine therapy.. Serotonin syndrome is a serious adverse reaction usually due to interactions with serotonergic drugs. There have been only 3 previous reports involving oxycodone. Most previous reports of serotonin syndrome involving analgesics have been associated with meperidine, dextromethorphan, and tramadol. Unlike these synthetic opioids, however, oxycodone does not inhibit the reuptake of serotonin. In addition, there are a number of other possible pharmacologic mechanisms for the interaction we observed.. Monitoring for serotonergic adverse events should be done when oxycodone is given to patients receiving serotonin-reuptake inhibitors.

Topics: Aged; Analgesics, Opioid; Depression; Drug Interactions; Female; Fluvoxamine; Humans; Oxycodone; Pain; Selective Serotonin Reuptake Inhibitors; Serotonin Syndrome

5-hydroxytryptamine (5-HT) syndrome is a dangerous condition of 5-HT excess that can occur in the case of co-administration of a monoamine oxidase (MAO) inhibitor and a serotonin reuptake inhibitor (SSRI). The goal of the present study was to investigate the effects of acute administration of MAO inhibitors and subchronic administration of fluvoxamine on 5-HT-related behaviors (head shaking and 5-HT syndrome) in rats treated with 5-hydroxytryptophan (5-HTP). Administration of the non-selective MAO inhibitor, pargyline, and the selective MAO-A inhibitor, clorgyline, resulted in 5-HT syndrome in 5-HTP-treated rats, and subchronic co-administration of fluvoxamine intensified the syndrome. However, administration of the selective MAO-B inhibitor, selegiline, did not induce 5-HT syndrome with or without subchronic fluvoxamine co-administration. These data suggest that non-selective MAO and selective MAO-A inhibitors can induce 5-HT syndrome in humans when co-administered with SSRI. Further, the risk of 5-HT syndrome may be lower with the selective MAO-B inhibitor, selegiline.

Topics: Analysis of Variance; Animals; Behavior, Animal; Brain; Clorgyline; Dose-Response Relationship, Drug; Drug Synergism; Fluvoxamine; Male; Monoamine Oxidase Inhibitors; Motor Activity; Pargyline; Rats; Rats, Sprague-Dawley; Selective Serotonin Reuptake Inhibitors; Selegiline; Serotonin; Serotonin Syndrome

There have been only a few reports of serotonin syndrome developing after mono-therapy with a selective serotonin reuptake inhibitor (SSRI). We report a case of serotonin syndrome caused by long-term therapy with fluvoxamine prior to treatment with paroxetine. An 18-year-old man with spinal cord injury (SCI) at thoracic level 2-3 presented with onset of serotonin syndrome after taking fluvoxamine (50 mg per day) for 8 weeks prior to treatment with paroxetine (10 mg per day) for 6 days. He had confusion, agitation, severe headache, tachycardia (124 beats/minute), hypertension (165/118 mmHg), high fever (39.1 degrees C), and myoclonus. All of the symptoms disappeared within 24 hours after discontinuation of administration of paroxetine. This is an interesting case of serotonin syndrome that developed after minimum doses of single therapy with an SSRI in a patient with SCI.

Topics: Adolescent; Antidepressive Agents, Second-Generation; Fluvoxamine; Humans; Male; Paroxetine; Selective Serotonin Reuptake Inhibitors; Serotonin Syndrome; Spinal Cord Injuries

Topics: Adolescent; Amphetamine-Related Disorders; Antidepressive Agents; Antitussive Agents; Anxiety Disorders; Child; Dextromethorphan; Diagnosis, Differential; Drug Interactions; Female; Fluvoxamine; Hallucinogens; Humans; Male; N-Methyl-3,4-methylenedioxyamphetamine; Obsessive-Compulsive Disorder; Seizures; Selective Serotonin Reuptake Inhibitors; Serotonin Agents; Serotonin Syndrome; Sertraline

The safety profile of the selective serotonin reuptake inhibitor, fluvoxamine, has been assessed in clinical and post-marketing studies. Post-marketing surveillance provides the opportunity to assess a drug's safety in every day clinical conditions in a much greater patient population than in clinical trials and therefore serves as a useful tool to detect signals for adverse effects with an incidence of less than 1 : 10,000. The safety profile of fluvoxamine was evaluated based on data from 17 years of global post-marketing surveillance in an estimated 28 million patients exposed to fluvoxamine. A total of 6,658 adverse drug reaction reports received from world-wide sources were reviewed and analysed. Post-marketing surveillance data confirmed the favourable safety profile already observed in clinical and post-marketing studies. A remarkably low level of suicidality, switch to mania, and sexual dysfunction was found. Serotonin syndrome appeared to be a very rare complication of fluvoxamine treatment. No signals for drug interactions unknown so far were identified. Withdrawal symptoms were observed in everyday clinical conditions, which were generally mild and resolved spontaneously. However, no cases suggestive for drug dependence have been reported. In conclusion, the data presented underlined that fluvoxamine offers a safe and well-tolerated option in the treatment of depression and obsessive-compulsive disorder.

Topics: Antidepressive Agents, Second-Generation; Bipolar Disorder; Cardiovascular Diseases; Death; Drug Interactions; Fluvoxamine; Humans; Product Surveillance, Postmarketing; Retrospective Studies; Selective Serotonin Reuptake Inhibitors; Serotonin Syndrome; Sexual Dysfunctions, Psychological; Substance Withdrawal Syndrome; Suicide

To document a case of serotonin syndrome associated with the combined use of fluvoxamine and mirtazapine, and to discuss the pharmacodynamic and pharmacokinetic interactions that were the likely causes of this potentially serious adverse drug reaction (ADR).. A 26-year-old white woman with a 12-year history of anorexia nervosa was being treated with fluvoxamine. After mirtazapine was added to her therapy, she developed tremors,restlessness, twitching, flushing, diaphoresis, and nausea,symptoms that are consistent with serotonin syndrome.. The possible causes of this ADR are discussed, including the effects of fluvoxamine and mirtazapine alone, the possible pharmacodynamic and pharmacokinetic interactions of these two drugs, and the patients underlying anorexia nervosa.. An increasing number of drugs that affect serotonin are available and are indicated for various disorders. Since there is a significant likelihood of these agents being prescribed concomitantly, clinicians must be aware of possible interactions that could lead to serotonin syndrome.

Topics: Adrenergic alpha-Antagonists; Adult; Adverse Drug Reaction Reporting Systems; Anorexia Nervosa; Drug Interactions; Female; Fluvoxamine; Humans; Mianserin; Mirtazapine; Selective Serotonin Reuptake Inhibitors; Serotonin Syndrome; Tissue Distribution

This preliminary study was performed to investigate the prevalence and severity of the serotonin-related symptoms for a group of patients in a clinical setting during fluvoxamine (FLU) using the Japanese version of the Serotonin Syndrome Scale (JSSS).. The subjects for the present study were 37 patients (20 and 17 patients with mood and anxiety disorders, respectively), meeting a diagnosis of DSM-IV. Each subject gave informed consent for the research involved in this study. Presence and severity of the serotonin-related symptoms were determined by Sternbach's criteria and the JSSS, respectively.. (1) At the time of assessment, none of the patients fulfilled the diagnostic criteria of SS proposed by Sternbach, or none of the total JSSS scores of the patients was sufficient to reach the cutoff point of 7. (2) Sixteen of the 37 patients (43.2%) showed at least one symptom in the JSSS. (3) Spearman's rank correlations showed that there was a positive but nonsignificant correlation between the total JSSS scores and dosages of FLU.. This preliminary study suggested that milder forms of the serotonin syndrome may exist for a group of patients in a clinical setting during FLU therapy.

Topics: Adult; Dose-Response Relationship, Drug; Female; Fluvoxamine; Humans; Male; Middle Aged; Mood Disorders; Prevalence; Psychiatric Status Rating Scales; Selective Serotonin Reuptake Inhibitors; Serotonin Syndrome; Severity of Illness Index

Topics: Drug Interactions; Fluvoxamine; Histamine H1 Antagonists; Humans; Mianserin; Mirtazapine; Selective Serotonin Reuptake Inhibitors; Serotonin Syndrome

Topics: Adult; Creatine Kinase; Depressive Disorder, Major; Dose-Response Relationship, Drug; Drug Administration Schedule; Fluvoxamine; Humans; Male; Selective Serotonin Reuptake Inhibitors; Serotonin Syndrome; Stress Disorders, Post-Traumatic

Serotonin syndrome, a potentially fatal iatrogenic complication of psychopharmacologic therapy, is most commonly reported with combinations of serotonergic medications. Serotonin syndrome is characterized by alterations in cognition, behavior, autonomic, and central nervous system function as a result of increased postsynaptic serotonin receptor agonism. We present the first reported case of serotonin syndrome after a single dose of fluvoxamine in a pediatric patient after ingestion of a single supratherapeutic dose of fluvoxamine.

Topics: Attention Deficit Disorder with Hyperactivity; Child; Diagnosis, Differential; Dose-Response Relationship, Drug; Emergencies; Fluvoxamine; Humans; Male; Neurologic Examination; Serotonin Syndrome

Topics: Adolescent; Anti-Anxiety Agents; Cyproheptadine; Female; Fluvoxamine; Humans; Selective Serotonin Reuptake Inhibitors; Serotonin Antagonists; Serotonin Syndrome