ECT and Memantine.

N/A

The efficacy of ECT for the treatment of mood disorders requires the induction of generalized seizures (Nobler et al.,
1993). Following the repeated induction of generalized seizures through ECT, enhanced excitability and altered
histologic characteristics of the hippocampus have been well demonstrated (Gombos et al., 1999; Perera et al., 2007).
Although hippocampal excitotoxicity is mediated in part by excessive calcium influx through over-activation of NMDA
receptors, physiological NMDA receptor activation is essential for normal neuronal function. Therefore, potential
neuroprotective agents that block virtually all NMDA receptor activity will very likely have unacceptable side effects.
In contrast to other clinically-available NMDA receptor antagonists, memantine has been demonstrated to substantially
reduce excitotoxic neuronal inury, as well as being clinically well-tolerated in humans. The superior efficacy and clinical
safety of memantine result from its highly advantageous pharmacological properties (Chen et al., 1998). Memantine has
the unique attributes of being an open-channel blocker, as well as having a relatively fast dissociation rate, compared
with other NMDAantagonists such as ketamine. Therefore, memantine will only block NMDAreceptors that are excessively stimulated (open-channel blockade) without disrupting normal synaptic transmission (fast dissociation rate).
Together, memantine represents a novel, low-affinity, open-channel NMDA antagonist that appears to enter the channel
preferentially when pathologically activated without interfering with normal synaptic transmission, yielding the potential to
provide neuroprotection.

During the course of ECT treatment and at 2 months follow-up.

1. The experimental group will receive once daily 20 mg/d memantine during ECT. This will be titrated before commencing
ECT;

2. The control group will receive an identical placbo once daily.