A Paradigm for Treatment of Severe PTSD developed by Dr. David Bakish
In an earlier BNN we mistakenly attributed the protocol developed by David Bakish, a renowned Canadian psychopharmacologist, to another doctor named Vaishali P. Bakshi. Our apologies to both individuals.
Dr. David Bakish is Medical Director at the Ottawa Psychopharmacology Clinic and a Former Professor of Psychiatry at the University of Ottawa in Ottawa, Ontario. He shared with this editor his novel treatment strategy for patients with exceptionally profound degrees of post-traumatic stress disorder (PTSD), which, particularly among military veterans, can be compounded by traumatic brain injury. He has had a distinguished academic career with an extensive CV and credentials including membership in the International College of Neuropsychopharmacology (CINP), the Royal College of Physicians and Surgeons of Canada, and the Canadian and European Colleges of Neuropsychopharmacology. Most importantly he has had great success in treating large numbers of patients with severe PTSD. Treatment options based on placebo-controlled clinical trials are sometimes insufficient for the treatment of seriously ill patients. FDA-approved treatment for PTSD consists of serotonin-selective antidepressants, while exposure therapies (in which the patient is gradually exposed to more of the stimuli that triggered symptoms) are the recommended psychotherapy, but these methods often leave patients highly disabled. We relay Dr. Bakish’s treatment strategy with several caveats.
Most of Bakish’s suggestions are “off-label” treatments for the treatment of PTSD or traumatic brain injury, i.e. treatments that are not FDA-approved for these purposes. In some of these instances, there is no controlled research to support the use of these drugs in patients with PTSD. Thus the ideas noted here are anecdotal, based on his personal experience, and have not been tested in controlled clinical trials. Accordingly, patients with their physicians must make their own decisions about any of the strategies reported in this or other issues of the BNN.
Bakish’s typical treatment algorithm goes well beyond the usual treatment guidelines to find solutions for hard-to-treat patients. Bakish first addresses sleep disturbance, which is almost universal in PTSD. He suggests the anticonvulsant levetiracetam (Keppra), for the hyperarousal and sleep disorder. He uses starting at doses of 125mg per night and increases by 125mg every three weeks. Once he gets to 500mg, he increases by 250mg increments as tolerated. If he gets to 1g daily, he increases by 500mg increments as needed. This highly sedating anticonvulsant not only improves sleep but may also help cognition, since it is structurally similar to other cognitive enhancers such as piracetam. Levetiracetam also decreases the hippocampal hyperactivity associated with some forms of cognitive dysfunction, as we’ve noted before. Trazodone (50 to 150mg) can be added for sleep if needed.
Instead of selective serotonin reuptake inhibitors (SSRIs), Bakish recommends the selective serotonin and norepinephrine reuptake inhibitors (SNRIs). Among these, he prefers desvenlafaxine (Pristiq) over venlafaxine, as desvenlafaxine has fewer interactions with other drugs and with opiates, cannabis, and alcohol which are often self administered. He finds that duloxetine (Cymbalta) has more interactions with these other agents. He starts with 25mg Pristiq as these patients are very sensitive and jumpy and increases slowly toward 200 to 400mg. He thinks that it makes no sense to start cognitive behavioral therapy until patients’ hyperarousal is controlled. If those with PTSD are smokers or have used cocaine he adds bupropion (Wellbutrin).
Bakish adds Topamax to maximum doses of 400mg to 1g/day which help with avoidance of alcohol and cocaine, as well as anger attacks. If the cognitive side effects of Topamax or levetiracetam are limiting, he uses brand name Lamictal instead. In the very small subgroup who have ideas of reference and paranoia, he uses an atypical antipsychotic where he prefers Abilify 1-2mg.
Bakish also cautions,
It is important to note that there is no evidence-based medicine on these types of patients. None of these patients would be suitable for a clinical trial because they all have different exclusion criteria. However, they do exist and they are quite ill. The suicide rate is quite high. This is especially true if they have a previous psychiatric family history, which includes bipolar disorder. Similarly if there is a family history of panic disorder, I am very careful with these patients….Another problem that is specific to the military is that soldiers sometimes do not come forward with their symptoms because they are worried about their career. They think that once they are diagnosed with PTSD, they have no future in the military.
In my experience, I always fight against this stigma. They may not be able to go back into combat, but they are still very effective soldiers in different roles. We also sometimes change their careers so that they can continue in the military….I usually see these patients every week at the beginning, then I space out the visits. However, in tandem with the medical officers, these patients are seen medically twice a week at the beginning and then spaced out.
As far as I’m concerned, this is an understudied group of patients, who deserve much more from the people they serve. They have put their life on the line for us.
As noted above, if patients remain symptomatic with depression, anger, irritability, or flashbacks, Bakish recommends adding lamotrigine (Lamictal). Lamotrigine has anti-glutamatergic effects, decreasing release of glutamate, the major excitatory neurotransmitter in the brain. Thus, while levetiracetam enhances the actions of the inhibitory neurotransmitter GABA, lamotrigine decreases glutamatergic over-excitation; thus providing a dual mechanism for decreasing neuronal hyperexcitability and reactivity that can occur with PTSD.
If mood remains dysregulated and/or there is a positive family of bipolar disorder, Bakish sometimes augments the above regimen with lithium carbonate.
Editor’s Note: Bakish’s treatment regimen is meant to target multiple neurotransmitter systems with moderate to high doses of a range of drugs that are not conventionally used or recommended in treatment guidelines for the treatment of PTSD sometimes compounded by traumatic brain injury. We highlight this treatment strategy he has used to treat many patients because too often patients with serious disability from PTSD are under-treated, and many elements of their symptomatology go unaddressed. Bakish indicated that his treatment plan often takes several months to show notable clinical effects, but he reports that he often sees dramatic clinical improvement in symptoms of both PTSD and traumatic brain injury. He sees that the longer they stay on their medication, the better they get.
As complex and unconventional is Bakish’s carefully sequenced protocol, there are still other potentially useful treatments for PTSD. The positive effects of prazosin, a noradrenergic alpha-1 receptor antagonist, are well-documented in 3 placebo-controlled trials by Murray Raskind et al. Prazosin is able to selectively inhibit nightmares associated with PTSD while leaving normal dreaming uninterrupted.
N-acetylcysteine (NAC) is also worthy of consideration in the treatment of PTSD, as it has shown efficacy in both unipolar and bipolar depression, anxiety disorders, and addictions, including cocaine, heroin, marijuana, alcohol, and gambling, all of which are common in PTSD. There is also on early report of its positive acute effects in TBI by Michael E. Hoffer et al. in the journal PLOS ONE in 2013.
Another theoretical treatment that deserves further study would be augmentation of lamotrigine with memantine (Namenda), as in 2012 Anand et al. reported that memantine increased the antidepressant effects of lamotrigine in the initial weeks of treatment. Memantine also improved mood stability in patients with treatment-resistant bipolar disorder in a study by Koukopoulos et al. in 2012. In addition, as an FDA-approved treatment for memory loss in Alzheimer’s disease, memantine holds the (as yet unstudied) possibility of helping treat the memory loss that often accompanies both PTSD and traumatic brain injury. Memantine is a weak blocker of the glutamate NMDA receptor, while the rapid-acting inravenous antidepressant drug ketamine is a potent blocker or this receptor. It is noteworthy that there is a positive report or ketamine’s effectiveness in treatment-resistant PTSD by Adriana Feder et al. in the journal JAMA Psychiatry in 2014.
We are indebted to David Bakish, MD for sharing his wide experience in treating patients with severe PTSD with the readers of the BNN. We again apologize for the mix up in attribution of his unique approach.
