Relevance of pharmacogenetic analyses and therapeutic drug monitoring of antidepressants for an individualized treatment of peripartum psychopathology.

OBJECTIVE: Psychiatric disorders burden the peripartum period, often requiring psychopharmacological treatment, including antidepressants. Efficacy and tolerability of antidepressants are influenced by the physiological changes of the peripartum and individual metabolic profiles, which in turn can be modified by pregnancy. The objective of this study is to assess the relationship between antidepressants' pharmacokinetic profiles during pregnancy and individual metabolic profiles, along with the efficacy of the treatment. METHODS: In total 87 outpatients with diagnoses of bipolar disorder, major depression, anxiety, obsessive-compulsive disorder and post-traumatic stress disorder who required antidepressant treatment during pregnancy were recruited. Genotyping analysis of hepatic cytochrome P450 (CYPs) individual isoforms was performed. Antidepressants' blood concentrations and psychometric assessments were collected at five time points. Antidepressants' cord blood concentrations were assessed at birth. RESULTS: Sertraline showed greater stability in plasma concentrations and a lower placental penetrance index. Most of the antidepressants' concentrations below the therapeutic range were found in women with an extensive/ultrarapid metabolic profile. Antidepressants mainly metabolized by CYP2C19 were less frequently below the therapeutic range compared with antidepressants metabolized by CYP2D6. CONCLUSIONS: Pregnancy modulates cytochrome activity and drugs' pharmacokinetics. Genotyping analysis of CYPs isoforms and therapeutic drug monitoring might be used to guide clinicians in a well-tolerated treatment of psychiatric symptoms in pregnant women.

Effectiveness, tolerability, and dropout rates of vortioxetine in comorbid depression: A naturalistic study.

OBJECTIVE: Vortioxetine is a novel antidepressant whose safety, tolerability, and therapeutic action have been supported by several studies. The present naturalistic study aimed to characterize its effectiveness, tolerability, and dropout rate in the real world. METHODS: Total sample consisted of 66 outpatients with major depressive episode, treated with vortioxetine, whose clinical variables were evaluated over three time points. RESULTS: Most common primary diagnoses were major depressive disorder (45.5%) and bipolar disorder (33.4%), with an overall comorbidity rate of 48.5% and concomitant medications in the 89.4%. The mean vortioxetine daily dosage was 12.90 ± 5.65 mg. Effectiveness of vortioxetine through a significant improvement on specific psychometric scales emerged, while only a nonsignificant trend of association between higher dosage and effectiveness was found. In the total sample, 51.5% were classified as responders and 36.4% as remitters. Two-thirds of subjects did not report side effects, while in the remaining patients, gastrointestinal ones were the most frequent (72.7%). Almost two-thirds of the sample could complete the follow-up, while 36.4% dropped out; the main reasons for dropout were side effects (37.5%) and lack of efficacy (29.2%). CONCLUSIONS: Larger sample studies are warranted to better characterize vortioxetine effectiveness and tolerability in the real world.

Duration of untreated illness and depression severity are associated with cognitive impairment in mood disorders.

Introduction: In this study we estimated the rate and the trajectory of cognitive impairment in a naturalistic sample of outpatients with major depressive disorder (MDD) and bipolar disorder (BD) and its correlation with different variables.Materials and methods: An overall sample of 109 outpatients with MDD or BD was assessed for multiple clinical variables, including duration of untreated illness (DUI), and tested using the Montreal Cognitive Assessment (MoCA) during Major Depressive Episodes (MDE) and after remission. Correlations between MoCA scores and the clinical variables were then computed.Results: About 50% of patients with MDD and BD showed mild cognitive impairment during MDE. Improvement of cognitive function between depression and remission was significant, even though residual symptoms were observed especially in the most impaired patients. Of note, cognitive performance during depression was negatively associated with depression severity and DUI.Discussion: Present findings confirm available evidence about patterns of cognitive impairment in mood disorders, in terms of prevalence and persistence beyond remission in most severe cases. Moreover, a longer DUI was associated with worse cognitive performance during depression, and consequently with poorer outcome, underlining the importance of prompt treatment of these disorders also in light of a cognitive perspective.KeypointsAlthough distinct entities, unipolar and bipolar depression determine similar patterns of cognitive impairment in terms of severity and types of altered domains.Depression (but not anxiety) severity is associated with cognitive performance in depression.Prolonged duration of untreated illness is associated with more severe cognitive impairment during depression, particularly but not specifically in bipolar disorder.

Using network analysis to explore cognitive domains in patients with unipolar versus bipolar depression: a prospective naturalistic study.

OBJECTIVE: Despite growing evidence in the field of cognitive function in mood disorders, the neurocognitive profiles of patients with unipolar and bipolar depression still need further characterization. In this study, we applied network analysis, hypothesizing this approach could highlight differences between major depressive disorder (MDD) and bipolar disorder (BD) from a cognitive perspective. METHODS: The cognitive performance of 109 patients (72 unipolar and 37 bipolar depressed outpatients) was assessed through the Montreal Cognitive Assessment (MoCA), and a series of clinical variables were collected. Differences in cognitive performance between MDD and BD patients were tested using non-parametric tests. Moreover, a network graph representing MoCA domains as nodes and Spearman's rho correlation coefficients between the domains as edges was constructed for each group. RESULTS: The presence of mild cognitive impairment was observed in both MDD and BD patients during depression. No statistical significant difference was found between the two groups in terms of overall cognitive performance and across single domains. Nonetheless, network analytic metrics demonstrated different roles of memory and executive dysfunction in MDD versus BD patients: in particular, MDD network was more densely interconnected than BD network, and memory was the node with the highest betweenness and closeness centrality in MDD, while executive function was more central in BD. CONCLUSIONS: From a network analytic perspective, memory impairment displays a central role in the cognitive impairment of patients with unipolar depression, whereas executive dysfunction appears to be more central in bipolar depression. Further research is warranted to confirm our results.

Slow vs standard up-titration of paroxetine in the treatment of panic disorder: a prospective randomized trial.

AIM: Patients with panic disorder (PD) might be sensitive to the stimulating effects of selective serotonin reuptake inhibitors (SSRI), thus requiring low dosages at treatment initiation. The aim of the present study was to assess eventual differences in terms of effectiveness and tolerability between a slow up-titration with paroxetine and a standard one. METHODS: In an open randomized, multicenter, primary-care study, 60 patients (44 women and 16 men) with PD with or without agoraphobia were enrolled and randomized to receive a slow up-titration with paroxetine (increments of 2.5 mg/day every 2 days) or a standard one (increments of 10 mg/day every week) up to a maximum daily dose of 20 mg. Repeated-measures anova on sub-items scores of the Panic Attack Anticipatory Anxiety Scale (PAAS) and Dosage Record and Treatment Emergent Symptom Scale (DOTES), respectively, used as outcome measures of effectiveness and tolerability, were performed. Significance level was set at 0.05 and it was not corrected. RESULTS: anova showed no differences between the two treatments in terms of effectiveness and tolerability. Post hoc analysis found only one significant difference in the intensity of spontaneous panic attacks (Panic and Anticipatory Anxiety Scale) in the first 9 days of treatment between the two treatment groups, which was that this item was less intense in the slow-titration group (treatment effect: F = 4.89, P = 0.03, effect size = 0.1). CONCLUSION: Present findings suggest only a small superiority for a slow up-titration regimen of paroxetine compared to a standard one in the first 9 days of treatment but no differences at end-point.