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      1Scopus© Citations 3
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    Dysconnectivity in Schizophrenia Revisited: Abnormal Temporal Organization of Dynamic Functional Connectivity in Patients With a First Episode of Psychosis
    (2022)
    Juan P Ramirez-Mahaluf
    ;
    Ángeles Tepper
    ;
    Luz Maria Alliende
    ;
    Carlos Mena
    ;
    Carmen Paz Castañeda
    <jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background and Hypothesis</jats:title> <jats:p>Abnormal functional connectivity between brain regions is a consistent finding in schizophrenia, including functional magnetic resonance imaging (fMRI) studies. Recent studies have highlighted that connectivity changes in time in healthy subjects. We here examined the temporal changes in functional connectivity in patients with a first episode of psychosis (FEP). Specifically, we analyzed the temporal order in which whole-brain organization states were visited.</jats:p> </jats:sec> <jats:sec> <jats:title>Study Design</jats:title> <jats:p>Two case-control studies, including in each sample a subgroup scanned a second time after treatment. Chilean sample included 79 patients with a FEP and 83 healthy controls. Mexican sample included 21 antipsychotic-naïve FEP patients and 15 healthy controls. Characteristics of the temporal trajectories between whole-brain functional connectivity meta-states were examined via resting-state functional MRI using elements of network science. We compared the cohorts of cases and controls and explored their differences as well as potential associations with symptoms, cognition, and antipsychotic medication doses.</jats:p> </jats:sec> <jats:sec> <jats:title>Study Results</jats:title> <jats:p>We found that the temporal sequence in which patients’ brain dynamics visited the different states was more redundant and segregated. Patients were less flexible than controls in changing their network in time from different configurations, and explored the whole landscape of possible states in a less efficient way. These changes were related to the dose of antipsychotics the patients were receiving. We replicated the relationship with antipsychotic medication in the antipsychotic-naïve FEP sample scanned before and after treatment.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>We conclude that psychosis is related to a temporal disorganization of the brain’s dynamic functional connectivity, and this is associated with antipsychotic medication use.</jats:p> </jats:sec>
      1Scopus© Citations 18
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    Efficacy and Tolerability of Combination Treatments for Major Depression: Antidepressants plus Second-Generation Antipsychotics vs. Esketamine vs. Lithium
    (2021)
    Gustavo H. Vázquez
    ;
    Anees Bahji
    ;
    UNDURRAGA FOURCADE, JUAN PABLO  
    ;
    Leonardo Tondo
    ;
    Ross J. Baldessarini
    <jats:sec><jats:title>Background:</jats:title><jats:p> Successful treatment of major depressive disorder (MDD) can be challenging, and failures ("treatment-resistant depression" [TRD]) are frequent. Steps to address TRD include increasing antidepressant dose, combining antidepressants, adding adjunctive agents, or using nonpharmacological treatments. Their relative efficacy and tolerability remain inadequately tested. In particular, the value and safety of increasingly employed second-generation antipsychotics (SGAs) and new esketamine, compared to lithium as antidepressant adjuncts remain unclear. </jats:p></jats:sec><jats:sec><jats:title>Methods:</jats:title><jats:p> We reviewed randomized, placebo-controlled trials and used random-effects meta-analysis to compare odds ratio (OR) versus placebo, as well as numbers-needed-to-treat (NNT) and to-harm (NNH), for adding SGAs, esketamine, or lithium to antidepressants for major depressive episodes. </jats:p></jats:sec><jats:sec><jats:title>Results:</jats:title><jats:p> Analyses involved 49 drug-placebo pairs. By NNT, SGAs were more effective than placebo (NNT = 11 [CI: 9–15]); esketamine (7 [5–10]) and lithium (5 [4–10]) were even more effective. Individually, aripiprazole, olanzapine+fluoxetine, risperidone, and ziprasidone all were more effective (all NNT &lt; 10) than quetiapine (NNT = 13), brexpiprazole (16), or cariprazine (16), with overlapping NNT CIs. Risk of adverse effects, as NNH for most-frequently reported effects, among SGAs versus placebo was 5 [4–6] overall, and highest with quetiapine (NNH = 3), lowest with brexpiprazole (19), 5 (4–6) for esketamine, and 9 (5–106) with lithium. The risk/benefit ratio (NNH/NNT) was 1.80 (1.25–10.60) for lithium and much less favorable for esketamine (0.71 [0.60–0.80]) or SGAs (0.45 [0.17–0.77]). </jats:p></jats:sec><jats:sec><jats:title>Conclusions:</jats:title><jats:p> Several modern antipsychotics and esketamine appeared to be useful adjuncts to antidepressants for acute major depressive episodes, but lithium was somewhat more effective and better tolerated. </jats:p></jats:sec><jats:sec><jats:title>Limitations:</jats:title><jats:p> Most trials of adding lithium involved older, mainly tricyclic, antidepressants, and the dosing of adjunctive treatments were not optimized. </jats:p></jats:sec>
      30Scopus© Citations 66