Yiannis G. Papakostas

Methysergide Reduces the Prolactin Response to ECT

One of the most consistently reported immediate effects of electroconvulsive therapy (ECT) is a rapid and transient increase of serum prolactin (PRL) (Ohman et al. 1976; Deakin et al. 1983), but the underlying mechanism mediating this response remains unclear. Interventions such as pretreatment with the alpha-adrenergic receptor blocker phentolamine (Klimes et al. 1978), diazepam (Arato and Bagdy 1982), or the opioid antagonist naloxone (Papakostas et al. 1985) do not seem to affect this ECT-induced PRL secretion. Similarly, omission of anticonvulsive premedication (Klimes et al. 1978), or omission of pretreatment with atropine (Scott et al. 1986), do not influence the PRL response to ECT. On the other hand, it has been suggested that ECT exerts a selective hypothalamic+uitary axis effect and that the secretion of PRL in particular is due to the stimulation of central serotonergic mechanisms (Whalley et al. 1987). In this study, the role of the serotonergic system in the ECT-induced PRL secretion was tested using the serotonin receptor blocking properties of methysergide.

Administration of citalopram before ECT: seizure duration and hormone responses.

From theoretical and clinical perspectives, it is important to know if selected serotonin-reuptake inhibitors (SSRIs), often administered concurrently with electroconvulsive therapy (ECT), modify seizure duration. In a study with a double-blind, cross-over design, the authors evaluated the effect of citalopram, the most selective SSRI available, on the length of electrically induced seizures and on hormone secretion during ECT. Ten depressed women were given either 20 mg citalopram or placebo orally 2 hours before the third and fourth ECT sessions. Seizure duration was assessed by the cuff technique and from electroencephalographic recordings, whereas blood for prolactin, thyrotropin, and cortisol assessment was sampled before ECT and 5, 10, 20, 30, 40, and 60 minutes after ECT. No adverse effects after the administration of citalopram were recorded. The length of seizures was not statistically different in the citalopram (29.3 ± 8.4 seconds) and placebo sessions (28.2 ± 9.4 seconds). Neither pre-ECT plasma hormone levels measured 2 hours after citalopram or placebo administration nor the patterns of ECT-induced hormone secretions differed between the two drug and placebo conditions. The lack of effect of citalopram on hormones in this study may be a result of possible deficiencies of the monoaminergic (i.e., serotoninergic) systems in depression. Although safety and efficacy issues were not fully addressed by coadministering citalopram for the long term and throughout the course of ECT, these findings support the view that challenges the typical clinical practice of discontinuing SSRIs before ECT.

Thyrotropin and prolactin responses to ECT in schizophrenia and depression

Thyroid stimulating hormone (TSH) and prolactin (PRL) plasma levels were studied during electroconvulsive therapy (ECT) in five schizophrenic patients in a simulated ECT (SECT) controlled experimental design. The data were compared to those obtained from a group of 10 depressed patients treated with ECT. In the schizophrenic group, both PRL and TSH increased significantly during ECT compared to SECT, as they did in the depressive group during ECT. Thus, the hormonal TSH and PRL profile during ECT is similar in schizophrenia and depression. It is concluded that the changes in TSH and PRL induced by ECT are specifically linked to the current or the seizure, and are not related to the type of psychopathology.

A survey of the attitudes of Greek medical students toward electroconvulsive therapy

Data on attitudes toward electroconvulsive therapy have been reported from various countries; no information, however, is available from Greece. In this survey, we report the results of a questionnaire reflecting the general attitude of Greek medical students toward ECT. A total of 161 sixth (final)-year medical students who had no previous exposure to a formal didactic experience on ECT, were asked to complete a questionnaire before attending a scheduled 90-minute lecture on ECT, as part of their regular curriculum. Questions in the questionnaire could be grouped to indicate a positive, a reserved, or a negative attitude toward ECT. Overall, before the lecture, 50.3% held a positive attitude toward ECT, 43.5% were reserved, and 6.2% held a negative attitude. A subgroup of these students (n = 137) were asked again to score the same questionnaire immediately following the lecture to rate the impact of the didactic seminar. The proportion of students with a positive attitude after the lecture was increased to 78.1%, (P < 0.001), while the proportion of students with reserved and negative attitudes were reduced to 20.4% (P < 0.001) and 1.5%, respectively. These encouraging findings reflect, however, only the immediate effects of the lecture and do not guarantee persistence of this change in attitudes over time.

Thyrotropin-releasing hormone administration does not affect seizure threshold during electroconvulsive therapy.

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.

Effects of TRH administration on orientation time and recall after ECT

Summary We investigated the effect of thyrotropin-releasing hormone (TRH) on orientation time and recall, in nine depressed female inpatients undergoing electroconvulsive therapy (ECT). In a balanced order crossover design, an intravenous bolus of 0.4 mg TRH or placebo was administered 20 min before ECT in the first two sessions. Orientation time and retrograde and anterograde components of the memory dysfunction, immediately and 24 h later, were assessed. Administration of TRH did not influence orientation time, word recall, or immediate short story recall compared with placebo. We did find, however, an improvement in the number of short story items recalled after 24 h when patients were given TRH compared with placebo. This indicates that TRH may have a protective role against the specific negative effect of ECT on delayed recall.

Ritanserin, a 5-HT2 receptor antagonist, does not modify ECT-induced prolactin release

The effect of pretreatment with ritanserin, a potent and selective serotonin-S2 (5-HT2) receptor antagonist, on the prolactin (PRL) response to electroconvulsive therapy (ECT) was studied in seven female patients suffering from major depressive disorder. They were given either ECT alone, or ECT after 10 or 20 mg ritanserin PO, and PRL was estimated in blood samples taken at times −5, 0, +5, +15, +30 and +60 min. The PRL responses after drug administration were not different from the responses after ECT alone. We conclude that, if serotonergic mechanisms are involved in the ECT-induced PRL increase, this neuroendocrine response seems to be rather a 5-HT1 than 5-HT2 receptor mediated event.

Prolactin and thyrotropin responses to ECT after pindolol administration. A placebo controlled study.

The effect of pindolol, a beta-receptor blocker with potent 5-HT1 receptor antagonistic properties, on the prolactin (PRL) and thyrotropin (TSH) responses to electroconvulsive therapy (ECT) was systematically studied in 12 female depressed patients. In a balanced order, crossover design, the patients were given placebo or pindolol 5 mg orally, 1 h prior to bilateral ECT. The last five patients were additionally tested with 10 mg pindolol during the third ECT. Plasma levels of PRL and TSH increased in all three trials, but no consistent effect of pindolol on these hormonal responses could be demonstrated. Pindolol tended to attenuate seizure duration, especially at the 10 mg dose. The participation of 5-HT1 receptor activity in the secretion of PRL and TSH during ECT remains uncertain.

The patterns of prolactin release by ECT and TRH compared

The patterns of prolactin release after bilateral ECT and after 0.4 mg TRH i.v. were studied in 11 female melancholic patients in a 5-min sampling protocol. Mean prolactin peaking times were 10.2 min after ECT and 20.5 min after TRH. The elimination rate coefficients were significantly lower--and the corresponding half-lives longer--for prolactin released by TRH than by ECT. A significant positive correlation of the maximal prolactin responses by the two stimuli was also found.

Horse madness (hippomania) and hippophobia

Anthropophagic horses have been described in classical mythology. From a current perspective, two such instances are worth mentioning and describing: Glaucus of Potniae, King of Efyra, and Diomedes, King of Thrace, who were both devoured by their horses. In both cases, the horses’ extreme aggression and their subsequent anthropophagic behaviour were attributed to their madness (hippomania) induced by the custom of feeding them with flesh. The current problem of ‘mad cow’ disease (bovine spongiform encephalopathy) is apparently related to a similar feeding pattern. Aggressive behaviour in horses can be triggered by both biological and psychological factors. In the cases cited here, it is rather unlikely that the former were the cause. On the other hand, the multiple abuses imposed on the horses, coupled with peoples’ fantasies and largely unconscious fears (hippophobia), may possibly explain these mythological descriptions of the ‘horse-monsters’.