Our studies have identified several factors which are clearly associated with CFH and which can be modified to improve headache frequency. Below I will discuss the clinical implications and ideas for future research.
Medication overuse
There is debate about the causal relationship between overuse of acute headache medication and CFH. Overuse is common in patients with CFH and considered the most important risk factor. However, it is also likely that patients with frequent headache take medication in response to pain. A returning argument against the idea of overuse as a risk factor is that there are no randomized placebo-controlled trials proving the efficacy of withdrawal, probably because the choice of a placebo control group is difficult. Remarkably, our withdrawal trial in General Practice failed to interest enough patients indicating that the perceived need for treatment in the general population is low. Informing patients about the paradoxical effect of analgesics and the possibility of dependence may increase awareness. Indeed, a letter with discontinuation advice was effective in reducing headache days. A randomized controlled trial in motivated patients with probable medication overuse headache is needed. It would be particularly interesting to analyze the determinants of success. Not all patients with medication overuse succeed in withdrawal and not all patients benefit from withdrawal.
Psychological factors
Factors other than analgesic overuse are important in the development of CFH. In our study 40% of CFH subjects did not overuse medication. We identified several psychological factors which were associated with CFH and high headache impact. Especially catastrophizing is of interest because it has shown to be an important cognitive factor in other chronic pain conditions as well and it can be successfully modified in cognitive therapy.1 In general, physicians should propose prophylactic medication to patients with increasing headache frequency to prevent overuse. Prophylactic medication is however not effective in at least one third of patients and medication options are limited in case of chronic tension-type headache, which is the most common headache type in the general population. Cognitive behavioral therapy can be a valuable alternative or adjunct treatment option and should be tried in randomized controlled trials in CFH patients.
It is increasingly recognized that headache patients often suffer from psychiatric comorbidity. Migraine has been associated with depression and anxiety disorders, suggesting shared etiologic factors. Alternatively, pain can exacerbate a pre-existing vulnerability to
psychopathology, which in turn intensifies the pain. In our study we found that the majority of CFH subjects screen positive for psychopathology. Whether psychiatric comorbidity is a cause or a consequence of CFH could not be determined. The co-occurrence of headache and psychiatric disorders warrants more attention. It may complicate diagnosis and has
implications for treatment. Screening headache patients for presence of psychiatric disorders and vice versa may be important to enable simultaneous treatment of both conditions in a multidisciplinary fashion.
Other risk factors
A pathologic change in central pain processing is thought to underlie chronification of headache. Patients with chronic tension-type headache have shown to have a generalized increased pain sensitivity.2 It is hypothesized that continuous nociceptive input from pericranial tissues induces sensitization of central neurons leading to generalized hyperalgesia. Genetic factors probably play a role in the susceptibility for chronic pain conditions. Possible mechanisms include influencing pain sensitivity. The variability in pain perception between people is substantial. Certain combinations of alleles encoding for the gene catecholamine-O-methyltransferase (COMT) determine levels of COMT enzymatic activity which inversely correlates with pain sensitivity and the risk of developing chronic pain conditions.3 There is also a large interindividual variability in the response to analgesics. Genetic polymorphisms of the µ-opioid receptor gene, the melanocortin-1 receptor gene, and cytochrome P450 gene influence opioid potency and metabolism which makes dose
adaptation necessary.4 Finally, genes involved in addictive behavior could also play a role in medication overuse and subsequent chronification of headache. It is clear that we should look carefully at different genotypes in CFH in future studies as genetic risk factors may become important predictors for CFH. In the long run, we will learn more about pathophysiologic mechanisms in the development of CFH which will hopefully open up new therapeutic options.
To conclude
In this thesis I demonstrated that CFH is a major health problem, which concerns one in 25 adults, and deserves more attention. Overuse of acute headache medication seems to be an important (iatrogenic) risk factor for the development of CFH in a vulnerable subgroup of patients. Physicians and patients should be aware of the possible paradoxical effect of acute headache medication when headache frequency increases. Although better prophylactic medication is needed, CFH patients do not optimally use the currently available medication. Pharmacists could cooperate with GP’s in monitoring triptan and analgesic use. Analgesic overuse however will be difficult to detect because these are OTC products. One way of increasing public awareness is to include an advice in the product information leaflet of analgesics to consult a physician when analgesics are used on more than 15 days per month for headache. GPs should monitor triptan prescriptions and consider prophylaxis earlier to prevent patients from overusing triptans and analgesics. When overuse is evident, withdrawal is the appropriate treatment. Patients are likely to comply better after consulting a neurologist who can confirm diagnosis and treatment. A multidisciplinary approach could be of additional value in case psychological and psychiatric risk factors are present.
References
1. Spinhoven P, Ter Kuile M, Kole-Snijders AM, Hutten MM, Den Ouden DJ, Vlaeyen JW. Catastrophizing and internal pain control as mediators of outcome in the multidisciplinary treatment of chronic low back pain. Eur J Pain 2004; 8(3):211-219.
2. Ashina S, Bendtsen L, Ashina M, Magerl W, Jensen R. Generalized hyperalgesia in patients with chronic tension-type headache. Cephalalgia 2006; 26(8):940-948.
3. Diatchenko L, Slade GD, Nackley AG, Bhalang K, Sigurdsson A, Belfer I et al. Genetic basis for
individual variations in pain perception and the development of a chronic pain condition. Hum Mol Genet 2005; 14(1):135-143.
4. Lotsch J, Geisslinger G. Current evidence for a genetic modulation of the response to analgesics. Pain 2006; 121(1-2):1-5.