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Author: search.filters.author.Leonardo TondoSubject: search.filters.subject.antidepressant agent

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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
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    Melancholia: does this ancient concept have contemporary utility?
    (2020)
    Gabriele Sani
    ;
    Leonardo Tondo
    ;
    Juan Undurraga  
    ;
    Gustavo H. Vázquez
    ;
    Paola Salvatore
    Scopus© Citations 10  3
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    Pharmacological treatment of bipolar depression
    (2014)
    Gustavo H. Vázquez
    ;
    Leonardo Tondo
    ;
    Juan Undurraga  
    ;
    Rodolfo Zaratiegui
    ;
    Valerio Selle
    <jats:title>Summary</jats:title><jats:p>Bipolar depression remains a major challenge for psychiatric therapeutics. It is associated with disability and excess mortality, and accounts for three-quarters of the time spent in morbid states by treated patients with bipolar disorder. Major limitations of research on the treatment of depression in bipolar disorder include a paucity of short-term and lack of long-term trials, probably reflecting concern about inducing mania. In addition, polytherapy with multiple drugs appears to be widespread, but it is virtually untested for efficacy and safety. Here, we summarise the evidence concerning efficacy of treatment of bipolar depression with antidepressants, mood-stabilising anticonvulsants, lithium and second-generation antipsychotics.</jats:p><jats:sec><jats:title>LEARNING OBJECTIVES</jats:title><jats:p><jats:list list-type="number"><jats:list-item><jats:label>•</jats:label><jats:p>Gain critical appreciation of the paucity of research on the treatment of bipolar depression.</jats:p></jats:list-item><jats:list-item><jats:label>•</jats:label><jats:p>Rationally balance the benefits and risks of using antidepressants in patients with bipolar disorder.</jats:p></jats:list-item><jats:list-item><jats:label>•</jats:label><jats:p>Assess the evidence supporting a range of research-based treatment options for bipolar depression.</jats:p></jats:list-item></jats:list></jats:p></jats:sec>
    Scopus© Citations 9  1