Expert psychopharmacologists like our readers should make sure they are well-versed in prescribing medications that may be helpful for difficult-to-treat illness.
One such medication is clomipramine (Anafranil®). Since clomipramine can be toxic at higher serum levels, a serum level should be checked.
There are a few special things to remember regarding how to check the serum clomipramine level:
1. There is usually little point checking the level until a dose of 150 mg/day is reached.
2. But, the level should be checked at a lower dose if a drug interaction is present that could raise the clomipramine level (Grant, 2014).
3. The half life of desmethylclomipramine, the main metabolite of clomipramine is about three to four days. So, it takes two to three weeks to reach steady levels. Unless there is some urgency, levels should be checked two to three weeks after the last dose change. Yes, that’s a lot more than what we are used to for other medications.
4. The blood should be drawn no less than 12 hours after the last dose of clomipramine. Otherwise, it will appear to be falsely elevated since it will not have come down to the trough level.
5. After the trough level is reached at about 12 hours, there is not as much of a further decrease in the level. So, we should tell the patient that it is better for the time since the last dose to be more than 12 hours rather than less. And, that more than 12 hours is OK.
Reference levels
The laboratory results will show a serum level for clomipramine, a level for desmethylclomipramine, and a total of the two.
“Normal” or desirable ranges for these are as follows:
– Clomipramine 50 to 250 mcg/L
– Desmethylclomipramine 150 to 350 mcg/L
– Total 200 to 500 mcg/L
Important! The combined trough plasma levels of clomipramine and desmethylclomipramine should not exceed 500 ng/mL because the risk of seizures and of cardiac conduction delay is clearly higher above that level (Fineberg et al 2012).
How to interpret the clomipramine level
At lower serum levels, response to clomipramine is inadequate. At high levels, there is no additional benefit and side effects tend to increase. So, we should aim for the recommended levels mentioned above.
Related Pages
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Add clomipramine to an SSRI for OCD?
How exactly to add clomipramine to an SSRI
References
Anafranil® Prescribing Information
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I disagree with the recommendation that the CMI level does not need to be checked until a dose of 150 mg daily is reached. This may not adequately take into account slow 2D6 metabolizers. I have had one patient that produced a level of 560 ng/ml while taking 50 mg daily only and another patient taking 300 mg whose level was only 55 ng/ml.The level should be checked on 50 mg daily or certainly on no more than 100 mg daily. I think that it is also useful to point out that dosing to the level as well as clinical response is easier with the other TCAs than with NTP where one is constrained by a window of 50-150 ng/ml. With the other tertiary and secondary amine TCAs you can dose to the clinical effect within the limits of tolerance without having to worry about a window.