Your Guide to Treating PTSD Comorbidities

Last updated: January 25, 2019

Host: Wegdan Rashad, MD

Today’s question is: How to manage the comorbidities of PTSD?

Here is a summary of this episode:

  • Screen for substance use and avoid prescription drugs like benzodiazepines. Desipramine and topiramate might help with comorbid alcohol use disorder.
  • In PTSD-related psychosis, try an SSRI first. If that doesn’t help, add a second-generation antipsychotic like risperidone.
  • Prescribe paroxetine with caution in women of childbearing potential.


Dr. Osser:
That is people who are having psychotic symptoms that are relevant or referable to the original trauma. So for example, it might be hearing soldiers on the battlefield who have been wounded, screaming. Or, experiencing visual hallucinations of an attacker attacking them.

That was Dr. David Osser from Harvard Medical School talking about psychotic experiences in patients with PTSD.

I am Dr. Wegdan Rashad and you are here with the Psychopharmacology Institute podcast, discussing topics that matter to you, the mental health clinician, in your practice.

Last time we talked about insomnia in PTSD. But today we cover a more morbid side of this condition. To be exact, it is a comorbid side. Yes, like psychosis, depression and substance abuse. We will find out how to identify and treat them. I will use snippets from Dr. Osser’s PTSD algorithm lecture available at

A disclaimer though before we start, PTSD is treated by both meds and psychosocial interventions. Our focus is on clinicians who decide to use medications in the treatment of PTSD.

Traumatized patients can resort to drugs. And it isn’t rare at all, apparently. In a sample of American patients, they found that just under half of them have a comorbid alcohol or substance use disorder. That is a big deal because it makes things complicated.

OK, so what to do about that?

Dr. Osser:
The two practical recommendations regarding substance use disorders is be sure you screen for them. They may be covert. The patient may not be quick to inform you about their substance use problem. Secondly, the role of benzodiazepines in the algorithm, which is not a very strong one, will drop further down and indeed mostly we think they should be avoided.

Now, are there specific medications you might consider, Dr. Osser?

Dr. Osser:
Well, there is one positive study of desipramine actually as a treatment for PTSD in people with comorbid alcohol use problems. Desipramine as far as we can tell has no effect on PTSD otherwise. I wouldn’t make too much of this study. It’s just one small but interesting reference. Another special medication would be topiramate. There is one small study of PTSD patients with alcohol use disorder where topiramate at an average dose of 300 milligrams a day was apparently helpful. Evidence on topiramate is modest, low to modest as a possible treatment for PTSD.

So to sum up, desipramine and topiramate might help.


Wait! This may sound a bit obvious, but make sure that your patient is sober for at least a week before you apply the treatment algorithm. Did you know that efficacy trials usually exclude patients who are actively abusing drugs? So we don’t have much evidence on how effective treatments are for them.

Do you know what other comorbidity is right up there with SUD? Depression. Yes. Research estimates that 30% to 50% of patients with PTSD have significant depressive symptoms. The only FDA-approved medications to treat PTSD are paroxetine and sertraline which are also antidepressants. So you’d think you’d be hitting two birds with one stone, but..

Dr. Osser:
What you need to know about what the evidence says is when you have both of these conditions together, you might think it would improve the prognosis for treatment. It might suggest that you can treat two disorders at once since they’re both thought to be responsive to antidepressants, however, the evidence is that actually, they are both less responsive when you have both disorders at the same time. That’s generally true, I’d say, among the comorbidities when they appear with PTSD. They reduce the prognosis for regular treatments working.

So, now what? Most likely you’ll need to use augmenting agents if a patient is not responding. We won’t cover augmentation today but if you’re interested, Dr. Osser’s lecture covers the details in full. And you can also check out his algorithm on

Anxiety and depression come hand-in-hand. My Psychopharmacology Insitute colleague, Dr. Dana Wang asked Dr. Osser about just that.

Dr. Wang:
Some non-SSRI medications such as Bupropion or Buspirone were not mentioned in the PTSD algorithms. Are there studies that support their use to address anxiety in PTSD?

Dr. Osser:
Well, first of all, bupropion has a placebo-controlled trial in PTSD showing no efficacy. And there are no positive placebo-controlled trials. So I would not be including it on the list of options for PTSD unless more or better evidence were to appear. Buspirone has only uncontrolled case series data. It’s old. There was a study from nine patients in a letter to the editor back in 1994 in which four out of the nine patients were either very much improved or much improved, all the others being not significantly improved or worse.

Oh and of course, in patients with depression, ask carefully about a history of mania or hypomania. If found to be bipolar, Dr. Osser recommends us to steer clear of SSRIs and use lamotrigine or antipsychotics.

At the beginning of today’s podcast, you heard Dr. Osser talk about psychotic experiences.

Dr. Osser:
Psychotic patients may have PTSD as well. In fact, some have suggested that the experience of psychosis as in schizophrenia can be so traumatizing as to induce PTSD as a comorbidity. There’s also psychosis that’s secondary to the actual PTSD.

Wow. There are also some special features of PTSD-related psychosis.

Dr. Osser:
Now there are other psychotic problems that your PTSD patients may present. They may have paranoid delusions. They could be related to the PTSD. They are typically non-bizarre and not associated with disorganized thought or flat affect. But if they are, they may have a comorbid psychotic disorder which almost certainly needs independent treatment with an antipsychotic right away, up front.

PTSD and psychosis are a toxic couple and up to 40% of combat veterans experience it. So, how to treat? Ditch the SSRIs and run for the antipsychotics? Maybe not…

Dr. Osser:
But if it’s PTSD-related symptoms of psychosis, we usually would try an SSRI first. Some evidence suggests that those symptoms can improve with an SSRI alone without having to add an antipsychotic. But if it fails, then we recommend considering adding an antipsychotic into these people. The medication of choice for that purpose would be a second-generation antipsychotic and risperidone has the best evidence. It actually has the only placebo-controlled, randomized controlled trial and the results were favorable. There are open-label studies with quetiapine and olanzapine. Quetiapine also has some data as an augmentation strategy in non-psychotic PTSD. So risperidone is our first suggestion for this group.

So I was wrong. We start with SSRIs and if doesn’t help then add a second-generation antipsychotic, like risperidone.

OK, we’ve covered a lot. To recap… we’ve reviewed substance abuse, unipolar and bipolar depression and psychotic symptoms in PTSD.

Now let’s see our last therapeutic nugget on PTSD in women of childbearing potential.

Dr. Osser:
There are certain drugs that increase the risk of fetal defects and other complications in pregnancy. Since 50% of pregnancies are unplanned, it’s certainly a good idea to think about avoiding those medications, even if there is no pregnancy present at this time. Paroxetine stands out as a particular medication that falls under that heading. It does have a D rating from the U.S. Food and Drug Administration because of evidence of fetal septal defects, cardiac defects. A study published by Reefhuis and colleagues also confirmed that paroxetine definitely is a problem with this particular defect, but also found that fluoxetine seemed to have a comparable amount of problems with fetal septal defects in this particular review. Although that is not reflected in a D rating right now by the FDA, it’s important new data that we’re trying to put into perspective.

Clinicians are in conflict on just how significantly teratogenic SSRIs are. But as far as the algorithm is concerned, prescribing paroxetine should be done with caution.

And that about concludes our podcast on the treatment of co-morbidities in posttraumatic stress disorder. I learned a couple of new things, I hope you did too. And if you zoned out in the middle, you’re lucky because here come the key points.

Key Points

  • Screen for substance and alcohol use disorder and then avoid prescription drugs like benzodiazepines.
  • There is some evidence that desipramine and topiramate might help in the treatment of PTSD with comorbid alcohol use disorder.
  • In PTSD-related psychosis try an SSRI first. If that doesn’t help then add a second-generation antipsychotic, like risperidone.
  • Prescribe paroxetine with caution in women of childbearing potential.

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. We would be thrilled to hear from you, drop us an email at

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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. David Osser, and Dr. Dana Wang, for being with us.

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


  1. Pietrzak, R. H., Goldstein, R. B., Southwick, S. M., & Grant, B. F. (2011). Prevalence and Axis I comorbidity of full and partial posttraumatic stress disorder in the United States: results from Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions. Journal of anxiety disorders, 25(3), 456-465.
  2. Campbell, D. G., Felker, B. L., Liu, C. F., Yano, E. M., Kirchner, J. E., Chan, D., … & Chaney, E. F. (2007). Prevalence of depression–PTSD comorbidity: Implications for clinical practice guidelines and primary care-based interventions. Journal of general internal medicine, 22(6), 711-718.
  3. Lindley, S. E., Carlson, E., & Sheikh, J. (2000). Psychotic symptoms in posttraumatic stress disorder. CNS spectrums, 5(9), 52-57.
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