Phosphodiesterase-5 inhibitors: Shedding new light on the darkness of depression?

Duarte-Silva, Eduardo; Filho, Adriano José Maia Chaves; Barichello, Tatiana; Quevedo, João; Macedo, Danielle; Peixoto, Christina Alves

doi:10.1016/j.jad.2019.11.114

Cited by 16 publications

(7 citation statements)

References 156 publications

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“…Recently, PDE inhibitors have emerged as potential adjunct treatments to current first-line MDD treatments such as SSRIs. A review conducted by Duarte-Silva et al . (2020) suggested a potential antidepressant effect of PDE-5 inhibitors but was limited due to the lack of RCTs in the review.…”

Section: Discussionmentioning

confidence: 99%

Phosphodiesterase inhibitor and selective serotonin reuptake inhibitor combination therapy versus monotherapy for the treatment of major depressive disorder: a systematic review and meta-analysis

Nawras

Beran

Yazdi

et al. 2023

International Clinical Psychopharmacology

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Selective serotonin reuptakeinhibitors (SSRIs) are the gold standard treatment for major depressive disorder (MDD). However, the use of phosphodiesterase (PDE) inhibitors in the treatment of MDD remains unclear.Our study aims to compare the effect of PDE inhibitor combination therapy to SSRI monotherapy for the treatment of MDD. We performed a comprehensive literature search using PubMed, EMBASE, and Web of Science databases, for studies that assess the impact of PDE inhibitor therapy on MDD patients. The primary outcome of our study was treatment response rate at the end of study time. Pooled odds ratio (OR) and corresponding 95% confidence intervals (CIs) were calculated using the random-effects model. A P-value <0.05 was considered statistically significant. A total of four randomized control trials (RCTs), including 270 patients with MDD, were included in the analysis. Follow-up periods ranged from 6 to 12 weeks. The PDE inhibitor group was associated with a significantly higher treatment response rate (OR, 4.77; 95% CI, 2.05-11.12; P = 0.0003). Our meta-analysis demonstrated that MDD patients receiving PDE inhibitor combination therapy had a higher treatment response rate than MDD patients receiving SSRI monotherapy. Further large-scale RCTs with long-term follow-ups are necessary to validate our findings.

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Section: Discussionmentioning

confidence: 99%

Phosphodiesterase inhibitor and selective serotonin reuptake inhibitor combination therapy versus monotherapy for the treatment of major depressive disorder: a systematic review and meta-analysis

Nawras

Beran

Yazdi

et al. 2023

International Clinical Psychopharmacology

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“…Generally, erectile dysfunction can be divided into organic erectile dysfunction and psychological erectile dysfunction 3 . At present, the most common drug for the treatment of erectile dysfunction is this as phosphodiesterase 5 inhibitors (PDE5i) [4][5][6] .…”

Section: Introductionmentioning

confidence: 99%

Combination of traditional Chinese medicine and PDE5i for diabetic erectile dysfunction: a systematic review and meta-analysis of randomized controlled trials

Zhang²,

Zhu³

et al. 2023

Preprint

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Although phosphodiesterase type 5 inhibitors (PDE5i) have a therapeutic effect on diabetic erectile dysfunction, its therapeutic effect is not as good as that of non-diabetic population. In recent years, several randomized controlled trials(RCTs) found that the therapeutic effect of traditional Chinese medicine(TCM) combined with PDE5i on diabetic erectile dysfunction may be better than that of PDE5i alone, and we now conduct a systematic review and meta-analysis of these studies. We searched China national knowledge internet (CNKI), Wanfang database, Pubmed, and Embase database. Mean difference (MD) or pooled odds ratio (OR), as well as their 95% confidence intervals (CIs) were calculated. Risk bias tool was used to evaluate the quality of RCTs included in the meta-analysis. Publication bias was estimated by Begg’s funnel plots and Egger’s test. Results of this systematic review and meta-analysis revealed that the change in the IIEF-5 score of TCM + PDE5i group was significantly higher than that of PDE5i group(MD = 3.6, 95% CI [2.34, 4.86]). The clinical efficacy of TCM + PDE5i group was significantly higher than that of PDE5i group(OR = 2.86, 95% CI [1.83, 4.48]). Furthermore, the sexual satisfaction of TCM + PDE5i group was significantly higher than that of PDE5i group (OR = 3.07, 95% CI[1.63, 5.80]). There was no significant difference of the number of adverse events between TCM + PDE5i group and PDE5i group(OR = 0.93, 95% CI [0.49,1.78]). According to the meta-analysis, compared with using PDE5i alone, the regimen combined TCM plus PDE5i has more advantages in terms of IIEF-5, efficiency, and sexual satisfaction, with no increase in adverse effects for erectile dysfunction in patients with type 2 diabetes mellitus. More strict and larger sample size RCTs are needed to verify the findings of this meta-analysis.

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“…The PDE5 is expressed in neurons of the brain which increases cGMP signaling by decreasing the degradation of this cyclic nucleotide (Teich et al, 2016). Tadalafil is a selective PDE5 inhibitor and routinely used for the management of erectile dysfunction; however, it is beneficial for cerebral ischemia injury, ischemic stroke, morphine withdrawal syndrome, anxiety, and neurologic diseases by regulatory intraneuronal cGMP levels (Duarte‐Silva et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Parental exposure of Tadalafil has beneficial effect on reflexive motor behaviors in mice offspring

Imani

Hassanpour

Asghari

et al. 2022

Intl J of Devlp Neuroscience

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Tadalafil has positive effects on neurodevelopment and antioxidant defense system, but there is no information for its possible role during gestation on reflexive motor behavior in offspring. So current study determined the effect of prenatal exposure to the Tadalafil on reflexive motor behaviors and antioxidant activity in mice offspring and antidepressive behaviors in postpartum dams. Forty pregnant female NMRI mice were allocated into four groups. In control group, mice received water while in Groups 2-4, female mice orally gavage with Tadalafil (0.4, 0.8, and 1.6 mg/kg) at gestation day (GD) 5, 8, 11, 14, and 17, respectively. Following delivery, pups were selected and reflexive motor behaviors determined using ambulation, hind-limb foot angle, surface righting, hind-limb strength, grip strength, front-limb suspension, and negative geotaxis tests. Also, serum malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx), and total antioxidant status (TAS) were determined in offspring. On Day 2 postpartum, antidepressant activity of Tadalafil was determined by open field test (OFT), rotarod, forced swimming test (FST), and tail suspension test (TST) in dams. Based on the findings, maternal exposure to Tadalafil improved ambulation score, hind-limb suspension score, grip strength, and front-limb suspension in offspring (P < 0.05).Prenatal exposure to Tadalafil decreased surface righting, hind-limb foot angle, and negative geotaxis in offspring (P < 0.05). Tadalafil decreased blood MDA and increased SOD and GPx levels in offspring (P < 0.05). Tadalafil significantly decreased immobility time in FST and TST and increased number of squares crossed in OFT and spending time on rotarod on postpartum mice (P < 0.05). These results suggested that parental exposure of Tadalafil has positive effect on reflexive motor and postpartum behaviors.

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Phosphodiesterase-5 inhibitors: Shedding new light on the darkness of depression?

Cited by 16 publications

References 156 publications

Phosphodiesterase inhibitor and selective serotonin reuptake inhibitor combination therapy versus monotherapy for the treatment of major depressive disorder: a systematic review and meta-analysis

Phosphodiesterase inhibitor and selective serotonin reuptake inhibitor combination therapy versus monotherapy for the treatment of major depressive disorder: a systematic review and meta-analysis

Combination of traditional Chinese medicine and PDE5i for diabetic erectile dysfunction: a systematic review and meta-analysis of randomized controlled trials

Parental exposure of Tadalafil has beneficial effect on reflexive motor behaviors in mice offspring

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