Given the severe burden, grave suffering, and lack of remission with standard therapeutics in many patients with PTSD, preliminary data on the role of ECT seems promising.
The risk of cognitive adverse effects (eg, long disorientation duration, memory impairments), has been one of the factors that historically limited ECT use. However, modern modifications of ECT parameters have substantially limited these cognitive risks to a smaller portion of patients. For instance, the modern development and use of rectangular instead of sine wave pulse, ultra-brief instead of brief pulse, and right unilateral (RUL) instead of bilateral (BL) electrode placement have improved cognitive effects of ECT.
Further improvement of the cognitive adverse effects has been suggested by using a lower current amplitude than standard ECT, thus more focal stimulation as in Low AmPlitude Seizure Therapy (LAP-ST). Despite the more favorable cognitive effects compared with standard ultra-brief RUL ECT, similar efficacy has been shown in 2 preliminary studies on depression and suicidality.1,2 Moreover, further modifications in electrode shape and electrode placements might also be helpful for Focal Electrically Administered Seizure Therapy (or FEAST).3 These proof of concept studies provide additional promise to eliminating or markedly minimizing these adverse effects.
Theoretical justification for use of ECT in PTSD and proposed mechanism of action
Hippocampal neurogenesis has been shown to contribute to the clearances of artificially induced long-term potentiation (a cellular model of learning and memory). This mechanism may have a role in treatment-resistant PTSD and related memories if clearance of hippocampal memory traces in the contextual fear conditioning can be accomplished. Since ECT induces neurogenesis, it might have a role in treatment of PTSD (Figure).
ECT has been suggested to induce neurogenesis and neuroplasticity in both brain imaging and in brain pathology studies. Olsen and collegues4 measured the number of newly formed neurons in the hippocampal subgranular zone in adult rats exposed to chronic restraint stress and electroconvulsive stimulation alone or in combination. This study found that chronic stress induced depression-like behavior without changing neurogenesis in the hippocampus, while electroconvulsive stimulation prevented stress-induced depression-like behavior and increased neurogenesis.
The role of ECT in inducing neuroplasticity in both animals and humans is best detailed in a comprehensive review by Bouckaert and colleagues.5 Since hippocampal neurogenesis has also been shown to ameliorate PTSD symptoms, it is plausible to hypothesize that ECT might help PTSD by inducing hippocampal neurogenesis.
Hippocampal neurogenesis may not be the only mechanism. Other mechanisms related directly to memory deconsolidation might also be possible, where ECT could cause more improvement in PTSD symptoms if delivered right after reconsolidation of the traumatic memories.6,7
In one study patients with severe treatment-resistant PTSD were administered 6 sessions of ECT after retrieving either traumatic (n = 4) or a neutral memory (n = 4).8 Study findings indicate that post traumatic-retrieval ECT tended to produce better reductions in skin conductance responses and subjective reactivity to the traumatic imagery (P = .026). Thus, supporting the theory that ECT may have its effects augmented if delivered right after reconsolidation of traumatic memories.
Further investigation is warranted, not only from a therapeutic standpoint, but also from mechanistic perspectives. Despite plausibility of these hypotheses, it must be stressed that these hypotheses need to be further tested to be proven or disproven in a well-powered controlled clinical trial, given the preliminary evidence.
Wider availability of ECT in facilities that treat a substantial number of patients with treatment-resistant PTSD and depression, such as VA hospitals, would not only improve care for patients with disorders indicated for ECT (according to the standard of care), but also provide a chance to investigate the potential role of ECT in treatment-resistant PTSD (or PTSD with depression) given that the number of patients needed for such a trial would be unlikely to be obtained by any one center or hospital.
Standard therapeutics fall short of helping many patients with PTSD
Several medications and combinations of medications, including SSRIs and other antidepressants have been studied for treatment of PTSD. For instance, 80% of veterans with PTSD seen at the VA receive pharmacologic treatment (with or without psychotherapy), of these, 89% are prescribed antidepressants.9
Most of the studies have been positive for the FDA-approved medications, paroxetine and sertraline, although the therapeutic effect size of antidepressants has been small.10 Moreover, the results of a large multicenter randomized trial of post-FDA-approved sertraline were not positive.11
Prazosin has shown evidence of efficacy in some well-designed clinical trials for nightmares (and some other PTSD symptoms).12-14 However, a recent, large multicenter clinical trial did not show benefit for nightmares or other PTSD symptoms in veterans with chronic PTSD.15 Neither did another study that examined prazosin for PTSD (but not nightmares).16
Trauma-based therapies such as cognitive processing therapy and prolonged exposure are considered the gold standard treatments for PTSD. However, despite all available standard therapeutics, a high percentage of patients still do not achieve remission (or response) from multiple trials of both pharmacotherapy and psychotherapy.
Genetic memory and comorbidities
Traumatic memories generate some of the most persistent memories and are the hardest to erase. This might be explained by the cellular mechanism for encoding durable memories that also involve structural change. At the intranuclear level, a recent review by our group suggests that the effect of these traumatic memories may even be passed to the next generations via epigenetic methylation effects.17 These persistently encoded memories might be, at least in part, why so many patients with PTSD are treatment-resistant or partial responders.
Many patients with treatment resistance suffer the burden of impairment, elevated risk of suicide and violence, and higher incidence of all-cause mortality. This obviously creates significant family and societal burden. Common PTSD psychiatric comorbidities include depression and substance use disorders. In addition, there are high rates of other psychiatric and physical illnesses including hypertension and cardiovascular events.
Preliminary evidence for the role of ECT in treating PTSD
A serious look at innovative solutions as well as established interventions that are known to be highly effective in other treatment-resistant disorders is needed. Modern ECT has a high level of safety compared with older techniques, not only in terms of anesthesia and muscle relaxation, but also in terms of the improvements in electric parameter modifications, and electrode placements.
In disorders where ECT is indicated, ECT generally has the advantage of working faster than medications and psychotherapy with an effectiveness rate that is usually at least twice as high as standard therapeutics. It also frequently works in more severe and treatment-resistant cases.
The literature that examined the role of ECT in treating PTSD in humans is scant and totals four preliminary studies (Table). (The reader interested in more details on the topic is referred to a recent synthesis of the existing evidence of the role of ECT in PTSD.6,7)
A retrospective chart review investigated the use of ECT in veterans with PTSD.18 The statistical analysis included 26 veterans with both MDD and PTSD. PTSD severity was assessed by the PTSD Checklist (PCL) and depression severity by the Montgomery-Asberg Depression Rating Scale (MADRS).19,20 Patients had significant reduction in both depressive and PTSD symptoms (P < .001) after the ECT course. However, only 35% of patients had reduction in symptoms on the PCL. The major limitations of this study are the retrospective nature (which could have cofounded the findings) and the small sample size.
A retrospective case-control study compared patients with comorbid PTSD and MDD who were treated with an ECT course (n = 92) to those with matched controls that did not receive ECT (n = 3393).21 PTSD and MDD symptoms improved as assessed using the Clinical Global Impression (CGI) scale. The ECT group improved more than those who did not receive ECT but were on antidepressant medications (P = .001).
The most recent retrospective case-control study compared patients treated with ECT who had MDD and comorbid borderline personality disorder, PTSD, or both (n = 75), and a matched group but with MDD alone without comorbidities (n = 75).22 The medical records were reviewed to determine treatment response and estimate CGI-improvement (CGI-I). Study findings showed no statistically significant difference in the CGI-I response rates between the 2 groups (P > .017). Limitations of the study were that no specific measures of PTSD were used other than the c-CGI-I, the retrospective design, and that the group of interest was heterogeneous (with comorbid borderline personality disorder, PTSD, or both).
The only clinical trial available in the literature for ECT in PTSD is an open-label non-controlled trial.23 Participants (N = 20) had severe, chronic, and treatment-resistant PTSD as evidenced by failure to respond to 4 or more adequate antidepressant trials, as well as 12 sessions of cognitive behavior therapy. This is also the only study that measured PTSD with the Clinician-Administered PTSD Scale (CAPS) as the primary measure. CAPS scores for the sample mean decreased by 34% (P < .001). The authors also reported that the correlation between improvement in CAPS and MADRS was low, suggesting that benefits for PTSD were independent from depression improvement.
This data seems encouraging; however, the overall evidence is still limited as this study was small and uncontrolled. No randomized controlled clinical trials exist so far. Thus, routine clinical use of ECT for PTSD cannot be recommended, at least not yet. The available studies either have small sample size or design limitations or both. However, most available evidence is positive, although publication bias could not be ruled out. The available evidence warrants further research in this area to provide definitive answers.
The preliminary data on the role of ECT in PTSD seems promising. However, I would caution that (although most studies are positive suggesting a helpful effect of ECT in PTSD), the studies so far are preliminary and publication bias (where negative studies may not have been published) cannot be ruled out.
Thus, definitive, well-powered, randomized controlled clinical trials to confirm or revoke the initial results are warranted, given the severe burden, grave suffering, and lack of remission with standard therapeutics in many patients with PTSD. Modification of the clinical trials using the innovative technique of trauma memory arousal to deconsolidate memories shortly before an ECT session may prove to be more fruitful in future clinical trials.
On the clinical side, there is not enough evidence to support the use of ECT for PTSD. However, since PTSD is commonly comorbid with other disorders where ECT is clinically indicated (such as depression and schizophrenia), comorbid PTSD should not dissuade the clinician from treating patients with ECT who are otherwise clinically appropriate to benefit from ECT.
Disclaimer: The views expressed are those of Dr. Youssef and do not represent Medical College of Georgia or the Department of Veterans Affairs.
Dr Youssef is Associate Professor Department of Psychiatry & Health Behavior, Medical College of Georgia at Augusta University, and Psychiatry Educator for medical students at the office of Academic Affairs, Augusta, GA.
Dr. Youssef is the principal investigator (PI) of the Low AmPlitude Seizure Therapy (LAP-ST) randomized clinical trial and prior PI on a proof of concept LAP-ST clinical trial. He is currently a co-investigator on the FEAST ECT study funded by MECTA, but did not receive any monetary or salary support from MECTA or other device or pharmaceutical companies (past 5 years) for any of the studies. Dr. Youssef received research support from the Veterans Administration, and a grant from ABR Corporation, and the NIH (past 5 years).
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