Naloxone fails to block ECT-induced prolactin increase

1326

BIOLPSYCHIATRY

Brief Reports

1985 ;20:1326-1327

Naloxone Fails to Block ECT-Induced Prolactin Increase Yiannis G. Papakostas, Costas C. Stefanis, Manolis Markianos, and George N. Papadimitriou

The rapid, but transient, prolactin (PRL) induring the electroconvulsive therapy (ECT) is well known (Ohman et al. 1976; Skrabanek et al. 1981; Papakostas et al. 1984), although the underlying mechanism mediating this effect remains speculative. It has been suggested that endogenous opioid peptides may be involved (Skrabanek et al. 1981; Deakin et al. 1983): these substances, among other effects, increase PRL in man, and this increase can be blocked by small doses of naloxone (Grossman and Rees 1983; Morley 1983). The question then arises whether or not the ECT-induced PRL increase is mediated via stimulation of opioid secretion. In this study, the role of opioids in the ECTinduced prolaetin increase was tested by the administration of the opioid receptor antagonist, naloxone, to five female melancholic patients who were undergoing treatment with ECT. The patients' ages ranged between 38 and 63 years. With the exception of low doses of benzodiazepines (flunitrazepam) given at bed time, they were free from psychotropics or any other drugs

From the ~ e n t of Psychiatry, Athens University Medical School, Eginition Hospital, Athens, Greece. Address reprint requests to Dr. Yiannis Papakostas, Department of Psychiatry, Athens University Medical School, Eginition Hospital, 74 Vas. Sophias Av., Athens, Greece. Received March 19, 1985.

known to affect PRL secretion for at least 1 week before ECT was started. Each patient received naloxone hydrochloride at the second (0.4 mg), fourth (1.2 mg), and sixth (4.0 mg) ECT session through saline infusions that started approximately 1.5 min before and terminated 30 min after the application of the electrical stimulus. Bilateral ECT was administered in all sessions, with the exception of the first one, in which a "simulated" ECT (SECT) was given (all ECT procedures were followed, but the current was not passed). The standard anesthesia procedures and the characteristics of the electrical stimulus are described elsewhere (Papakostas et al. 1984). Blood samples were taken during the first seven ECT sessions. In each session, five blood samples were collected through an intravenous cannula: the first before anaesthesia, the second immediately after succinylcholine administration, and the remaining three at 5, 15, and 30 min after the induction of a seizure monitored by the "cuff" method. Plasma samples were stored at - 3 0 ° C , and PRL was assessed with BIODATA radioimmunoassay kits. Paired t-testing was used to evaluate the statistical significance among the various ECT sessions as far as PRL release was concerned. The degree of PRL increase after pretreatment with naloxone in any of the three doses tested did not differ from that

Brief Reports

BIOLPSYCHIATRY

1327

1985;20:1326-1327

max Prolactin ng/m}

~

70-

605O

SECT ECT* Naloxone ECT

i

40 3O

10

1

2

(0.4 rag)

3

4

5

(1.2 rag) ECT SESSIONS

6

(4.0rng)

Figure 1. Prolactin responses (mean --- SEM)tO ECT in five melancholic patients. A max Prolactin: highest post-ECT prolactin value minus baseline value.

induced by ECT alone. Compared with SECT, however, ECT alone or after pretreatment with naloxone did induce significantly higher PRL secretion (Fig. 1). Although opiates and opioid peptides have PRL-releasing properties that can be blocked by small doses of naloxone, the effect of naloxone itself on PRL secretion has not been adequately defined. In man, naloxone appears to have no effect on basal PRL secretion and its effect on stimulated PRL release (as occurs for example after thyrotropin-releasing hormone (TRH) or insulin administration) varies from study to study (Grossman and Rees 1983, Morley 1983). Overall, the effect of naloxone on PRL secretion does not seem to be impressive (Morley 1983)---a conclusion that is in line with the findings of this study. However, a minor contribution of opioids in the ECT-induced prolactin response cannot be excluded. If such is the case, the mechanism should be further elucidated by more refined methods.

References Deakin JFW, Ferrier IN, Crow TJ, Johnstone EC, Lawler P (1983): Effects of ECT on pituitary hormone release: Relationship to seizure, clinical variables and outcome. Br J Psychiatry 143:618-624. Grossman A, Rees LH (1983): The neuroendocrinology of opioid peptides. Br Med Bull 39:83-88. Morley JE (1983): Neuroendocrine effects of endogenous opioid peptides in human subjects: A review. Psychoneuroendocrinology 8:361-379. 0hman R, Balldin J, Walinder, Wallin L (1976): Prolactin response to electroconvulsive therapy. Lancet ii:936-937. Papakostas Y, Stefanis C, Sinouri A, Trikkas G, Papadimitriou G, Pitoulis S (1984): Increases in prolactin levels following bilateral and unilateral ECT. Am J Psychiatry 141:1623-1624. Skrabanek P, Balfe A, Webb M, Maguire J, Powell D (1981): Electroconvulsive therapy (ECT) increases plasma growth hormone, prolactin, luteinising hormone and follicle-stimulating hormone but not thyrotropin or substance P. Psychoneuroendocrinology 6:261-267.