This review found that duloxetine was equally effective for treatment of painful diabetic neuropathy and fibromyalgia pain and was well tolerated. It was likely to be a useful drug in these difficult-to-treat conditions. Overall this was a clearly reported review and the conclusions are likely to be reliable.

To review the efficacy of duloxetine in the management of painful diabetic neuropathy (PDN) and fibromyalgia.

PUBMED, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) were searched to June 2008. Search terms were reported. Reference lists were searched for additional papers. The UK distributor of the drug was contacted. An online pharmaceutical company trial register was searched. Only full publications were considered for inclusion.

Double-blind randomised controlled trials (RCTs) that compared duloxetine with placebo for treatment of painful neuropathies in adult patients were considered eligible. Trials were required to last at least four weeks and have treated a minimum of 10 patients per treatment arm. The primary outcome was 50% pain relief. Secondary outcomes included withdrawals, adverse events and other pain relief measures.

Half of the included studies enrolled patients with PDN and half enrolled patients with fibromyalgia. PDN studies excluded patients with diagnosed psychological disorders. Between 23% and 38% of fibromyalgia patients were diagnosed with major depression. All patients had at least moderate severity of baseline pain according to validated scales. Mean participant age ranged from 49 to 61 years. The proportion of men ranged from 0% to 61% across the trials. Duration ranged from 12 to 13 weeks. Duloxetine was given as 20mg, 60mg or 120mg daily. Acetaminophen was allowed as a rescue pain medication, up to 2mg for fibromyalgia patients and up to 4mg daily for PDN patients.

Studies were selected by three reviewers independently. Any discrepancies were resolved by consensus.

Methodological quality was assessed using the Jadad/Oxford five-point scale of randomisation, blinding and withdrawals. Only studies that scored a minimum of 2 points (blinded and randomised) could be included in the review. Study validity was assessed separately using Oxford Pain Validity score, a validated 16-point scale (no further details reported).

Studies were quality assessed by three reviewers independently. Any discrepancies were resolved by consensus.

Data were extracted for each included study using a standard form that included primary and secondary outcomes as prespecified. One trial reported 13-week continuation phase data; this was not extracted so as to ensure comparability across all included studies. Continuous outcomes were extracted as mean differences and dichotomous outcomes as relative risks. Where at least one arm of a trial reported no events 0.5 was added to both treatment and comparator arms.

Extraction was carried out by three reviewers independently. Any discrepancies were resolved by consensus.

A fixed-effects model was used to pool the primary studies and calculate relative risk with 95% confidence intervals (CI) and number needed to treat or harm (NNT or NNH). Continuous variables were pooled to calculate weighted mean differences (WMD) with 95% CI. The authors stated an a priori decision to pool only where there was clinical and methodological homogeneity between studies with adequate numbers of events.

Heterogeneity was assessed using graphs rather than statistical tests of funnel plots, but I² was reported alongside weighted mean differences. Sensitivity analyses were planned to assess the impact of trial quality/validity, duloxetine dose and pain syndrome where at least two trials and 250 patients were available.

A total of six trials was included (n=2,216). Overall the trials were judged to be of good methodological quality: most scored 3 or more on the Oxford/Jadad scale and all scored 13 or better on the Oxford Validity Score. No significant heterogeneity was reported for any of the analyses.

50% Pain Relief (six trials): Duloxetine of any dose overall provided significantly greater numbers of patients who reported better than 50% pain relief than placebo (RR 1.7, 95% CI 1.4 to 1.9, NNT=5.9, 95% CI 4.8 to 7.7). Analysis of these results by duloxetine dose and by patient group did not significantly alter the findings.

Average Pain Score (five trials): Duloxetine patients reported significantly lower 24-hour average pain scores when compared with placebo for both 60mg dose (WMD 0.98, 95% CI 0.72 to 1.23, p<0.001) and 120mg dose (WMD 1.12, 95% CI 0.87 to 1.38, p<0.00001) regardless of pain syndrome.

Adverse events: Withdrawals due to adverse events occurred significantly more frequently in duloxetine than placebo patients (RR 1.8, 95% CI 1.4 to 2.4, NNH=15, 95% CI 11 to 25). Serious adverse events were not always well reported, but appeared to be infrequent.

Duloxetine was equally effective for treatment of painful diabetic neuropathy and fibromyalgia pain and was well tolerated. It was likely to be a useful drug in these difficult-to-treat conditions.

This review addressed a clear clinical question with relevant inclusion criteria. The searches covered major databases and some sources of grey literature, although only full papers were considered for inclusion; it was difficult to say whether publication and language biases may have influenced this review. Overall the methodological processes were well reported and carried out in a way likely to minimise reviewer error and bias. It would have been useful for further details of the quality/validity assessments to be presented (summary scores tend to obscure useful details about primary study reliability). The analyses appeared appropriate and potential clinical differences were explored. Overall this was a clearly reported review and the conclusions are likely to be reliable.

Practice: Duloxetine was likely to be a useful drug in treatment of painful diabetic neuropathy and fibromyalgia pain. Doses higher than 60mg did not provide additional pain relief and may increase withdrawals due to adverse events.

Research: No recommendations were made for research.

No direct funding was received for this review.

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.