New drugs in psychiatry: focus on new pharmacological targets

Caraci, Filippo; Leggio, Gian Marco; Salomone, Salvatore; Drago, Filippo

doi:10.12688/f1000research.10233.1

Cited by 30 publications

(23 citation statements)

References 51 publications

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“…Recent clinical studies do not suggest a global greater efficacy of multimodal antidepressants such as vortioxetine compared with SSRIs or SNRIs, but an improved efficacy on specific clinical domains (e.g., deficits in memory and executive functioning) where SSRIs or SNRIs are less effective (Thase et al, 2016). The multimodal profile of vortioxetine described on NbN classification is consistent with the results of these clinical studies (Caraci et al, 2017b).…”

Section: The New Neuroscience-based Nomenclature and The Classifimentioning

confidence: 52%

“…This new nomenclature also shows specific advantages in incorporating the most relevant advances in drug discovery for depression (Zohar et al, 2015;Caraci et al, 2017b). For example, if a new target or an innovative mechanism of action is identified behind the classic monoaminergic hypothesis of depression [e.g., modulation of mammalian target of rapamycin (mTOR) pathway by ketamine in TRD], NbN can be expanded in a meaningful way to incorporate such new advances in drug development.…”

Section: The New Neuroscience-based Nomenclature and The Classifimentioning

confidence: 99%

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International Union of Basic and Clinical Pharmacology CIV: The Neurobiology of Treatment-resistant Depression: From Antidepressant Classifications to Novel Pharmacological Targets

et al. 2018

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Major depressive disorder is one of the most prevalent and life-threatening forms of mental illnesses and a major cause of morbidity worldwide. Currently available antidepressants are effective for most patients, although around 30% are considered treatment resistant (TRD), a condition that is associated with a significant impairment of cognitive function and poor quality of life. In this respect, the identification of the molecular mechanisms contributing to TRD represents an essential step for the design of novel and more efficacious drugs able to modify the clinical course of this disorder and increase remission rates in clinical practice. New insights into the neurobiology of TRD have shed light on the role of a number of different mechanisms, including the glutamatergic system, immune/inflammatory systems, neurotrophin function, and epigenetics. Advances in drug discovery processes in TRD have also influenced the classification of antidepressant drugs and novel classifications are available, such as the neuroscience-based nomenclature that can incorporate such advances in drug development for TRD. This review aims to provide an up-to-date description of key mechanisms in TRD and describe current therapeutic strategies for TRD before examining novel approaches that may ultimately address important neurobiological mechanisms not targeted by currently available antidepressants. All in all, we suggest that drug targeting different neurobiological systems should be able to restore normal function but must also promote resilience to reduce the long-term vulnerability to recurrent depressive episodes.

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Section: The New Neuroscience-based Nomenclature and The Classifimentioning

confidence: 52%

Section: The New Neuroscience-based Nomenclature and The Classifimentioning

confidence: 99%

International Union of Basic and Clinical Pharmacology CIV: The Neurobiology of Treatment-resistant Depression: From Antidepressant Classifications to Novel Pharmacological Targets

et al. 2018

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“…New Antidepressant Medication: Benefits Versus Adverse Effects http://dx.doi.org/10.5772/intechopen.72003 pyramidal cells) [80,94]. Positive results on cognitive function (memory and executive functioning) were also highlighted in clinical trials [92].…”

Section: Vortioxetinementioning

confidence: 99%

“…It enhances 5-HT (more than a SSRI), NE, DA, acetylcholine, and HA levels in rat brain regions associated with MDD (like the PFC and the ventral hippocampus). Furthermore, it increases glutamatergic neurotransmission, probably through inhibiting GABA interneurons [80,92,94].…”

Section: Pharmacological Propertiesmentioning

confidence: 99%

New Antidepressant Medication: Benefits Versus Adverse Effects

Bogdan¹,

Gofita²,

Călina³

et al. 2018

Pharmacokinetics and Adverse Effects of Drugs - Mechanisms and Risks Factors

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Depression [major depressive disorder (MDD)] is a mood disturbance of multifactorial origin, associated with high rates of morbidity and mortality, lack of work productivity, adverse health behaviors, and increased healthcare expenses. MDD is a leading cause of suicide, and it affects the prognosis of chronic conditions (heart diseases, diabetes, and cancer, among others). Current pharmacological treatment for MDD covers different classes of drugs, including tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), and atypical antidepressants. The aim of this chapter is to review the literature, highlight the side effects of newer antidepressants, and especially point out the most important aspects of the latest agents approved for the treatment of MDD in adults: desvenlafaxine, levomilnacipran, vilazodone, and vortioxetine. Desvenlafaxine is a SNRI and the primary active metabolite of venlafaxine; also a SNRI, levomilnacipran is an enantiomer of the racemate milnacipran. Vilazodone and vortioxetine are multimodal antidepressants, which combine SSRI activity with additional receptor activity. Although they have proven efficacy in treating MDD and are being investigated for other possible indications, further detailed clinical trials are needed to establish their pharmacotoxicological profile, following prolonged administration in patients who may suffer from various comorbidities.

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“…Appropriate consideration of pharmacodynamic and pharmacokinetic drug‐drug interactions (DDIs) can be essential to ensure safe and effective drug use . Psychotropic drug‐drug interactions (pDDIs) are of particular interest because psychopharmacologic agents mark one of the fastest growing therapeutic drug classes over the past 2 decades, and prescribing multiple psychotropic drugs has become increasingly prevalent in clinical practice …”

mentioning

confidence: 99%

Quality of Evidence Supporting Major Psychotropic Drug‐Drug Interaction Warnings: A Systematic Literature Review

et al. 2020

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Among pharmacodynamic and pharmacokinetic drug-drug interactions (DDIs), psychotropic drug-drug interactions (pDDIs) are of particular interest because psychopharmacologic agents mark one of the fastest growing therapeutic drug classes over the past 2 decades, and prescribing multiple psychotropic drugs has become increasingly prevalent in clinical practice. However, the documentation of pDDIs across drug references has lacked consistency. Thus we set out to review the primary evidence directly supporting 58 pDDIs that were uniformly reported as "major" or "contraindicated" in three prominent drug references: Clinical Pharmacology, Micromedex, and Lexicomp. We identified 134 citations from Micromedex in December 2017 and 4251 citations from Medline in March 2018 involving any of the 58 pDDIs. The included articles directly observed a clinical adverse effect or effects on drug plasma concentrations from the concomitant use of the two listed drugs in each pDDI. These articles were classified as controlled studies (e.g., randomized controlled trials, clinical trials, or observational studies) or uncontrolled studies (case reports). A total of 124 studies with 2716 patients were included in this review. Commonly evaluated adverse effects related to the studied pDDIs included decreased effectiveness, central nervous system depression, neurotoxicity, QT-interval prolongation, and serotonin syndrome. Among the 58 pDDIs, 18 (31%) were not supported by any primary studies. Among the remaining 35 pDDIs supported by studies on clinical adverse effects, only 14 (40%) included evidence from controlled study designs. Only 7 (12.1%) of the 58 pDDIs had evidence from studies with a combined sample size of more than 100 patients. This literature review highlights the poor quality of evidence supporting major or contraindicated psychotropic DDI warnings. Most DDIs lacked support from controlled studies that evaluated clinically significant adverse effects, leaving uncertainty about the clinical relevance of the warning. More postmarketing studies are needed to evaluate the safety of psychotropic combination therapy.

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New drugs in psychiatry: focus on new pharmacological targets

Cited by 30 publications

References 51 publications

International Union of Basic and Clinical Pharmacology CIV: The Neurobiology of Treatment-resistant Depression: From Antidepressant Classifications to Novel Pharmacological Targets

International Union of Basic and Clinical Pharmacology CIV: The Neurobiology of Treatment-resistant Depression: From Antidepressant Classifications to Novel Pharmacological Targets

New Antidepressant Medication: Benefits Versus Adverse Effects

Quality of Evidence Supporting Major Psychotropic Drug‐Drug Interaction Warnings: A Systematic Literature Review

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