Abstract
Medication overuse headache (MOH), formerly referred to as analgesic rebound headache, is now an International Headache Society (IHS) classified entity (1). Although the biological basis for MOH resides in receptor physiology, it is probable that the initiation and sustaining dynamics of this condition involve factors beyond pain alone. In some cases, addictive disease, a relapsing disorder characterized by compulsive drug seeking and drug taking despite negative consequences, underlies the MOH disorder (2). To be sure, not all patients with frequent headache eventually overuse their medications, and of those that do, not all appear to develop MOH. Nonetheless, proper treatment of medication overuse and preventing relapse (3) require recognition of the elements that contribute to and underlie its development and perpetuation.
Certain behaviours and psychological states seem particularly important in prompting and sustaining the overuse of medication. These include fear of headache (cephalgiaphobia (4)); anticipatory anxiety; obsessional drug-taking behaviours; and psychological drug dependence, among others. Additionally, persons with Axis II personality disorders, particularly cluster B entities, act out certain behaviours that promote medication overuse. Among these are defiance of limits regarding medication usage, battles of control over treatment, and attitudes of entitlement regarding pain control (5). True addictive disease, which is defined by specific behaviours in addition to physical dependency, is in our view often overlooked when present, though it is likely that only a small percentage of cases of MOH actually involve true addictive disease.
In our early ergot studies (J.R.S.) (6, 7) numerous ergot-dependent patients acknowledged that anticipation and fear of the next headache were important in inducing treatment prior to the onset of the headache. In what may have been a prelude to the development of dependency, some patients ritualistically medicated each evening before retiring and then again upon awakening in the morning to ‘prevent’ the development of a headache.
A large number of our patients with MOH identify coexistent anxiety. We believe it is not coincidental that several, but not all, of the medications that are among the most overused have sedative/anxiolytic effects (the opioids and mixed analgesics containing butalbital, a long-acting barbiturate). It may be that the use of certain drugs, such as opioids and others with these effects, are particularly attractive to anxiety-prone patients. Independent of what they do for the pain, these agents also mollify anxiety, which can be as compelling as the pain and perhaps more so.
Thus, an argument can be made that behavioural dynamics are fundamental elements in many, perhaps most, cases of overuse. It is likely that several of these factors, as in the case of the pain, involve an intermingling of limbic and brainstem mechanisms (8–10). The characterization of these phenomena as biobehavioural phenomena seems defendable.
Moreover, the willingness and commitment to discontinue overused medications may necessarily involve motivational factors, as does the commitment to maintain appropriate medication use after withdrawal. Abstinence symptoms during the discontinuation process include fear, anxiety, and anger. These responses may in part be mediated through neurobiological mechanisms in the brainstem and elsewhere. Nonetheless, this escalation of pain, together with emotional distress during withdrawal, can and does influence an individual's willingness and motivation to endure the process of drug discontinuance. Tolerating this distress is often difficult in and of itself, but in a patient in whom emotionality and behavioural factors are problematic, the defeat of a potentially successful effort is even more likely. Relapse rates may reach as high as 40% within 1 year of discontinuing the overused medication (11). Some people appear to medicate to gain a life, while others take medication to hide from life.
In our experience, effective treatment of MOH involving ergots and triptan agents is more easily achieved and less complex a task than that which involves opioid or barbiturate-containing analgesics. If true, it could, among other variables, reflect the presence of enhanced (rebound) anxiety and emotional distress when anxiolytic agents are discontinued, as distinct from that when discontinuing non-anxiolytic agents. (Perhaps pre-existing anxiety predisposed the patient to overuse certain, particular medications in the first place.) During our 5-year opioid observational study (12), we identified many patients who appeared to use opioids for symptoms apart from pain reduction. Many resisted discontinuation even when it was demonstrated that the opioids did not significantly control the pain. In headache patients undergoing withdrawal from opioids, many seek any and all medications that have a sedating effect, whether or not they provide specific pain relief. We have termed this sedation-seeking behaviour ‘soporophilia’ (love of sedation), and it applies to many patients during the withdrawal process.
Finally, a patient's behaviour and his/her interaction with the physician may influence the physician's judgement with respect to the choice of medication and the dosing schedule. Patients who are eventually administered opioids for benign pain disorders and obtain increasing amounts of these medications from their physicians may display certain behaviours that distinguish these individuals from other painful patients. It may not be the patients’ degree of pain or actual treatment refractoriness alone that motivates a physician's decision to administer these agents. We suspect that certain patients are more likely to obtain these medicines as a direct result of the effect on the physician of their behaviour and persistence. Behaviours that might induce a physician to prescribe these medicines include, but are not limited to, histrionic and theatrical displays, repetitive demands, anger, frequent contacts with the physician's office requesting drugs, prolonged office visits, protests over inadequate pain therapy, emergency department visits, and others. Patient behaviours influence physicians’ judgement, for better and for worse.
While the intermingling of emotion and pain is well recognized, the symbiotic importance of these has received little attention in the descriptions, classifications, and deliberations on medication overuse syndromes. The dynamic appears fundamental. Behaviour matters, and biology matters. Identification and treatment of both are likely to be essential to achieve successful outcomes. We recommend that subsequent iterations of the IHS classification system consider recognition of both physiological and emotional dynamics in medication overuse phenomena. Perhaps having the designation of ‘simple MOH’ and ‘complex MOH’ (or some other appropriate designation) might provide a means of distinguishing straightforward cases (little behavioural influence) from more complex ones. Treatment differs substantially. Were the IHS classification system to recognize this dynamic, it is our view that it would promote the development of more specific treatment guidelines and thus perhaps better long-term outcome results.