Paroxetine for the treatment of depression: a critical update

Gibiino, Sara; Serretti, Alessandro

doi:10.1517/14656566.2012.652085

Cited by 176 publications

(14 citation statements)

References 90 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A review of tolerability based on data from randomized controlled clinical trials involving about 4000 patients with short-term and long-term treatments indicated that paroxetine was associated with significantly higher incidence of adverse events related to sexual dysfunction, as well as more discontinuation symptoms, than escitalopram (Baldwin et al , 2007b). In general, these findings are consistent with a recent review on the overall profile of paroxetine (Gibiino and Serretti, 2012). …”

Section: Clinical Efficacy and Tolerabilitysupporting

confidence: 92%

A comparative review of escitalopram, paroxetine, and sertraline

Sanchéz

Reines

Montgomery

2014

International Clinical Psychopharmacology

234

139

View full text Add to dashboard Cite

It is known that newer antidepressants, such as the selective serotonin reuptake inhibitors (SSRIs), provide advantages in tolerability over antidepressants such as the tricyclics. However, even within the SSRI class, differences in efficacy or tolerability exist between the individual drugs. Among the three most widely prescribed SSRIs are paroxetine, sertraline, and escitalopram. Escitalopram is commonly referred to as an SSRI, but also has well-documented allosteric properties, and thus can be further classed as an allosteric serotonin reuptake inhibitor. All three antidepressants are efficacious compared with placebo, but there is evidence that escitalopram is more effective than a range of other antidepressants. There are no direct data to regard either paroxetine or sertraline as a superior antidepressant. Escitalopram is superior compared with paroxetine, which has a less favorable tolerability profile. Paroxetine is associated with cholinergic muscarinic antagonism and potent inhibition of CYP2D6, and sertraline has moderate drug interaction issues in comparison with escitalopram. Overall, as an allosteric serotonin reuptake inhibitor that is somewhat different from classical SSRIs, escitalopram is the first choice judged by combined efficacy and tolerability, and nonclinical data have offered possible mechanisms through which escitalopram could be more efficacious, based on its interaction with orthosteric and allosteric binding sites at the serotonin transporter.

show abstract

Section: Clinical Efficacy and Tolerabilitysupporting

confidence: 92%

A comparative review of escitalopram, paroxetine, and sertraline

Sanchéz

Reines

Montgomery

2014

International Clinical Psychopharmacology

234

139

View full text Add to dashboard Cite

show abstract

“…Paroxetine is approved and marketed for use in treating patients with a number of depression- and anxiety-related disorders (30, 31). A wealth of data is available from clinical trials and postclinical application regarding human bioavailability, toxicity, adverse effects, and contraindications.…”

Section: Discussionmentioning

confidence: 99%

Paroxetine-mediated GRK2 inhibition reverses cardiac dysfunction and remodeling after myocardial infarction

et al. 2015

View full text Add to dashboard Cite

Heart failure (HF) is a disease of epidemic proportion and is associated with exceedingly high health care costs. G protein (heterotrimeric guanine nucleotide–binding protein)–coupled receptor (GPCR) kinase 2 (GRK2), which is up-regulated in the failing human heart, appears to play a critical role in HF progression in part because enhanced GRK2 activity promotes dysfunctional adrenergic signaling and myocyte death. Recently, we found that the selective serotonin reuptake inhibitor (SSRI) paroxetine could inhibit GRK2 with selectivity over other GRKs. Wild-type mice were treated for 4 weeks with paroxetine starting at 2 weeks after myocardial infarction (MI). These mice were compared with mice treated with fluoxetine, which does not inhibit GRK2, to control for the SSRI effects of paroxetine. All mice exhibited similar left ventricular (LV) dysfunction before treatment; however, although the control and fluoxetine groups had continued degradation of function, the paroxetine group had considerably improved LV function and structure, and several hallmarks of HF were either inhibited or reversed. Use of genetically engineered mice indicated that paroxetine was working through GRK2 inhibition. The beneficial effects of paroxetine were markedly greater than those of β-blocker therapy, a current standard of care in human HF. These data demonstrate that paroxetine-mediated inhibition of GRK2 improves cardiac function after MI and represents a potential repurposing of this drug, as well as a starting point for innovative small-molecule GRK2 inhibitor development.

show abstract

“…Paroxetine is a selective serotonin reuptake inhibitor that is widely used in the treatment of mental disorders, including depression, panic disorders, and obsessive compulsive disorder 1. Two previous studies suggested that the plasma drug con centration is associated with the therapeutic response to paroxetine 2,3.…”

Section: Introductionmentioning

confidence: 99%

Possible impact of the CYP2D6*10 polymorphism on the nonlinear pharmacokinetic parameter estimates of paroxetine in Japanese patients with major depressive disorders

Saruwatari¹,

Nakashima²,

Tsuchimine³

et al. 2014

PGPM

View full text Add to dashboard Cite

It has been suggested that the reduced function allele with reduced cytochrome P450 (CYP) 2D6 activity, CYP2D6*10, is associated with the interindividual differences in the plasma paroxetine concentrations, but there is no data presently available regarding the influence of the CYP2D6*10 polymorphism on the pharmacokinetic parameters, eg, Michaelis–Menten constant (Km) and maximum velocity (Vmax), in Asian populations. The present study investigated the effects of the CYP2D6 polymorphisms, including CYP2D6*10, on the pharmacokinetic parameters of paroxetine in Japanese patients with major depressive disorders. This retrospective study included 15 Japanese patients with major depressive disorders (four males and eleven females) who were treated with paroxetine. The CYP2D6*2, CYP2D6*4, CYP2D6*5, CYP2D6*10, CYP2D6*18, CYP2D6*39, and CYP2D6*41 polymorphisms were evaluated. A total of 56 blood samples were collected from the patients. The Km and Vmax values of paroxetine were estimated for each patient. The allele frequencies of CYP2D6*2, CYP2D6*4, CYP2D6*5, CYP2D6*10, CYP2D6*18, CYP2D6*39, and CYP2D6*41 were 6.7%, 0%, 10.0%, 56.7%, 0%, 26.7%, and 0%, respectively. The mean values of Km and Vmax were 50.5±68.4 ng/mL and 50.6±18.8 mg/day, respectively. Both the Km and Vmax values were significantly smaller in CYP2D6*10 allele carriers than in the noncarriers (24.2±18.3 ng/mL versus 122.5±106.3 ng/mL, P=0.008; 44.2±16.1 mg/day versus 68.3±15.0 mg/day, P=0.022, respectively). This is the first study to demonstrate that the CYP2D6*10 polymorphism could affect the nonlinear pharmacokinetic parameter estimates of paroxetine in Asian populations. The findings of this study suggest that the CYP2D6*10 polymorphism may be associated with the smaller values of both the Km and Vmax in Japanese patients with major depressive disorders, and these results need to be confirmed in further investigations with a larger number of patients.

show abstract

Paroxetine for the treatment of depression: a critical update

Cited by 176 publications

References 90 publications

A comparative review of escitalopram, paroxetine, and sertraline

A comparative review of escitalopram, paroxetine, and sertraline

Paroxetine-mediated GRK2 inhibition reverses cardiac dysfunction and remodeling after myocardial infarction

Possible impact of the CYP2D6*10 polymorphism on the nonlinear pharmacokinetic parameter estimates of paroxetine in Japanese patients with major depressive disorders

Contact Info

Product

Resources

About