Placebo Effect and Clinical Trials in Migraine Therapy

Abstract

Migraine is a cyclical condition in which the cycles may occur or remit in an unpredictable fashion. The goal of prophylactic antimigraine therapy is to induce remission of an active cycle of migraine or to inhibit occurrence of individual headaches until the cycle remits for other reasons. The placebo effect probably takes advantage of these cycles. The placebo effect is significant and quite potent. The placebo effect may be divided into (1) the initial effect and (2) the continuing effect which is seen following a stabilization period. The initial placebo effect is dramatic with 62% of 188 subjects improving by 75% after 4 weeks of placebo. The continuing effect is demonstrated by occurrence of 75% further improvement in 28% of 282 subjects in 7 studies in which comparison of results after 4–12 weeks was made with a placebo stabilization period. The placebo effect is a very potent one and must be taken into account in designing and carrying out studies of migraine therapy.

Efficacy and Safety of Eptinezumab in Patients With Chronic Migraine

“…High placebo rates may be attributed to a number of factors, including the novelty of treatment, route of administration, number of active treatment arms increasing patient expectations, and number of patients previously naive to preventive therapy. [29][30][31][32][33][34][35] The intensive amount of patient contact with migraine care experts throughout the trial also may have contributed to the higher-than-expected placebo response, including professionally supervised IV administration and frequent follow-up contact via telephone and in-person visits. Despite the high placebo rates, statistical significance was achieved for eptinezumab 100 mg and 300 mg for the primary and all secondary endpoints.…”

Use of Auricular Acupressure to Improve the Quality of Life in Diabetic Patients with Chronic Kidney Diseases: A Prospective Randomized Controlled Trial

“…The effect size is rarely found and indicates a nonoverlap of 93% in the two arms, since Cohen defined the magnitudes of effect sizes as “small, d = 0.2,” “medium, d = 0.5,” and “large, d = 0.8.” Several reasons are considered to explain this effect size. First, we thought that it might be a placebo effect, which could be seen in trials using self-report outcomes [ 30 , 31 ], and we used a self-reported scale (the KDQOL-SF) as the primary outcome for this study. Moreover, acupuncture related therapies induced larger placebo effect than other placebos, such as placebo drugs [ 32 ].…”