Table 3.

Human studies in mood disorders.

Author	Aim and Study Design	Numer of Subjects	Population	Lamotrigine Dose and Root	Ketamine Dose and Root	Tests and Measures	Outcome
Abdallah et al. 2017 [14]	To investigate prefrontal GBCr in treatment-resistant depression (TRD) at baseline and following treatment. Randomized, double blind, placebo controlled crossover trial Mean ± SEM	22 patients with TRD 29 healthy control	Patients with TRD, healthy controls	Lamotrigine 300 mg oral, or placebo, about 2 h prior to ketamine	Ketamine 0.23 mg/kg IV in 2 min followed by 0.58 mg/kg for approximately 70 min Single infusion	BPRS CADSS GBC	Ketamine significantly increased BPRS and CADSS scores but pretreatment with lamotrigine had no significant effect on the ketamine-induced increases. Lamotrigine significantly reduced the ketamine-induced GBCr surge by inhibition of glutamatergic transmission. Ketamine did not significantly reduce vPFC GBCr in TRD subjects but it did reduce vPFC GBCr in healthy subjects. Following pretreatment with lamotrigine, ketamine showed no significant effects on the GBCr in the vPFC.
Mathew et al. 2010 [51]	To replicate the acute efficacy of single-dose intravenous (i.v.) ketamine; test the efficacy of the glutamate-modulating agent riluzole in preventing postketamine relapse; and examine whether pretreatment with lamotrigine would attenuate ketamine’s psychotomimetic effects and enhance its antidepressant activity Randomized, double blind, placebo controlled trial Response and remission rates (%) Mean ± SD	26	Medication free patients with a diagnosis of MDD, of at least moderate severity and nsufficient response to >2 adequate antidepressant trials in the current episode.	Lamotrigine 300 mg oral, or placebo, 2 h prior to ketamine infusion	Ketamine 0.5 mg/kg iv for 40 min Single infusion	BPRS CADSS MADRS	Lamotrigine pretreatment did not attenuate side-effects associated with ketamine. There was no difference detected in MADRS scores and no differences on BPRS positive symptoms between lamotrgine and placebo treatment groups. No difference in CADSS scores was found.

TRD = treatment resistant depression; TRBD = treatment resistant bipolar depression; MADRS = Montgomery-Asberg Depression Rating Scale,;BPRS = Brief Psychiatric Rating Scale; CADSS = Clinician-Administered Dissociative States Scale; GBCr = global brain connectivity with global signal regression; vPFC = ventral prefrontal cortex; SEM = standard error of the mean; SD = standard deviation.