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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 -
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 -
Journal of the American Veterinary... Nov 2019To describe abnormal clinical signs following duloxetine ingestion in dogs.
OBJECTIVE
To describe abnormal clinical signs following duloxetine ingestion in dogs.
ANIMALS
364 client-owned dogs that ingested duloxetine.
PROCEDURES
The American Society for the Prevention of Cruelty to Animals, Animal Poison Control Center electronic database was searched for records of dogs with duloxetine ingestion between January 2012 and December 2016. Data collected included age, body weight, breed, duloxetine exposure and dose, clinical signs, and overall outcome. Clinical signs were categorized as either neurologic, digestive, cardiovascular, respiratory, or metabolic and endocrine. Outcomes were categorized as no clinical signs, fully recovered, died, or unknown.
RESULTS
Clinical signs developed in 55 of the 364 (15.1%) dogs with known ingestion of duloxetine. The most common clinical signs were lethargy (22/55 [40%]), mydriasis (18/55 [33%]), vomiting (11/55 [20%]), and trembling (6/55 [11%]). Dogs that ingested an estimated dose of duloxetine ≥ 20 mg/kg (9.1 mg/lb) were more likely to have had abnormal clinical signs than were dogs that ingested < 20 mg/kg.
CONCLUSIONS AND CLINICAL RELEVANCE
Findings indicated that most dogs in the present study did not have clinical signs associated with ingestion of duloxetine and that development of clinical signs varied by individual dog. Further information is needed to determine toxic dose ranges for duloxetine ingestion in dogs. ( 2019;255:1161-1166).
Topics: Animals; Dog Diseases; Dogs; Duloxetine Hydrochloride; Poison Control Centers; Retrospective Studies
PubMed: 31687894
DOI: 10.2460/javma.255.10.1161 -
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 -
The Clinical Journal of Pain Nov 2016To systematically review the evidence for duloxetine in the management of painful diabetic neuropathy (PDN). (Review)
Review
OBJECTIVE
To systematically review the evidence for duloxetine in the management of painful diabetic neuropathy (PDN).
METHODS
Electronic searches of Medline and PubMed were performed from 2005 till October 2015 using medical subject headings and free-text words. Two independent reviewers extracted the data and assessed the methodological quality of the selected studies.
RESULTS
Twenty-three studies met our inclusion criteria and 8 were considered of high quality and were included to this review. Because of heterogeneity of the studies included in this review, statistical pooling of the data was not possible. We found good evidence for use of duloxetine in PDN over placebo and pregabalin but there was no benefit of duloxetine over amitriptyline.
CONCLUSIONS
Duloxetine has a beneficial effect over placebo. Nevertheless, the evidence of superiority of duloxetine over pregabalin and amitriptyline should be explored further as there was only 1 trial for each category. Provided majority of the PDN patients share cardiovascular complications, use of duloxetine will be a good option for treating pain associated with PDN over amitriptyline. Future randomized controlled trials should be designed keeping this in mind.
Topics: Analgesics; Diabetic Neuropathies; Duloxetine Hydrochloride; Humans; Neuralgia; Randomized Controlled Trials as Topic
PubMed: 26710221
DOI: 10.1097/AJP.0000000000000343 -
Zeitschrift Fur Rheumatologie May 2019Peripheral neuropathies are probably an under-diagnosed complication of many rheumatic diseases. In some cases they take a mild clinical course, in others they cause... (Review)
Review
Peripheral neuropathies are probably an under-diagnosed complication of many rheumatic diseases. In some cases they take a mild clinical course, in others they cause severe impairment of patients' quality of life. A precise diagnosis and etiological classification are of major importance for successful treatment and prognosis of peripheral neuropathies. A detailed patient history and physical examination are the foundation of every diagnostic approach. Electrophysiological studies are obligatory when peripheral neuropathy is suspected, whereas nerve or nerve-muscle biopsies are indicated only in selected cases. Therapeutic approaches are often complicated by a lack of evidence. They correspond to frequently tested immunosuppressive treatment of the underlying disease, such as glucocorticoids, cyclophosphamide, mycophenolate mofetil and intravenous immunoglobulins and are based on the symptomatic pain treatment of other neuropathies. As first-line treatment gabapentin, pregabalin, duloxetine, venlafaxine and tricyclic antidepressants are frequently used.
Topics: Duloxetine Hydrochloride; Humans; Pain Management; Peripheral Nervous System Diseases; Quality of Life; Rheumatic Diseases
PubMed: 30944998
DOI: 10.1007/s00393-019-0621-z -
Fundamental & Clinical Pharmacology Dec 2022Depression is common among people with cardiovascular diseases. Therefore, the combined use of antidepressants and cardiovascular drugs is very common, which increases...
Depression is common among people with cardiovascular diseases. Therefore, the combined use of antidepressants and cardiovascular drugs is very common, which increases the possibility of drug interaction. Simultaneously compare the effects of duloxetine and fluoxetine on metoprolol metabolism, and provide evidence-based guidance for medication safety. Sprague-Dawley rats were randomly divided into three groups: group A (10.3 mg/kg metoprolol alone), group B (10.3 mg/kg metoprolol + 6.2 mg/kg fluoxetine), and group C (10.3 mg/kg metoprolol + 6.2 mg/kg duloxetine). Tail vein blood was collected and subjected to the ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) detection. Moreover, in vitro inhibition of fluoxetine and duloxetine were assessed by incubating liver microsomes and CYP2D6.1 with metoprolol. In in vivo study, the administration of fluoxetine or duloxetine significantly increased the AUC and AUC of metoprolol (P < 0.05). Differences between fluoxetine and duloxetine in plasma concentration were also investigated, and their pharmacokinetic parameters such as AUC and AUC were significantly distinct (P < 0.05). In vitro, fluoxetine and duloxetine inhibited the metabolism of metoprolol via mixed competitive mechanism of cytochrome P450. IC values of fluoxetine and duloxetine were 12.86 and 2.51 μM, respectively. Moreover, the metabolism rate of metoprolol was inhibited to 19.62% and 17.14% in recombinant human CYP2D6.1 by fluoxetine and duloxetine, respectively. Duloxetine showed a more significant inhibitory potential compared to fluoxetine in vitro, but the main pharmacokinetic parameters of fluoxetine and duloxetine revealed differences in inhibiting metoprolol metabolism in vivo.
Topics: Rats; Animals; Humans; Fluoxetine; Metoprolol; Duloxetine Hydrochloride; Cytochrome P-450 CYP2D6; Chromatography, Liquid; Tandem Mass Spectrometry; Rats, Sprague-Dawley
PubMed: 35510497
DOI: 10.1111/fcp.12795 -
Journal of Affective Disorders May 2023Desvenlafaxine and duloxetine are selective serotonin and norepinephrine reuptake inhibitors. Their efficacy has not been directly compared using statistical hypotheses.... (Randomized Controlled Trial)
Randomized Controlled Trial
A multicenter, randomized, double-blind, duloxetine-controlled, non-inferiority trial of desvenlafaxine succinate extended-release in patients with major depressive disorder.
BACKGROUND
Desvenlafaxine and duloxetine are selective serotonin and norepinephrine reuptake inhibitors. Their efficacy has not been directly compared using statistical hypotheses. This study evaluated the non-inferiority of desvenlafaxine extended-release (XL) to duloxetine in patients with major depressive disorder (MDD).
METHODS
In this study, 420 adult patients with moderate-to-severe MDD were enrolled and randomly assigned (1:1) to receive 50 mg (once daily [QD]) of desvenlafaxine XL (n = 212) or 60 mg QD of duloxetine (n = 208). The primary endpoint was evaluated using a non-inferiority comparison based on the change from baseline to 8 weeks in the 17-item Hamilton Depression Rating Scale (HAMD) total score. Secondary endpoints and safety were evaluated.
RESULTS
Least-squares mean change in HAM-D total score from baseline to 8 weeks was -15.3 (95% confidence interval [CI]: -17.73, -12.89) in the desvenlafaxine XL group and - 15.9 (95% CI, -18.44, -13.39) in the duloxetine group. The least-squares mean difference was 0.6 (95% CI: -0.48, 1.69), and the upper boundary of 95% CI was less than the non-inferiority margin (2.2). No significant between-treatment differences were found in most secondary efficacy endpoints. The incidence of the most common treatment-emergent adverse events (TEAEs) was lower for desvenlafaxine XL than for duloxetine for nausea (27.2% versus 48.8%) and dizziness (18.0% versus 28.8%).
LIMITATIONS
A short-term non-inferiority study without a placebo arm.
CONCLUSIONS
This study demonstrated that desvenlafaxine XL 50 mg QD was non-inferior to duloxetine 60 mg QD in efficacy in patients with MDD. Desvenlafaxine had a lower incidence of TEAEs than duloxetine did.
Topics: Adult; Humans; Duloxetine Hydrochloride; Depressive Disorder, Major; Desvenlafaxine Succinate; Antidepressive Agents; Double-Blind Method; Treatment Outcome
PubMed: 36813043
DOI: 10.1016/j.jad.2023.02.067 -
The Korean Journal of Internal Medicine Sep 2019About 21% of adults with osteoarthritis (OA) are diagnosed with concomitant depression in addition to chronic pain. Duloxetine, an anti-depressant medication, has been... (Meta-Analysis)
Meta-Analysis
About 21% of adults with osteoarthritis (OA) are diagnosed with concomitant depression in addition to chronic pain. Duloxetine, an anti-depressant medication, has been recently approved for managing Knee OA. We performed a systematic review to ascertain the efficacy and safety of duloxetine for OA. We searched MEDLINE, EMBASE, Web of Science, Google Scholar, and the Cochrane Database from inception to December 2018. Randomized clinical trials (RCTs) assessing the efficacy and/or safety of duloxetine versus placebo in OA patients were included. Data extraction and quality assessment were undertaken by two independent reviewers. Seven RCTs (n = 2,102 participants) met our inclusion criteria, and five RCTs (n = 1,713) were eligible for meta-analysis. The results of our analyses indicate that duloxetine has statistically significant, moderate benefits on pain, function, and quality of life in knee OA patients for up to 13 weeks. Reported incidences of gastrointestinal adverse events were three to four times higher in participants who received duloxetine versus placebo. Duloxetine may be an effective treatment option for individuals with knee OA, but use of the drug is associated with a significantly higher risk of adverse events. Patient preferences and clinicians' judgment must be considered before the initiation of duloxetine.
Topics: Aged; Antirheumatic Agents; Duloxetine Hydrochloride; Female; Humans; Male; Middle Aged; Osteoarthritis, Knee; Quality of Life; Remission Induction; Risk Factors; Treatment Outcome
PubMed: 30871298
DOI: 10.3904/kjim.2018.460 -
European Urology Focus May 2021The recommended treatment of postprostatectomy stress urinary incontinence (PPSUI) after failure of pelvic floor muscle training is primarily surgical intervention with... (Review)
Review
CONTEXT
The recommended treatment of postprostatectomy stress urinary incontinence (PPSUI) after failure of pelvic floor muscle training is primarily surgical intervention with a male sling or artificial urinary sphincter. The use of pharmacological therapy in this setting is unlicensed and controversial.
OBJECTIVE
To systematically review the available evidence regarding the efficacy and safety of duloxetine for the treatment of stress urinary incontinence following prostate surgery (radical or endoscopic).
EVIDENCE ACQUISITION
The EMBASE, MEDLINE/PubMed, and Cochrane Central Register of Controlled Trials were searched from inception up until April 17, 2020. All studies evaluating the role of duloxetine in men with PPSUI were included. Two reviewers independently screened all articles, searched the reference lists of retrieved articles, and performed data extraction. The quality of evidence and risk of bias were assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE); Cochrane; and Risk of Bias in Nonrandomised Studies of Interventions (ROBINS-I) tools.
EVIDENCE SYNTHESIS
The search yielded 234 studies. After excluding duplicates, 140 titles and abstracts were screened, and eight reports (348 patients) were eligible for inclusion in the final review. Duloxetine was assessed in two scenarios: (1) early use to reduce the time to attain continence and (2) treatment of persistent PPSUI. Most men had mild-to-moderate incontinence at baseline. Overall, duloxetine resulted in a mean dry rate of 58% (25-89%), mean improvement in pad number of 61% (12-100%), and mean improvement in 1-h pad weight of 68% (53-90%) at short-term follow-up (mean 1-9 mo; low to moderate certainty of evidence). However, mean adverse event rates were relatively high, and treatment was discontinued in 38% (low certainty of evidence).
CONCLUSIONS
Duloxetine has demonstrated good short-term cure and/or improvement in treating men with persistent PPSUI, as well as in reducing the time to attain continence. However, a proportion of men discontinue treatment due to adverse events. The overall certainty evidence is moderate to low, with heterogeneity between studies and methodological limitations. However, we have highlighted the need for further randomised trials with longer follow-up, utilising consistent outcome reporting measures. Despite these limitations, the findings from this review will aid patient counselling regarding this less invasive treatment option, thereby allowing personalisation of care centred around the values and preferences of individual patients.
PATIENT SUMMARY
Duloxetine has good success rates in the short term, in terms of improving incontinence symptoms in men who have undergone prostate surgery. However, some men experience side effects bad enough to require cessation of treatment. Further studies are needed to determine whether duloxetine maintains its effectiveness in the long term.
Topics: Duloxetine Hydrochloride; Humans; Male; Prostatectomy; Suburethral Slings; Urinary Incontinence; Urinary Incontinence, Stress
PubMed: 32605820
DOI: 10.1016/j.euf.2020.06.007