Drugs related to Tourette-like syndrome: A case/non-case study in the French Pharmacovigilance database

SANTIAGO PÉREZ LLORET; MARIA VERÓNICA REY; EMMANUELLE BONDON-GUITTON; OLIVIER RASCOL; JEAN-LOUIS MONTASTRUC

Congreso; 16th International Congress of Parkinson?s Disease and Movement Disorders; 2012

Background: The occurrence of multiple motor and/or vocal tics (i.e. Tourette-like syndrome) is sometimes observed in connection with drugs such as antipsychotics, serotoninergic antidepressants or methylphenidate. Objective: To detect alert signals of drugs potentially connected with Tourette-like syndrome in the French Pharmacovigilance Database (FPDB). Methods: The FPDB contains more than 400,000 spontaneous reports of Adverse Drug Reactions (ADRs) since 1984. We selected all ADRs reports from 1st January 1984 to 31st December 2010 coded by MeDRA as ?tics? or ?Tourette syndrome?. Demographics data of the patients and ?suspected? drugs were extracted. Reporting Odds Ratios (ROR) and their 95% confidence intervals were calculated for ?suspected? drugs with more than 2 case reports. An alert signal was established when the confidence interval of the ROR excluded ?1?. Results: 36 ADR reports were found, of whom 66% were females. Median age was 14 years (range: 1 to 90 y). Eight cases (22%) were considered ?serious? as they caused disability (n=1), led to hospitalization (n=4) or were considered as such by the reporting physician (n=3). Alert signals were detected for hidden neuroleptics such as metoclopramide, oxatomide or niaprazine (ROR=11.65 [3.57-38.01]), vaccines against Influenza H1N1 Virus (2 cases; 51.06 [12.23-213.11]) or Hepatitis B virus (4 cases; 15.65 [5.53-44.28]), tramadol (3 cases; 9.64 [2.96-31.45]), methylphenidate (6 cases; 541.62 [222.25-1319.88]) or serotoninergic antidepressants such as fluoxetine, fluvoxamine, mirtazapine, venlafaxine or agomelatine (10.47 [4.07-26.94]). Other case reports included adenosine, celiprolol, cefaclor, moxifloxacine, zolmitriptan, carbamacepine, valpromide, pregabalin, theophyline or montelukast. Cases related to vaccines were younger (vaccines:9.2±4.4 vs drugs: 32.2±27, p<0.01), were more frequently considered as ?serious? (100% vs 7%, p<0.001) and their outcome was more frequently unrecovered (67% vs 3%, p<0.001). Conclusions: We found alert signals of tourette-like syndrome in connection with hidden neuroleptics, tramadol, methylphenidate or serotoninergic antidepressants. This ADR was ?unexpected? for adenosine, celiprolol or montelukast. The results with vaccines could represent a ?notoriety bias?. Cases with vaccines were younger, more frequently serious and remained unrecovered after exposition.