A Randomized Controlled Trial

L Carlsen et al

Gerry Gajadharsingh writes:

“headache and migraine are a very common presentation in Osteopathic practice. Like many other complex pain scenarios, the aetiology is normally complicated and involves many factors. The tendency of many professions is to simply apply what they think is in their toolbox to the problem they are seeing. The problem with that approach is that it is often ineffective given the fact that there are usually multiple other factors going on.

 The research below focuses mostly on medication, the strategy with dealing with a specific category of headache, medication overuse headache (MOH).

Overall headache days/month were reduced from 24.6 (23.4–25.8) to 15.0 (13.0–17.0). To a patient this doesn’t sound it a lot, but it just goes to show sometimes how complicated headaches are. The treatment strategy over one year was to withdraw the medication the patient was using to manage the headache whilst introducing preventative medication.

 It’s interesting to note that as an adjunct they also referred patients on for Physiotherapy advice (it doesn’t seem that manual therapy was provided) and psychotherapeutic support.

 Whilst the wish of many patients is to simply not have headache/migraine, it’s quite clear that the most that treatment interventions are aiming for is a reduction in the frequency and severity of the headache/migraine.

 My experience is slightly different and it’s interesting with seeing increasing numbers of patients presenting post Covid infection with chronic headache/migraine. The vast majority seem to be doing incredibly well by adopting a more integrated approach to both the diagnosis of the problem and therefore the treatment.

 The caffeine question is interesting. If people are regular caffeine consumers, they often suffer from headaches if they stop caffeine, at least initially. Many pain medications and headache medications contain amounts of caffeine. Some of my patients are finding that a quick fix with Gerry’s Daytime, which contains organic green coffee beans and Guarana (a herbal form of caffeine and L Theanine (which mitigates the negative effect of caffeine), in conjunction with other very interesting functional ingredients are very helpful in managing their headache whilst treatment aims to provide a more permanent fix.”

 

Abstract and Introduction

Abstract

Background: Combined withdrawal and early preventive medication was the most effective treatment for medication overuse headache (MOH) within the first 6 months in a previous study, but results from a longer follow-up period are lacking.

Objective: (1) To measure the efficacy at 1 year of three different treatment approaches to MOH; (2) to compare withdrawal and early preventives (W+P), preventives with potential withdrawal therapy after 6 months (P+pW), and withdrawal with delayed potential preventives (W+pP); and (3) to identify predictors of chronic headache after 1 year.

Methods: Patients with MOH and migraine and/or tension-type headache were randomly assigned to one of the three outpatient treatments. Headache calendar and questionnaires were filled out. Primary outcome was a reduction in headache days/month after 1 year.

Results: Of 120 patients, 96 completed 1-year follow-up, and all were included in our analyses. Overall headache days/month were reduced from 24.6 (23.4–25.8) to 15.0 (13.0–17.0) (p < 0.0001), and only 11/96 patients (11%) relapsed. Reduction in monthly headache days was 10.3 days (95% CI: 6.7–13.9) in the W+P group, 10.8 days (95% CI: 7.6–14) in the P+pW group, and 7.9 days (95% CI: 5.1–10.7) in the W+pP group. No significant differences in treatment effect were seen between the three groups (p = 0.377). After 1 year, 39/96 (41%) had chronic headache. Predictors of chronic headache after 1 year were higher headache frequency (aOR 1.19; 1.09–1.31), more days with acute medication (aOR 1.11; 1.03–1.19), higher pain intensity (aOR 1.04; 1.01–1.08), and depression (aOR 4.7; 1.38–18.95), whereas higher self-rated health (aOR 0.61; 0.36–0.97) and high caffeine consumption (aOR 0.40; 0.16–0.96) were predictors of a lower risk of chronic headache. No adverse events were reported.

Conclusions: All treatment strategies proved effective in treating MOH with a low relapse rate. The W+P strategy leads to the fastest effect, confirming earlier treatment recommendations. Identification of predictors for chronic headache may help identify more complex patients.

Introduction

Medication overuse headache (MOH) is a chronic secondary headache caused by medication overuse. The condition is a common clinical problem that should be managed in an effective manner because these patients are highly impaired. However, the best treatment strategy for MOH has been debated for years. Questions have been raised about when and how preventive medication should be initiated and how the overused medication should be withdrawn. Recently, we addressed some of these questions in an open-label, randomized, controlled study comparing three treatment strategies for MOH: withdrawal and immediate preventive medication, preventive medication without withdrawal, and withdrawal therapy with delayed optional preventive medication after 2 months. We concluded that a combination of abrupt withdrawal and early preventive medication should be the recommended treatment strategy

Our first study had a 6-month follow-up period. In previous studies, between 13% and 41% of patients relapse within the first year after the start of the treatment for MOH. It is, therefore, of utmost importance to follow these patients over a longer period. The purpose of this paper was, therefore, to report the effect of treatment of patients with MOH followed for a whole year after the start of treatment, measured in various parameters, and to compare the three treatment strategies: (a) withdrawal with immediate preventive treatment (W+P), (b) preventive treatment with potential withdrawal after 6 months (P+pW), and (c) withdrawal with optional preventive treatment after 2 months (W+pP) (Figure 1). Furthermore, we aimed to identify clinical predictors of still having chronic headache after 1 year. Our hypothesis was that the treatment strategy including withdrawal with immediate preventive treatment would have the largest treatment effect, including reduction in monthly headache days and days with acute medication.

Methods

Study Population

Patients with MOH referred to the Danish Headache Center were considered for participation. Patients were invited to participate if they fulfilled the following criteria: MOH diagnosis according to the International Classification of Headache Disorders, 3rd edition (beta version), where information about headache frequency and acute medication use was obtained from detailed history or at least 1 month filled-out headache calendar; MOH arising from preexisting migraine and/or tension-type headache; minimum 18 years old and capable of providing informed consent; considered eligible for outpatient treatment based on the type of medication overuse (without daily or almost daily use of opioids or barbiturates); personal resources and motivation; capable of completing a headache calendar; no severe physical illness (e.g., severe comorbid pain, uncontrolled diabetes, serious heart disease, cancer) or psychiatric disorders (requirement of antidepressant medication, ongoing treatment by a psychiatrist, or in a psychiatric clinic); no alcohol or drug addiction; no pregnancy, breastfeeding, or planned pregnancy within the next 12 months; ability to provide information about medical history (without linguistic barrier); and no preventive headache treatments at baseline.

The study was approved by the regional Ethics Committee (H-16029763). All participants signed informed consent, and the study was registered at Clinicaltrials.gov, identifier: NCT02993289.

Withdrawal Approach

Patients received advice on withdrawal and MOH from trained headache nurses before the start of withdrawal. Patients were recommended to completely discontinue acute analgesics and migraine medications for the first 2 months. Patients were offered rescue medication (levomepromazine or promethazine maximally 75 mg per day) and antiemetics (metoclopramide or domperidone 10 mg) during the withdrawal period. After 2 months, patients could use acute migraine-specific medication up to 9 days per month, or 14 days per month for simple analgesics alone.

Patients in the P+pW group were offered withdrawal therapy after 6-month follow-up if they still fulfilled the MOH criteria. It was voluntary to follow the advice on withdrawal. Importantly, patients in the P+pW group did not receive any specific advice or information about withdrawal in the first 6 months of treatment. Note that the change in the P+pW group was predefined in the study design.

Preventive Medication

Before starting the treatment, patients received information about specific preventive medications chosen according to current guidelines. For migraine, the following preventive medications were considered: beta-blockers, candesartan, lisinopril, topiramate, amitriptyline, and botulinum toxin A injections according to the PREEMPT protocol. For tension-type headache, amitriptyline or mirtazapine was considered. If patients experienced unacceptable adverse effects or lack of effect, preventive medication was changed. Patients in the W+pP group were offered preventive treatment at the end of the withdrawal period (2 months) if the treatment team identified an indication, and the patients consented to receiving the additional medication. Effective preventive treatment was continued throughout the study period.

Multidisciplinary Treatment

During the 1-year study period, all patients were offered voluntary therapy sessions with a psychologist, and sessions with a physiotherapist, as part of standard treatment at the Danish Headache Center. Therapy sessions with a psychologist focused on coping strategies for living with headache, trigger factors for headache, for example, stress and anxiety, and acceptance of a life with chronic pain. Sessions with a physiotherapist included, for example, correction of posture, biofeedback, active exercises, and relaxation techniques.

Prognostic Factors for Still Having Chronic Headache After 1 Year

At 1-year follow-up, the percentage of patients using preventives was 66% in the W+P group, 85% in the P+pW group, and 62% in the W+pP group. Candesartan was by far the most used preventive medication, used by 43% of the total study population.

Approximately 71% of patients (79% in the W+P group, 64% in the P+pW group, and 71% in the W+pP group) were referred to physiotherapy, and 34% of patients were referred to therapy sessions with a psychologist.

Prognostic Factors for Still Having Chronic Headache After 1 Year

After 1 year, 39 out of 96 patients (41%) had chronic headache.

The low relapse rate might be explained by frequent follow-up during the study period. All participants received patient education, 71% went to a physiotherapist, and one-third were seen by a psychologist at the Danish Headache Center. Because prevention of relapse is an important part of the treatment of MOH, we suggest a combination of frequent follow-up, patient education, and nonpharmacological preventive treatment. This multimodal and multidisciplinary approach has also been advocated in other studies.

On Predictors

The third aim of this study was to identify predictors of nonresponse to treatment, that is, still having chronic headache after 1 year. This may help to identify patients requiring more intensive care and frequent follow-up. We found that high headache frequency, more frequent use of acute medication, high pain intensity, and depression at baseline were predictors of nonresponse.

Caffeine is known to have an effect on nociception through its antagonism of the adenosine receptors,and there is some evidence that caffeine monotherapy is associated with more pain relief than placebo in treating patients with migraine or with migraine and tension-type headache.Another hypothesis could be that daily caffeine consumption may be a proxy for other protective factors, for example that these people share good coping strategies. Nonetheless, high caffeine consumption has been found to be a risk factor for MOH when comparing a daily caffeine intake of more than 540 mg with an intake of less than 240 mg. It could be hypothesized that a moderate dose of caffeine has a protective effect on patients with severe headache conditions. Further investigation about the role of caffeine as a predictor of remission to episodic headache is needed.