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Despite the fact that a role for thyrotropin-releasing hormone (TRH) in seizure modulation has been consistently hypothesized, the exact nature of this role remains unclear. In this study, we investigated the effects of TRH administration on seizure threshold and seizure duration in 13 depressed inpatients undergoing electroconvulsive therapy (ECT). In a balanced order crossover design, an intravenous bolus of 0.4 mg TRH or placebo was administered immediately before anesthesia, during the first two sessions, in a series of bilateral ECT. In both of these sessions, a threshold titration procedure was applied by using gradual increments of the electrical charge delivered until seizure elicitation, a procedure that has been safely used in the past. Seizure threshold was defined as the lowest energy level required for induction of a grand mal seizure, by use of this titration procedure. Seizure duration was estimated both by simultaneous EEG recording and by the cuff method. Results showed that neither seizure threshold, nor seizure duration (either by cuff or by EEG) differed between the TRH and the placebo conditions, regardless of the order in which TRH or placebo were administered in the two ECT sessions. This was the case regardless of whether the patients had at baseline a blunted TSH response to TRH or not. Our findings do not support a role for TRH on seizure modulation, at least when TRH is administered exogenously. Such an effect, if it exists, could be obscured, however, by several factors, including pharmacokinetics.

The relationship between the thyrotropin (TSH) response to thyrotropin-releasing hormone (TRH) and the duration of seizures induced by electroconvulsive therapy (ECT) in depressed patients was investigated. In a balanced-order cross-over design, 16 depressed women were given 0.4 mg TRH or placebo intravenously, 20 min before ECT in the first two sessions, In the third ECT session TRH was given just Frier to ECT. Thyrotropin (TSH) levels at various sampling times, as well as the duration of seizures, were measured. There was a significant inverse correlation between plasma TSH concentrations 20 min after TRH administration (Delta TSH) and seizure duration. Furthermore, when patients were categorized according to their TSH response to TRH, the group with blunted responses (Delta TSH < 6 mu IU/mL, n=7) had a longer seizure time during ECT than the group with non-blunted responses (Delta TSH > 6 mu IU/mL, n = 9), Finally, the seizure duration in the group with blunted TSH responses was reduced significantly when TRW. was co-administered, while it remained unchanged in the group with non-blunted TSH responses. It is concluded that a blunted TSH response to TRH might indicate a seizure susceptibility as measured by the duration of seizures induced by ECT. The fact that TRH pre-administration had a reducing effect suggests that this substance might be involved in the pathophysiology of ECT-induced seizures.

The effects of thyrotropin-releasing hormone (TRH) administration on electroconvulsive therapy (ECT)-induced prolactin (PRL) secretion and the duration of the seizure were studied in 14 depressed women. In a balanced order crossover design the patients were given 0.4 mg TRH or placebo intravenously 20 min before ECT during the first two sessions. In the third ECT session TRH was given just prior to ECT. ECT elicited the expected PRL response when given alone and when given 20 min after TRH when PRL plasma levels were high. During the coadministration design (third ECT session) PRL levels were raised not as a sum of the two stimuli but even significantly more. TRH failed to modify the duration of the seizure induced by ECT. Therefore, if TRH is involved in seizure modulation during ECT, our findings suggest a postictal rather than ictal role for TRH.

Despite extensive study of the effects of various pharmacological agents on the thyrotropin (TSH) and prolactin (PRL) responses to TRH challenge, the effect of serotoninergic agents remains inconclusive. We studied the effect of the serotonin antagonists methysergide (non-selective 5-HT1/5-HT2 blocker with dopaminergic properties) and ritanserin (selective 5-HT2 blocker) on the TSH and PRL responses to TRH stimulation in two groups of medication-free female depressed patients in a double-blind, within-subject design. Methysergide was found to decrease significantly the PRL response to TRH, while ritanserin had no effect. Neither compound influenced the TSH response. Results suggest that 5-HT2 mechanisms do not mediate the PRL and TSH responses to TRH challenge in depression. The reduction in PRL observed after methysergide is probably due to either 5-HT1 or dopaminergic mechanisms.