Talk:Phenobarbital

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I work as a volunteer in a local excellent hospital Seattle Childrens Hospital. I can assure you that phenobarbital has been used for every patient with seizures that I've visited in the last month. This is in an affluent country in a very good hospital. Where is the claim that it is not used in affluent countries from? Perhaps not in the UK, I understand that, but the generalization doesn't hold. laddiebuck 01:51, 7 September 2006 (UTC)

Thanks for your comments. I don't doubt what you say. I can only go on what I've been able to research and source. Here are some statements:

• In affluent societies, phenobarbital is unlikely to represent the best choice for most people with newly diagnosed epilepsy. [1]
• Although its purported propensity to cause sedation and other cognitive and behavioral side effects has relegated it to second- or third-line use in many parts of the industrialized world, it remains a popular choice in many developed countries [2] (Note "popular choice" doesn't indicate first-choice - the source paper for that statement had carbamazepine and valproic acid in first positions for two main seizure groups).
• Once considered to be a first line drug, it is now generally thought to be a second-line therapy because of its side effects, which include sedation, depression and agitation. [3]
• Phenobarbital remains a very useful drug in adults, whether or not it is the only drug available, but there is a real ethical dilemma in children in whom it should be used with caution if it is the only available drug. [4]
• The UK NICE guidelines put it amongst the third-line drugs. The Scottish SIGN guidelines don't mention it when discussing chronic epilepsy treatment. These guidelines emphasise the drug side-effects and interactions rather than efficacy as being the main rationale for grading the drugs into 1st/2nd/3rd line.
• US guidelines that I have found, do not grade epilepsy drugs – some may be more appropriate for certain conditions, but they are more-or-less equivalent in terms of efficacy. It is left to the physician to determine the most appropriate drug for an individual patient. Phenobarbital is the cheapest epilepsy drug in the "Drug Formularly".[5] Go figure :-)

It would be good to find a source that indicates actual prescribing practice for these drugs. We can only include verfied information in Wikipedia. Colin°^Talk 17:45, 7 September 2006 (UTC)

Thanks for your meticulous research. I will try to find information for you. The behavioral side-effects of phenobarbital are known, I've heard them being discussed in the care conferences for patients. Here is some info:

• The three main drugs prescribed are phenobarbital, dilantin, and keppra (I realize I'm mixing trade names and chemical names, but I am just repeating usage). The ketogenic diet, which Wikipedia describes as not mainstream, is also used.
• I see mainly young patients, between the ages of 0-9. I sometimes see patients above that age, but not enough to be statistically significant.

I will ask the next chance I have for some more concrete documentation on the consensus on using these drugs in the US, or at least this hospital's policy on them. I'll post that to the talk page. laddiebuck 23:49, 7 September 2006 (UTC)

BTW the Wikipedia ketogenic diet article could do with some work. If by "not mainstream" you mean "alternative therapy" then the article is certainly giving the wrong impression. Although not a first-line choice, the diet is certainly an accepted option for refractory epilepsy in children. For example, NICE guidelines recommend "The ketogenic diet should not be recommended for adults with epilepsy" but "The ketogenic diet may be considered as an adjunctive treatment in children with drug-resistant epilepsy." The SIGN guidelines say "The ketogenic diet has a role to play in the management of intractable epilepsy and significant proportions of children will experience clinically significant seizure reduction. This technique should be supervised in a unit where expertise in the diet exists." In other words, it requires referral to a tertiary hospital or clinic in order to get access to the experts. Typically this means a neurologist and dietician with experience – which is probably the biggest problem. Colin°^Talk 10:18, 8 September 2006 (UTC)

I totally support Colin here. Phenobarbital is not used first-line in adults in the UK and the Netherlands, countries where I have practiced. Phenytoin is generally first-line, with valproic acid as adjuctive therapy. I have seen phenobarbital used as second-line therapy. In third-world countries phenobarbital remains a cheap and fairly effective anticonvulsant; the main drawbacks are dependence and sedation. For children, I have not seen phenobarb used first-line, but this is limited by my short time (1 week) in paediatric neurology. JFW | T@lk 21:35, 5 October 2006 (UTC)

[edit] Uses in children

From what I've been able to gather, although phenobarbital is not really used for adults, it is preferred for use for patients under 12... laddiebuck 01:40, 18 September 2006 (UTC)

I propose modifying the last sentence of the introduction by adding the words "for adults", thus: "In more affluent countries, it is no longer recommended as a first or second-line choice anticonvulsant for adults.[2][3]" laddiebuck 03:38, 4 October 2006 (UTC)

I'm not sure it is correct to say it isn't used for adults. There are lots of adults taking phenobarbital or primidone (a pro-drug of phenobarbital), though there were probably started on these drugs a long time ago. The drug has merely been relegated to second/third line, it hasn't gone completely. You need to provide evidence (either online or quoting a modern reliable medical textbook) that it is "preferred for use for patients under 12". That certainly doesn't seem to be the case in the UK and is contradicted by many of the quotes/sources listed above. I'm opposed to the change suggested. Both references (currently [2] and [3]) apply to both adults and children. There are other sources specifically warning against its use in children (due to risk of learning impairment). Even if you find sources backing the "preferred for use for patients under 12" guideline, it is clear that the wording would then have to state that the guidelines vary. If you feel strongly that the change should be made, I suggest we seek input from others by asking on one of the medical/neurology wiki projects. Let me know if this is what you would like, and I'd be happy to post a neutral request for comment. Colin°^Talk 08:37, 4 October 2006 (UTC)

I'm unclear on the matter myself, all I have is my own observations and questions answered by the local neurology team in a children's hospital. So yes, I'd be glad if you could do so. Thank you. laddiebuck 18:38, 5 October 2006 (UTC)

This may be a case of differences between countries and differences between adults and kids. In the US, in the many hospitals I've worked in, phenobarbital is the first line agent for maintenance in young children with seizures. It is used almost exclusively in the neonatal intensive care unit due to its long track record and availability in both IV and po forms with known effective levels. I'm obviously a proponent of full referencing of everything on Wikipedia and provide one here in a recent study design proposed in Pediatrics (Pediatrics. 2006 Mar;117(3 Pt 2):S23-7. PMID 16777818). I appreciate the other references, but they do not provide an accurate picture of reality therapy in infants and young children in the United States. The article should reflect this and the above proposed change ("for adults") makes the most sense. InvictaHOG 23:16, 5 October 2006 (UTC)

UK practice is I think different. In some 20 years of working as a doctor, I don't think I've encountered anyone being started on Phenobarbital - sure I've had patients who are already on this, and if they are well controlled there is no need to switch to newer drugs (oh many were the happy occasions as a junior hospital doctor suddenly finding a patient was either Nil-by-mouth pre/post an operation or too weak to swallow their normal pills and requiring intravenous administration requiring the on-call pharmacist to be called in - anyway I digress). Phenobarbital is not first-line treatment for any childhood epilepsy except neonatal seizures. British National Formulary for Children 2006, section 4.8.1 Control of epilepsy (p255) gives:

• Partial seizures with or without secondary generalisations - 1st Carbamazepine, lamotrigine, sodium valproate & topiramte. "Phenobarbital & Primidone are also effective but they are more sedating and are not used as first-line drugs"
• Generalised seizures
  • Tonic-Clonic seizures(grand mal) - 1st Carbamazepine, lamotrigine, sodium valproate & topiramate. 2nd clobazam, levetiracetam and oxcarbazepine. Then lists Phenobarbital amongst other drugs used (i.e. 3rd line)
  • Absence seizures (petit mal) 1st ethosuximide & sodium valproate. 2nd Lamotrigine.
  • Myoclonic seizures 1st sodium valproate, 2nd clobazam, clonazepam, ethosuximide, levetiracetam, lamotrigine or topiramate
  • Atypical absence - sodium valproate, lamotrigine or ethosuximide
  • Atonic seizures - sodium valproate, lamotrigine, ethosuximide or topiramate
  • Tonic seizures - sodium valproate or topiramate
• Epilepsy syndromes
  • Infantile spasms - Vigibatrin if associated with tuberous sclerosis, in spasms of other causes Prednisolone may be more effective. 2nd line clobazam, clonazepam, sodium valproate and topiramate
  • Lennox-Gestaut syndrome - 1st line lamotrigine, sodium valproate, topiramate
  • Lansau-Kleffner syndrome - 1st line Prednisolone, sodium valproate
  • Neonatal seizures (due to "encephalopathy, biochemical disturbances, inborn errors of metabolism, hypoxic ischaemia, drug withdrawal, severe jaundice, meningitis or cerebral damage"). Seizures caused by biochemical imbalance and those with inherited abnormal pyridoxine or biotin metabolism - correct underlying cause. Seizures due to drug withdrawal treated with a drug withdrawal regimen. "Phenobarbital may be preferred when there is a risk of seizure recurrence in neonates; phenytoin is an alternative"
• Status epilepticus - 1st line midazolam into buccal cavity or intranasally or rectal diazepam. In hospitals iv lorazepam (or emulsion formula of diazepam) or Clonazepam. 2nd line is iv phenytoin by slow iv . Phenobarbital is listed as 3rd line

However none of this suggests routine ongoing 1st or 2nd line use for children, and with just short-term use in neonatal units (and neonate generally taken to mean up to 1 month of age). As a GP, I have never encountered a child out in the community (vs. a neonate inpatient) on Phenobarbital. David Ruben ^Talk 01:14, 6 October 2006 (UTC)

[edit] Veterinary uses

I changed the indication from "the drug of choice in dogs" to "one of the initial drugs" because both phenobarbital and bromide are currently considered the two first-line drugs for dogs with epilepsy.

I added that phenobarbital is the initial drug of choice for cats.

I removed the mention of phenobarbital in the treatment of status because although it is a good drug to prevent further seizures, it's relatively low lipid solubility means it does not enter the brain quickly, even with intravenous administration, so it's not as useful in the emergency treatment of status. In dogs and cats with status refractory to diazepam, pentobarbital or propofol are usually preferred because of their more rapid onset of anti-seizure activity.

Merck may not be the best reference for my changes. Better might be: Thomas WB. Seizures and narcolepsy. In: Dewey CW (ed). A Practical Guide to Canine and Feline Neurology. Iowa State Press. 2003.

But I was not sure exactly if it's better to add a reference or change a reference. Please feel free to add this reference or not.

Thanks

Loupe 21:25, 11 October 2006 (UTC)

Thanks for your edit – I am not a veterinarian, and added information from the Merck Manual simply because it was easily available to me and I am familiar with it, not because it was the best source. I will add the reference you provided; if you'd like to expand this section, feel free to. The phenobarbital article has been sort of an unofficial collaborative project on WP:DRUGS, and I'm sure any further reliable information you could add would be much appreciated. Thanks again, Fvasconcellos 21:45, 11 October 2006 (UTC)

[edit] Concerns about febrile seizures in children

In the section "Indications", there is a cited quote, that

Concerns that neonatal seizures in themselves could be harmful make most physicians treat them aggressively. There is, however, no reliable evidence to support this approach.^[18]

while this is provided by a link to source, it is disputable in my opinion. Every seizure is considered a medical emergency per se. Even more so to be concerned in little children, since their skeletons are not fully developped and the central nervous system can take bad damages due to the seizure itself, or due to hypoxia caused by respiration problems during seizure. Thus, the "aggressive therapy" is important, in my opinion.--Spiperon 00:06, 22 October 2006 (UTC)