By Rajnish Mago, MD (bio)
What are dose equivalents?
It is common for a patient to be changed from one antipsychotic to another. This is particularly true for oral preparations of antipsychotics. On another page on this website, we noted that the term “dose equivalents” means-–how many milligrams of one antipsychotic are approximately equivalent in their clinical efficacy to how many milligrams of the other antipsychotics?
Why do we need to know about them?
Clinicians need to know this to be able to start on the appropriate, equivalent dose of the next antipsychotic. Researchers and academics need to know about dose equivalents when designing clinical trials comparing one antipsychotic to another or when conducting meta-analyses of clinical trials and comparing one antipsychotic to another.
We try to start long-acting injectable (LAI) antipsychotics after we know that the antipsychotic is effective and is being tolerated. But, despite this, it is not uncommon for a patient to be changed from one long-acting injectable (LAI) antipsychotic to another. So, we also need to know how much of the next long-acting injectable (LAI) antipsychotic to start the patient on, based on the dose and frequency of the current LAI antipsychotic. That is, we need to know the dose equivalents for LAI second-generation antipsychotics. For example, if a patient was on LAI risperidone (Risperdal Consta®) 25 mg every two weeks and is being changed to paliperidone palmitate (Invega Sustenna®) taken every four weeks, how many milligrams of paliperidone palmitate should be given to keep the antipsychotic dose approximately the same in moving from LAI risperidone (Risperdal Consta®) to paliperidone palmitate (Invega Sustenna®)?
How were dose equivalents for LAI antipsychotics determined?
This question of dose equivalents for long-acting injectable second-generation antipsychotics was addressed by a systematic review of clinical trials (Rothe et al., 2018). That paper described how the dose of each LAI antipsychotic that is equivalent in efficacy to 1 mg of olanzapine was calculated. This is similar to how we saw in discussing the dose equivalents for oral second-generation antipsychotics on another page that the equivalent dose of each antipsychotic was stated in reference to haloperidol 5 mg or olanzapine 10 mg. In fact, the only reason olanzapine was chosen as the reference was that it was the reference for the analyses done for oral second-generation antipsychotics by the same team.
I think that knowing how these dose equivalents were determined helps us decide how seriously we want to take them. So, I’ll describe the method in a nutshell along with an example. I wasn’t able to understand the method until I did the math myself on some examples. I then realized that it was very simple and, hopefully, you will too.
1. The minimum effective dose of each antipsychotic was identified from clinical trials of that antipsychotic. For example, for olanzapine pamoate, several different doses were tried in a clinical trial but the lowest dose that was more effective than placebo was 210 mg given every two weeks. So, that was considered to be the “minimum effective dose.”
2. Based on the minimum effective dose of the LAI antipsychotic in step 1 and the interval between injections, it’s minimum effective DAILY dose was calculated, which is easy. For example, for olanzapine pamoate, 210 mg given every 14 days means that the minimum effective daily dose was 210 mg divided by 14 days = 15 mg of olanzapine pamoate per day. Of course, the LAI was not been given daily, so the “daily dose” is just a number that was calculated.
3. Having determined the minimum effective daily dose for each LAI, these doses were converted to the dose equivalent to 1 mg of olanzapine pamoate. How? By simply dividing the minimum effective daily dose of that antipsychotic by 15 since for olanzapine pamoate, 15 mg per day was the minimum effective dose.
Seeing this approach in an example will make it clear if it isn’t already.
An example of the method
Let’s do an example to make sure the approach described above is clear.
For paliperidone palmitate (Invega Sustenna®), many different doses were tried in clinical trials and 25 mg given by injection every four weeks was the minimum dose that was statistically significantly better than placebo, that is, the “minimum effective dose.”
Note: This 25 mg dose of paliperidone is provided in the form of paliperidone palmitate 39 mg. In the body, paliperidone palmitate is hydrolyzed into paliperidone. Paliperidone palmitate injection (Invega Sustenna®) is available in 39 mg, 78 mg, 117 mg, 156 mg, and 234 mg strengths. These doses of paliperidone palmitate are equivalent to 25 mg, 50 mg, 75 mg, 100 mg, and 150 mg, respectively.
Anyway, the minimum effective dose of paliperidone palmitate 25 mg given every four weeks is the same as 25 mg divided by 28 days = 0.89 mg of paliperidone palmitate per day.
So, the minimum effective dose for paliperidone palmitate was 0.89 mg per day and we already saw above that for olanzapine pamoate it was 15 mg per day. These daily doses of the two antipsychotics are being considered to be equivalent. If so, this means that 0.89 mg divided by 15 mg = 0.06 mg of paliperidone palmitate is equivalent to 1 mg of olanzapine pamoate.
This is how for each LAI second-generation antipsychotic, the dose equivalent to 1 mg of olanzapine pamoate was calculated.
The results: Dose equivalents of LAI second-generation antipsychotics
IMPORTANT WARNING! Due to differences absorption and metabolism between oral and LAI antipsychotics, everything we have discussed on this page about doses and dose equivalents applies ONLY to LAI antipsychotics. Please do NOT think of or use the numbers on this page in relation to oral antipsychotics.
The dose equivalents for the LAI second-generation antipsychotics (Rothe et al., 2018) are shown in the table below.
Note in the table that, due to different pharmacokinetic properties, the dose equivalents for two different preparations of LAI aripiprazole (Aristada® and Abilify maintena®) and of LAI risperidone (Risperdal Consta® and Perseris®) are quite different from each other.
|Dose equivalent to every 1 mg of olanzapine pamoate (Zyprexa Relprevv®)
|0.71 mg (of aripiprazole, not of aripiprazole lauroxil)
|Guess how much?
|0.6 mg (of paliperidone, not of paliperidone palmitate)
|Risperidone long-acting injection
|Risperidone extended-release injectable suspension, for
subcutaneous use (Perseris®)
Note: The whole point of dose equivalents is that since the doses in the table above are all equivalent to each 1 mg of LAI olanzapine pamoate (Zyprexa Relprevv®), they are, obviously, equivalent to each other as well. That is, 0.6 mg of LAI paliperidone palmitate (Invega Sustenna®) is equivalent to 0.95 mg of LAI aripiprazole (Abilify maintena®) or to 0.21 mg of risperidone extended-release injectable suspension for subcutaneous use (Perseris®), and so on.
Rothe PH, Heres S, Leucht S. Dose equivalents for second generation long-acting injectable antipsychotics: The minimum effective dose method. Schizophr Res. 2018 Mar;193:23-28. doi: 10.1016/j.schres.2017.07.033. Epub 2017 Jul 21. Review. PubMed PMID: 28735640.
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