Population pharmacokinetic modeling of sustained release lithium in the serum, erythrocytes and urine of patients with bipolar disorder.

PURPOSE: Lithium (Li), the first-line treatment of bipolar disorder, was first developed as an immediate-release form with a routine therapeutic drug monitoring 12 h after the last dose. In Europe, the most commonly prescribed form is a sustained release (srLi). Yet no pharmacokinetics (PK) study has been published of srLi, administered once a day, in adults. The present study describes srLi PK in the serum and erythrocytes of bipolar patients. METHODS: To assess srLi PK, we studied prospectively 17 French bipolar patients on a median dose of 1000 mg (600-1600) for at least 2 years. Serum (S), erythrocyte (E) concentrations, and urinary (U) amount were collected over 8 h after 15 days of morning intake using monitoring electronic medical system (MEMs). Population PK parameters were estimated using the SAEM algorithm (MONOLIX 4.3.3 software). RESULTS: Using a population approach, we built a PK population model of srLi including one S compartment (VS = 23.0 L, ClS = 1.21 L h-1), one E compartment (VE = 64.7 L, ClSE = 3.63 L h-1, ClES = 9.46 L h-1), and one U compartment (F = 0.62) and estimate the ratio of concentrations to Li in E over S at 0.38 with 27% between-subject variability. CONCLUSION: This is a PK model of srLi once a day in bipolar patients using a population approach simultaneously describing Li concentrations in serum, erythrocytes, and urine which provide an estimate of the ratio of concentration in erythrocyte over serum and its between-subject variability (BSV).

Modeling the Longitudinal Effects of Insight on Depression, Quality of Life and Suicidality in Schizophrenia Spectrum Disorders: Results from the FACE-SZ Cohort.

BACKGROUND: Up to half of the patients with schizophrenia attempt suicide during their lifetime. Better insight is associated with better functioning but also with increased suicidality. The direction of the relationship between insight and suicidality is not clear, hence we aimed to provide new elements using structural equation modeling. METHODS: Insight, quality of life (QoL), depression, and suicidality were measured at baseline and at 12 months in individuals with schizophrenia spectrum disorders. The relationships between these variables were investigated by latent difference score models, controlling for chlorpromazine doses, positive and negative symptoms, and general psychopathology. RESULTS: 738 patients were included, and 370 completed the study. Baseline levels of insight predicted changes in suicidality, whereas baseline levels of suicidality did not predict changes in insight, suggesting that better insight underlies suicidality and predicts its worsening. Our results suggest this temporal sequence: better insight → worse QoL → increased depression → increased suicidality, while insight also affects the three variables in parallel. CONCLUSION: Better insight predicts a worsening of QoL, depression and suicidality. These findings contribute to our global understanding of the longitudinal influence of insight on suicidality. We advocate that insight-targeted interventions should not be proposed without the monitoring of depression and suicide prevention.

Anxiety disorders are associated with early onset of heroin use and rapid transition to dependence in methadone maintained patients.

Early onset of heroin use is a severity marker of heroin use disorder. We studied the interaction between early onset and rapid transition to heroin dependence recorded with retrospective interviews in 213 patients with severe heroin dependence and history of methadone maintenance treatment. General linear models were used to identify independent factors associated with early onset, factors associated with rapid transition to dependence, and a multivariate model was used to study the interaction of those two dimensions. Lifetime history of anxiety disorders and age at onset of cannabis use are shared common risk factors and are associated with the interaction.

Childhood trauma are not associated with the intensity of transient cocaine induced psychotic symptoms.

A personal history of childhood trauma has been associated with the severity of psychotic symptoms in several disorders. We evaluated retrospectively cocaine-induced psychotic symptoms with the SAPS-CIP and childhood trauma with the CTQ in a clinical sample of 144 cocaine users. The SAPS-CIP score was not statistically associated with the presence or number or intensity of trauma, but was associated with rapid routes of administration (intravenous and smoked) and with frequent cocaine use.