This large study aimed to provide updated incidence rates and prescribing practices for four neuropathic pain conditions as seen by UK general practitioners rather than in secondary care clinics. The population was similar to that of the UK in terms of age and sex, 51% were female as in the UK 2001 census data, while there were slightly fewer elderly patients, 20% over 60 years of age compared to 21% [14].
The incidence rate of 28.2 per 100,000 patient years for post-herpetic neuralgia is in-line with other published findings [15, 16] which give rates of 34 and 49 per 100,000 person years one month after acute herpes zoster. When compared to data from a similar general practice study, the incidence had decreased since 1998–2001, age-adjusted incidence of 56.8 per 100,000 population compared to 27.3 in 2002–2005 [8]. This may relate to the definition of PHN which included a GP diagnosis of post-herpetic neuralgia. A GP's perception of post herpetic neuralgia may include acute or sub-acute zoster pain. In addition to inflating the true incidence rate, if perceptions change with time and possibly education, this could explain the declining rates. Alternatively, treatment of acute herpes zoster with antiviral agents has been reported to reduce both the risk of developing post-herpetic neuralgia and the overall the duration of pain [17]. No UK data were available on the use of antivirals in herpes zoster, but information from the Netherlands suggest that, while they are used in a minority of patients (22.5%), treatment is more common in those at higher risk of complications [18]. Without intervention the rising age of the UK population might be expected to result in higher rates of post-herpetic neuralgia as age is a risk factor for both acute herpes zoster and post-herpetic neuralgia in acute herpes zoster [19].
Our finding of an incidence of trigeminal neuralgia of 27 per 100,000 person years is consistent with the previous database study, however these rates are considerably higher than those previously published (2.1 to 4.7 per 100,000 patient years and 8 per persons per annum [20–22]). This further supports the view that primary care physicians use a wide definition when they diagnose trigeminal neuralgia. The incidence of phantom limb pain of 0.8 per 100,000 person years is slightly less than the 1998–2001 rate of 0.9 [8] (age-adjusted rates of 0.8 per 100,000 person years and 1.3 in 1998–2001) as might be expected given the lower rate of limb amputations [23]. No other community based incidence rates were found for phantom limb pain.
Incidence rates for painful diabetic neuropathy, from both this and the previous UK general practice study are considered to be maximum incidences. The data source did not allow separation of patients with non-painful diabetic neuropathy who had a treatment for depression or other pain initiated at the same time as the neuropathy was first recorded from those treated for painful diabetic neuropathy. Although the crude incidence of painful diabetic neuropathy increased, age-adjusted rates (taking into account the new dataset) were the same for the 1998–2001 and 2002–2005 data.
Neuropathic pain treatment
A treatment was initiated at the time of diagnosis for between 40% and 74% of patients in the neuropathic cohorts. Other patients may have been established on a treatment before a firm diagnosis was made, particularly as definitions for both phantom limb pain and post-herpetic neuralgia include a delay between the precipitating event and diagnosis. The prescribing of antidepressants and antiepileptics is in-line with UK guidelines for neuropathic pain treatment [13, 24], although amitriptyline is not included in these recommendations for the first line treatment of trigeminal neuralgia. Amitriptyline is the tricyclic antidepressant of choice in all cohorts despite evidence that imipramine and nortriptyline are also effective [24]. Prescribing paracetamol alone, or in combination with codeine, is recommended for post-herpetic neuralgia patients with mild to moderate pain [10]. Our finding that combination therapy was more common than paracetamol alone could, in part, be due to the availability of over the counter paracetamol.
When compared to prescribing in the previous, similar UK primary care study [8] the 2002 to 2005 data show an increase in the use of antidepressants and antiepileptics while prescribing of conventional non-opioid analgesics declined. Across all four conditions there was a two to four fold increase in use in amitriptyline between the January 1992 to April 2002 and May 2002 to July 2005 cohorts (1992-April 2002 data:12%, 6%, 8% and 24% for post-herpetic neuralgia, trigeminal neuralgia, phantom limb pain and painful diabetic neuropathy respectively). Gabapentin is now one of the five most common initial treatments in three of the conditions, the exception being post-herpetic neuralgia, and has replaced carbamazepine as the most commonly prescribed antiepileptic for phantom limb pain and painful diabetic neuropathy. Gabapentin was not licensed for neuropathic pain until 2000 and so was not a frequently prescribed treatment for any condition in the earlier analysis. Carbamazepine use increased only in the treatment of post-herpetic neuralgia. While the negative press reports concerning the association of co-proxamol and fatal overdose may have accounted for some of the change, the decreased use of all non-opioid analgesics is probably due to increased evidence and acceptance of efficacy of other agents [25–29]. The withdrawal of co-proxamol was not announced until February 2005 so will have had little effect on this study. Another change was the inclusion of the rubefacient capsaicin in the top five most frequently prescribed items for post-herpetic neuralgia, possibly because it was not licensed for neuropathic pain for all of the earlier study period and was not included in previous management recommendations.
The study used the most up to date records available. This allowed us to provide current incidence figures, but meant that we had one year of follow-up on 56% to 66% of the cohorts. The remainder will either have left the practice before the end of the year or have been diagnosed within a year of either the last data collection or the end of the study period. Fewer patients with post-herpetic neuralgia and trigeminal neuralgia were followed to stable regimen than those with phantom limb pain and painful diabetic neuropathy. This difference may be partly the result of our definition rather than an indication that patients with post-herpetic neuralgia and trigeminal neuralgia have more difficulty achieving effective pain relief. Stable therapy was defined as more than two prescriptions for the same treatment. As post-herpetic neuralgia may wane while trigeminal neuralgia can be intermittent these patients may not require a third consecutive prescription.
Results of the January 1992 to April 2002 analysis suggested that, for the most commonly prescribed treatments, changes to a treatment regimen appeared to be less frequent when initial therapy was with frequently used antidepressants or antiepileptics rather than compound analgesics. Our ability to explore this further in more recent cohorts is limited given that conventional analgesics were prescribed less frequently and severity of pain or underlying disease cannot be accounted for in the dataset. However, the mean change in therapy within cohorts was slightly greater in this study (2–3 changes compared to 1–2 changes) despite a larger proportion receiving antiepileptics and antidepressants. Conversely, the mean duration of the initial treatment increased, 50 to 90 days compared to 47 to 76 days previously, as did the number of initial prescriptions with more than one item (28% to 43% compared to 7% to 19% previously) [8].