Mg Of Duloxetine Research Articles

Suspected duloxetine-induced restless legs syndrome phenotypic variant: a case report

BackgroundRestless arms syndrome (RAS) is the most common variant of restless legs syndrome (RLS), which is easy to be ignored in clinical practice due to the lack of specific diagnostic criteria. When effective therapeutic agents induced RAS and symptoms persisted after briefly observation, clinicians will face the challenge of weighing efficacy against side effects.Case presentationA 67-year-old woman was admitted to a geriatric psychiatric ward with depression. Upon admission, the escitalopram dose was reduced from 15 mg to 10 mg per day, and the duloxetine dose was increased from 60 mg to 80 mg per day. The next night before bedtime, she developed itching and creeping sensations deep inside bilateral shoulders and arms, with the urge to move, worsening at rest, and alleviation after hammering. The symptoms persisted when escitalopram was discontinued. A history of RLS was confirmed. Treatment with 40 mg of duloxetine and 0.125 mg of pramipexole significantly improved depression, and the paresthesia disappeared, with no recurrence occurring 6 months after discharge.Discussion and conclusionsThis case suggests that psychiatrists should pay attention to RLS variants when increasing doses of duloxetine. Long-term improvement can be achieved through dosage reduction combined with dopaminergic drugs instead of immediate discontinuation.

Duloxetine as an Analgesic in Patients Who Do Not Have Central Sensitivity Undergoing Single-Setting, Bilateral Total Knee Arthroplasty: A Prospective, Double-Blinded, Randomized, Placebo-Controlled Trial

BackgroundPain control and patient satisfaction after total knee arthroplasty (TKA) have room for improvement. While studies have reported better analgesic outcomes with antidepressants like duloxetine in patients who do not have central sensitivity (CS), we undertook this trial to determine the short and midterm analgesic role of low-dose duloxetine in patients who do not have CS. MethodsThis prospective, double-blinded, randomized, placebo-controlled trial was conducted in 106 patients undergoing single-setting, bilateral TKA under spinal anesthesia. There were 2 matched groups, with one given 20 mg of duloxetine and the other given a placebo (similar in appearance and weight) from preoperative day 2 to postoperative day 28. Follow-ups were scheduled at 48-hours, 1-week, 2-weeks, 4-weeks, and 3-months. Pain was measured using a visual analogue scale at rest and visual analogue scale at mobilization (mVAS). Secondary measures included additional non-steroidal anti-inflammatory drug consumption, patient satisfaction, and safety profile. ResultsThe visual analogue scale at rest in the duloxetine group was better in the first 48 hours (6.38 ± 1.32 versus 7.02 ± 0.99; P = .017), 1-week (4.76 ± 1.24 versus 5.89 ± 1.06; P < .001), and 2-weeks (3.34 ± 1.19 versus 4.26 ± 1.02; P < .001) follow-up. The mVAS remained significantly higher in the duloxetine group in the first 48 hours (7.23 ± 1.12 versus 8.21 ± 0.69; P < .001), 1-week (5.83 ± 1.11 versus 6.82 ± 0.92; P < .001), and 2 weeks (3.70 ± 0.89 versus 4.60 ± 1.03; P < .001) follow-up. Both outcomes became comparable from 4-week follow-up onward. Patient satisfaction (8.44 ± 1.68 versus 7.17 ± 1.04; P < .001) and additional non-steroidal anti-inflammatory drug consumption (2,770 ± 533.05 versus 3,566.04 ± 464.54; P < .001) were better in the duloxetine group, with a comparable safety profile. ConclusionsIn patients who did not have CS, persistent pain after bilateral TKA can be managed safely and successfully by a daily dose of 20 mg Duloxetine, improving patient satisfaction and analgesic consumption in the acute postoperative phase.

Comparison of the Efficacy of Duloxetine Versus Pregabalin for Pain Relief of Neuropathy in Diabetics

Background: Neuropathy is a common complication in diabetic patients with clinical manifestations of feet and hands paresthesia, pain in the lower legs, and a burning sensation in the soles. A wide variety of medications are used for diabetic neuropathy with varying degrees of pain relief reported. The study objective was to compare the efficacy of duloxetine versus pregabalin for pain relief of neuropathy in diabetics. Methods: The study was a six-week, single-blind, Randomized Controlled Trial conducted at HBS Medical and Dental College and Hospital in Islamabad. Patients were randomly designated to either of the groups (A or B) with 50 participants in each group. Group A received 150mg of pregabalin twice a day while group B received 60mg of duloxetine once a day. Pain relief was the primary outcome which was considered as a ≥ 50% decrease in pain score on the Visual Analog Scale at 6 weeks from baseline. Results: A total of 100 diabetic patients were registered in the study. The mean age in groups A&amp;B was 48.36 and 50.56 (SD± 6.64) years respectively. The majority of the study population were males 39 (78%) and 42 (84%) in both groups. A total of 66% (n=33) in Group A and 74% (n=37) of the patients in Group B achieved pain relief. A comparison of the pain relief achieved between the two groups showed no statistical significance (p-value 0.383). Conclusion: The study revealed that duloxetine and pregabalin are both efficacious in terms of pain relief for diabetic neuropathy in our population.

Efficacy and safety of duloxetine in painful diabetic peripheral neuropathy: a systematic review and meta-analysis of randomized controlled trials

BackgroundPainful diabetic peripheral neuropathy (PDPN) is a key concern in clinical practice. In this systematic review and meta-analysis, we compared duloxetine and placebo treatments in terms of their efficacy and safety in patients with PDPN.MethodsFollowing the PRISMA guidelines, we searched the Cochrane Library, PubMed, and Embase databases for relevant English articles published before January 11, 2021. Treatment efficacy and safety were assessed in terms of pain improvement, patient-reported health-related performance, and patients’ quality of life.ResultsWe reviewed a total of 7 randomized controlled trials. Regarding pain improvement, duloxetine was more efficacious than placebo (mean difference [MD] − 0.89; 95% confidence interval [CI] − 1.09 to − 0.69; P < .00001). Furthermore, duloxetine significantly improved the patients’ quality of life, which was assessed using the Clinical Global Impression severity subscale (MD − 0.48; 95% CI − 0.61 to − 0.36; P < .00001), Patient Global Impression of Improvement scale (MD − 0.50; 95% CI − 0.64 to − 0.37; P < .00001), and European Quality of Life Instrument 5D version (MD 0.04; 95% CI 0.02 to 0.07; P = .0002). Severe adverse events were rare, whereas nausea, somnolence, dizziness, fatigue, constipation, and decreased appetite were common; approximately, 12.6% of all patients dropped out because of the common symptoms.ConclusionsDuloxetine is more efficacious than placebo treatments in patients with PDPN. The rarity of severe adverse events indicates that duloxetine is safe. When a 60-mg dose is insufficient, 120 mg of duloxetine may improve PDPN symptoms. Our findings may help devise optimal treatment strategies for PDPN.Systematic review registrationPROSPERO CRD42021225451

Randomized active-controlled study of a single preoperative administration of duloxetine to treat postoperative pain and numbness after posterior lumbar interbody fusion surgery

This prospective, randomized, double-blinded, active controlled trial assessed whether a single preoperative administration of 40 mg of duloxetine could decrease postoperative pain and numbness after posterior lumbar interbody fusion surgery (PLIF). Patients with an American Society of Anesthesiologists physical status I or II undergoing PLIF were included. At 2 hours before inducing anesthesia, patients were administered 40 mg duloxetine or 4 mg diazepam (control drug). Postoperative pain and other symptoms were evaluated on the basis of a visual analog scale, amount of fentanyl used, fentanyl dose request times, rate of use of adjunctive analgesics (diclofenac sodium or pentazocine), and lower limb numbness score (0-3) during the first 2 postoperative days. Forty-six patients were randomly assigned to the duloxetine and diazepam groups (n = 23 each); 6 were lost to follow-up, and analysis was performed on data from 22 patients in the duloxetine group and 18 in the diazepam group. No significant differences were detected in the patient background, postoperative visual analog scale score at rest in the lumbar region and lower limbs, fentanyl use, rate of analgesic adjuvant use, or incidence of side effects. The numbness score in the lower limbs, however, was significantly lower in the duloxetine group. A single preoperative 40-mg dose of duloxetine did not improve postoperative pain after PLIF, but did improve lower limb numbness. Duloxetine may suppress neuropathic pain-like symptoms after PLIF surgery.

Management of Diabetic Neuropathy: A Comparison of Duloxetine with Amitriptyline

Objective: To evaluate the pain-relieving effects of duloxetine vs those of amitriptyline in the treatment of diabetic neuropathy. Methodology: In this randomized trial control, 150 cases of diabetic neuropathy by using convenient sampling technique from Medical Department of Madinah Teaching Hospital, Faisalabad were enrolled and divided in 2 equal groups randomly. Group A was assigned to (Duloxetine) and B assigned to (Amitriptyline). Patients received the trial drug in the morning with water for 6 weeks. Group A got 60 mg of Duloxetine and Group B 75 mg of amitriptyline. VAS pain rating. Patient consultations included a diary card. Patients recorded daily improvements on a visual analogue scale for the first three weeks. We administered three weeks of medicine and arranged an examination in week 6. When pain levels were 50% lower than baseline, we rated them as reduced. Patients were phoned. Results: The mean age was 46.19+6.39 years. 41(54.67%) of Group-A and 39(52%) of Group-B were male, whereas 34(45.33%) and 36(48%) were female. Both groups' mean VAS pain ratings were 1.48+0.50; p = 0.746 shows no difference. Group-A (0.48+0.50) and Group-B (0.92+0.69) vary significantly (p=0.0001). Group-A (52%) and Group-B (28%) were effectively treated after 6 weeks, p=0.002. Conclusion: Our research shows that duloxetine is superior to amitriptyline for the management of diabetic neuropathy, especially in terms of minimising the frequency with which patients report experiencing pain. Keywords: Diabetic neuropathy, management, duloxetine, amitriptyline, efficacy

Effectiveness of duloxetine on severity of pain and quality of life in chronic low back pain in patients who had posterior spinal fixation

Background: In this study, we want to search the effectiveness of Duloxetine on the severity of pain and quality of life in patients with chronic low back pain who had posterior spinal fixation. Methods: In this randomized, placebo-controlled trial done in 6 months 50 patients who had CLBP and were candidates for PSF surgery selected and divided into two groups (drug and placebo). They filled the VAS, SF-36, and Hamilton questionnaires before surgery and after 6 weeks from using 30 mg of duloxetine or placebo. Results: Significant differences were evidenced among groups for the Visual Analogue Scale (P = 0.005) and Verbal Analogue Scale (p = 0.003). Patients in the Duloxetine group have more visual and verbal pain scores than the placebo group. In the quality of life, there was a significant difference between the two groups before the intervention. Also, significant differences were evidenced among groups for the Hamilton Anxiety Rating Scale (p = 0.17). After the intervention, only the Hamilton Anxiety Rating Scale (p = 0.001) and ‘bodily pain’ and ‘general health’ subscales of quality of life (p = 0.008, 0.004, respectively) have a significant difference between the two groups. There was a significant difference between pre and post-intervention in the Hamilton Anxiety Rating Scale only in the duloxetine group. Also, in terms of quality of life, the subscales of ‘physical role’, ‘emotional role’, ‘physical pain’ and ‘total score of quality of life’ in the duloxetine and placebo groups were significantly different between pre and post-intervention. However, the subscales of ‘physical function’ and ‘general health’ were significantly different only in the duloxetine group between pre and post-intervention. Conclusion: The results suggest that the use of duloxetine in patients who had spinal surgery can help to better control back pain, on the other hand, it can cause a better psychological condition that affects the quality of life.

Long-term efficacy and safety of duloxetine in the management of painful chemotherapy induced peripheral neuropathy.

236 Background: Accordingly, Quality of life in the survivorship of patients with cancer is becoming one of the important issues with a development of systemic anticancer treatment. About 40% of the patients who receive chemotherapeutic agents which have neuropathic potential suffer from painful CIPN. Various approaches to relieve the pain associated with CIPN have been attempted in clinical practice. Previously duloxetine, a dual reuptake inhibitor of serotonin and norepinephrine, has been reported to reduce painful CIPN when administered for 5 weeks. We retrospectively investigated the effect of duloxetine on the pain associated with CIPN over a prolonged period of administration. Methods: Between December 2014 and December 2016, patients with advanced cancer who complained of CIPN during or after systemic chemotherapy were eligible. Initially, 30 mg of duloxetine was administered daily for the first week and 60 mg daily was administered from the second week thereafter. The severity of pain was evaluated using a numerical rating scale from 0 to 10. Study follow-up was performed at regular visits according to the chemotherapy schedule or at the time of evaluation of disease status in the patients who completed systemic chemotherapy. However, the patients were allowed to visit whenever needed. Results: Twenty-seven patients were evaluable, the median age was 64 years (range, 23-83 years), and 11 patients were male and 16 patients were female. Twenty-four of the 27 patients received neurotoxic chemotherapeutic agents such as cisplatin, oxaliplatin, taxane and vinca alkaloid. Patients receiving duloxetine showed a significant reduction in the pain intensity from baseline and the mean decrease in the average pain score was 2.85 (95% CI 2.26-3.44, P &lt; 0.001). Twenty-five (92.5%) of the 27 patients showed decreased pain after the use of duloxetine. Mean duration of treatment was 29 weeks (range, 1~130 weeks). Median duration of response was 19 weeks (range, 4~99 weeks). Treatment-related adverse events were nausea (17.2%), vomiting (3.4%) and dizziness (6.8%). Conclusions: Duloxetine demonstrated a durable efficacy and tolerability for painful CIPN in patients with advanced cancer.

Impact of Functional Allelic Variations on Drug-Drug Interactions Involving CYP2D6

CYP2D6 genetically-predicted Extensive Metabolizers (gEMs) may carry one or two functional alleles. Currently phenotypes of carriers of two fully-functional alleles (genetic activity score 2, gAS2) and carriers of one fully-functional and one non-functional allele (genetic activity score 1, gAS1) are predicted EMs. However, drug-drug interactions (DDIs) might be underestimated among gAS1 patients. This study explores the impact of functional allelic variations on DDIs among gEMs. 34 healthy volunteers were allocated to two parallel study groups: gAS1 and gAS2. Dextromethorphan/dextrorphan metabolic ratio (UMR) in urine sampled for 10 hours after administration of 5 mg dextromethorphan was used to determined CYP2D6 phenotype in each of three study sessions. Volunteers additionally received 12 and 2 hours prior to dextromethorphan administration 60 mg of duloxetine in session 2 and 20 mg of paroxetine in session 3. Baseline phenotype distribution was not significantly different between the two genotypes. Higher proportion of IM was observed with the moderate inhibitor duloxetine: 71% of gAS1 and 25% of gAS2 subjects (p=0.009). With the strong inhibitor paroxetine, almost all gAS1 subjects were phenoconverted into PM (94%) whereas this proportion was lower in gAS2 subjects (56%, p=0.011). UMR values were significantly higher in gAS1 subjects than in gAS2 subjects in all conditions tested: 0.030 (CI95% 0.027–0.070) versus 0.009 (CI95% 0.007–0.022) (p=0.006) at baseline, 0.046 (CI95% 0.039–0.093) versus 0.017 (CI95% 0.012–0.038) with duloxetine (p=0.005) and 1.106 (CI95% 1.052–1.650) versus 0.344 (CI95% 0.249–0.745) with paroxetine (p<0.001). The proportion of PM phenoconversion with a strong inhibitor is higher in gEMs subjects carrying a non-functional CYP2D6 allele. Therefore, those individuals might be prone to adverse drug-drug interactions and might benefit from special attention when administered a CYP2D6 inhibitor.

The effect of duloxetine on chemotherapy-induced peripheral neuropathy in advanced pancreatic cancer patients receiving gemcitabine plus nab-paclitaxel treatment.

453 Background: Recently, gemcitabine plus nab-paclitaxel (GN) has come to be used frequently as the first-line chemotherapy for advanced pancreatic cancer. It has been reported that chemotherapy-induced peripheral neuropathy (CIPN) associated with nab-paclitaxel (nab-PTX) may impair the quality of life of the patients, and may, moreover, necessitate dose reduction or early cessation of the chemotherapy, thereby potentially impacting patient survival. However, there are no established treatments against CIPN. Several reports have suggested that duloxetine, which has been proved to be highly effective in managing diabetic peripheral neuropathy, is also effective against CIPN induced by platinum agents and taxanes. The aim of this study was to examine the frequency of nab-PTX related CIPN, its various influences, and the efficacy of duloxetine in the management of CIPN. Methods: Data of 121 pancreatic cancer patients who received GN as first chemotherapy between December 2014 and December 2015 at the National Cancer Center Hospital East, Japan, were analyzed retrospectively. Results: The frequency of CIPN of any grade was 60.3% (73 patients) and that of CIPN of grade ≥ 2 was 21.5% (26 patients). Among the patients who showed CIPN, 34 patients received 20-60 mg of duloxetine once daily, and the remaining patients never received it (no duloxetine group). 18 patients were on duloxetine for more than four weeks (the duloxetine group). 8 patients discontinued duloxetine in less than four weeks because of its side effects, such as, nausea, and somnolence. In the duloxetine group, CIPN was improved in 4 patients, and remained non-progressive in 12 patients. The relative dose intensity (RDI) of nab-PTX since the emergence of CIPN in the duloxetine group was higher than that in the no duloxetine group (63.2 % vs. 48.2 %, p = 0.0046). Conclusions: The frequency of nab-PTX related CIPN at our hospital was almost similar to that of previous reports. The results of this study suggest the possibility that duloxetine not only improves nab-PTX-related CIPN, but delays its progression. Therefore, it might contribute to continuing GN with a high RDI for longer periods of time.

Self-Limited Kleptomania Symptoms as a Side Effect of Duloxetine.

Introduction. Impulse control disorders (ICDs) have been described as a side effect of dopamine agonists, frequently used in neurodegenerative conditions affecting the nigrostriatal pathway. Serotonin-norepinephrine reuptake inhibitors (e.g., duloxetine) have dose-dependent differential affinity for monoaminergic transporters, inhibiting the dopamine transporter at higher doses, thus increasing availability of synaptic dopamine, with the potential for similar impulse control side effects. Case Presentation. A 19-year-old Asian-American female with a history of depression developed new-onset stealing behaviors after an increase in her dose of duloxetine from 60 mg to 90 mg; she described these actions as “compulsive” and irresistible, later experiencing either relief or guilt, features compatible with an ICD. Her symptoms eventually subsided with continued use of 90 mg of duloxetine. Discussion. To the knowledge of the authors, this is the first report of a patient developing new-onset ICD behaviors after being placed on a higher dose of duloxetine, which can inhibit the dopamine transporter and cause difficulty with impulse control. The self-resolving nature of the symptoms may result from compensatory upregulation of dopamine transporters, increasing reuptake of dopamine. Asian populations may be at a higher risk due to the frequent occurrence of CYP2D6 polymorphisms, which decrease the conversion of duloxetine to its inactive metabolites.

Effect of duloxetine on chemotherapy-induced painful peripheral neuropathy.

181 Background: Approximately 20% to 40% of patients with cancer who receive neurotoxic chemotherapy will develop painful chemotherapy-induced peripheral neuropathy. Smith et. al firstly reported that duloxetine was effective on above neuropathy after taxanes and platinums (JAMA 2013), so we planed to evaluate the duloxetine effect in Japanese patients after above drugs and more expanding drugs include vinca alkaloids and bortezomib. Methods: Patients were randomized to receive either duloxetine followed by vitamin(V)B12 or VB12 by duloxetine. The initial treatment consisted of 20 mg of duloxetine or 1.5g VB12 for the first week and 40mg of duloxetine or VB12 daily for 3 additional weeks (an open label, randomized, crossover). Dose reduction by the adverse effects was permitted. The primary hypothesis was that duloxetine would be more effective than VB12 in decreasing chemotherapy-induced peripheral neuropathic pain. Numbness and Pain severity were assessed weekly using visual analogue scale (VAS). This research was approved by the Research Ethics Committee of Higashi Sapporo Hospital and University Hospital Medical Information Network (UMIN) Center in Japan.Thirty-four cases (Breast cancer: taxanes 2, gastric cancer: taxane 5, colon cancer: oxaliplatin 6, Malignant lymphoma: vincristine 13, multiple myeloma: bortezomib 8) were made an entry in our institution. Five cases dropped out because of the adverse effect with sleepy and general malaise. Results: Obvious improvements of VAS scores of numbness and pain were observed in duloxetine group. Significant differences of delta VAS (pre VAS scale – 4 weeks VAS after drug administration) were observed between duloxetine group and VB12 group in the aspect of numbness (p=0.02) and pain (p=0.03). Conclusions: Among patients with painful chemotherapy-induced peripheral neuropathy, the use of duloxetine compared with VB12 for 4 weeks resulted in a reduction in numbness and pain, but there are many cases with drop out by the adverse effects. Clinical trial information: 000011554.

O2-6-2 - Effect of Duloxetine on Painful Chemotherapy-Induced Peripheral Neuropathy

Approximately 20-40% of cancer patients who receive neurotoxic chemotherapy develop painful chemotherapy-induced peripheral neuropathy.Smith et al. were the first to report that duloxetine was effective for neuropathy after administration of taxanes and platinums (JAMA 2013). Therefore, the aim of this study was to evaluate the effect of duloxetine in Japanese patients after administration of the above-mentioned drugs as well as additional drugs such as vinca alkaloids and bortezomib.In this open-label randomized crossover study, patients were randomly allocated to receive either duloxetine followed by vitamin (V) B12 or VB12 followed by duloxetine. The initial treatment consisted of 20 mg of duloxetine or VB12 for the first week and 40 mg of duloxetine or VB12 daily for 3 additional weeks. Dose reduction was permitted if adverse effects were observed. The primary hypothesis was that duloxetine would be more effective than VB12 in reducing chemotherapy-induced peripheral neuropathic pain. The numbness and pain severity were assessed weekly using a visual analogue scale (VAS). (UMIN 000011554)Eighteen cancer cases (breast cancer [2 cases]: taxane, gastric cancer [1]: taxane, colon cancer [3]: oxaliplatin, malignant lymphoma [8]: vincristine, multiple myeloma [4]: bortezomib) presented at our institution. Four patients dropped out because of the adverse effects, such as drowsiness and general malaise. The observed mean difference in the average pain scores between patients administered duloxetine and VB12 was 0.46 (p = 0.03). That of numbness scores was 0.63 (p = 0.04). In patients with painful chemotherapy-induced peripheral neuropathy, administration of duloxetine resulted in increased pain reduction as compared to the group that was administered VB12 for 4 weeks; however, many patients dropped out of the study because of the adverse effects of the treatment.

A Comparison of Duloxetine Plasma Levels in Postbariatric Surgery Patients Versus Matched Nonsurgical Control Subjects

Bariatric surgery such as the Roux-en-Y gastric bypass (RYGB) is currently used as a treatment for severe obesity. Alteration of the gastrointestinal tract by this procedure suggests a potential for clinically significant alterations in the bioavailability of ingested medications including antidepressants. The purpose of this trial was to determine to what extent the RYGB procedure alters the area under the plasma concentration/time curve (AUC(0-infinity)) of the antidepressant, duloxetine. Ten subjects who were 1 year post-RYGB where compared with healthy control subjects matched for body mass index, age, and sex. Ultrarapid or poor metabolizers for cytochrome P450 2D6 were excluded from the study. Subjects received a single dose of 60 mg of duloxetine. Nineteen plasma samples were obtained during 72 hours to characterize the plasma level profile. The mean AUC(0-infinity) was significantly smaller for the postbariatric surgery (PBS) group (646.74 ng × h/mL [SD, 79.70; range, 539.57-791.62], P = 0.017) compared to the nonsurgical control group (1119.91 ng × h/mL [SD, 593.40; range, 415.5-2426.56]). The Tmax was also significantly shorter for the PBS group (2.2 hours) compared to the nonsurgical control group (6 hours; P = 0.005). No significant difference in Cmax or half-life was identified. To our knowledge, this is the first reported study exploring duloxetine pharmacokinetics PBS. This trial found that the bariatric surgery group was exposed to only 57.7% of duloxetine as compared to the nonsurgery group. This finding suggests that clinicians need to monitor patients closely after bariatric surgery and that further exploration of the effects of bariatric surgery on antidepressant pharmacokinetic parameters is warranted.

Effect of Duloxetine on Pain, Function, and Quality of Life Among Patients With Chemotherapy-Induced Painful Peripheral Neuropathy

There are no known effective treatments for painful chemotherapy-induced peripheral neuropathy. To determine the effect of duloxetine, 60 mg daily, on average pain severity. Randomized, double-blind, placebo-controlled crossover trial at 8 National Cancer Institute (NCI)-funded cooperative research networks that enrolled 231 patients who were 25 years or older being treated at community and academic settings between April 2008 and March 2011. Study follow-up was completed July 2012. Stratified by chemotherapeutic drug and comorbid pain risk, patients were randomized to receive either duloxetine followed by placebo or placebo followed by duloxetine. Eligibility required that patients have grade 1 or higher sensory neuropathy according to the NCI Common Terminology Criteria for Adverse Events and at least 4 on a scale of 0 to 10, representing average chemotherapy-induced pain, after paclitaxel, other taxane, or oxaliplatin treatment. The initial treatment consisted of taking 1 capsule daily of either 30 mg of duloxetine or placebo for the first week and 2 capsules of either 30 mg of duloxetine or placebo daily for 4 additional weeks. The primary hypothesis was that duloxetine would be more effective than placebo in decreasing chemotherapy-induced peripheral neuropathic pain. Pain severity was assessed using the Brief Pain Inventory-Short Form "average pain" item with 0 representing no pain and 10 representing as bad as can be imagined. Individuals receiving duloxetine as their initial 5-week treatment reported a mean decrease in average pain of 1.06 (95% CI, 0.72-1.40) vs 0.34 (95% CI, 0.01-0.66) among those who received placebo (P = .003; effect size, 0.513). The observed mean difference in the average pain score between duloxetine and placebo was 0.73 (95% CI, 0.26-1.20). Fifty-nine percent of those initially receiving duloxetine vs 38% of those initially receiving placebo reported decreased pain of any amount. Among patients with painful chemotherapy-induced peripheral neuropathy, the use of duloxetine compared with placebo for 5 weeks resulted in a greater reduction in pain. clinicaltrials.gov Identifier: NCT00489411.

Acute Massive Pulmonary Thromboembolism Due to Acute Intoxication by Duloxetine: A Case Report

Duloxetine (Cymbalta) is a potent serotonin norepinephrine reuptake inhibitor used for the management of major depression and pain associated with diabetic peripheral neuropathy. Cymbalta delayed-release capsules contain Duloxetine HCl equivalent to 20, 30, 60mg of Duloxetine. The ingestion of high quantities of Duloxetine may have serious outcomes such as venous thrombosis, causing cardiac respiratory arrest. The Authors outline a case report of an elderly woman, suffering from depression, found dead in her apartment. The cause of death was attributed to acute massive pulmonary thromboembolism due to acute intoxication of Duloxetine bought the day before. The thesis supported by the authors and confirmed by the data from other studies is that a massive intake of Duloxetine drug increases considerably the medication's side effects such as somnolence, dry mouth, fatigue, insomnia, dizziness, constipation, considerable increases in recumbent systolic and diastolic blood pressure, and a small decrease in heart rate.

Augmentative Effects of Fluvoxamine on Duloxetine Plasma Levels in Depressed Patients

Duloxetine is a potent and selective inhibitor of serotonin and norepinephrine reuptake with weak activity on dopamine reuptake. Enzymes involved in duloxetine metabolism are cytochrome P450 isoenzymes (CYP) CYP1A2 and to a lesser extent CYP2D6 whereas the selective serotonin reuptake inhibitor Fluvoxamine is known to be a potent inhibitor of CYP1A2. Changes in plasma levels of duloxetine revealing pharmacokinetic interactions with fluvoxamine, clinical effects and adverse effects of adding fluvoxamine in thirteen patients with a steady-state duloxetine treatment by intraindividual comparisons were analyzed in this retrospective survey. Patients had been treated with duloxetine under steady-state conditions until fluvoxamine was added. Plasma duloxetine levels were measured at steady state of different daily doses due to lacking experience with the combination of DLX and FLX. Adding 25 mg of fluvoxamine (FLX) per day to a steady-state treatment with 30 mg of duloxetine (DLX) in 8 patients led to an average increase of duloxetine plasma levels that was 3-fold with a magnitude of 50-506%. Our findings indicate that duloxetine plasma levels can be enhanced by a potent CYP1A2 inhibition by FLX and that DLX, even in higher plasma levels, seems to be well tolerated. The use of combined treatments, however, underscores the importance of understanding pharmacokinetic interactions.

Augmentative effects of fluvoxamine on duloxetine plasma levels in depressed patients

Duloxetine is a potent and selective inhibitor of serotonin and norepinephrine reuptake with weak activity on dopamine reuptake. Enzymes involved in duloxetine-metabolism are cytochrome P450 isoenzymes (CYP) CYP1A2 and to a lesser extent CYP2D6 whereas the selective serotonin reuptake inhibitor Fluvoxamine is known to be a potent inhibitor of CYP1A2. Changes in plasma levels of duloxetine revealing pharmacokinetic interactions with fluvoxamine, clinical effects and adverse effects of adding fluvoxamine in twelve patients with a steady-state duloxetine treatment by intraindividual comparisons were analyzed in this retrospective survey. Patients had been treated with a monotherapy of duloxetine under steady-state conditions until fluvoxamine was added. Serum duloxetine levels were measured at steady-state of different daily doses due to lacking experience with the combination of DLX and FLX. Adding 25 mg of fluvoxamine (FLX) per day to a steady-state treatment with 30 mg of duloxetine (DLX) in eight patients led to an average increase of duloxetine plasma levels that was threefold with a magnitude of 50% to 506%. Our findings indicate that duloxetine-plasma levels can be enhanced by a potent CYP1A2 inhibition by FLX and DLX, even in higher plasma levels, seems to be well tolerated. The use of combined treatments, however, underscores the importance of understanding pharmacokinetic interactions.

Average daily dose, medication adherence, and healthcare costs among commercially-insured patients with fibromyalgia treated with duloxetine

Objective:What is the relationship between average daily dose (ADD) of duloxetine, adherence to therapy, and healthcare costs among patients with fibromyalgia?Methods:Employing a retrospective cohort design, this study assessed administrative claims data for commercially-insured fibromyalgia patients who initiated duloxetine in 2006. Initiation was defined as a 90-day clean period without access to duloxetine. Five study cohorts were constructed based on the ADD of duloxetine, calculated from all prescriptions dispensed over the 12-month follow-up period: <30 mg, 30 mg, 31–59 mg, 60 mg, and >60 mg (duloxetine starting dose: 30 mg/day; target dose: 60 mg/day). Medication possession ration (MPR) was used to assess duloxetine adherence, with MPR ≥0.8 as ‘high’ adherence. Multivariate regressions were applied to examine the association between ADD, duloxetine adherence, and healthcare costs (total, inpatient, outpatient, and pharmacy), adjusting for differences in demographic and clinical characteristics between cohorts.Results:Of the 4869 patients with fibromyalgia, 3% had an ADD of <30 mg, 12% had 30 mg, 21% had 31–59 mg, 46% had 60 mg, and 18% had >60 mg. High adherence to duloxetine ranged from 16% to 41% across cohorts. Controlling for demographic and clinical characteristics, patients with an ADD of 31–59 mg or >60 mg were more likely to adhere to duloxetine therapy than those in the 60 mg cohort, while patients in the <30 mg cohort were less likely to adhere to duloxetine (all p < 0.05). Total costs were significantly higher for individuals in the 31–59 mg or >60 mg ADD cohorts ($1834 and $5766) than those maintaining an ADD of 60 mg, as were outpatient ($1167 and $2275) and pharmacy costs ($502 and $2983) (all p < 0.05). Patients with an ADD of 30 mg had significantly lower total (−$1770), inpatient (−$1524), and pharmacy (−$827) costs (all p < 0.05) than those with an ADD of 60 mg.Limitations:This study is subject to selection bias because some confounders might be unobserved in the administrative claims database. Indirect costs or over-the-counter medication costs were also not available.Conclusions:Fibromyalgia patients with an ADD of 60 mg of duloxetine had better adherence than patients with an ADD ≤30 mg. Duloxetine patients with an ADD of 30 mg (31–59 or >60 mg) had significantly lower (higher) healthcare costs than those maintaining an ADD of 60 mg.

Treating fibromyalgia with duloxetine among elderly patients: what is the association between average daily dose, medication adherence, and healthcare costs?

The objective of this study is to understand the relationship between average daily dose (ADD) of duloxetine, medication adherence, and healthcare costs among elderly fibromyalgia patients. This study employed a retrospective cohort design to analyze medical and pharmacy claims data for patients with Medicare supplemental insurance diagnosed with fibromyalgia. Selected patients were ≥ 65 of age who initiated (a 90-day duloxetine medication gap) duloxetine in 2006. Dispense date of the first duloxetine prescription was defined as the index date. All patients selected were required to have at least 30 days of duloxetine supply in the 12-month post-index period. Patients with diagnosis of diabetic peripheral neuropathic pain or depression during the 12-month pre-index period were excluded. Five cohorts were constructed based on ADD: <30mg, 30mg, 31-59mg, 60mg, and >60mg. Adherence was measured via medication possession ratio (MPR) over 12-month post-index period, with MPR≥0.8 defined as high adherence. Multivariate regression models were used to examine the relationships between ADD, medication adherence, and healthcare costs. The study sample included 566 fibromyalgia patients (mean age 73, 84% female), of which 6.7% had ADD of <30mg, 16.4% of 30mg, 24.0% of 31-59mg, 43.5% of 60mg, and 9.4% of >60mg. Approximately one-third of the duloxetine patients achieved high adherence. Adjusting for demographic and clinical characteristics, patients with ADD ≤30mg were less likely to adhere to duloxetine than those with 60mg (OR=0.34 and 0.43 for <30mg and 30mg, respectively; both p<0.05), while patients with ADD >60mg were more likely (OR=2.03, p<0.05). Total healthcare costs ranged from $17,971 to $30,374 among cohorts, but differences were not statistically significant. In conclusion, elderly fibromyalgia patients with an ADD ≥ 60mg of duloxetine were more likely to adhere to the therapy. Total healthcare costs appear to be similar across ADD cohorts. (Funding was provided by Eli Lilly and Company.)