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Background  Difficulty in controlling attention can lead to mental fatigue in the healthy population. We identified one trial reporting a benefit in patients’ attention using a homeopathic formula preparation. One component of the preparation was potassium phosphate, widely available off the shelf as  Kali phos  6x for cognitive problems. The aim of this exploratory trial was to assess the effectiveness of  Kali phos  6x for attention problems associated with mental fatigue.    Methods  We recruited student and staff volunteers (University of York) with self-reported mental fatigue, excluding any using homeopathy or prescribed stimulants, or with a diagnosis of chronic fatigue syndrome. In a triple blind, cross-over, placebo-controlled clinical trial, 86 volunteers were randomized to receive  Kali phos  6x or identical placebo 10 minutes before taking a psychological test of attention (Stroop Colour-Word Test). One week later they were crossed over and took the other preparation before repeating the test.    Results  We found no evidence of a treatment effect in a comparison of  Kali phos  6x with placebo ( Kali phos  minus placebo = −1.1 (95% CI −3.0 to 0.9, P = 0.3) Stroop score units, Cohen effect size = −0.17) even when allowing for a weak period effect with accuracy scores in the second period being higher than those in the first (P = 0.05). We observed a ceiling effect in the Stroop test which undermined our ability to interpret this result.    Conclusions   Kali phos  6x was not found to be effective in reducing mental fatigue. A ceiling effect in our primary outcome measure meant that we could not rule out a type II error. Thorough piloting of an adequate outcome measure could have led to an unequivocal result.    Current Controlled Trials  ISRCTN16521161

Homeopathy for mental fatigue: lessons from a randomized, triple blind, placebo-controlled cross-over clinical trial