duloxetine

Efficacy of Duloxetine in Patients with Central Post-Stroke Pain: A Randomized Double Blind Placebo Controlled Trial.

Posted by

0


OBJECTIVE: Central post-stroke pain (CPSP) refers to neuropathic pain in areas of the body corresponding to stroke lesions. Duloxetine, a serotonin-norepinephrine reuptake inhibitor, is safe and effective against neuropathic pain. In this randomized double-blind placebo-controlled study, we studied the effect of duloxetine in CPSP patients.

METHODS: Consecutive patients satisfying the inclusion criteria were enrolled in the study and were randomized in a simple 1:1 randomization to duloxetine and placebo groups. Baseline demographic, clinical and imaging data were obtained. Prespecified primary outcome was comparison of change in pain intensity from baseline to 4 weeks, as assessed on Numeric Rating Scale (NRS) in both groups. Prespecified secondary outcomes were comparison of change in average pain severity from baseline to 4 weeks as measured on Short-form McGill Pain Questionnaire-2 (SFMPQ-2) score and Pain Disability Index (PDI) score and comparison of Patient Global Impression of Change (PGIC) score at the end of 4 weeks of treatment in both groups. Duloxetine at doses of 30 mg and similarly appearing placebo tablets were given and the dose was doubled if there was no response at the end of 2 weeks. Response to treatment was defined as = 2 points reduction of NRS pain score.

RESULTS: Total 82 patients were enrolled in the study, 41 in each group. There was a significant difference in reduction in NRS score between duloxetine and placebo group from baseline (6.51 ± 1.03 vs 6.37 ± 1.41) to 4 weeks (3.02 ± 1.70 vs 4.40 ± 1.77, p = 0.02 for difference in reduction between groups). SFMPQ-2 score (p = 0.032) and Pain Disability Index score (p = 0.005) also differ significantly from baseline to 4 weeks between the two groups. PGIC score at the end of 4 weeks was significantly different between the two groups (5.15 ± 1.54 versus 3.89 ± 1.51; p < 0.001). Responder rate (defined as % of patients with = 2 points reduction on NRS pain score from baseline to end of 4 weeks), on post-hoc analysis was found to be significantly higher in duloxetine group (80.5%) than placebo group (43.9%) (p = 0.042).

CONCLUSION: Duloxetine can be an effective treatment option for patients with moderate to severe central post-stroke pain.

Combination of pregabalin with duloxetine for fibromyalgia: a randomized controlled trial.

Posted by

0


Fibromyalgia is a syndrome characterized by chronic widespread pain and associated with sleep disturbance, depression, fatigue, and cognitive dysfunction. Polypharmacy is commonly used, but supportive evidence is limited. Most fibromyalgia trials focus primarily on pain reduction with monotherapy. This trial compares a pregabalin-duloxetine combination to each monotherapy. Using a randomized, double-blind, 4-period crossover design, participants received maximally tolerated doses of placebo, pregabalin, duloxetine, and pregabalin-duloxetine combination-for 6 weeks. Primary outcome was daily pain (0-10); secondary outcomes included global pain relief, Fibromyalgia Impact Questionnaire, SF-36 survey, Medical Outcomes Study Sleep Scale, Beck Depression Inventory (BDI-II), adverse events, and other measures. Of 41 participants randomized, 39 completed ≥2 treatments. Daily pain during placebo, pregabalin, duloxetine, and combination was 5.1, 5.0, 4.1, and 3.7, respectively (P < 0.05 only for combination vs placebo, and pregabalin). Participants (%) reporting ≥moderate global pain relief were 18%, 39%, 42%, and 68%, respectively (P < 0.05 for combination vs placebo, pregabalin, and duloxetine). Fibromyalgia Impact Questionnaire scores were 42.9, 37.4, 36.0, and 29.8, respectively (P < 0.05 for combination vs placebo, pregabalin, and duloxetine). SF-36 scores were 50.2, 55.7, 56.0, and 61.2, respectively (P < 0.05 for combination vs placebo, pregabalin, and duloxetine). Medical Outcomes Study Sleep Scale scores were 48.9, 35.2, 46.1, and 32.1, respectively (P < 0.05 only for combination vs placebo, and duloxetine). BDI-II scores were 11.9, 9.9, 10.7, and 8.9, respectively (P < 0.05 only for combination vs placebo). Moderate-severe drowsiness was more frequent during combination vs placebo. Combining pregabalin and duloxetine for fibromyalgia improves multiple clinical outcomes vs monotherapy. Continued research should compare this and other combinations to monotherapy for fibromyalgia.

Comments from Clinical Raters
General Internal Medicine-Primary Care(US)

The study is small (40 patients) and based on the medications involved, patients were not on antidepressants. Additionally, as stated by the authors, many fibromyalgia patients are already on combination therapy. While this combination is now tested, it is also more expensive and requires pre-authorization for many patients, limiting its generalizability. It is useful that a large % of pts reported at least moderate pain control, but I cannot see choosing these 2 medications specifically based on this study as opposed to cheaper medications or tailoring medications based on side effects.

Antidepressants Associated With Hyponatremia

Posted by

0


TAKE-HOME MESSAGE

  • A cohort of 638,352 people was evaluated from 1998 through 2012 to investigate the relationship between the use of antidepressants and the risk of hyponatremia. The incidence rate ratio for the association with hyponatremia after initiation of treatment was highest for citalopram (7.80) and lowest for mianserin (0.90). The incidence rate ratio for other agents were: clomipramine 4.93, duloxetine 2.05, venlafaxine 2.90, and mirtazapine 2.95.
  • Apart from mianserin, all antidepressant agents are associated with an increased risk of hyponatremia, with the highest risk seen with citalopram.

Antidepressants are associated with the development of several metabolic abnormalities. This study reports an association between antidepressants and the development of hyponatremia. With the wide use of antidepressants such as SSRIs and SNRIs, it is important to remember to monitor patients periodically on such medications for electrolyte disturbances, glucose intolerance, and lipid abnormalities. Elderly patients are especially at risk and may warrant closer monitoring as the use of other chronic medications and decreased renal clearance may further increase the risk for hyponatremia.

OBJECTIVE

To examine the association between classes of antidepressants and hyponatremia, and between specific antidepressants and hyponatremia.

DESIGN

Retrospective register-based cohort study using nationwide registers from 1998 to 2012.

SETTING

The North Denmark Region.

PARTICIPANTS

In total, 638 352 individuals were included.

PRIMARY AND SECONDARY OUTCOME MEASURES

Plasma sodium was obtained from the LABKA database. The primary outcome was hyponatremia defined as plasma sodium (p-sodium) below 135 mmol/L and secondary outcome was severe hyponatremia defined as p-sodium below 130 mmol/L. The association between use of specific antidepressants and hyponatremia was analysed using multivariable Poisson regression models.

RESULTS

An event of hyponatremia occurred in 72 509 individuals and 11.36% (n=6476) of these events happened during treatment with antidepressants. Incidence rate ratios and CIs for the association with hyponatremia in the first p-sodium measured after initiation of treatment were for citalopram 7.8 (CI 7.42 to 8.20); clomipramine 4.93 (CI 2.72 to 8.94); duloxetine 2.05 (CI 1.44 to 292); venlafaxine 2.90 (CI 2.43 to 3.46); mirtazapine 2.95 (CI 2.71 to 3.21); and mianserin 0.90 (CI 0.71 to 1.14).

CONCLUSIONS

All antidepressants except mianserin are associated with hyponatremia. The association is strongest with citalopram and lowest with duloxetine, venlafaxine and mirtazapine.