-
Pain Practice : the Official Journal of... Mar 2023
Topics: Humans; Duloxetine Hydrochloride; Fibromyalgia; Analgesics; Drug-Related Side Effects and Adverse Reactions
PubMed: 36263613
DOI: 10.1111/papr.13174 -
Progress in Neuro-psychopharmacology &... Jun 2019Major Depressive Disorder (MDD) is associated with a high rate of inadequate treatment response, which is mainly due to the large inter-individual genetic variability in...
BACKGROUND
Major Depressive Disorder (MDD) is associated with a high rate of inadequate treatment response, which is mainly due to the large inter-individual genetic variability in pharmacokinetic and pharmacodynamic targets of antidepressant drugs. Little is still known about the exact association between plasma level of first-line antidepressants and clinical response. This is particularly true for duloxetine, a dual serotonin and norepinephrine reuptake inhibitor recommended as first-line treatment for MDD. The aim of this study was to investigate the association between serum concentration of duloxetine (SCD) and antidepressant response (AR).
METHODS
66 MDD patients treated with duloxetine 60 mg/day monotherapy were recruited in an outpatient setting and followed for three months. Hamilton Depression Rating Scale - 21 (HAMD-21) was administrated at baseline, at month 1, and at month 3 to assess AR. SCD was measured at steady state. Linear regression analysis and nonlinear least-squares regression were used to estimate association between SCD and AR.
RESULTS
SCD showed a high inter-individual variability in our sample, despite the duloxetine fixed oral dosage. We found a strong association between SCD and AR following a bell-shaped function at month 1 and at month 3. Nonetheless, within the recommended SCD range of 30-120 ng/mL a more linear correlation between SCD and AR was observed.
DISCUSSION
Our results suggest that for duloxetine the association between SCD and AR likely follows a bell-shaped quadratic function with poor AR at subtherapeutic SCD and progressive decrease of AR at higher SCD. The maximum antidepressant efficacy seems to require SCD values next to the highest recommended SCD (30-120 ng/mL), probably because of the optimal saturation of both serotonin and norepinephrine transporters. Thus, taking into account the observed high interindividual variability of SCD, our findings suggest that for MDD patients treated with duloxetine, SCD could be a useful tool to guide the treatment by optimizing the oral dosage in order to increase the AR rate.
Topics: Administration, Oral; Ambulatory Care; Antidepressive Agents; Biological Variation, Individual; Depressive Disorder, Major; Drug Monitoring; Duloxetine Hydrochloride; Female; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Time Factors; Treatment Outcome
PubMed: 30611837
DOI: 10.1016/j.pnpbp.2019.01.001 -
The Medical Letter on Drugs and... Apr 2020
Topics: Acetaminophen; Analgesics, Opioid; Anti-Inflammatory Agents, Non-Steroidal; Duloxetine Hydrochloride; Humans; Osteoarthritis
PubMed: 32324175
DOI: No ID Found -
Medicine Aug 2023Duloxetine, a serotonin-norepinephrine dual reuptake inhibitor, may improve analgesia after total joint arthroplasty (TJA). However, there is still no consensus on its... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Duloxetine, a serotonin-norepinephrine dual reuptake inhibitor, may improve analgesia after total joint arthroplasty (TJA). However, there is still no consensus on its effectiveness and safety. We conducted the meta-analysis to investigate the analgesic effect and safety of duloxetine for the treatment of patients received total knee or hip arthroplasty.
METHODS
Pubmed, Cochrane Central Registry for Clinical Trials, Embase, OVID, Web of Science, and Google Scholar were searched using a predetermined search strategy from inception to September 21, 2022. Only randomized controlled trials of duloxetine in treatment of patients after total knee or hip arthroplasty were included. Data collection and extraction, quality assessment, and data analyses were performed according to the Cochrane standards.
RESULTS
A total of 8 randomized controlled trials with 739 patients were included in the literature review of postoperative pain and adverse effects. The result of meta-analysis showed statistically significant lower opioid requirement with duloxetine (P < .05) for the different postoperative period. Duloxetine group had significant reductions in visual analog score for the 24-hour (walking: WMD = -0.98; 95% confidence interval [CI] = -1.69 to -0.26, P = .007; resting: WMD = -1.06; 95%CI = -1.85 to -0.27, P = .008) and 1-week (walking: WMD = -0.96; 95%CI = -1.42 to -0.50, P < .001; resting: WMD = -0.69; 95%CI = -1.22 to -0.16, P = .01); knee injury and osteoarthritis outcome score over 3-month (WMD = 2.94; 95%CI = -0.30 to 6.18, P = .008) and complication (odds ratio = 4.74; 95%CI = 0.23 to 96.56, P = .01) postoperative period compared with the control group. However, no difference on numeric rating scale (P > .05) for the different postoperative period; visual analog score (P > .05) for the 6-week or 3-month and knee injury and osteoarthritis outcome score (P > .05) for the 6-week postoperative period. Furthermore, it did not increase the incidence of adverse effects (odds ratio = 0.87; 95%CI = 0.72 to 1.05, P = .15).
CONCLUSION
Duloxetine could decrease the opioids consumption and relieve early postoperative pain without increasing the risk of adverse medication effects in patients undergoing total knee or hip arthroplasty. Considering the ongoing opioid epidemic, duloxetine could act as a good supplement in multimodal pain management protocol for patients undergoing total joint arthroplasty.
Topics: Humans; Arthroplasty, Replacement, Hip; Duloxetine Hydrochloride; Arthroplasty, Replacement, Knee; Pain Management; Knee Joint; Drug-Related Side Effects and Adverse Reactions; Analgesics, Opioid; Randomized Controlled Trials as Topic
PubMed: 37653762
DOI: 10.1097/MD.0000000000034895 -
Cancer Research Communications Nov 2022Oxaliplatin-induced peripheral neurotoxicity (OIPN) is a debilitating side effect that afflicts ~90% of patients that is initiated by OCT2-dependent uptake of...
UNLABELLED
Oxaliplatin-induced peripheral neurotoxicity (OIPN) is a debilitating side effect that afflicts ~90% of patients that is initiated by OCT2-dependent uptake of oxaliplatin in DRG neurons. The antidepressant drug duloxetine has been used to treat OIPN, although its usefulness in preventing this side effect remains unclear. We hypothesized that duloxetine has OCT2-inhibitory properties and can be used as an adjunct to oxaliplatin-based regimens to prevent OIPN. Transport studies were performed in cells stably transfected with mouse or human OCT2 and in isolated mouse DRG neurons . Wild-type and OCT2-deficient mice were used to assess effects of duloxetine on hallmarks of OIPN, endogenous OCT2 biomarkers, and the pharmacokinetics of oxaliplatin, and the translational feasibility of a duloxetine-oxaliplatin combination was evaluated in various models of colorectal cancer. We found that duloxetine potently inhibited the OCT2-mediated transport of several xenobiotic substrates, including oxaliplatin, in a reversible, concentration-dependent manner, and independent of species and cell context. Furthermore, duloxetine restricted access of these substrates to DRG neurons and prevented OIPN in wild-type mice to a degree similar to the complete protection observed in OCT2-deficient mice, without affecting the plasma levels of oxaliplatin. Importantly, the uptake and cytotoxicity of oxaliplatin in tumor cell lines and were not negatively influenced by duloxetine. The observed OCT2-targeting properties of duloxetine, combined with the potential for clinical translation, provide support for its further exploration as a therapeutic candidate for studies aimed at preventing OIPN in cancer patients requiring treatment with oxaliplatin.
SIGNIFICANCE
We found that duloxetine has potent OCT2-inhibitory properties and can diminish excessive accumulation of oxaliplatin into DRG neurons. In addition, pre-treatment of mice with duloxetine prevented OIPN without significantly altering the plasma pharmacokinetics and antitumor properties of oxaliplatin. These results suggest that intentional inhibition of OCT2-mediated transport by duloxetine can be employed as a prevention strategy to ameliorate OIPN without compromising the effectiveness of oxaliplatin-based treatment.
Topics: Humans; Mice; Animals; Oxaliplatin; Antineoplastic Agents; Duloxetine Hydrochloride; Peripheral Nervous System Diseases; Neurotoxicity Syndromes
PubMed: 36506732
DOI: 10.1158/2767-9764.crc-22-0172 -
Anasthesiologie, Intensivmedizin,... Sep 2016
Randomized Controlled Trial
Topics: Adult; Analgesics; Analgesics, Opioid; Double-Blind Method; Drug Administration Schedule; Duloxetine Hydrochloride; Female; Humans; Hysterectomy; Pain Measurement; Pain, Postoperative; Prospective Studies; Quality of Life; Recovery of Function; Treatment Outcome
PubMed: 27631441
DOI: 10.1055/s-0042-113427 -
Neurologia Apr 2021
Topics: Duloxetine Hydrochloride; Humans; Opsoclonus-Myoclonus Syndrome
PubMed: 32674858
DOI: 10.1016/j.nrl.2020.05.009 -
Journal of Gynecology Obstetrics and... Mar 2022To evaluate the efficacy and safety of preoperative duloxetine on postoperative pain management after gynecologic laparoscopic surgeries. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To evaluate the efficacy and safety of preoperative duloxetine on postoperative pain management after gynecologic laparoscopic surgeries.
METHODS
A systematic search was done in Cochrane Library, PubMed, ISI web of science, and Scopus from inception to September 2021. We selected randomized clinical trials (RCTs) that compared preoperative duloxetine (intervention group) versus placebo (control group) among women undergoing gynecologic laparoscopic surgeries. Our primary outcomes were pain scores evaluated by the Visual Analog Scale (VAS) at 2, 6, 12, and 24 h postoperatively. Our secondary outcomes were the time required for the first analgesic request in minutes, postoperative analgesic consumption in milligrams, length of hospital stay in days, and side effects.
RESULTS
Four RCTs with a total number of 244 patients were included in our systematic review and meta-analysis. We found duloxetine was linked to a significant reduction in VAS pain scores at different time intervals. The first analgesic request was significantly earlier in the placebo group than in the duloxetine group (p = 0.03). In addition, duloxetine significantly reduced the postoperative analgesic consumption compared to placebo (MD= -41.97, 95% CI [-53.23, -30.72], p<0.001). However, both groups did not differ in the length of hospital stay and side effects.
CONCLUSIONS
Duloxetine administration prior to gynecological laparoscopic surgeries is safe and effective in improving postoperative pain and analgesia.
Topics: Duloxetine Hydrochloride; Female; Gynecologic Surgical Procedures; Humans; Laparoscopy; Pain, Postoperative; Randomized Controlled Trials as Topic
PubMed: 34974147
DOI: 10.1016/j.jogoh.2021.102305 -
International Journal of Molecular... May 2023Paclitaxel, a widely used cancer chemotherapeutic agent, has high incidence of neurotoxicity associated with the production of neuropathic pain, for which only...
Paclitaxel, a widely used cancer chemotherapeutic agent, has high incidence of neurotoxicity associated with the production of neuropathic pain, for which only duloxetine has shown significant but moderate analgesic effect. Since statins, classically used to reduce hypercholesterolemia, have shown antinociceptive effect in preclinical studies on neuropathic pain, we studied whether the antinociceptive efficacy of duloxetine could be synergistically potentiated by rosuvastatin in a model of paclitaxel-induced neuropathy in mice. The astrocytic and microglial responses in the spinal cord of paclitaxel-treated mice were also assessed by measuring GFAP and CD11b proteins, respectively. Paclitaxel treatment did not impair motor coordination and balance in rotarod testing. Rosuvastatin, duloxetine, and the rosuvastatin/duloxetine combination (combined at equieffective doses) dose-dependently decreased mechanical allodynia (ED, von Frey testing) and thermal hyperalgesia (ED, hot plate testing) in paclitaxel-treated mice. Isobolographic analysis showed a superadditive interaction for rosuvastatin and duloxetine, as both the ED and ED for the rosuvastatin/duloxetine combination contained only a quarter of each drug compared to the individual drugs. The rosuvastatin/duloxetine combination reversed paclitaxel-induced GFAP overexpression, indicating that such effects might depend in part on astrocyte inactivation. Results suggest that statins could be useful in synergistically enhancing the efficacy of duloxetine in some chemotherapy-induced neuropathic conditions.
Topics: Mice; Animals; Paclitaxel; Duloxetine Hydrochloride; Rosuvastatin Calcium; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Pain Measurement; Neuralgia; Hyperalgesia; Analgesics
PubMed: 37176065
DOI: 10.3390/ijms24098359 -
Drug Delivery Nov 2017Duloxetine hydrochloride (DH) is a serotonin-norepinephrine reuptake inhibitor (SSNRI) indicated for the treatment of depression. Duloxetine suffers from reduced oral... (Comparative Study)
Comparative Study Randomized Controlled Trial
Duloxetine hydrochloride (DH) is a serotonin-norepinephrine reuptake inhibitor (SSNRI) indicated for the treatment of depression. Duloxetine suffers from reduced oral bioavailability (≈50%) due to hepatic metabolism. This study aims to develop DH buccoadhesive films to improve its bioavailability. DH buccoadhesive films were prepared adopting the solvent casting method using hydroxypropyl methylcellulose (HPMC) and polyvinyl alcohol (PVA). The prepared films were evaluated for weight uniformity, drug content, surface pH, swelling index, mucoadhesion strength and drug release percentages. Accelerated stability and bioavailability studies in healthy human volunteers were also performed for the selected films. Results of the evaluation tests showed that the optimum physicochemical characters were obtained by the films prepared with 2% HPMC using 10% propylene glycol (F2 films). Accelerated stability studies revealed that DH showed proved stability throughout the experiment time. DH bioavailability from F2 films was determined and compared with that of the marketed oral capsules (Cymbalta 30 mg). The pharmacokinetic results showed that C for F2 was higher than the market product. In addition, ANOVA analysis showed that a T of F2 film was significantly lower, while, the AUC of F2 was significantly higher than that of Cymbalta capsules. The percentage relative bioavailability of DH from F2 was found to be 296.39%. Therefore, the prepared buccal films offer an alternative route for the administration of DH with the possibility of improving its bioavailability.
Topics: Adhesiveness; Administration, Buccal; Animals; Biological Availability; Chemistry, Pharmaceutical; Chickens; Cross-Over Studies; Drug Delivery Systems; Drug Liberation; Duloxetine Hydrochloride; Humans; Hypromellose Derivatives; Mouth Mucosa; Polyvinyl Alcohol
PubMed: 29172829
DOI: 10.1080/10717544.2017.1402216