Efficacy and tolerability of lisdexamfetamine as an antidepressant augmentation strategy: A meta-analysis of randomized controlled trials

Giacobbe, Peter; Rakita, Uros; Lam, Raymond W.; Milev, Roumen; Kennedy, Sidney H.; McIntyre, Roger S.

doi:10.1016/j.jad.2017.09.041

Cited by 7 publications

(4 citation statements)

References 27 publications

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“…Our ANN analysis also showed a highly probable relation between proteins targeted by vLDX and depression. In this sense, current available evidence in the literature points toward a slight improvement in depressive symptoms when using LDX as antidepressant augmentation therapy (Corp et al, 2014;Madhoo et al, 2014;Giacobbe et al, 2018). In our study, vLDX was found to act upon DAT1, MAO (Popovic et al, 2009), TAAR1 (Moore et al, 2018), NET1, SERT (Guerdjikova et al, 2016), and NOS2 (Inserra et al, 2019), all of which have been linked with the characteristic impairment in neurotransmission observed in depressive patients (Sung et al, 2003;Sotnikova et al, 2009;Gaweska and Fitzpatrick, 2011;Vaughan and Foster, 2013;Moore et al, 2018;Inserra et al, 2019;Kegg Pathway Database, 2020).…”

Section: Frontiers Insupporting

confidence: 58%

In silico evaluation of the role of lisdexamfetamine on attention-deficit/hyperactivity disorder common psychiatric comorbidities: mechanistic insights on binge eating disorder and depression

Gutiérrez-Casares,

Segú-Vergés,

Sabate Chueca

et al. 2023

Front. Neurosci.

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Attention-deficit/hyperactivity disorder (ADHD) is a psychiatric condition well recognized in the pediatric population that can persist into adulthood. The vast majority of patients with ADHD present psychiatric comorbidities that have been suggested to share, to some extent, the pathophysiological mechanism of ADHD. Lisdexamfetamine (LDX) is a stimulant prodrug approved for treating ADHD and, in the US, also for binge eating disorder (BED). Herein, we evaluated, through a systems biology-based in silico method, the efficacy of a virtual model of LDX (vLDX) as ADHD treatment to improve five common ADHD psychiatric comorbidities in adults and children, and we explored the molecular mechanisms behind LDX’s predicted efficacy. After the molecular characterization of vLDX and the comorbidities (anxiety, BED, bipolar disorder, depression, and tics disorder), we created a protein-protein interaction human network to which we applied artificial neural networks (ANN) algorithms. We also generated virtual populations of adults and children-adolescents totaling 2,600 individuals and obtained the predicted protein activity from Therapeutic Performance Mapping System models. The latter showed that ADHD molecular description shared 53% of its protein effectors with at least one studied psychiatric comorbidity. According to the ANN analysis, proteins targeted by vLDX are predicted to have a high probability of being related to BED and depression. In BED, vLDX was modeled to act upon neurotransmission and neuroplasticity regulators, and, in depression, vLDX regulated the hypothalamic-pituitary-adrenal axis, neuroinflammation, oxidative stress, and glutamatergic excitotoxicity. In conclusion, our modeling results, despite their limitations and although requiring in vitro or in vivo validation, could supplement the design of preclinical and potentially clinical studies that investigate treatment for patients with ADHD with psychiatric comorbidities, especially from a molecular point of view.

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Section: Frontiers Insupporting

confidence: 58%

In silico evaluation of the role of lisdexamfetamine on attention-deficit/hyperactivity disorder common psychiatric comorbidities: mechanistic insights on binge eating disorder and depression

Gutiérrez-Casares,

Segú-Vergés,

Sabate Chueca

et al. 2023

Front. Neurosci.

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“…For instance, some evidence suggests that the stimulant lisdexamfetamine, Food and Drug Administration (FDA)-approved to treat attention deficit hyperactivity disorder, may help relieve symptoms of depression. 28 The RADIEMS cohort is a deeply phenotyped sample of persons with early MS; however, it is unknown whether the current findings would generalize to older patients with longer standing disease. Also, as noted, the observational and cross-sectional design prohibits statements of directionality or mechanism; however, the planned three-year follow-up of this cohort may improve understanding of directionality.…”

Section: Bdi-fsmentioning

confidence: 86%

Depression and cognitive function in early multiple sclerosis: Multitasking is more sensitive than traditional assessments

et al. 2020

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Background: Persons with multiple sclerosis (MS) and depression symptoms report real-world cognitive difficulties that may be missed by laboratory cognitive tests. Objective: To examine the relationship of depressive symptoms to cognitive monotasking versus multitasking in early MS. Method: Persons with early MS ( n = 185; ⩽5 years diagnosed) reported mood, completed monotasking and multitasking cognitive tests, and received high-resolution 3.0 T magnetic resonance imaging (MRI). Partial correlations analyzed associations between mood and cognition, controlling for age, sex, estimated premorbid IQ, T2 lesion volume, and normalized gray matter volume. Results: Depression symptoms were more related to worse cognitive multitasking (−0.353, p < 0.001) than monotasking ( r = −0.189, p = 0.011). There was a significant albeit weaker link to cognitive efficiency composite score ( r = −0.281, p < 0.001), but not composite memory ( r = −0.036, p > 0.50). Findings were replicated with a second depression measure. Multitasking was worse in patients with at least mild depression than both patients with no/minimal depression and healthy controls. Multitasking was not related to mood in healthy controls. Conclusions: Depression symptoms are linked to cognitive multitasking in early MS; standard monotasking cognitive assessments appear less sensitive to depression-related cognition. Further investigation should determine directionality and mechanisms of this relationship, with the goal of enhancing treatment for cognitive dysfunction and depression in MS.

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“…There is currently not convincing evidence to recommend these medications as an augmentation strategy or monotherapy for treatment of major depression (Pary et al, 2015;Giacobbe et al, 2018). However, their efficacy in depression has not been examined within the context of inflammation, and given impairment in DA release, these drugs should be a consideration.…”

Section: B Neurotransmittermentioning

confidence: 99%

Aiding and Abetting Anhedonia: Impact of Inflammation on the Brain and Pharmacological Implications

et al. 2021

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Efficacy and tolerability of lisdexamfetamine as an antidepressant augmentation strategy: A meta-analysis of randomized controlled trials

Cited by 7 publications

References 27 publications

In silico evaluation of the role of lisdexamfetamine on attention-deficit/hyperactivity disorder common psychiatric comorbidities: mechanistic insights on binge eating disorder and depression

In silico evaluation of the role of lisdexamfetamine on attention-deficit/hyperactivity disorder common psychiatric comorbidities: mechanistic insights on binge eating disorder and depression

Depression and cognitive function in early multiple sclerosis: Multitasking is more sensitive than traditional assessments

Aiding and Abetting Anhedonia: Impact of Inflammation on the Brain and Pharmacological Implications

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