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Melatonin (Read 144 times)
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Jan 12th, 2020 at 7:56pm
Melatonin is in the Tryptamine family, although unrelated in effects...
Preventive treatment

Verapamil was found to be effective initially in an open-label study31 and subsequently in two randomised clinical trials.32 33 It is widely accepted as the first-line preventive treatment for cluster headache, typically starting with 80 mg three times a day with view to increasing it by 80 mg every 2 weeks according to response; the maximum recommended dose is 320 mg three times a day (see table 2).

Recommended verapamil titration regimen34

Treating clinicians should aware that up to one in five patients taking verapamil develop cardiac arrhythmia, bradycardia or lengthening of the PR interval.34 Hence, it is recommended to perform a baseline 12-lead ECG before starting treatment, then at 10 days after each dose increment. After reaching a stable dose, ECGs should be checked once every 1–2 months and then every 6 months. There are reports of delayed onset of ECG abnormalities up to 2 years after being on a stable verapamil maintenance dose.35 Other less serious side effects to verapamil therapy include constipation and pedal oedema.34

Once a bout of cluster headache is over, the patient should withdraw verapamil cautiously to stop, with view to going straight on the effective dose of verapamil in the next cluster bout, provided the baseline ECG is normal. It is important not to keep patients on verapamil after their bout ends; anecdotally, we have found that this prolongs future bouts and there is a risk of tachyphylaxis.


The evidence is limited for lithium33 36 37 however it is generally accepted as a reasonable second-line option. It is more commonly used in chronic compared with episodic cluster headache but its potential impact on thyroid function and risk of interference with diuresis may complicate and limit its use.38 Lithium therapy requires regular blood monitoring to maintain a serum concentration between 0.4 and 1.2 mEq/L, due to its narrow therapeutic index and potential risk of toxicity manifesting as a wide array of gastrointestinal and neurological symptoms.38

Lithium dosing starts at 300 mg once a day, with weekly 300 mg increments according to response, to a maximum dose of 1200 mg/day; serum concentrations are best checked 12 hours after dosing; once the dose is stable and attacks controlled, serum lithium should be checked once every 1–2 months.38


There are many plausible theories to explain the potential link between melatonin and cluster headache attacks.39 Melatonin 10 mg at night can help to prevent attacks of episodic cluster headache,40 however, a trial of melatonin in chronic cluster headache41 could not reproduce that positive effect. However, one might argue that the formulation used or the timing of dosing might have been confounding factors.

Due to its tolerable side effect profile, melatonin is still widely used in preventing cluster headache, at doses between 10 and 25 mg in the evening.42 43

The evidence for efficacy of topiramate in preventing cluster headache is limited to an open-label study using high doses (100–200 mg/day) with reported good efficacy in up to more than two thirds of patients.44

Side effects are major hurdle for topiramate use, in particular cognitive slowing, teratogenicity, nephrolithiasis and low mood as well as its potential effect on oral contraceptive efficacy, which can be a significant factor on preventive choice.45
When to stop preventive therapy

There is no clear guideline on how long to continue oral preventive therapy; it is generally accepted that preventive therapy should continue for up 4 weeks after attacks have settled, as evidenced by lack of ‘shadows’ or response to triggers, or after the usual length of the bout.

Patients’ experience with their previous bouts can guide the decision to stop preventive therapy in episodic cluster headache.38 It is important to stop preventive treatment after each bout and not to have patients simply continue, given the wide range of side effects as well as the possibility of losing efficacy. When restarting a preventive such as verapamil for future bouts, there is usually no need to retitrate; provided the baseline ECG is normal, patients can be restarted at the dose that was effective for the last bout.
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Re: Melatonin
Reply #1 - Mar 28th, 2020 at 6:58am
Hmmm, this is interesting. Didn't know a lot of things about melatonin. Thank you for sharing
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