Seizure in venlafaxine overdose: a 10-year retrospective review of the California poison control system.

Background: The optimal observation time period with respect to seizures after venlafaxine overdose is unclear. We conducted a 10-year retrospective review of calls to the California Poison Control System to describe the time of onset of seizures in adult and pediatric overdose of venlafaxine.Methods: Inclusion criteria included adult and pediatric patients with exposure to venlafaxine, who were admitted to a health care facility and who had at least one seizure. We did not exclude cases in which co-ingestions of other drugs were reported. Data extraction of a priori defined variables was recorded. Descriptive statistics were used to characterize the cohort of patients, including means, medians, and interquartile ranges.Results: The total number of cases included in the data analysis was 123 (12.9% of all venlafaxine ingestions). The longest time to last seizure was 24 h. Twenty-five percent of participants had a seizure from hour 7 to 24 h. This did not differ significantly between IR and XR formulations.Conclusions: Optimal observation time with respect to seizures after overdose of immediate-release formulation of venlafaxine is 18 h (24 h if ingested with other medications), and 21 h for patients who are poisoned with the sustained-release formulation.

5-HT receptors involved in opioid-activated descending inhibition of spinal withdrawal reflexes in the decerebrated rabbit.

The role of 5-HT(1B/1D), 5-HT(2) and 5-HT(3) receptors in mediating descending inhibition of spinal reflexes activated by application of fentanyl to the fourth ventricle has been studied in rabbits decerebrated under N(2)O/isoflurane anaesthesia. In the control state, intraventricular fentanyl (3-30 microg kg(-1)) depressed, to an equal extent, short- and long-latency reflexes in the medial gastrocnemius muscle nerve evoked by electrical stimulation of all sural nerve afferents. Inhibition of reflexes resulted from a decreased base line excitability in the reflex pathway accompanied by a reduction in the rate of temporal summation of responses. Fentanyl-induced suppression of short- and long-latency reflexes was significantly reduced after intrathecal administration of the selective 5-HT(2)-receptor antagonist ICI 170,809 (300 microg). The same dose of the selective 5-HT(1B/1D) blocker GR 127,935 reduced inhibition from intraventricular fentanyl only for long-latency reflexes (i.e. those parts of the response for which the afferent drive is provided mainly by Adelta and C-fibre afferents). The 5-HT(3) antagonist tropisetron (also 300 microg intrathecal) did not significantly alter the descending inhibition of reflexes evoked by fentanyl. Both GR 127,935 and tropisetron reduced temporal summation of reflexes per se, effects that were reversed by intraventricular fentanyl. These data suggest that the descending pathway(s) activated by intraventricular fentanyl liberate 5-HT in the spinal cord to inhibit withdrawal reflexes by acting at 5-HT(2) and 5-HT(1B/1D), but not 5-HT(3) receptors. 5-HT(1B/1D), and to a lesser extent 5-HT(3) receptors also appear to have a role in modulating temporal summation of reflexes evoked by repetitive stimuli.