A possible case of natalizumab-dependent suicide attempt: A brief review about drugs and suicide
A 32-year-old woman was diagnosed with relapsing-remitting MS in 2001, displaying typical MS features on magnetic resonance imaging (MRI) and in the cerebrospinal fluid (presence of oligoclonal bands) according to McDonald's criteria. Initially, she was treated with subcutaneous high-dose interferon β-1a (44 mcg) thrice a week, for one year, and amitriptyline (25 mg/day), because she complained of migraine without aura and depression (Beck Depression Inventory score: 15). She was unable to tolerate the flu-like syndrome and she switched to glatiramer acetate for further three years. In October 2008, after discontinuation of glatiramer acetate due to adverse drug events (recurrent syncope), a significant progression in lesions was observed, on MRI investigation. In July 2010, the patient was admitted to our Clinical Neurology Department and she was commenced on natalizumab immunotherapy (300 mg every fourth week). At this point, she presented with an Extended Disability Status Scale Score estimated at 5 and a Beck Depression Inventory Score estimated at 4. We decided to continue the antidepressant therapy with amitriptyline (25 mg/every day) because she had benefit both in mood disturbance and migraine attacks (assessed on two attacks every month). After the twenty-fifth natalizumab infusion, she was brought into the Emergency Department, as she had collapsed next to an empty bottle of amitriptyline. She had a Glasgow coma scale score of 7 / 15, was tachycardic and twitchy. After a rapid sequence induction and intubation, she had benefit from gastric lavage. Unfortunately the toxicological assessment of dosage of drugs was not performed.\nShe was admitted to our Neurology Department and underwent a comprehensive clinical and laboratory investigation. In particular, the MRI examination did not show a progression of brain lesions, cerebrospinal fluid study was negative for JC virus, and anti-drug antibodies against natalizumab were not detected. A progressive multifocal leukoencephalopathy diagnosis was excluded and after psychiatric evaluation, a diagnosis was made of severe depressive disorder and psychosis. Indeed, as a precautionary measure natalizumab therapy was stopped, with improvement of psychosis after two weeks. On the basis of the Naranjo probability scale, we have documented a possible association between a suicidal attempt and natalizumab treatment, and we have reported this case as adverse drug reaction. Nevertheless, the exact contribution of amitriptyline and natalizumab to the genesis of suicidal attempts remains unclarified. We thought that natalizumab had induced suicidal ideation, because the depression disturbance was well-controlled by amitriptyline for several years and psychosis appeared after the introduction of natalizumab. However, it was not possible to exclude a synergic action of both drugs in the suicidal attempt.