fluvoxamine and tandospirone

We experienced the first death case of the serotonin syndrome in Japan caused by fluvoxamine and tandospirone. A 15-year-old man was transported to our hospital for shock, muscle hypertonia and hyperthermia after cardiopulmonary arrest. His serum concentrations of fluvoxamine and tandospirone were 3,554 ng/mL and 698 ng/mL respectively after 24 hours from oral intake. He was dead in spite of intensive treatments. The progress of the serotonin syndrome is usually rapid. So, it should be monitored appropriately a patient with serotonin syndrome. If he has hyperthermia, immediate paralysis should be induced. We should aware of the serotonin syndrome a case of overdose on a serotonergic agent.

Topics: Adolescent; Anti-Anxiety Agents; Drug Overdose; Fatal Outcome; Fever; Fluvoxamine; Heart Arrest; Humans; Isoindoles; Japan; Male; Muscle Hypertonia; Piperazines; Pyrimidines; Selective Serotonin Reuptake Inhibitors; Serotonin Receptor Agonists; Severity of Illness Index; Shock; Syndrome

In a previous study it was demonstrated that the anxiolytic action of tandospirone, a 5-hydroxytryptamine (5-HT)(1A) receptor agonist, is facilitated by cytochrome P450 (CYP) 3A4 inhibitors, such as ketoconazole and cimetidine. It is also known that fluvoxamine, a selective serotonin re-uptake inhibitor (SSRI), inhibits CYP3A4. The purpose of the present study was to clarify the pharmacokinetic interaction between tandospirone and fluvoxamine and to evaluate their combined effect in the rat anxiety model.. The anxiolytic action of co-administration of tandospirone and fluvoxamine was examined using the rat contextual conditioned fear stress model. After testing the conditioned fear, plasma concentrations of tandospirone and its major metabolite 1-(2-pyrimidyl) piperazine were determined.. One day after fear conditioning, both tandospirone (60 mg/kg, p.o.) and fluvoxamine (60 mg/kg, p.o.) significantly inhibited conditioned freezing and their combination effect was additive. In addition, plasma concentration of tandospirone was increased by fluvoxamine.. There is a CYP3A4-related drug-drug interaction between tandospirone and fluvoxamine. Therefore, fluvoxamine may facilitate the anxiolytic effect of tandospirone via CYP3A4 inhibition.

Topics: Administration, Oral; Animals; Anti-Anxiety Agents; Conditioning, Classical; Cytochrome P-450 CYP3A; Cytochrome P-450 CYP3A Inhibitors; Drug Synergism; Electroshock; Fear; Fluvoxamine; Isoindoles; Male; Piperazines; Pyrimidines; Rats; Rats, Sprague-Dawley

Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia defined by intermittent loss of electromyographic atonia during REM sleep with emergence of complex and vigorous behaviors. Although the efficacy of several agents for treating RBD has been reported, a rationale for medication has not been established and the exact pathophysiological mechanisms of RBD are uncertain. We encountered a patient with idiopathic RBD that dramatically improved with selective serotonin reuptake inhibitors (SSRIs) and deteriorated with a 5-HT1A partial agonist, tandospirone. We report on the effects of these serotonin-modulating agents, which yield clues to a possible pharmacological approach to RBD.

Topics: Aged; Female; Fluvoxamine; Humans; Isoindoles; Paroxetine; Piperazines; Polysomnography; Pyrimidines; Reaction Time; REM Sleep Behavior Disorder; Selective Serotonin Reuptake Inhibitors; Serotonin Receptor Agonists; Sleep, REM; Treatment Outcome

Case 1: female, age 76. Fluvoxamine (50 mg/day) initiated a reduction of pain on the 14th day of administration and completely ameliorated pain as well as depression. Case 2: female, age 76. Fluvoxamine (25 mg/day) was administered with tandospirone (15 mg/day) which augments the effect of an SSRI. This combination regimen induced a reduction of PHN-pain on the 10th day and as the analgesic effect attained nearly 50%, there occurred a reflaming of pain on the 35th day. Increasing fluvoxamine to 50 mg/day reameliorated pain on the 49th day, and a further increase to 75 mg/day finally eliminated pain and depression at the end of the 3rd month. The long latency of fluvoxamine action, its shortening by tandospirone and the parallel changes of PHN and depression are all indicative of that the same mechanism, namely renormalization of the dysfunctioned central serotonergic transmission would be underlying both the anti-PHN and antidepressant actions. It would be concluded that fluvoxamine alleviates PHN by restoration of the descending serotonergic inhibition of primary afferent activity that carries pain impulses.

Topics: Aged; Chronic Disease; Drug Therapy, Combination; Female; Fluvoxamine; Herpes Zoster; Humans; Isoindoles; Neuralgia; Piperazines; Pyrimidines; Selective Serotonin Reuptake Inhibitors; Serotonin Receptor Agonists; Treatment Outcome

Topics: Animals; Anti-Anxiety Agents; Benzodiazepines; Blood Pressure; Diazepam; Fluvoxamine; Isoindoles; Piperazines; Pyrimidines; Rats; Rats, Wistar; Weightlessness

Topics: Animals; Atrophy; Cerebral Cortex; Chorea; Dementia; Dopamine Antagonists; Female; Fluvoxamine; Haloperidol; Humans; Isoindoles; Mice; Mice, Neurologic Mutants; Mice, Transgenic; Middle Aged; Piperazines; Pyrimidines; Receptors, Serotonin; Receptors, Serotonin, 5-HT1; Selective Serotonin Reuptake Inhibitors; Serotonin Receptor Agonists; Trinucleotide Repeat Expansion