Neuropsychiatric Symptoms of Epilepsy

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M. Yogarajah and M. Mula
At the moment, calcium channel blockers represent an emerging class of compounds
that showed potential benefits in anxiety disorders. In reality, the use of this
class of drugs is not completely original considering that older agents globally
reduce widespread activating pathways.
Gabapentin
GBP modulates calcium currents by binding to the α 2 -δ subunit of voltage-gated
calcium channels [ 1 ]. In a double-blind, placebo-controlled, parallel-group trial, 69
patients with social phobia were randomized to flexible-dose (900–3600 mg/day)
GBP ( n = 34) or placebo ( n = 35) for 14 weeks [ 179 ]. Compared to placebo, GBP
was associated with a significant improvement in a number of measures such as the
Liebowitz Social Anxiety Scale, the Brief Social Phobia Scale, and the Social
Phobia Inventory. Initial open-label studies suggested that GBP could be effective
in the treatment of bipolar disorder [ 49 ]. However, a randomized, double-blind,
placebo-controlled, add-on trial failed to demonstrate the superiority of GBP over
placebo in the acute therapy of mania [ 180 ]. Similar results were obtained in patients
with refractory bipolar or unipolar mood disorders [ 181 ]. A small, randomized,
double-blind, placebo-controlled trial suggested that adjunctive GBP may be useful
in maintenance treatment of bipolar disorder [ 182 ], but larger studies are needed. As
previously described for other AEDs, GBP showed a paradoxical effect in children
and patients with severe intellectual disabilities with the occurrence of hyperactivity
and aggression [ 183 , 184 ].
Pregabalin
Similarly to GBP, PGB is a ligand for α 2 -δ subunit of voltage-gated calcium channels.
Several randomized, double-blind, placebo-controlled trials have found that
PGB is effective in generalized anxiety disorder and social anxiety disorder, and it
has been licensed by the EMA for use in the former condition [ 185 – 188 ].
Furthermore, studies comparing PGB to benzodiazepines [ 189 ], and to venlafaxine
[ 190 ], in the acute and long-term treatment of anxiety, respectively, have demonstrated
its efficacy. Other controlled studies suggest that PGB may be effective in
the amelioration of comorbid depressive symptoms [ 191 ], especially in elderly subjects
with generalized anxiety disorder [ 192 ]. In one study, 273 elderly patients with
generalized anxiety disorder were randomized in a 2:1 ratio to flexible-dose (150–
600 mg/day) PGB ( n = 177) or placebo ( n = 96) for 8 weeks [ 185 ]. PGB was associated
with a greater improvement, starting in the 2nd week of treatment, in the
Hamilton Rating Scale for Anxiety (HRSA) total scores as compared to placebo
( p < 0.05). Greater improvements were also found in the HRSA psychic and somatic
anxiety factors and in the Hamilton Rating Scale for Depression total scores. Finally,
the long-term efficacy of PGB in the treatment of generalized anxiety disorder has
also been demonstrated [ 193 ]. Although a few reports suggest that PGB may be