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One of the most prominent and debilitating features of POTS is a very marked increase in heart rate upon adopting an upright posture. This causes the patient to experience very fast heart palpitations which are both scary and very uncomfortable. The patient therefore will try and sit down or lie down to feel better but this is at the cost of becoming increasingly deconditioned in the medium and long term. In the overwhelming majority of patients, this excessive rise in heart rate is explained by an exaggerated release of ‘flight or fight’ hormones such as adrenaline and noradrenaline. Why this happens we don’t understand but if we can in some way blunt the increase in heart rate then there is a likelihood that we can potentially improve the ability of the patient to stand for longer with less symptoms. We already have some medications which can help with this such as beta-blockers and Ivabradine and in those patients who can tolerate them, this strategy of reducing the heart rate does result in some symptom improvement. It is worth noting however that for some reason POTS patients tend to be particularly prone to side effects and many of them simply don’t tolerate the commonly used medications. We, as POTS doctors, are therefore always on the lookout for any other medications which can help reduce the heart rate and why may possibly be better tolerated by patients. This is where the medication I am going to talk about today comes into the discussion. Melatonin is an endogenous compound which is secreted by our pineal gland and is involved in regulating the circadian rhythm and acts as a signal for darkness. It is both a hypnotic and chronobiotic (an agent that can cause phase adjustment of a disrupted body clock) There was a really interesting study published in the American Journal of Cardiology in 1999 (Lead author – Arangino et al) where they studied 17 healthy women and found that when you compare 1 mg dose of melatonin with placebo, melatonin seemed to reduce noradrenaline levels after 5 minutes of standing.