Why do we dose long acting meds BID/TID/QID

[Scorcher31]

I know psych med receptors and side effect profiles etc, but I'm a bit rusty in terms of pharmicokinetics, pharmicodynamics, etc. I'm reviewing before I start my residency, but I can't come to grips with why we would dose meds like Librium or Valium with long 100 hour+ half lives TID. Shouldn't it last throughout the day?


I would think that even if we gave Valium once daily assuming it has ~ 96 hour half life for convenience sake only 1/8 of the medicine would be gone per day. So if we gave 5 mg of valium the next day at dosing time there would still be 4.375 mg left from the previous day wouldn't there? I know it will take weeks to establish a steady state and have the concentration level off given the half life, but why dose it multiple times in one day when it breaks down nowhere near as quickly as Xanax which we also can dose TID?

Thanks for any input guys!!

---

Members don't see this ad.

 

[whopper]

I think the majority of it is just lack of insight on the part of the prescriber.

Seroquel XR for example is supposed to be given once a day. I've seen several patients on it twice to 3x a day.

Abilify is supposed to be given in the morning. The manufacturer recommends it and with reason. Several people who take it claim it wakes them up. I've seen several doctors tell their patients to take it at night. Why? I don't know.

There are of course outliers. I've encountered a rare patient who claims that ironically Abilify makes him tired. I tell that guy he can take it at night, but I document in the chart why I recommended he do that.

The patients could themselves be having reactions to the meds that don't make sense. Some patients may claim that if they take it all at once in a once daily dose, it causes a side effect that is mitigated if they break it up.

 

[snarfer]

I know psych med receptors and side effect profiles etc, but I'm a bit rusty in terms of pharmicokinetics, pharmicodynamics, etc. I'm reviewing before I start my residency, but I can't come to grips with why we would dose meds like Librium or Valium with long 100 hour+ half lives TID. Shouldn't it last throughout the day?


I would think that even if we gave Valium once daily assuming it has ~ 96 hour half life for convenience sake only 1/8 of the medicine would be gone per day. So if we gave 5 mg of valium the next day at dosing time there would still be 4.375 mg left from the previous day wouldn't there? I know it will take weeks to establish a steady state and have the concentration level off given the half life, but why dose it multiple times in one day when it breaks down nowhere near as quickly as Xanax which we also can dose TID?

Thanks for any input guys!!

Because it is unethical to give patients placebo.

However, half lives, for any drugs, can vary depending on GFR and hepatic impairement. One example is THC. All the textbooks say urine can stay positive for thirty days. In reality, particulary in healthy adolescents and at 1-2 joints daily, thc can be completely metabolized out of the body in as little as 2-3 days.

 

[Regnvejr]

F.ex. Abilify, long half-life, but main start-up problem is not as much akathisia, but rather nausea. So I give 1/2 dose with breakfast and dinner, at least the 1st 2 wks, then they can do whatever works for them.

 

[Scorcher31]

As always thank you very much everyone that does clear it up quite a bit

Sorry, my questions was a little convoluted by I def didn't want to substitute a placebo.

It slipped my mind Regnvejr that we can use it as a way to split up the dose. Still though I have to wonder If I give a patient one 10 mg dose of abilify or 2 5 mg doses of abilify is it really going to cut down on the side effects that greatly? I guess if the nausea is a direct effect of the pill on the stomach than it would. Assuming it has a 3 day half life, any side effects related to the level absorbed should hypothetically be almost the exact same because the first dose 5 mg has only degraded to about 4.58 mg before we add on the second 5 mg dose for the day.

Anyways sorry for the silly topic I think I've figured it out a bit. I'm sure a lot of it will be judgment based and I'll have see and monitor responses to truly get a feel for it.

 

[Regnvejr]

As always thank you very much everyone that does clear it up quite a bit

Sorry, my questions was a little convoluted by I def didn't want to substitute a placebo.

It slipped my mind Regnvejr that we can use it as a way to split up the dose. Still though I have to wonder If I give a patient one 10 mg dose of abilify or 2 5 mg doses of abilify is it really going to cut down on the side effects that greatly? I guess if the nausea is a direct effect of the pill on the stomach than it would. Assuming it has a 3 day half life, any side effects related to the level absorbed should hypothetically be almost the exact same because the first dose 5 mg has only degraded to about 4.58 mg before we add on the second 5 mg dose for the day.

Anyways sorry for the silly topic I think I've figured it out a bit. I'm sure a lot of it will be judgment based and I'll have see and monitor responses to truly get a feel for it.

Blood levels are comparable, but the GI effects are less. Whether it is a placebo effect or not, tolerability has increased since I began advising this.

 

[Scorcher31]

Well either way it's a plus then. Thanks again! I was just refreshing myself on how things work. I've been out of school for a few months now and been out of psych rotations even longer so I'm just getting back into the grind of things. I’m a little anxious albeit happy to be starting my residency in a few days.

 

[kugel]

With patients who are agitated and/or violent, it's common to dose BID/TID for meds that could otherwise be given q Day. When someone is very acutely ill, I'll often dose the antipsychotic BID or TID upon admission in order to reduce the chance of very short-term side-effects and so that 1-2 refused doses creates a stir among the treatment team and signif efforts to get back on track before the pt regresses dramatically. After a few days, you can start weighting the doses toward HS.

As pointed out earlier, pt's side-effects often don't read the textbooks. If a med that's normally activating is making him sleepy, I'll try to switch to night. And vice versa.
XR, XL, ER given more than once per day - usually someone's not being careful in transcribing previous orders.

 

[whopper]

Talk about outliers, I had a patient who claimed to be allergic to Lexapro but not Celexa.

What was going on there I do not know. The only rational explanation I could come up with was maybe she was allergic to the medium that contained the active ingredient. With Citalopram, these could vary depending on the manufacturer.

Of course she could've been mistaken or lying, but she didn't seem to be, and I couldn't identify anything she could gain by manipulating the information.

 

[xthine]

^Just out of curiosity, what kind of allergic reaction did your patient have to Lexapro?

 

[whopper]

She claimed she got hives from Lexapro.

 

[TexasPhysician]

I think the majority of it is just lack of insight on the part of the prescriber.

Abilify is supposed to be given in the morning. The manufacturer recommends it and with reason. Several people who take it claim it wakes them up. I've seen several doctors tell their patients to take it at night. Why? I don't know.

There are of course outliers. I've encountered a rare patient who claims that ironically Abilify makes him tired. I tell that guy he can take it at night, but I document in the chart why I recommended he do that.

A patient of mine was given the first dose of Abilify in the pm by a nurse as a mistake. I asked the patient if I could "switch" his dose of Abilify to am and if it seemed to help the first night. He said he liked the drug and he doesn't want me to mess with what works.

I wonder if the psych doc at the county health department doesn't think I'm odd for prescribing qHS now.

 

[michaelrack]

but I can't come to grips with why we would dose meds like Librium or Valium with long 100 hour+ half lives TID. Shouldn't it last throughout the day?

!!

I don't remember the explanation any more, but benzo's can be tricky to dose. Benzo's with long half lives often do require several times a day dosing. It may have something to do with half life in the blood vs the duration of effect in the brain?

 

[whopper]

I wonder if the psych doc at the county health department doesn't think I'm odd for prescribing qHS now.

The only thing you can do is document why you dosed it the way you did and explain it to the patient. This way when the next doctor questions, he at least will have something of a possible source to explain.

I wish I could say strange dosing was only because of outliers and the doctors did what they reasonably could to accommodate them. Unfortunately this is not the case. It's more the case of poor prescription practice by doctors who did not keep up with data and don't listen to their patients.

 

[Regnvejr]

The only thing you can do is document why you dosed it the way you did and explain it to the patient. This way when the next doctor questions, he at least will have something of a possible source to explain.

I wish I could say strange dosing was only because of outliers and the doctors did what they reasonably could to accommodate them. Unfortunately this is not the case. It's more the case of poor prescription practice by doctors who did not keep up with data and don't listen to their patients.

Reality of Abilify is that some people get tired from it, some get activated. Some get nausea, some don't. Some gain weight, some loose weight. Some get restless, some don't. Abilify dosing is highly individual. The trick is indeed to listen to your patients.

 

[Regnvejr]

A patient of mine was given the first dose of Abilify in the pm by a nurse as a mistake. I asked the patient if I could "switch" his dose of Abilify to am and if it seemed to help the first night. He said he liked the drug and he doesn't want me to mess with what works.

I wonder if the psych doc at the county health department doesn't think I'm odd for prescribing qHS now.

About 1/2 of my Abilify dosing is evening dosing per sedation or patient preference (easier to remember to take if it is taken with rest of meds.)

 

[whopper]

According to data I received from the manufacturer, and I have not seen this in published journal, from their own studies, while Abilify is usually activating, the higher the dosage, the less likely this is the case. When Abilify is given at dosages over 30mg, the likelihood of activation shifts from the majority to the minority. Where this exactly happens is somewhere around 40mg.

 

[Regnvejr]

According to data I received from the manufacturer, and I have not seen this in published journal, from their own studies, while Abilify is usually activating, the higher the dosage, the less likely this is the case. When Abilify is given at dosages over 30mg, the likelihood of activation shifts from the majority to the minority. Where this exactly happens is somewhere around 40mg.

To some extend, but I see a fair number of patients with some sedation at 15 mg. Not just the temporary mellowing of mood, but needing a nap.

 

[whopper]

Same here. The majority I find, still find Abilify activating, but it's effects seem to be on the slightly more variable side.

I have seen patients gain tremendous amounts of weight on it, people put to sleep by it, and people experience tremendous akithesia from it, which is ironic considering its supposed to be a partial agonist.

I have a suspicion that Abilify's effects, because it's a partial agonist (variably blocking antagonizing or agonizing dopamine) is more variable in it's effects than the usual antipsychotic.

 

[Encephalopathy]

With Valium and Librium, it's the active metabolites that have the long half-lives. I think the tid-qid dosing is to ensure stable blood levels (i.e., higher troughs to minimize breakthrough anxiety/EtOH withdrawal/etc.)

It's my experience that higher doses of Abilify are more sedating.