S-fluoxetine in the prophylaxis of migraine: a phase II double-blind randomized placebo-controlled study

Abstract

S-fluoxetine is the long-acting enantiomer of the racemic antidepressant serotonin reuptake inhibitor. Sixty-five patients needing migraine prophylaxis were recruited into a phase II, double-blind, placebo-controlled trial. After a 1-month placebo run-in, 53 patients met entry criteria with regard to attack frequency and were randomized, 27 to S-fluoxetine and 26 to matching placebo. Three failed to start treatment and there were 17 early discontinuations, 9 from S-fluoxetine, 8 from placebo, at similar times and for similar reasons. The primary efficacy variable was attack frequency and analysis compared decline-from-baseline in the two groups. This was earlier and greater (1.7 attacks/28 days, or 52%) on active therapy than on placebo (1.1 attacks/28 days, or 27%), and statistically significant in month 2 (F = 4.93; p = 0.033) and month 4 (F = 4.55; p = 0.041). As secondary measures of efficacy, migraine-days per month and Patient's Global Impression of Disease Severity coherently reflected the changes in attack frequency. Mean attack severity and acute medication use (doses per attack) were unaltered by either treatment. There were no serious adverse events. Withdrawals for adverse events were four from each group but none was considered causally related. The finding of greater efficacy of S-fluoxetine than of placebo should be interpreted conservatively, since the analysis in the final month was made on only half of the entered patients. It supports progression to phase III evaluation, which was the purpose of the study.

Advances in the enantioseparation of second‐generation antidepressant drugs by electrodriven methods

“…Of these, only fluvoxamine does not possess any chiral centres; FLU and CIT are marketed or under study both as racemates and single enantiomers ((R)-FLU and escitalopram), while paroxetine and SRT are marketed as single enantiomers. seems to be quite similar [18] (the (S)-enantiomer also seems to have antimigraine activity [19]). On the other hand, the enantiomers of the main active metabolite of FLU (norfluoxetine) have very different pharmacological and pharmacokinetic properties [20].…”

Newer aspects of migraine preventive therapies

“…An additional, placebo-controlled trial reinforced the potential benefit of this agent in the longterm treatment of migraine [d 'Amato et al, 1999]. The S-isomer of fluoxetine may also have clinical benefit in migraine prevention [Steiner et al, 1998]. A comparative trial of venlafaxine, an SNRI antidepressant, with the tricyclic amitriptyline showed both agents to be equally effective in reducing attack frequency [Bulut et al, 2004].…”

Fluoxetina: profilo terapeutico e farmacoeconomico di un prodotto generico

“…I dati disponibili indicano un moderato livello di efficacia nella cefalea cronica giornaliera e una mancanza di efficacia nel controllare i sintomi dell'emicrania [167,168].…”

“…Quest'attività sembra essere dovuta all'isomero S-fluoxetina. [168] Disfunzione sessuale: eiaculazione prematura La fluoxetina è efficace nel trattamento sintomatico della eiaculazione prematura. I risultati obiettivi (prolungamento da 1 a 6-10 minuti dell'intervallo pre-eiaculatorio intravaginale) si possono osservare dopo almeno due settimane di trattamento.…”