half-life and side effects and withdrawal

[AD04]

1) Patient used to take prozac 60mg daily. His last use of it was a few months ago.

Would you feel comfortable restarting at 60mg? Would the risk of side effects be reduced due to its long half-life compared to starting the same comparative dose in a drug with a short half-life?

2) Are seizure risks for abruptly stopping long-acting benzodiazepines lower than abruptly stopping short-acting benzodiazepines?

It makes sense as many medication with long half-lives self taper. If so, how much lower?

The only thing I found in Kaplan & Saddock was that the onset of seizure would be delayed with long-actings compared to short-actings.

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[birchswing]

The half-life of diazepam is very fuzzy. Its metabolites all have different half-lives, and people have variable responses to diazepam due to CYP2C19 variations—which predominantly affects those of Asian descent. It's also metabolized more slowly in the elderly. I'm not sure which of the metabolites would be more or less anticonvulsant, but I know some benzodiazepine metabolites tend to be preferential for anxiolytic, soporific, hypnotic, or anticonvulsant effects.

 

[wolfvgang22]

1) Patient used to take prozac 60mg daily. His last use of it was a few months ago.

Would you feel comfortable restarting at 60mg? Would the risk of side effects be reduced due to its long half-life compared to starting the same comparative dose in a drug with a short half-life?

2) Are seizure risks for abruptly stopping long-acting benzodiazepines lower than abruptly stopping short-acting benzodiazepines?

It makes sense as many medication with long half-lives self taper. If so, how much lower?

The only thing I found in Kaplan & Saddock was that the onset of seizure would be delayed with long-actings compared to short-actings.

I recommend in general to always titrate paroxetine up from a lower dose after more than a week or two has gone by off the medication. Many times I find a patient actually didn't need 60mg but now does fine with 30mg. Long acting benzos do self taper for people on them only a few days, but it is much better to very slowly taper people who have been on them for months or years. The worry is less about seizure risk, which is possible, than anxiety and habituation. You'll get a whole lot less phone calls if you do a very slow taper for outpatients.

 

[AD04]

The half-life of diazepam is very fuzzy. Its metabolites all have different half-lives, and people have variable responses to diazepam due to CYP2C19 variations—which predominantly affects those of Asian descent. It's also metabolized more slowly in the elderly. I'm not sure which of the metabolites would be more or less anticonvulsant, but I know some benzodiazepine metabolites tend to be preferential for anxiolytic, soporific, hypnotic, or anticonvulsant effects.

Benzodiazepines overall is quite fuzzy -- in terms of conversion to half-life. According to different sources, half-life for diazepam it can range from 20 hours to 200 hours (including the metabolite).

I recommend in general to always titrate paroxetine up from a lower dose after more than a week or two has gone by off the medication. Many times I find a patient actually didn't need 60mg but now does fine with 30mg. Long acting benzos do self taper for people on them only a few days, but it is much better to very slowly taper people who have been on them for months or years. The worry is less about seizure risk, which is possible, than anxiety and habituation. You'll get a whole lot less phone calls if you do a very slow taper for outpatients.

I agree with titrating from lower dose and you make a good point about patient functioning well with a lower dose. I was looking at this from a more theoretical view -- if drugs with longer-half lives are more gentile in terms of side effects due to the increased time to reach steady state. Theoretically, it just makes sense.

 

[DisorderedDoc417]

If it was a few months ago — restart and titrate to lowest effective dose.

 

[NickNaylor]

Agreed with above - I would not restart fluoxetine at 60 mg if they haven't taken it in several months. Even with a long half-life, "a few months" is several half-lives of even norfluoxetine, so any medication present in the blood would be negligible.

For #2, don't know if this has been shown in a true trial but it somewhat makes sense pharmacologically that longer acting BZDs would be associated with a lower risk of seizures/withdrawal symptoms/etc. compared to shorter acting BZDs because the level of CNS GABA activity wouldn't swing abruptly, but who knows unless it's been specifically studied.