This is an open label study made to evaluate the possible efficacy and tolerability of atenolol in CM. The results in the study indicate benefit in preventing CM by significantly reducing the number of headache days per month at 1.5 months and in the 3rd month of treatment compared with the run-in period. Atenolol was also able to significantly reduce the severity of the attacks at 1.5 months and in the 3rd month of treatment compared with the run-in period. To my knowledge, this is the first prospective study of atenolol as preventive treatment for CM.
The study contradicts earlier results in CM. No beta-blocker has a Class I study showing effectiveness in reducing CM (Couch 2011). Up to know, only topiramate and local injections of botulinum toxin have shown efficacy in large placebo-controlled randomized trials (Couch 2011).
However, these results are in accordance with previous studies including migraineurs in whom an effect of prophylactic atenolol has been shown. Beta-blockers are approximately 50% effective in producing a > 50% reduction in attack frequency (Stensrud & Sjaastad 1980; Forssman et al. 1983; Johannsson et al. 1987; Olesen et al. 2006). Propranolol is effective in migraine prevention at a daily dose of 80–240 mg (Barbanti et al. 2011). A Cochrane review of studies 2004 concluded that propranolol is effective in preventing migraine in the short term (Barbanti et al. 2011). The relative efficacy of the different beta-blockers has not been established. Most studies show no significant difference between drugs.
The action of beta-blockers is most likely central. Blockade of β1-mediated effects and consequent inhibition of Na+ release and tyrosine hydroxylase activity are considered the main mechanisms of action. Beta-blockers reduce the neuronal firing rate of noradrenergic neurons of the locus coeruleus, regulate the firing rate of PAG neurons and probably interact with the serotonergic system by blocking 5-HT2C and 5-HT2B receptors. It has been hypothesized that beta-blockers exert some of their prophylactic effects in migraine through an action at the ventroposteromedial thalamic nucleus and inhibition of cortical spreading depression (Barbanti et al. 2011).
Earlier studies have shown that compared with episodic migraine, patients suffering from CM are more likely to be depressed, anxious, suffering from other forms of chronic pain, and overusing acute pain medications. Epidemiologic and clinical research consistently documents an association between depressive, bipolar, and anxiety disorders with migraine (Diener et al. 2011; Olesen et al. 2006). All beta-blockers can cause behavioural adverse events as fatigue, lethargy and depression (Nappi & Moskowitz 2011). Because propranolol may predispose to depression, its use as an antimigraine preventive agent is limited (Couch 2011). However, in this study the subjects showed no signs of depression. The subjects were young and otherwise healthy. No medication overuse was found. These facts may have contributed to the good efficacy results.
Atenolol is associated with risks for pregnant and lactating women as well as for diabetics. Studies have shown that women with chronic hypertension that is treated with atenolol have higher rates of intrauterine growth restriction and preterm delivery (Orbach et al. 2013). Atenolol is also associated with significant effects on some nursing infants and should be given to nursing mothers with caution. There is one report of hypotension, bradycardia, and cyanosis in a breast-fed infant of a mother taking 100 mg daily (Hutchinson et al. 2013). Beta- blockers are also contraindicated in patients with brittle diabetes mellitus (Olesen et al. 2006).
Although the patients were observed prospectively, the study has limitations. It is limited by its small sample size and open-label nature. The good efficacy results obtained here must be interpreted with caution, as they come from an open research in a condition with a high placebo response. Nevertheless, the patients were carefully selected and all patients satisfied the criteria for CM. In the study, the persistence of therapeutic effect (29% of patients being headache-free since the run-in period) can hardly be attributed to a placebo effect only.
