P HARMACOVIGILANCE Thérapie 2007 Juillet-Août; 62 (4): 357–359 DOI: 10.2515/therapie:2007057 c  2007 Société Française de Pharmacologie et de Thérapeutique Neuro-psychiatric Disorders Induced by Amiodarone High Levels (Cordarone  ) Troubles neuro-psychiatriques induits par des concentrations élevées d’amiodarone (Cordarone  ) Issam Salouage, Anis Klouz, Sameh Trabelsi, Ahmed Zaïem, Emma Gaïes, Mohamed Hédi Loueslati, Mohamed Lakhal and Chalbi Belkahia Centre National de Pharmacovigilance, Tunis, Tunisie Texte reçu le 08 février 2007 ; accepté le 20 juillet 2007 Cas notifié le 18 août 2003 au Centre National de Pharmacovigi- lance de Tunis, Tunisie Keywords: amiodarone; pharmacovigilance; neurotoxicity; psychiatric disorders Mots clés : amiodarone ; pharmacovigilance ; neurotoxicité ; troubles psychiatriques 1. Introduction Amiodarone, a potent antiarrhythmic agent (class III antiar- rhythmic), is highly effective in the treatment of ventricular and supraventricular arrhythmia. [1] The amiodarone adverse reactions are well documented. The most commonly reported are corneal microdepositis, hypothy- roidism, hyperthyroidism, cutaneous photosensitivity and pul- monary toxicity (including pulmonary fibrosis and interstitial pneumonitis). [1,2] Amiodarone is also known to be responsible for frequent neurologic side effects. The most common neurotoxic finding in- cludes tremor, ataxia and peripheral neuropathy, [3] psychiatric dis- turbances have been rarely associated with amiodarone–induced delirium and one case of depression associated with this drug have been reported in the literature. [4,5,6,7] We report a first case of association of neurologic and psychi- atric disorders with amiodarone (Cordarone  ), according to the French method of imputability described by Begaud et al. [8] 2. Case report A 71 year-old woman has no previous psychiatric, neuro- logical, or substance abuse history, she was hypertensive since 20 years treated with 100 mg/day of metoprolol (Lopressor  ). On June 12, 2003 (= day 1), she developed atrial fibrillation, she was treated with amiodarone 400 mg/day, acenocoumarol (Sintrom  ) 1 mg/day, and metoprolol was discontinued (figure 1). On day 5, she had dyspnea and no improvement of atrial fibrillation, that’s why she received amiodarone 800 mg/day by parenteral route during three days. Eight days later, she developed tremor of the limb extremity associated with asthenia. The first episode of agi- tation, anguish and obnubilation happened on day 26, so she was treated by fluoxetine (Prozac  ) 20 mg/day, without disappearance of these neuro-psychiatric disorders. In front of the aggravation of clinical symptomatology (auditive hallucinations, nightmares, anguish and insomnia) fluoxetine was discontinued on day 41 and changed by sertraline (Zoloft  ) 50 mg/day which was discontin- ued on day 52. Electro encephalogram and cerebral tomodensito- metry were normal. In front of the persistance of neuro-psychiatric disorders, amiodarone was suspected and withdrawn on day 61. Seven days later (August 18, 2003), the patient was addressed to the Tunisian National Centre of Pharmacovigilance, and the monitoring of the amiodarone plasmatic level (APL) found was 2.46 μg/mL. Disappearance of nightmares and hallucinations, and a decrease of the trembling intensity were noticed on day 76, with APL = 0.96 μg/mL. On day 90, our patient had only a minor tremor and APL = 0.77 μg/mL. She was asymptomatic on day 100, and the APL = 0.63 μg/mL (figure 2). Two years later, the patient remained asymptomatic. The at- tributed intrinsic score for amiodarone responsibility was I3, with a chronologic score of C2 and a semiologic score of S3. Although some neurological side effects have already been described, so a bibliographic score of B1 was attributed. 3. Discussion Responsibility of the amiodarone in the genesis of the neuro- psychiatric disorders was retained according to a compatible chronology (13 days) with an iatrogenic origin, a favourable course after amiodarone withdrawal (39 days) that was sustained by the decrease of the amiodarone plasmatic levels, a nega- tive etiologic investigation and the no recurrence two years after amiodarone withdrawal. Our patient had developed a tremor associated to psychi- atric disorders (agitation, anguish, auditive hallucination, night- mare and insomnia). Rare cases of psychiatric disturbance (delir- ium, depression) due to amiodarone have been reported. [4−7] It is known that amiodarone can cause serious neurologic toxicity. [1,3] Article published by EDP Sciences and available at http://www.journal-therapie.org or http://dx.doi.org/10.2515/therapie:2007057