14 mai 2015

Oxybutynin pour les bouffées de chaleur

J'ai un patient qui présente des bouffées de chaleur importantes et pour qui le md a prescrit de l'oxybutynin. Aucune indication officielle ou non-officielle pour cette indication dans Vigilance.

Par contre, j'ai trouvé deux études dans Pub Med:


2007 May-Jun;

Oxybutynin for refractory hot flashes in cancer patients.

There is little information available on the treatment of hot flashes in patients refractory to pharmaceutical interventions. Anecdotal evidence led to the use of oxybutynin for the management of hot flashes in refractory cancer patients; therefore, we performed a retrospective chart review of such patients to determine the effect of oxybutynin in treating hot flashes and to observe the side effects of the drug in these patients.


A prospective database of all patients treated for hot flashes was started in July 2004 and was retrospectively analyzed as of March 2006. Also included were individual charts preceding July 2004. Fifty-two patient charts were examined. Demographic information was obtained along with baseline severity and frequency of hot flashes, dose and duration of treatment with oxybutynin, patient response to oxybutynin, and side effects.


More than 90% of patients analyzed were refractory to hot flash treatments before starting oxybutynin. Seventy percent of patients showed a partial or excellent response to oxybutynin. The duration of oxybutynin use ranged from 2 weeks to 5 years with more than half of patients currently on oxybutynin or taking oxybutynin for longer than 6 months. Of those patients who experienced an excellent or partial response to treatment, 12% stopped because of documented oxybutynin-related side effects within 4 weeks.


Oxybutynin seems promising in the management of hot flashes with tolerable side effects in the majority of refractory patients. A placebo-controlled, randomized study is being developed to look more closely at the effectiveness of oxybutynin in reducing hot flashes.


2012 May

Effective and clinically meaningful non-hormonal hot flash therapies.

Although many non-hormonal compounds have shown statistically significant benefit over placebo in hot flash randomized controlled trials (RCTs), these studies have varied considerably in basic methodology making it challenging to deduce which compounds have the greatest potential to provide clinically meaningful benefit. This review used evidence-based methodology closely mirroring the FDA and EMEA guidelines as a template to identify "well-designed" RCTs from which effective and clinically meaningful non-hormonal hot flash therapies could be identified. In addition, pertinent safety information was reviewed. Out of 3548 MEDLINE citations and abstracts, 51 well-designed hot flash RCTs were identified. From these trials, gabapentin, oxybutynin ER, desvenlafaxine, soy-derived isoflavones and black cohosh each showed a clinically meaningful treatment effect in at least 1 RCT. Among these 5 compounds, only gabapentin demonstrated consistent and statistically significant benefit over placebo in all of its well-designed RCTs. Desvenlafaxine, soy-derived isoflavones, and black cohosh demonstrated statistically significant benefit over placebo in 75%, 21%, and 17% of the well-designed RCTs for each compound, respectively. There was only 1 well-designed RCT using oxybutynin ER, which showed it to have a robust and clinically meaningful benefit. In terms of safety, there have been cardiovascular risks associated with desvenlafaxine use in postmenopausal women with hot flashes. The use of anticonvulsants, in general, has been associated with an absolute 0.21% increase in suicidal thoughts and behavior. Further research is needed with several of these nonhormonal compounds to replicate these findings and to also directly compare their efficacy and tolerability with those of hormone replacement therapy.

10 mai 2015

À propos de la mélatonine chez l'enfant

Voici deux textes intéressants à propos de l'utilisation de la mélatonine chez l'enfant.


Warning on use of drug for children's sleep

Wednesday, 25 February 2015
Sleep researchers at the University of Adelaide are warning doctors and parents not to provide the drug melatonin to children to help control their sleep problems.

In a paper published in the Journal of Paediatrics and Child HealthProfessor David Kennaway, Head of the Circadian Physiology Laboratory at the University of Adelaide's Robinson Research Institute, warns that providing melatonin supplements to children may result in serious side effects when the children are older.

"Melatonin is registered in Australia as a treatment for primary insomnia only for people aged 55 years and over, but it's easily prescribed as an 'off label' treatment for sleep disorders for children."

Professor Kennaway says there is extensive evidence from laboratory studies that melatonin causes changes in multiple physiological systems, including cardiovascular, immune and metabolic systems, as well as reproduction in animals.

"Melatonin is also a registered veterinary drug which is used for changing the seasonal patterns of sheep and goats, so they are more productive for industry. If doctors told parents that information before prescribing the drug to their children, I'm sure most would think twice about giving it to their child," Professor Kennaway says.

"The word 'safe' is used very freely and loosely with this drug, but there have been no rigorous, long-term safety studies of the use of melatonin to treat sleep disorders in children and adolescents.

"Considering the small advances melatonin provides to the timing of sleep, and considering what we know about how melatonin works in the body, it is not worth the risk to child and adolescent safety," he says.

(Globe and mail, juillet 2013)
Doctors are warning parents about the risks of giving their children melatonin supplements – an increasingly popular solution to achieve a desired bedtime – as the supplement is not regulated and the effects on a child’s development are largely unknown.
“The long-term safety data is simply not there,” says Dr. Mark Feldman, director of community pediatrics at the University of Toronto.
While sleep disorders in children are a common problem, summer brings its own challenges with longer daylight hours, changes in routine and often a relaxation of rules – all of which can make it harder to get the kids into bed and sleeping soundly.
Approximately one in four parents complain to their family doctor that their child has trouble sleeping, according to Dr. Shelly Weiss, a neurologist at the Hospital for Sick Children in Toronto.
Pediatricians say they have seen a sharp increase in recent years of parents giving melatonin supplements to their kids to make bedtime easier.
Melatonin is naturally produced by the body in the pineal gland, which releases the hormone in response to several factors, including the amount of light and both physical and mental activity.
“It sort of tricks our own biological clock into thinking that it’s nighttime a little earlier,” Feldman says.
Health Canada classifies melatonin as a natural health product and stresses that it should only be used to treat sleep disorders in adults.
“We wouldn’t recommend it for the average healthy kid,” says Feldman, one of the authors of the report.
It is unclear whether there is a long-term downside to children taking melatonin, because widespread use of the supplement by children is a relatively recent issue. In a report released last summer, the Canadian Paediatric Society emphasized that no long-term studies have been done on its safety or effectiveness.
But other experts disagree, arguing melatonin use is safe. Dr. James Jan, a neurologist who has been studying the impact of melatonin on children for the past 32 years, says he has not seen any long-term side-effects.
“There is no risk in large doses, because once the body is flooded with melatonin, what’s not needed is washed out,” Jan says.
But because melatonin is a hormone, Weiss says, it could delay a child’s development during puberty.
“You’re giving a natural hormone in an unnatural amount,” Weiss says.
There’s also the risk that a child will come to rely on the melatonin supplements to fall asleep.
“It’s a psychological risk – you’re using a pill instead of using good sleep hygiene,” Weiss says, noting that you’re teaching the child that healthy sleep depends on a pill.
Melatonin should not be ruled out entirely. It can effectively be used to combat jet lag, or in more serious cases of children with neurological or behavioural disorders.
At the end of the day, pediatricians say parents need to think twice before reaching for the pills and work with their doctor to get to the bottom of their child’s sleeping problems.
“The most important thing is to talk to their physician about the cause of their insomnia,” Weiss says.
- Establish a regular time to wake up and go to bed, and stick to it – even on weekends. “If you go to bed at different times, it’s harder to fall asleep.”
- Remove all electronics from a child’s room. No TV, no computer, no cellphone. “They’re just so distracting,” Dr. Feldman says.
- Make sure your child gets regular exercise.