Venlafaxine for neuropathic pain in adults.

BACKGROUND: Neuropathic pain, which is caused by nerve damage, is increasing in prevalence worldwide. This may reflect improved diagnosis, or it may be due to increased incidence of diabetes-associated neuropathy, linked to increasing levels of obesity. Other types of neuropathic pain include post-herpetic neuralgia, trigeminal neuralgia, and neuralgia caused by chemotherapy. Antidepressant drugs are sometimes used to treat neuropathic pain; however, their analgesic efficacy is unclear. A previous Cochrane review that included all antidepressants for neuropathic pain is being replaced by new reviews of individual drugs examining chronic neuropathic pain in the first instance. Venlafaxine is a reasonably well-tolerated antidepressant and is a serotonin reuptake inhibitor and weak noradrenaline reuptake inhibitor. Although not licensed for the treatment of chronic or neuropathic pain in most countries, it is sometimes used for this indication. OBJECTIVES: To assess the analgesic efficacy of, and the adverse effects associated with the clinical use of, venlafaxine for chronic neuropathic pain in adults. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) via The Cochrane Library, and MEDLINE and EMBASE via Ovid up to 14 August 2014. We reviewed the bibliographies of any randomised trials identified and review articles, contacted authors of one excluded study and searched www.clinicaltrials.gov to identify additional published or unpublished data. We also searched the meta-Register of controlled trials (mRCT) (www.controlled-trials.com/mrct) and the WHO International Clinical Trials Registry Platform (ICTRP) (apps.who.int/trialsearch/) for ongoing trials but did not find any relevant trials. SELECTION CRITERIA: We included randomised, double-blind studies of at least two weeks' duration comparing venlafaxine with either placebo or another active treatment in chronic neuropathic pain in adults. All participants were aged 18 years or over and all included studies had at least 10 participants per treatment arm. We only included studies with full journal publication. DATA COLLECTION AND ANALYSIS: Three review authors independently extracted data using a standard form and assessed study quality. We intend to analyse data in three tiers of evidence as described by Hearn 2014, but did not find any first-tier evidence (ie evidence meeting current best standards, with minimal risk of bias) or second-tier evidence, that was considered at some risk of bias but with adequate participant numbers (at least 200 in the comparison). Third-tier evidence is that arising from studies with small numbers of participants; studies of short duration, studies that are likely to be of limited clinical utility due to other limitations, including selection bias and attrition bias; or a combination of these. MAIN RESULTS: We found six randomised, double-blind trials of at least two weeks' duration eligible for inclusion. These trials included 460 participants with neuropathic pain, with most participants having painful diabetic neuropathy. Four studies were of cross-over design and two were parallel trials. Only one trial was both parallel design and placebo-controlled. Mean age of participants ranged from 48 to 59 years. In three studies (Forssell 2004, Jia 2006 and Tasmuth 2002), only mean data were reported. Comparators included placebo, imipramine, and carbamazepine and duration of treatment ranged from two to eight weeks. The risk of bias was considerable overall in the review, especially due to the small size of most studies and due to attrition bias. Four of the six studies reported some positive benefit for venlafaxine. In the largest study by Rowbotham, 2004, 56% of participants receiving venlafaxine 150 to 225 mg achieved at least a 50% reduction in pain intensity versus 34% of participants in the placebo group and the number needed to treat for an additional beneficial outcome was 4.5. However, this study was subject to significant selection bias. Known adverse effects of venlafaxine, including somnolence, dizziness, and mild gastrointestinal problems, were reported in all studies but were not particularly problematic and, overall, adverse effects were equally prominent in placebo or other active comparator groups. AUTHORS' CONCLUSIONS: We found little compelling evidence to support the use of venlafaxine in neuropathic pain. While there was some third-tier evidence of benefit, this arose from studies that had methodological limitations and considerable risk of bias. Placebo effects were notably strong in several studies. Given that effective drug treatments for neuropathic pain are in current use, there is no evidence to revise prescribing guidelines to promote the use of venlafaxine in neuropathic pain. Although venlafaxine was generally reasonably well tolerated, there was some evidence that it can precipitate fatigue, somnolence, nausea, and dizziness in a minority of people.

Improving the working relationship between doctors and pharmacists: is inter-professional education the answer?

Despite their common history, there are many cultural, attitudinal and practical differences between the professions of medicine and pharmacy that ultimately influence patient care and health outcomes. While poor communication between doctors and pharmacists is a major cause of medical errors, it is clear that effective, deliberate doctor-pharmacist collaboration within certain clinical settings significantly improves patient care. This may be particularly true for those patients with chronic illnesses and/or requiring regular medication reviews. Moreover, in hospitals, clinical and antibiotic pharmacists are successfully influencing prescribing and infection control policy. Under the new Irish Pharmacy Act (2007), pharmacists are legally obliged to provide pharmaceutical care to their patients, thus fulfilling a more patient-centred role than their traditional 'dispensing' one. However, meeting this obligation relies on the existence of good doctor-pharmacist working relationships, such that inter-disciplinary teamwork in monitoring patients becomes the norm in all healthcare settings. As discussed here, efforts to improve these relationships must focus on the strategic introduction of agreed changes in working practices between the two professions and on educational aspects of pharmaceutical care. For example, standardized education of doctors/medical students such that they learn to prescribe in an optimal manner and ongoing inter-professional education of doctors and pharmacists in therapeutics, are likely to be of paramount importance. Here, insights into the types of factors that help or hinder the improvement of these working relationships and the importance of education and agreed working practices in defining the separate but inter-dependent professions of pharmacy and medicine are reviewed and discussed.