<b>Preclinical discovery of duloxetine for the treatment of depression</b>

Torres-Sánchez, Sonia; Pérez-Caballero, Laura; Micó, Juan Antonio; Elorza, J.; Berrocoso, Esther

doi:10.1517/17460441.2012.693912

Cited by 10 publications

(4 citation statements)

References 75 publications

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“…DUL lacks affinity for monoamine receptors within the central nervous system and shows few effects on the histaminic H1, muscarinic, α1-adrenergic, and opioid receptors (8). Chronic duloxetine treatment exerts a long-term modulatory effect on 5-HT and NE pathways, demonstrating no effect on basal 5-HT, NE, or dopamine levels in the cerebral cortex, a moderate effect on 5-HT and NE release in the hippocampus, and a substantial desensitization of terminal α2-heteroreceptors but not 5-HT1B receptors (9). Based on these evidences, it can be hypothesized that chronic DUL treatment involves adaptive changes of autoreceptor functions, similarly to what happens in chronic treatment with selective serotonin reuptake inhibitors (SSRIs) and noradrenaline reuptake inhibitors (NRIs), which fail to modify 5-HT and NE levels, respectively (10).…”

Section: Introductionmentioning

confidence: 99%

Duloxetine in Psychiatric Disorders: Expansions Beyond Major Depression and Generalized Anxiety Disorder

et al. 2019

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Background: Duloxetine hydrochloride (DUL) is an antidepressant included in the pharmacological class of serotonin–norepinephrine reuptake inhibitors approved for the treatment of major depressive disorder, generalized anxiety disorder, diabetic peripheral neuropathic pain, fibromyalgia, and chronic musculoskeletal pain. The aim of this review was to elucidate current evidences on the use of DUL in the treatment of a variety of psychiatric disorders.Methods: This systematic review was conducted according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. PubMed database was searched from January 1, 2003, to September 30, 2018, using 11 key terms related to psychiatric disorders (“persistent depressive disorder,” “dysthymic disorder,” “bipolar disorder,” “seasonal affective disorder,” “obsessive-compulsive disorder,” “social phobia,” “panic disorder,” “posttraumatic stress disorder,” “schizophrenia,” “eating disorders,” “sexual disorders,” “personality disorders”) and one key term related to duloxetine (“duloxetine hydrochloride”). Article titles and abstracts were scanned to determine relevance to the topic. For additional studies, the authors also examined the reference lists of several of the included papers.Results: Duloxetine may be an effective treatment for mood spectrum disorders, panic disorder, several symptom clusters of borderline personality, and as add-on drug in schizophrenia. Modest or conflicting results have been found for the efficacy of duloxetine in obsessive–compulsive disorder, posttraumatic stress disorder, eating, and sexual disorders.Conclusion: Major limitations of the reviewed studies were short trial duration, small sample sizes, and the lack of control groups. Defining the potential role of DUL in the treatment of psychiatric disorders other than major depressive disorder and generalized anxiety disorder needs further randomized, placebo-controlled studies.

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Section: Introductionmentioning

confidence: 99%

Duloxetine in Psychiatric Disorders: Expansions Beyond Major Depression and Generalized Anxiety Disorder

et al. 2019

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“…4,5) A number of reports have indicated that the medication is generally well tolerated and has significant efficacy, although a few reports have suggested inconclusive data. [6][7][8] These evaluations have been mainly focused on the socio-economical impact as well as on the induction of co-lateral health damage; however, very limited reports have been published regarding the effect of duloxetine on the genetic material, which may be a significant biomarker for future disease development. In the genotoxicity area of research we only found a report that measured genotoxicity in mice with negative results in blood and brain cells.…”

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confidence: 99%

Evaluation of Duloxetine as Micronuclei Inducer in an Acute and a Subchronic Assay in Mouse

Madrigal-Bujaidar

Álvarez-González

Morales-González

2015

Biological & Pharmaceutical Bulletin

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Duloxetine is a widely used antidepressant worldwide. In the present report, we evaluated its capacity to induce micronucleated polychromatic erythrocytes (MNPEs) and micronucleated normochromatic erythrocytes (MNNEs) in mice. Two assays were performed, one with a single chemical administration and the other with daily chemical administration. In the first, we administered the antidepressant once to groups of 5 mice by the intragastric (i.g.) route (2, 20, and 200 mg/kg) and performed the analysis at 24, 48, and 72 h postadministration. A control group administered i.g. distilled water was included in the assay, as well as another treated with the micronuclei-inducing chemical daunorubicin (2.5 mg/kg, injected intraperitoneally (i.p.)). In this assay, we found significant damage induced by duloxetine starting from the first time evaluated, showing the highest MNPE increase at the end of the assay. We observed a saturation effect as well, suggested by a decreasing relative efficiency with respect to each tested dose. In a second assay, we administered the antidepressant i.g. every day for 5 weeks (2, 6, and 12 mg/kg), and micronuclei analysis was performed at the end of each week. In this study, we also found a significant increase in both MNPEs and MNNEs which was clear by the second week of administration. Our results suggest that short-term as well as cumulative damage is produced by duloxetine. Thus, confirmation of the observed genotoxic potential in other models seems advisable, as well as caution when prescribing this antidepressant.

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“…Firstly, in vitro experimental studies had shown that duloxetine preferentially inhibits 5-HT reuptake more than NE reuptake [ 29 , 30 ]. Furthermore, chronic duloxetine administration has a long-term modulatory effect on 5-HT and NE pathways without an effect on basal 5-HT, NE, or dopamine levels in the cerebral cortex, a moderate effect on 5-HT and NE release in the hippocampus and a substantial desensitization of terminal α2-heteroreceptors but not 5-HT1B receptors [ 31 ]. Thus, it can be suggested that chronic duloxetine administration results in adaptive changes of autoreceptor functions equivalent to chronic administration of selective serotonin reuptake inhibitors and noradrenaline reuptake inhibitors [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

Daily intake of 30 mg duloxetine is effective in decreasing premature ejaculation severity: a prospective randomized placebo-controlled cross over clinical trial

Zaazaa,

Nasr Eldin,

GamalEl Din

et al. 2023

Basic Clin. Androl.

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Background Premature ejaculation (PE) is considered to be the most common male sexual disorder affecting 20% to 66% of sexually active men. Most of the patients had already tried on demand dapoxitine with no improvement. We aimed in the current study to assert the efficacy and safety profile of daily intake of 30 mg duloxetine in treating patients with lifelong premature ejaculation (LPE) as well as patients with acquired premature ejaculation (APE). Results The current study showed significant improvement in intravaginal ejaculatory latency time (IELT) after intake of duloxetine. All participants had a median Arabic index of premature ejaculation (AIPE) of 26, median IELT of 180 s, median male sexual quality of life (SQOL) of 43 after being treated with duloxetine (p value < 0.001 for all). While median AIPE after placebo was 19, median IELT after placebo was 60 s and median male SQOL after placebo was 21. Paired comparison of AIPE, IELT (Secs), inter quartile range (IQR) and male SQOL in group (A) patients at baseline and after duloxetine intake showed statistically significant improvement among treated patients (p values < 0.001 for all). Paired comparison of AIPE, IELT (Secs), IQR and male SQOL in group (A) patients at baseline and after placebo treatment showed no significant improvement of male SQOL. Furthermore, AIPE and IELT returned to baseline scores after discontinuation of duloxetine (p values 0.729; 0.892, respectively). Paired comparison of AIPE, IELT (Secs), IQR and male SQOL in group (B) patients at baseline and after placebo treatment showed almost same scores of patients in group (A) who received placebo for 2 months after a 2 month washout period (p values 1.000 for all). Paired comparison of AIPE, IELT (Secs), IQR and male SQOL in group (B) patients at baseline and after duloxetine treatment showed statistically significant improvement among all treated patients (p values < 0.001 for all). Conclusion Duloxetine is an effective drug for treatment of LPE and APE patients. Further, larger studies are needed to compare duloxetine to different known therapeutic modalities for PE to assert it’s efficacy and superiority.

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Preclinical discovery of duloxetine for the treatment of depression

Cited by 10 publications

References 75 publications

Duloxetine in Psychiatric Disorders: Expansions Beyond Major Depression and Generalized Anxiety Disorder

Duloxetine in Psychiatric Disorders: Expansions Beyond Major Depression and Generalized Anxiety Disorder

Evaluation of Duloxetine as Micronuclei Inducer in an Acute and a Subchronic Assay in Mouse

Daily intake of 30 mg duloxetine is effective in decreasing premature ejaculation severity: a prospective randomized placebo-controlled cross over clinical trial

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