Three Experts’ Different Approaches to Treating PTSD in Veterans
In the BNN we have previously described some experts’ preferred treatment algorithms for patients with treatment-resistant post-traumatic stress disorder (PTSD), which is often complicated by traumatic brain injury (TBI). In this article, we update and expand upon these expert views.
David Bakish has worked as Medical Director at the Ottawa Psychopharmacology Clinic and is a former professor of psychiatry at the University of Ottawa in Ottawa, Ontario. In addition, he works with the Canadian military seeing patients with PTSD, substance abuse, and traumatic brain injuries. He uses a symptom-driven approach to PTSD, including 6 to 7 targeted medications added in sequence.
Albert Sattin is a professor of psychiatry and biobehavioral sciences at UCLA, belongs to their Brain Research Institute, and is affiliated with both the Ronald Reagan UCLA Medical Center and the Veterans Affairs Greater Los Angeles Healthcare System. He prefers to treat PTSD with a three-part combination of the blood pressure–lowering drug prazosin, a selective serotonin reuptake inhibitor (SSRI) antidepressant, and the atypical antidepressant mirtazapine.
Murray Raskind pioneered placebo-controlled studies of prazosin for PTSD and served as director of the Veterans Affairs Puget Sound Health Care System Mental Health Service, in addition to serving in the Department of Psychiatry and Behavioral Sciences at the University of Washington School of Medicine. Raskind’s approach to PTSD includes prazosin, the tricyclic antidepressant amitriptyline, and if needed for sleep, the sedative zolpidem.
Only SSRIs are approved by the US Food and Drug Administration (FDA) for the treatment of PTSD, but these on their own are rarely sufficient to handle the insomnia and other symptoms that accompany PTSD. Exposure therapy, in which patients are gradually led to approach trauma-related memories, feelings, and situations they previously avoided, is the most recommended type of therapy, but it too is often insufficient to treat all the complexities of the illness. Read on for more on each doctor’s approach to treating PTSD.
Bakish’s Approach
As of early 2014, Bakish’s preferred regimen for patients with severe PTSD and traumatic brain injury began with levetiracetam (Keppra) to improve sleep and cognition. If needed, he also added trazodone for better sleep. Second, for mood, Bakish would add desvenlafaxine (Pristique) because it causes fewer interactions with other drugs than venlafaxine. Third, for mood, energy, cognition, and smoking cessation, Bakish recommends bupropion (Wellbutrin). Fourth, for alcohol and drug abuse and anger attacks, he would add topiramate (Topamax) to the regimen. Fifth, for depression, anxiety, and irritability, and particularly if topiramate caused cognitive dysfunction, Bakish would add lamotrigine (Lamictal). Sixth, patients with paranoia would be prescribed an atypical antipsychotic such as aripiprazole (Abilify). Lastly, patients with mood instability would be prescribed lithium (which can also provide neuroprotection, anti-suicide effects, and overall health benefits).
By carefully and sequentially adding each of these medications at low doses and titrating the doses slowly upward while remaining below each patient’s threshold for side effects, Bakish found that this complex combination treatment was well tolerated by patients and regularly brought about excellent response, often including symptom remission and good cognitive function after 3 to 4 months in highly impaired Canadian special forces soldiers. (See more details of his dosing strategy in the original article.)
Sattin’s Approach
Sattin’s key insight (discussed with this editor in late 2015) is that prazosin should be administered three times a day because of its short half-life. This allows for the treatment of daytime as well as sleep-related PTSD symptoms. Sattin has patients choose one of three different schedules: 6am/2pm/10pm, 7am/3pm/11pm, or 8am/4pm/12am. Prazosin comes in 1 mg, 2 mg, and 5 mg tablets, but patients must begin by taking the 1 mg doses to reduce the risk of orthostatic hypotension (low blood pressure upon standing up). The dose is slowly increased as tolerated and as needed for symptom improvement. For patients with elevated blood pressure at baseline, which Raskind has shown is a predictor of good response to prazosin, Sattin starts his sequence with prazosin, and then follows with an SSRI and mirtazapine (Remeron).
For patients without elevated blood pressure at baseline, Sattin begins by prescribing one of the two selective serotonin reuptake inhibitors (SSRIs) approved by the FDA for use in PTSD—sertraline (Zoloft) or paroxetine (Paxil)—and then adds mirtazapine if necessary, which additionally targets the insomnia typically associated with PTSD. If these patients still remain symptomatic, Sattin then adds prazosin to their regimen.
Raskind’s Approach
Raskind’s approach, which he shared with this editor in late 2016, resembles Sattin’s more closely than Bakish’s. Raskind recommends beginning with prazosin with the triple goal of improving PTSD symptoms and nightmares, preventing migraines, and helping patients avoid alcohol. Raskind then suggests adding amitriptyline (Elavil) for its ability to treat depression and sleep disturbance, its anti-pain effects, and its prevention of migraines. Lastly, Raskind adds zolpidem (Ambien) if needed for continued insomnia.
Additional Options
To add to this diversity of opinion, this editor would also suggest consideration of a few other treatments. N-acetylcysteine (NAC) can improve depression and obsessive ruminations as well as decreasing cravings for substances such as alcohol, tobacco, cocaine, and marijuana. Dosage can begin at 500/600 mg twice daily and be increased to 1000/1200 mg twice daily. A recent study by Susie E. Back and colleagues reported success using NAC to treat combined PTSD and substance abuse.
Neuropsychological approaches such as those that make use of the memory reconsolidation window also deserve further consideration. See page 6 for more details on these approaches. This therapy has some similarities to processes used in Eye Movement Desensitization and Reprocessing (EMDR) therapy, also used for trauma.
Vagal nerve stimulation, consisting of a pacemaker-like device implanted under the skin in the chest that delivers regular, mild electrical pulses to the brain via the left vagus nerve, can enhance extinction learning such as eliminating a fear response that is no longer appropriate to a patient’s current environment.
The histone deacetylase inhibitor valproate has also been shown to enhance extinction learning in animals, by increasing an allele of brain-derived neurotrophic factor (BDNF) that is important for extinction learning.
There is some literature that suggests that anticonvulsants such as carbamazepine and valproate could be used to improve sleep and reduce flashbacks in PTSD. This requires further study.
Intravenous ketamine has also been found to improve treatment-resistant PTSD.
A wealth of data now supports the finding that patients with PTSD have increased inflammatory markers (such as CRP, Il-1, Il-6, and TNF alpha). How best to approach these abnormalities from a treatment perspective remains to be studied.
Editor’s Note: There is a vast array of treatment options (almost none of which are FDA-approved) for patients with difficult-to-treat PTSD, which is often complicated by traumatic brain injury. How best to choose among them and in what order to introduce them in a given patient is a bit of a mystery. Traditional placebo-controlled studies of single medications are not likely to be clinically helpful in determining the appropriate sequence of available treatments.
Making patients aware of the multiple options and the diversity of opinions about treatment of PTSD might be a good place to start, and could give hope to patients who might believe they are untreatable. Using a series of targeted medications that are likely to improve specific aspects of the illness may be necessary. The sleep disturbances that accompany PTSD, while addressed differently by the three experts above, are a key element to treat, especially since the FDA-approved SSRIs for PTSD typically do not help much with this difficult symptom.
Perhaps the single most important thing is to let patients know that their physician will continue to work intensively with them using sequential treatments until good results are achieved. It is also important to convey that the use of multiple medications, virtually all of which may be off-label, will likely be necessary.
With complex combination therapy like the expert approaches described above, it is crucial that patients provide detailed and systematic feedback about any side effects they may experience and the impact of each drug on the targeted symptoms at each point in the treatment sequence. This allows the additions and combinations of drugs to be optimized for each individual.
Monitoring symptoms, treatment response, and side effects can be done using resources such as MyMoodMonitor/What’s My M3?, a website and app that covers depression, anxiety, PTSD symptoms, alcohol and drug use, and suicidal ideation. Making daily ratings of mood, sleep, medications, side effects, anxiety, flashbacks, nightmares, etc. using a personal calendar would also be valuable.
There is a moderately high incidence of PTSD and head trauma in patients with bipolar disorder, and approaching bipolar mood instability and PTSD symptoms at the same time is typically necessary.
Finally, patients must remember that treatment decisions should be based on discussions with their treating physicians. The BNN provides often preliminary or in some cases anecdotal information about drugs (such as the three expert opinions above). Only a treating physician is qualified to decide whether a given treatment would be appropriate for a given patient. The actions of physicians and therapists must be based on their own judgment, expertise, and review of the published literature rather than our reports here.
