rufinamide (?)

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A new drug that decreases anxiety and stabilizes mood?

18 May 2010 Journal of Psychotherapy and Psychosomatics,

This study formulates the hypothesis that rufinamide, a drug so far used against

epilepsy, may also be effective in bipolar disorder, depressive and anxiety

disorders, panic disorder and obsessive-compulsive disorder, eating disorders,

and substance use disorders. It is just an hypothesis based on two cases that

needs to be confirmed by specific studies.

Rufinamide is a triazole derivative indicated in the USA for adjunctive

treatment of seizures associated with Lennox-Gastaut syndrome in children 4

years and older and adults. Rufinamide has activity in the maximal electroshock

model and the pentylenetetrazol test, although the ED 50 (median effective dose)

is an order of magnitude higher in the pentylenetetrazol test, and in a wide

range of other animal models, including seizures induced by GABA-A receptor

antagonists, and models of neocortical epilepsy. Based on in vitro studies, the

principal mechanism of action of rufinamide is considered to be the modulation

of the activity of sodium channels and, in particular, prolongation of the

inactive state of the sodium channel. Rufinamide has a low degree of protein

binding (34%), and its half-life is approximately 6–10 h, which has led to its

recommended twice-daily administration. The most commonly observed adverse

experiences seen in association with rufinamide and at a higher frequency than

in placebo-treated patients are headache, dizziness, fatigue, somnolence and

nausea. This study reports on 2 cases where the off-label use of rufinamide led

to marked clinical improvements in patients with complicated psychiatric

histories.

The first patient was a woman with bipolar disorder and multiple psychiatric

comorbidities (panic disorder, obsessive-compulsive disorder, eating disorder),

who had been extraordinarily refractory to treatment and had failed countless

pharmacological and nonpharmacological treatment attempts, including ECT. In the

context of progressive worsening of her condition, rufinamide 400 mg 1 tablet

twice daily was added to her complicated pharmacological regimen, leading to a

marked clinical improvement. The patient reported a marked improvement in

depressive and obsessive symptoms, a reduction in anxiety and panic attacks, and

a significant mood stabilization and reduction in mood swings. The dose was

subsequently adjusted to 800 mg twice daily and the patient's improvement

persisted over the following 2 months.

The second patient was another woman with bipolar disorder and multiple

psychiatric and medical comorbidities (panic disorder, alcohol abuse, chronic

pain) who also had been extraordinarily refractory to treatment and had failed

countless pharmacological and nonpharmacological treatment attempts. In the

context of an acute worsening of her condition, rufinamide 400 mg 1 tablet twice

daily was added to her pharmacological regimen, leading to a very rapid (within

days) clinical improvement. The patient reported a marked improvement in

depressive and anxiety symptoms, significant mood stabilization and reduction in

mood swings, and a reduction in craving for alcohol and binge eating.

These 2 cases are highly suggestive of potent therapeutic effects of rufinamide

and its metabolites with respect to bipolar disorder, depressive and anxiety

disorders, panic disorder and obsessive-compulsive disorder, eating disorders,

and substance use disorders. Since these are just anecdotal reports of off-label

uses of rufinamide in highly refractory cases, the Authors cannot rule out the

possibility that these marked clinical changes were due to nonspecific effects

or to the concomitant treatments, which seemed ineffective prior to rufinamide

treatment initiation. On the other hand, these observations may merit further

investigation of the potential therapeutic benefits of this antiepileptic drug.

Full bibliographic information

Fava, M. The Possible Antianxiety and Mood-Stabilizing Effects of Rufinamide.

Psychother Psychosom 2010;79:194-195.