Psychosis with use of amphetamine drugs, methylphenidate and atomoxetine in adolescent and adults.

BACKGROUND: Use of psychostimulants and relative drugs has increased worldwide in treatment of attention-deficit hyperactivity disorder (ADHD) in adolescents and adults. Recent studies suggest a potential association between use of psychostimulants and psychotic symptoms. The risk may not be the same between different psychostimulants. OBJECTIVE: To assess whether amphetamine or atomoxetine use is associated with a higher risk of reporting symptoms of psychosis than methylphenidate use in adolescents and adults, particularly in patients with ADHD. METHODS: Using VigiBase, the WHO's pharmacovigilance database, disproportionality of psychotic symptoms reporting was assessed among adverse drug reactions related to methylphenidate, atomoxetine and amphetamines, from January 2004 to December 2018, in patients aged 13-25 years. The association between psychotic symptoms and psychostimulants was estimated through the calculation of reporting OR (ROR). FINDINGS: Among 13 863 reports with at least one drug of interest, we found 221 cases of psychosis with methylphenidate use, 115 with atomoxetine use and 169 with a prescription of an amphetamine drug. Compared with methylphenidate use, amphetamine use was associated with an increased risk of reporting psychotic symptoms (ROR 1.61 (95% CI 1.26 to 2.06)]. When we restricted the analysis to ADHD indication, we found a close estimate (ROR 1.94 (95% CI 1.43 to 2.64)). No association was found for atomoxetine. CONCLUSION: Our study suggests that amphetamine use is associated with a higher reporting of psychotic symptoms, compared with methylphenidate use. CLINICAL IMPLICATIONS: The prescription of psychostimulants should consider this potential adverse effect when assessing the benefit-risk balance.

Comparative effects of 15 antidepressants on the risk of withdrawal syndrome: A real-world study using the WHO pharmacovigilance database.

BACKGROUND: While case reports and clinical trials reported withdrawal syndrome after reduction and/or discontinuation of antidepressant drugs, no large study has been conducted to compare the risk between the different antidepressants. METHODS: Using data recorded from January 1st, 1988, and December 31st, 2020 in VigiBase®, the World Health Organization's Global Individual Case Safety Reports database, we performed disproportionality analysis to investigate the risk of reporting withdrawal syndrome in patients treated by short half-life antidepressants compared with patients treated by long half-life antidepressants. In addition, we aimed to better inform clinical practice by comparing 15 antidepressants for the risk of reporting withdrawal syndrome. RESULTS: Among the 338,498 reports with antidepressants of interest, we found 15,507 cases of withdrawal syndrome. Short half-lives antidepressants were associated with an increased risk of reporting a withdrawal syndrome compared to long half-life antidepressants (ROR 5.38; 95% CI 5.16-5.61). The risk was higher for 18-44 years old (ROR 6.88; 95% CI 6.17-7.62), women (ROR 1.38; 95% CI 1.33-1.43) and patients treated with Paroxetine, Desvenlafaxine, Venlafaxine and Duloxetine. LIMITATIONS: The limitations of this study stem from the case-reporting process. CONCLUSIONS: This large observational study in a real-world setting suggests that the use of short half-life antidepressants increases the risk of reporting withdrawal syndrome compared to long half-life antidepressants. Among the most common antidepressants, paroxetine and serotonin-noradrenaline reuptake inhibitors are associated with a greater risk of reporting withdrawal syndrome, while agomelatine and vortioxetine present a lower risk. Additional studies are needed to corroborate our results.

Lacosamide-induced personality changes: An unexpected adverse effect.

OBJECTIVES: To describe an 'unexpected' case of abrupt personality following the introduction of lacosamide. METHODS: A description of an 82-year-old male receiving neurological follow-up since 2010 due to epilepsy secondary to haemorrhagic stroke. We report a case of abrupt personality change in an 82-year-old male following the introduction of lacosamide with a return to the previous state after its discontinuation. We explored possible mechanisms and pharmacokinetic concerns explaining this personality change. RESULTS: In fact, a few days after introducing lacosamide, the patient was described as 'gentle', 'calm' and apologetic for his past aggressions against his family and caregivers which was in complete contrast to his usual personality. There was also marked insistence and the use of sexualised language towards women in his close circle, especially his home nurses. In view of his insistent behaviour towards his nurses and unusual sexualised language, lacosamide was withdrawn. A few days later, the patient displayed his usual, vindictive, aggressive and forceful character. He no longer made any sexualised remarks to his home nurses. CONCLUSION: To our knowledge, this is the first case of a sudden behavioural and personality change reported by family, friends and carers following the introduction of lacosamide.

ß-adrenoceptor antagonists and nightmares: A pharmacoepidemiological-pharmacodynamic study.

AIM: To compare different ß-adrenoceptor antagonists for the risk of reporting nightmare. METHODS: The study involved two approaches: first, we investigated in VigiBase®, the World Health Organization Individual Case Safety Report (ICSR) database, the disproportionality between exposure to each ß-adrenoceptor antagonists and reports of nightmares between 1967 and 2019. Second, in a pharmacoepidemiological-pharmacodynamic analysis, we assessed whether use of ß-adrenoceptor antagonists with moderate and high lipid solubility or strong 5-HT1A affinity were associated with an increased risk of reporting nightmares. We conducted multivariate logistic regression to estimate reporting odds ratios (RORs) of nightmares compared to all other adverse drug reactions. RESULTS: Of the 126,964 reports recorded with ß-adrenoceptor antagonists, 1138 (0.9%) were nightmares. The highest risk of reporting a nightmare was found with exposure of pindolol (adjusted ROR 2.82, 95%CI, 2.19-3.61), metoprolol (1.89, 1.66-2.16), and alprenolol (1.77, 1.06-2.97). Compared to use of low lipid solubility ß-adrenoceptor antagonists, use of moderate or high lipid solubility ß-adrenoceptor antagonists were significantly more associated with nightmare reports (aROR moderate vs. low 1.72, 95%CI 1.47-2.00 and aROR high vs. low 1.84, 95%CI 1.53-2.22). Use of moderate or high 5-HT1A affinity of ß-adrenoceptor antagonists was associated with an increased ROR of nightmares compared with low 5-HT1A affinity of ß-adrenoceptor antagonists (aROR moderate vs. low 1.22, 95%CI 1.04-1.43 and aROR high vs. low 2.46, 95%CI 1.93-3.13). CONCLUSION: In our large pharmacovigilance study, nightmares are more frequently reported for pindolol and metoprolol, and among ß-adrenoceptor antagonists with high lipid solubility and high 5-HT1A receptor affinity.