Taking Benzodiazepine (Lorazepam) With Mirtazapine & Risk Of Respiratory Depression

In our latest question and answer discuss the risk of respiratory depression in someone taking the benzodiazepine lorazepam with mirtazapine.

Taking Benzodiazepine (Lorazepam) With Mirtazapine & Risk Of Respiratory Depression
Oct 21, 2017

David asked

Hi I'm currently taking 30mg of Mirtazapine and 10mg of Lorazepam prescribed by my doctor. My psychiatrist and my doctor are aware I'm taking both these medications, however I searched online for any interactions and it turns out there's a significant interaction but not a major interaction between Mirtazapine & Lorazepam.
I don't drink any alcohol while I take Lorazepam nor do I take any other benzodiazepines, as I heard this mixture could cause respiratory failure & CNS Depression. So my question is : Is there any risk of me getting respiratory failure or CNS depression by taking the 2 medications prescribed to me: Mirtazapine & Lorazepam??
I've been taking Mirtazapine for 5 years & Lorazepam for 2 years ( during the last 2 years I've been switching fromone benzo to another as first it works but then it doesn't work anymore... I think I've built a tolerance and that's why at first lorazepam,xanax,valium were working but now even if I take the maximum dose it doesn't work).
My question is can I take slightly more than the maximum dose? ( the maximum dose of lorazepam is 10mg )  10mg used to work but because I've built a tolerance over the years. As well as taking them everyday, I tried taking 11mg then 12.5mg but it still doesnt' work but I feel better taking them than not taking anything at all. People have told me unless it's combined with another benzo or alcohol I'd need to take a much higher dose for it to be a lethal overdose?? But I am taking another medication ( Mirtazapine, I know its not alcohol or another benzo but it's an antidepressant) So can I continue to take 30mg Mirtazapine (normal dose) with 11 or 12.5mg of Lorazepam?? Is it safe or could I get respiratory failure or CNS depression?? Hope to get a reply.   Thanks in advance.

Answer

Female PharmacistHello! There were a few questions in your submission so let's break them out and answer them separately:

Is there any risk of me getting respiratory failure or CNS depression by taking the 2 medications prescribed to me: Mirtazapine & Lorazepam?? 

If you have been on the mirtazapine for 5 years and the lorazepam for 2 years, you have an extremely small risk of respiratory depression at your current doses. For starters, being on both medications for a long period of time, you have certainly built up a tolerance to their effects. Like many medications, you build up a tolerance with prolonged use. This is especially true with benzodiazepines, such as lorazepam. This is why people who have taken these drugs for extended periods, tend to be on higher doses...they need it for continued effectiveness.  You would never start a new patient on lorazepam at the higher doses that some people take who have been on it for longer periods. 

In regards to benzodiazepines and respiratory depression, contrary to popular belief, benzodiazepines are rarely fatal, even after very large overdoses. The real problem occurs when taken concomitantly with other CNS depressants (e.g. alcohol, opioid drugs etc...). This isn't too say they aren't dangerous.... they certainly can be if used incorrectly or when taken in addition to the wrong medication... which brings us to mirtazapine.

Mirtazapine is not typically considered a major CNS depressant and has very little risk of respiratory depression, alone or in combination. It certainly is associated with sedation and the interaction concern with lorazepam is that additive sedative effect that can occur. Unless you have some sort of underlying respiratory problems (e.g. sleep apnea, COPD), potential respiratory depression would be of little concern on this combination.

Can I take slightly more than the maximum dose?

Whether or not your dose needs to be increased should come from a conversation between you and your doctor.  In regards to if it possible to take more than 10 mg in general, then the answer is yes, doses over 10 mg, while not common, certainly have a place in therapy. While 10 mg is listed as the max daily dose by the manufacturer, doses above that may be needed based on tolerance level and indication. Much like opioid pain medications, you typically see someone have their dose increased over time to maintain effectiveness. Increasing your dose to slightly more than 10 mg typically would not put you at an increased risk of respiratory depression. As mentioned above, unless combined with other significant respiratory depressants, you should be safe.

Your doctor may recommend yet another switch to a different benzodiazepine. Lorazepam is rapid acting and has an intermediate duration of action. You may need to switch to something that lasts longer in the body.

Can I continue to take 30mg Mirtazapine (normal dose) with 11 or 12.5mg of Lorazepam?? Is it safe or could I get respiratory failure or CNS depression?

This typically would not put you at a dangerous risk of respiratory depression (as we talked about above) for various reasons:

  • Benzodiazepines, by themselves, are typically difficult to overdose to the point of respiratory depression. Very large doses are needed.
  • Mirtazepine is not considered a major CNS depressant.
  • You have built up a tolerance to both mirtazapine and lorazepam for some time.

Having said all that, everyone is different and it is difficult to predict how someone will react to any given therapy. Please speak with your doctor regarding your concerns and hopefully you can come up with a treatment plan to adequately address your concerns. 

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