One of the challenges with initiating long-acting injectable (LAI) antipsychotic regimens is achieving relevant drug levels quickly. After first injection of the LAI antipsychotic aripiprazole lauroxil (AL), the lag to reaching relevant plasma aripiprazole levels was initially addressed using supplemental oral aripiprazole for 21 days. A 1-day AL initiation regimen using a NanoCrystal® Dispersion formulation of AL (ALNCD; Aristada Initio®) combined with a single 30 mg dose of oral aripiprazole has been developed as an alternative approach. We compared the 1-day AL initiation regimen (ALNCD + 30 mg oral aripiprazole for 1 day) with the 21-day AL initiation regimen (AL + 15 mg/day of oral aripiprazole for 21 days) using kinetic modeling. Observed and modeled data demonstrate that the 1-day AL initiation regimen provides continuous aripiprazole exposure comparable to the 21-day AL initiation regimen. Each component of the 1-day AL initiation regimen (30 mg oral aripiprazole, ALNCD, and AL) contributes to aripiprazole plasma levels at different times, with oral aripiprazole predominating in the first week, then ALNCD and AL over time. In a double-blind, placebo-controlled, phase 1 study in patients with schizophrenia, the 1-day initiation regimen resulted in rapid achievement of relevant plasma aripiprazole levels comparable to those from the 21-day initiation regimen. Safety and tolerability of the 1-day regimen were consistent with the known profile of aripiprazole. Each part of the 1-day initiation regimen, together with AL, is necessary for continuous aripiprazole exposure from treatment initiation until the next regularly scheduled AL injection is administered.

Part II of this paper contains some general considerations on tricyclic antidepressant (TCA) monitoring. Long-term assessment of TCA plasma levels is advised by the few existent studies, although each of these focusses on different aspects. Cardiovascular and central nervous system toxicity is reviewed as well as pharmacokinetics and the importance of protein binding. Some consideration is also given to their use in elderly patients. The authors conclude that although available data support its usefulness in many situations, routine measurement of TCA levels is not warranted.

Une étude contrôlée comparative de la viloxazine et de la clomipramine injectables, par la méthode du cotateur aveugle avec temps aveugle, a été conduite chez 30 sujets des 2 sexes hospitalisés dans un service spécialisé lors de la survenue d’un épisode dépressif majeur. Une répartition homogène de la population recrutée pour cet essai a été obtenue en recourant à la méthode d’homogénéisation décrite par Taves. La comparabilité des 2 groupes ainsi recrutés à partir des variables définies préalablement à cet essai s’est révélée satisfaisante. Deux sujets n’ont pas terminé l’essai, un dans chaque groupe de traitement. Les résultats globaux mettent en évidence une efficacité antidépressive non significativement différente entre les 2 groupes à 21 jours de traitement dont 7 jours de perfusion à la posologie de 300 mg de viloxazine ou 75 mg de clomipramine suivis d’un relais à 600 mg de viloxazine ou de 150 mg de clomipramine. Une analyse en composante principale des instruments d’évaluation semble indiquer une polarité d’action plus marquée de la clomipramine sur l’humeur, tandis que la viloxazine voit ses effets plus marqués sur le ralentissement. Le suivi des concentrations plasmatiques de viloxazine réalisé dans le cadre de cet essai a confirmé les principales caractéristiques pharmacocinétiques de la viloxazine et mis en évidence l’absence de modification des concentrations après le passage de la forme IV à la forme comprimés. Elle n’a pas, enfin, mis en évidence de corrélation entre les taux plasmatiques et la réponse thérapeutique.

Part I of this paper presents a comprehensive review of plasma level monitoring of tricyclic antidepressants (TCAs) and their relationship to clinical response to antidepressant therapy. Imipramine, nortriptyline, amitriptyline, clomipramine and desipramine are the most widely studied TCAs in this regard. Typical therapeutic plasma concentration ranges are suggested for some of these agents, although a consensus is lacking.

Benzodiazepines are assumed to cause drowsiness and sedation. Rating scales such as the Massachusetts General Hospital Sedation Scale and the Morning Evaluation of Drug Induced Sedation Scale allow testing of this hypothesis and assessment of the effects of benzodiazepines. We performed a five-week study of prazepam in 63 anxious outpatients. Plasma levels of desmethyldiazepam were assessed weekly. Placebo was given the first week, followed by active drug for three weeks, and placebo the final week. One group received prazepam 30 mg/h, the other received prazepam 10 mg three times per day. Drowsiness-sedation and anxiolytic efficacy were assessed at baseline and weekly. Plasma desmethyldiazepam levels were similar in both treatment groups. Efficacy was profound in both groups. Drowsiness-sedation measured high at baseline and decreased significantly (P=0.05) over the 3 weeks when active drug was administered. Sedation decreased by as much as 40%. Sleep was improved with prazepam, and this may have resulted in decreased drowsiness. We conclude that anxious outpatients have significant levels of drowsiness-sedation and that treatment with benzodiazepines reduces the occurrence of this symptom.