Update on Medications for PTSD

Update on Medications for PTSDWhile psychotherapy remains the gold standard for treatment of post traumatic stress disorder (see for example, Foa EB et al, Effective Treatments for PTSD: Practice Guidelines from the International Society for Traumatic Stress Studies. New York: Guilford Press; 2008), medications are often used to alleviate the symptoms of the illness. Since we last visited the topic of pharmacologic treatment for PTSD (TCPR, June 2007), there’s been some interesting research on this subject, including the use of antibiotics, steroids, and even the drug of abuse, ecstasy.

First, though, a quick review of more mainstream treatment. Keep in mind that the current general aim of psychopharmacology in PTSD is to minimize its symptoms, rather than to “cure” it. Getting some comfort from meds can often enable a patient to more easily face the tough work of exposure or other psychotherapies. Symptoms that are most easily addressed by medications include those of hyperarousal, along with nightmares.

SSRIs. Sertraline (Zoloft) and paroxetine (Paxil) are still the only drugs that are FDA approved for the treatment of PTSD, and SSRIs in general are recommended as first-line treatment by the APA practice guidelines (from 2004—now frightfully out of date). While most studies to date have shown a rather modest effect for SSRIs in PTSD (as low as 60% for response and 40% for remission), they all seem to have similar efficacy for its treatment and are well-tolerated in this population. Dose SSRIs as you would for depression.

Other antidepressants. SNRIs, MAOIs, tricyclics, nefazodone (Serzone), trazodone (Oleptro), and mirtazapine (Remeron) have all been shown to have some efficacy with PTSD. Since disrupted sleep is a frequent complaint of patients with PTSD and this often does not completely improve with psychotherapy or SSRIs, mirtazapine or a sedating tricyclic such as doxepin (Sinequan) can be helpful, alone or in combination with an SSRI (van Liempt S et al, Internat Clin Psychopharmacol 2006;21(4):193–202).

What about a non-sedating antidepressant to address the dysphoric mood that is often seen in these patients? It may not be of much use. In a placebo-controlled trial, bupropion (Wellbutrin) had no significant effect even as an adjunct for PTSD (Becker ME et al, J Clin Psychopharm 2007;27(2):193–197).

Atypicals. Again, the more sedating of these can be effective in addressing hyperarousal. Risperidone (Risperdal), quetiapine (Seroquel), and olanzapine (Zyprexa) have all had positive results in some studies—not surprising given their sedating properties. Risperidone has probably been the most studied. (For a review of studies on risperidone and PTSD, see Berger W et al, Prog Neuropsychopharmacol Biol Psychiatry 2009;33(2):169–180. They conclude that it is “an effective add-on therapy when patients did not fully benefit from previous treatment with SSRIs.”)

Obviously, given the metabolic and other side effect concerns of atypicals, these are not a first-line treatment in providing what is essentially sedation, since that can come from other medications with gentler side effect profiles.

This article originally appeared in The Carlat Psychiatry Report -- an unbiased monthly covering all things psychiatry.
Want more, plus easy CME credit?
Subscribe today!

Mood stabilizers. Because hyperarousal can include mood lability, you might think of using a mood stabilizer for these patients. Although results are mixed, in general, mood stabilizers have surprisingly often been shown to be ineffective in PTSD, especially as monotherapy. Among others, a double-blind randomized trial of divalproex (Depakote) as monotherapy in combat veterans showed no difference from placebo (Davis L et al, J Clin Psychopharm 2008;28(1):84–88).

Benzodiazepines. These are a sticky topic. Since PTSD is by definition an anxiety disorder, and since the hyperarousal of PTSD can often be its most disabling feature, a benzodiazepine would seem to be a natural choice. However, benzodiazepines are sometimes found to be not only not very helpful in PTSD, but potentially harmful. Why? There are multiple reasons. First, there is significant comorbidity of substance use disorders in people with PTSD—up to 40% and even perhaps as high as 75% for combat veterans with PTSD (Jacobsen LK et al, Am J Psychiatry 2001;158(8):1184–1190). Prescribing benzodiazepines to either actively or recently substance abusing patients is something we’d prefer to avoid if possible.

A second disadvantage of benzos is that they might contribute to the emotional numbing of PTSD and prevent integration of the traumatic event. While there is not much actual clinical evidence of this, in animal models benzodiazepines given after a stressor are found to inhibit normal HPA-axis response to stress, and even increase vulnerability to future stressors (Matar MA et al, European Neuropsychopharm 2009;19(4):283–295).

And finally, benzodiazepines just may not be very effective for the disorder. Although there is surprisingly little direct research on this topic, one small prospective study found no improvement on multiple PTSD scales compared to the placebo group after one or six months of treatment (Gelpin E et al, J Clin Psychiatry 1996;57(9):390–394).

However, with these caveats, we often still find benzos useful for a selected group of patients, particularly for treating sleep disruption. Buspirone (BuSpar) theoretically might address the hyperarousal without worsening numbing, but there has been little evidence one way or another for this medication in PTSD.

Other Potentially Effective Medications

Much of the pharmacologic treatment of PTSD involves addressing particular symptoms. For hypervigilance and activation symptoms, try a beta blocker like propranolol (Inderal), an alpha-2-agonist like clonidine (Catapres), or the alpha-1 antagonist prazosin (Minipress)—these can be quite helpful and do not carry the stigma that patients new to psychiatric treatment can associate with classic psychiatric meds. A good starting dose of propranolol is 10 mg taken three or four times daily. While you do not need to monitor heart rate or blood pressure in the typical patient, check for interaction with other cardiac meds.

Prazosin, discussed in our 2007 PTSD issue as helpful with both sleep and daytime PTSD symptoms (TCPR, June 2007), is dosed initially at 1 mg at bedtime and increased gradually, watching for orthostasis. Prazosin works by decreasing CNS adrenergic activity, which makes sense since this is heightened in PTSD.

For nightmares, another common and debilitating complaint in PTSD, a thorough meta-analysis of drug treatment for sleep disruption in PTSD found an astounding number of medications that have been effective in studies ranging from case reports to clinical trials, including buspirone, gabapentin (Neurontin), topiramate (Topamax), imipramine (Tofranil), phenelzine (Nardil), mirtazapine, prazosin, clonidine, and multiple atypical antipsychotics (van Liempt S et al, op.cit). In my experience, topiramate (25 mg to 100 mg at bedtime), clonidine (0.1 mg to 0.2 mg at bedtime; warn patients of orthostasis when getting up in the morning initially), and quetiapine (at a dose as low as 25 mg at bedtime) are particularly helpful for nightmares.

Drugs in the Pipeline

D-cycloserine (Seromycin). This drug is an antibiotic developed for the treatment of tuberculosis. However, it also acts as a partial agonist at the NMDA glutamate receptor, and glutamate is found throughout the nervous system, being our major excitatory neurotransmitter. In randomized double blind trials, D-cycloserine has been shown to enhance the effectiveness of exposure therapy for both social phobia and acrophobia (the fear of heights). (For social phobia, see Hofmann SG et al, Arch Gen Psychiatry 2006;63(3); 298–304). While there have not yet been any human studies published on D-cycloserine in PTSD, it has shown efficacy in animal models of conditioned fear (Cukor J et al, Ann N. Acad Sci 2010;1208:82–89). Perhaps in the future we will see patients taking this medication while undergoing exposure therapy for PTSD to enhance its effects.

Steroids. After the World Trade Center bombing, there was a lot of interest in immediate pharmacologic interventions that could be done in the emergency room after a traumatic exposure, with the idea that these could lessen development of acute stress and then PTSD further down the road. With the aim of decreasing initial activation, propranolol was one of the more common interventions, with mixed results. Now researchers are suggesting that giving glucocorticoids in the emergency room may decrease later development of symptoms. At the 2011 American Psychosomatic Society annual meeting, Douglas Delahanty et al presented results of a randomized, double blind, placebo controlled study in which patients with a recent trauma were started on hydrocortisone 20 mg twice a day at hospital admission, and had fewer PTSD symptoms one and three months later (Delahanty D et al, Abstact 1755. Presented at: 69th Annual Meeting of the American Psychosomatic Society; 2011; San Antonio, TX). The theory behind this is that HPA axis activation is involved in the development of PTSD.

Interestingly, steroids have also been implemented to enhance extinction learning during exposure therapy, similar to D-cycloserine, with positive results. Veterans with PTSD underwent a single session of exposure therapy after being given either glucocorticoid or placebo, and a week later the subjects who had the glucocorticoid had a reduction in symptoms. This was transient, however, and the effect was gone by the onemonth assessment (Suris A et al, Ann Clin Psychiatry 2010;22(4):274–279).

MDMA. What? Ecstasy for PTSD? Well, don’t expect to see it anytime soon. However, MDMA, a Schedule I drug, has been employed in a small (n=20) randomized, double blind, placebo controlled trial for PTSD, with the idea that when given before exposure therapy, its use induces relaxation and a sense of well-being and helps the patient tolerate and incorporate a greater degree of exposure. Significant improvement in PTSD symptoms was found up to two months later in the treatment group (Mithoefer MC et al, Psychopharmacol 2011;25(4):439–452).

TCPR VERDICT: Medications for PTSD? The research base remains pretty thin, but there are plenty of options to try. Psychotherapy is still the bedrock of treatment for most PTSD patients. For a review of treatments, see Bisson J, Clin Evid (Online) 2010;Feb 3.

Update on Medications for PTSD

This article originally appeared in:

The Carlat Psychiatry Report
Click on the image to learn more or subscribe today!

This article was published in print 7 & 8/2011 in Volume:Issue 9:7 & 8.


APA Reference
Berlin,, R. (2013). Update on Medications for PTSD. Psych Central. Retrieved on August 13, 2020, from


Scientifically Reviewed
Last updated: 1 Oct 2013
Last reviewed: By John M. Grohol, Psy.D. on 1 Oct 2013
Published on All rights reserved.