Chronic neuropathic pain is defined as ‘chronic pain caused by a lesion or disease of the somatosensory nervous system’ (Nicholas et al, 2019). This pain is persistent or recurrent, lasting 3 months or longer. As a chronic condition, neuropathic pain negatively impacts an individual's function and quality of life, as well as carrying a high healthcare cost. Individuals with chronic neuropathic pain have more complaints of sleep disorders and mood disorders, such as anxiety and depression (Haanpää and Treede, 2010). Adequate treatment of neuropathic pain results in improvements in quality of life, sleep and fatigue, among other complaints (Moore et al, 2014).
Common conditions such as post-herpetic neuralgia (PHN) and painful diabetic neuropathy (PDN) are classified as chronic neuropathic pain and are associated with pain lasting for longer than 3 months, emotional distress, hampered daily functioning and disability. In order to reduce the pain and improve function, non-pharmaceutical and pharmaceutical measures are used for management. Non-pharmaceutical measures include comfort therapy, physical and occupational therapy, psychosocial/therapy counselling and neurostimulation. Pharmaceutical therapies that have been used to treat neuropathic pain include anti-epileptics, tricyclic antidepressants and selective serotonin re-uptake inhibitors.
Objective/s
Wiffen et al (2017) conducted a meta-analysis seeking to assess the efficacy of gabapentin, an antiepileptic agent, in relieving chronic neuropathic pain in adults. In addition, the authors also assessed the adverse effects of the drug.
Intervention/methods
The authors assessed the efficacy of gabapentin in chronic neuropathic pain in adults aged 18 years and above. They used Cochrane Central Register of Controlled Trials, MEDLINE, and Embase as primary databases to conduct their search of eligible studies. The meta-analysis included randomised controlled trials with double-blind assessment of participant-reported outcomes with at least 2 weeks of treatment. The intervention used in the studies included in the review was gabapentin administered in any dose and by any route for the relief of neuropathic pain compared with placebo or any other active comparator. Two review authors independently assessed the risk of bias using criteria from the Cochrane Handbook for Systematic Reviews of Interventions. The authors assessed each study for random sequence generation, allocation concealment, blinding, incomplete outcome data and size of the study. A pooled analysis was conducted using the fixed-effects model using dichotomous outcomes to determine risk ratio (RR) and the number needed to treat (NNT) for an additional beneficial outcome or harmful outcome. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. No sensitivity analysis was conducted, because there were insufficient data with regard to the formulation of gabapentin and the nature and type of neuropathic pain at the participant level.
The main pain outcomes were: substantial, that is, at least 50% pain relief over the baseline or a very much improved patient global impression of change (PGIC) score; or moderate, that is, at least 30% pain relief over the baseline or a much or very much improved PGIC score. These are outcomes desired by people with pain (Moore et al, 2013).
Results
The meta-analysis included 37 studies involving 5914 participants. The majority of studies involved participants with PHN and PDN.
For the studies with participants who experienced PHN, 32% of patients given gabapentin reported a substantial benefit, while 17% of those given placebo reported a substantial benefit, yielding an RR of 1.8 and NNT of 6.7. Some 46% of participants who were given gabapentin reported a moderate benefit, while 25% of those given placebo reported a moderate benefit, yielding an RR of 1.8 and NNT of 4.8.
For studies with participants who experienced PDN, 38% of patients given gabapentin reported a substantial benefit, while 21% of those given placebo reported a substantial benefit, yielding an RR of 1.9 and NNT of 5.9. Some 52% of participants given gabapentin reported a moderate benefit, while 37% of patients given placebo reported a moderate benefit, yielding an RR of 1.4 and NNT of 6.6.
For the analysis of adverse events, the authors pooled data from all participants. At least one adverse event occurred in 63% of patients given gabapentin and in 49% given placebo, yielding a RR of 1.3.
The authors assessed the quality of evidence to be moderate for both studies that included participants who experienced PHN and those including participants who experienced PDN; the results between studies were consistent. However, there were uncertainties and differences between dosing, dosing schedules and formulation used. Other studies included in the analysis involved neuropathic pain conditions related to spinal cord injury, phantom limb pain, cancer, nerve injury pain, complex regional pain syndrome, HIV and radicular leg pain, with several studies involving a mixture of types of neuropathic pain. However, the authors assessed the quality of evidence for those as very low due to the small number of studies, participants and events.
Conclusions
The authors concluded that gabapentin at daily doses of 1800–3600 mg provided ‘good levels’ of pain relief in some patients, especially those with PHN and PDN. The reported effects of gabapentin were both beneficial and undesirable (adverse effects). The beneficial effects included less sleep interference, less fatigue and a decrease in depressive symptoms. The adverse effects included somnolence, dizziness, peripheral oedema and gait disturbance.
Implications for practice
Nurses in practice must be aware of the pharmacokinetics and pharmacodynamics of gabapentin if it is prescribed for pain management. Nurses should also be actively involved in educating and counselling the patient about the drug, for which the material used should include administration information; adverse effects, such as increased risk of suicidal thoughts and behaviour and effects on driving and operating heavy machinery; symptoms of hypersensitivity; and when to seek medical care. In addition, nurses should advise the patient to read the approved patient labelling or medication guide. Lastly, nurses should be familiar with pain assessment tools in order to evaluate the effectiveness of the gabapentin treatment.