Prescribing Psychotropics in the Medically Ill

Last updated: December 28, 2018


Host: Wegdan Rashad, MD

  • Today’s question is: how to prescribe psychotropics in the medically ill?
  • In patients with liver impairment, it is better to use drugs that are metabolized by phase II enzymes or drugs that are not metabolized by the liver at all.
  • Patients with severe renal impairment may also have liver impairment. Use ⅔ of the recommended dose.
  • Benzodiazepines and Z-drugs are contraindicated in CO2 retainers and those with severe sleep apnea. Opiates are better than benzodiazepines in patients with terminal breathlessness.


Hello everyone and welcome to the Psychopharmacology Institute podcast. I’m your host, Dr. Wegdan Rashad. In this series we will be discussing topics that matter to you, the mental health clinician, in your practice, sharing expert opinions and the latest research.

What kind of dose adjustments do we need to make for patients with liver disease? What drugs should you avoid in patients with renal failure? And why are benzodiazepines frowned upon in patients with lung disease? All these questions, you’ll be able to answer by the end of this podcast. We will do this with the help of snippets from Dr. James Levenson’s lecture entitled, “Prescribing for the medically ill”. Dr. Levenson is a Professor of Psychiatry and Department Chair of Consultation-Liaison at the Virginia Commonwealth University School of Medicine.

The first part of our podcast we will feature liver impairment and how to select medications for this special group.

Dr. Levenson:
There are two key sets of metabolic reactions for the handling of most medications we prescribe for patients. These are phase I and phase II metabolisms. Phase I reactions are generally reduced in chronic liver disease with relative chronic liver disease with relative sparing of phase II metabolism. So when we have the option, one prefers to prescribe drugs metabolized by phase II or those drugs that are renally excreted.

Like what?
Well, for starters lorazepam, oxazepam, temazepam, and lamotrigine are primarily metabolized by phase II enzymes.

Dr. Levenson:
After phase II metabolism, most metabolites are inactive and are water soluble and then suitable for the body to excrete them either renally or through biliary excretion. Lithium, gabapentin, and pregabalin do not undergo any hepatic metabolism and directly go to water-soluble forms of excretion.

So, obviously, it is better to choose medications metabolized by phase II enzymes or those who do not undergo hepatic metabolism altogether. So in summary, if you want to prescribe a benzo it is better to choose lorazepam, oxazepam, and temazepam. For mood stabilizers, lamotrigine, lithium, gabapentin, and pregabalin. For antidepressants, desvenlafaxine among others.

Moving on to part two.

What if you have a patient who has a renal disease? How does that affect prescribing?

Dr. Levenson:
In general, we would prefer hepatically metabolized drugs in patients with serious renal disease because they’re not dependent on renal excretion but that’s not a reason to give up all caution. For one reason, renal disease itself seems to reduce hepatic and intestinal metabolic activity. The mechanism for this is not entirely clear. It is maybe through reduced gene expression. Both phase I and phase II reactions, metabolic reactions may be affected in renal disease. Therefore, it’s generally a good idea to avoid drugs with active metabolites or complex metabolism in patients who have significant renal impairment. And as a general rule, we advise starting with 2/3 of the normal beginning dose unless there is specific renal dosing information available and such information does exist for some of our medications.

Whoa! Hold up, Dr. Levenson. Are you telling me that if the kidneys are impaired, the liver is also impaired? I think we will need our expert consultations host, Dr. Dana Wang, to investigate this further.

Dr. Wang:
You’ve made the important point that renal diseases not only decrease renal clearance but also reduce hepatic and intestinal metabolic activities, perhaps through gene expression.

Dr. Levenson:
First, just to comment on why we have to still be cautious with hepatically metabolized drugs in patients who may have apparently normal liver function but have serious kidney disease, in addition to changes in gene expression, some patients with renal disease develop ascites and other forms of edema, which, in turn, may affect hepatic blood flow. Chronic renal disease patients tend to have a pH of their blood that is lower; these are all things that can affect absorption and metabolism and excretion of even hepatically metabolized drugs.

Interesting indeed. So, in patients with renal impairment, a general rule of thumb is to start with ⅔ of the recommended dose.

Next, we will be naming names and seeing which medications can be put on the ‘prescribing white-list’.

It is pretty expected that some of our patients might be taking medications for hypertension, diabetes, heart disease et cetera. So what are some psychotropics that are relatively free of drug interactions with other medical drugs? And I stress on the word relatively.

Dr. Levenson:
All the atypical antipsychotics are relatively free of causing drug interactions as are anticholinergics, cognitive enhancers, benzodiazepines, buspirone, all the Z hypnotics, and the commonly prescribed psychostimulants. So when one has a choice, these are preferable in place of, instead of drugs in the same class that have frequent P450 interactions.

For antidepressants, tricyclics in general, SSRIs like citalopram, escitalopram, sertraline, and mirtazapine. As for SNRIs venlafaxine and desvenlafaxine are relatively drug-interaction free.

Let’s shift to part 3 of this podcast and that is to take a look at the use of benzodiazepines in patients with lung disease. Oftentimes, patients with lung conditions, particularly COPD can suffer from significant anxiety and sleep disturbances. It is common knowledge that benzos can cause respiratory depression. So, they seem clearly counterproductive to use. Let’s listen to Dr. Levenson’s summary of the use of benzos in lung disease.

Dr. Levenson:
Benzodiazepines and Z hypnotics are contraindicated in patients who are CO2 retainers. And for similar reasons, they’re contradicted in patients with severe sleep apnea with steep desaturation because those are patients whose oxygen levels are dropping and we don’t want to sedate that hypoxic respiratory drive that wakes them up and get some breathing more effectively.

Fair enough. So for CO2 retainers, hypnotics are to be generally blacklisted. So what are the alternatives?

Dr. Levenson:
If a patient has generalized anxiety disorder and COPD, treatment with buspirone or SSRIs would be preferred over benzodiazepines. In a patient with severe COPD who requires acute treatment of panic attacks or other severe acute anxiety, an antipsychotic would be the first choice.

Clinicians who work in hospices or with patients with terminal lung disease can come across the term ‘terminal breathlessness’. Dr. Levenson explains.

Dr. Levenson:
One related question is whether benzodiazepines are effective in treating the severe breathlessness that occurs at the end of life in terminal COPD patients, in other words, in the provision of palliative care to such patients. And the answer is that benzodiazepines were not shown to be beneficial. Opiates are the drug of choice for terminal breathlessness in a dying COPD patient.

So opiates are better than benzodiazepines in that respect.
And that about concludes our review of prescribing in the medically ill. I would recommend you watch the full lecture, available for our premium members.

Now don’t sign out just yet! We have some exciting news to share, but not after the…key points!

Key Points

  • In patients with liver impairment, it is better to use drugs that are metabolized by phase II enzymes. Another option is to use drugs that are not metabolized by the liver at all.
  • Keep in mind that patients with severe renal impairment may also have liver impairment so in general, use ⅔ of the recommended dose when starting out.
  • Psychotropics that are relatively interaction-free with medical drugs include, atypical antipsychotics, anticholinergics, cognitive enhancers, benzodiazepines and buspirone among others.
  • Benzodiazepines and Z-drugs are contraindicated in CO2 retainers and those with severe sleep apnea.
  • Opiates are more appropriate to use than benzos in patients with terminal breathlessness.

Liked our podcast? Visit us at where you can find more podcasts and some lectures absolutely free. You can choose to become a premium member to access all lectures and interviews. Also, we would be thrilled to hear from you, drop us an email at

The good news we wanted to share is that we have launched a new CME platform called Psychotherapy Academy. And we have just released our first lecture on the essentials of dialectical behavioral therapy. So, if you’re interested in polishing you psychotherapy skills, visit

The following people participated in this episode: Dr. Flavio Guzman as the general editor, Mark Young as the audio engineer, Pamela Gonzalez as the project manager and myself, Dr. Wegdan Rashad as the host. We’d also like to thank Dr. James Levenson and Dr. Dana Wang, for being with us.

Thank you for joining us in today’s podcast until the next episode, goodbye!


  1. Levenson, J. L., & Ferrando, S. J. (Eds.). (2016). Clinical manual of psychopharmacology in the medically ill. American Psychiatric Pub.
  2. Levenson, J. (2019). The American Psychiatric Association Publishing textbook of psychosomatic medicine and consultation-liaison psychiatry. Washington, D.C: American Psychiatric Association Publishing.
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