Modulation of Neuroendocrine Response and Non-Verbal Behavior during Psychosocial Stress in Healthy Volunteers by the Glutamate Release-Inhibiting Drug Lamotrigine

Abstract

The present work was aimed at verifying the following hypotheses: (a) lamotrigine, a drug used to treat mood disorders, affects regulation of stress hormone release in humans, and (b) non-verbal behavior during mental stress situations (public speech) is related to hormonal responses. To achieve these aims, we performed a controlled, double-blind study investigating hormonal responses and non-verbal behavior during public speech in healthy subjects with placebo or lamotrigine (300 mg per os) pretreatment. The stress procedure was performed in 19 young healthy males 5 h following drug or placebo administration. Data were obtained from cardiovascular monitoring, blood and saliva samples, as well as the video-recorded speech. Pre-stress hormone levels were not affected by lamotrigine treatment. Lamotrigine significantly inhibited diastolic blood pressure, growth hormone and cortisol increases during psychosocial stress. In contrast, it potentiated plasma renin activity and aldosterone responses. Non-verbal behavior analysis revealed a correlation between catecholamines and submissive or flight behavior in controls, while between catecholamines and displacement behavior following lamotrigine administration. In conclusion, effects of lamotrigine on hormone release might be of value for its mood-stabilizing action used in the treatment of bipolar disorder. The data are in support of a stimulatory role of glutamate in the control of cortisol and growth hormone release during psychosocial stress in humans; however, further studies using more selective drugs are needed to prove this suggestion. The effects on plasma renin activity and aldosterone release observed seem to be related to other actions of lamotrigine.

Effects of peritraumatic ketamine medication on early and sustained posttraumatic stress symptoms in moderately injured accident victims

“…Glutamate-efflux-reducing drugs such as lamotrigine (Makatsori et al 2004) and riluzole (Kniest et al 2001), or agonization of metabotropic glutamate receptors that suppress excessive glutamate excitation (Coplan et al 2001), lead to a declined stress-induced HPA system activity. Conversely, high dissociative PTSD subjects show elevated cortisol levels after recounting traumatic experiences (Koopman et al 2003).…”

Renin-Angiotensin-Aldosterone System: The Forgotten Stress Hormone System: Relationship to Depression and Sleep

“…Several observations link the RAAS to stress and stress-related disorders. Increased RAAS activity in psychosocial stress was described in healthy humans [ 72 ] and in animal models [ 73 ] . In patients with depression, several biomarkers of melancholic depression were found to be induced by the administration of the MR antagonist spironolactone, including an increase in the HPA activity and a reduction of slow-wave sleep [ 74 , 75 ] whereas MR agonists like deoxycorticosterone (DOC) [ 76 ] and fl udrocortisone [ 31 ] suppressed the HPA axis in humans.…”

Anti-Stress Effects of Mood Stabilizers and Relevance to Their Therapeutic Actions

“…A systemic review suggest that valproate can be effective for the treatment of PTSD by reducing hyperarousal, improving irritability, anger outburst, and mood although it remains that more double blind studies are needed (Adamou et al, 2007). Lamotrigine significantly suppressed stress responses to public speech including suppression of stress hormones such as growth hormones and cortisol (Makatsori et al, 2004).…”