Aripiprazole

Schizophrenia is a chronic mental illness, with a prevalence of about 1%. The symptoms are classified in three categories: positive symptoms, negative symptoms and deficits in cognitive function. Regarding the pharmacological treatment, current antipsychotics mainly improve positive symptoms while negative and cognitive symptoms remain inadequately treated. Among them, aripiprazole, through its pharmacological properties results in regulation of positive symptoms and, to a lesser extent, to negative and cognitive ones. Drug treatment studies in animals typically employ administration methods such as injection or gavage, which is time-consuming over long periods, does not reflect route of administration used in patients, and cause substantial stress in animals. We assessed herein the pharmacokinetic properties and behavioural effects of aripiprazole after chronic administration via drinking solution in C57Bl/6 mice. Results show that subchronic administration of 1 and 10 mg/kg doses of aripiprazole via drinking solution present significant blood concentrations, without any significant effect on the spontaneous activity of mice (between 10 a.m. and 3 p.m.). Furthermore, we described for the first time to our knowledge the main pharmacokinetic parameters of aripiprazole after gavage acute administration (10 mg/kg). Collectively, all of these data will be very useful in future projects including chronic administrations (several months) of this antipsychotic.

Intranasal esketamine, approved with oral antidepressants for adults with treatment-resistant depression (TRD), is the S-enantiomer of ketamine and has higher potency and affinity for N-Methyl-d-Aspartate receptors. Administered intranasally, it offers rapid absorption and onset, essential for severe depressive symptoms or suicidal impulses. Comparative studies on esketamine and ketamine's urological safety profiles show esketamine has lower or comparable risks of renal and urinary disorders. Ketamine, however, has documented cases of nephrotoxicity and severe urological issues in recreational users. The study aims to further evaluate and compare these profiles against other antidepressants and antipsychotics using the Food and Drug Administration (FDA) Adverse Events Reporting System (FAERS) data. ADR cases were reported to the FDA up to May 12, 2024, being drugs listed including esketamine, ketamine, quetiapine, aripiprazole, olanzapine, risperidone, citalopram, escitalopram, paroxetine, fluoxetine, sertraline, duloxetine, venlafaxine, amitriptyline, and clomipramine. Risperidone showed the highest ADRs (107,418) and serious cases (71,515), with significant renal and urinary disorders reported, including acute kidney injury and urinary incontinence. Olanzapine, quetiapine, and aripiprazole also had high serious ADRs. Venlafaxine and fluoxetine were notable among antidepressants for acute kidney injury. Esketamine and ketamine were associated with lower urinary tract symptoms and nephrolithiasis. Disproportionality analysis revealed ketamine had higher odds of renal and urinary disorders compared to other drug classes, while esketamine had lower or comparable odds. The data suggest a relatively favorable tolerability profile for these drugs, especially esketamine. However, the results highlight the necessity for more extensive studies to evaluate long-term safety and optimize treatment protocols.