Clinical anecdotes from subjective reports
Findings indicate that ketamine’s robust RAAD and RAAS effects have a positive downstream effect in which the improvement in symptoms, especially in lassitude and negative mood and cognitions, kick-starts therapeutically beneficial practices. In addition to self-initiated engagement outside the study, the behavioral activation of participating in a clinical trial (eg, the structure provided by study visits, required outing, engaging with research staff) seems to be highly therapeutic as well.
One man in his early 50s who had struggled with treatment-resistant MDD for several decades reported a single infusion of ketamine gave him the boost he needed to re-engage in hobbies and to feel invigorated for both work and family life. The day after his infusion, he reported that he had slept well, cooked his family breakfast, practiced an instrument, and planned to walk his dog in the evening—all of which he enjoys but has not had the motivation for recently. Although he reported a re-emergence in some symptoms at 2-week and 4-week follow-up, he experienced ketamine-promoted re-engagement in mood-enhancing activities, which helped extend the effects.
A Vietnam Veteran with treatment-resistant PTSD and chronic suicidal ideation, said he had attempted to take his own life on three occasions since the late 1960s, when he experienced significant trauma in combat. Following the ketamine infusion, he was “totally stunned to wake up without a single idea about suicide” and reported a significant reduction in negative mood and cognitions, specifically guilt, shame, and related self-talk. He was able to talk with his spouse about things he had never discussed previously, which not only was cathartic for him, but also brought them closer together. He reported a slight re-emergence in overall symptoms, including suicidal ideation at the 4-week follow-up visit, but noted the “memory of hope and better days” kept him pushing forward.
An Army Veteran in his mid-40s endorsed only relatively minor improvements on formalized measures of PTSD symptoms. However, he noted that his quality of life and level of irritability improved significantly after he received a single open-label dose of ketamine (0.5 mg/kg). The treatment increased his cognitive flexibility, reduced his rigidity, and diminished the sense that any minor disruption in his plans was “catastrophic” and would throw his entire day (sometimes up to a week) into unrest. He reported that following the infusion, he was much more able to “roll with the punches” and “take things as they come.” At a 4-week follow-up visit, he indicated this change in emotion, cognition, and behavior had been maintained despite other symptoms that resurfaced.
As in the last vignette, some of the meaningful improvements reported by participants are not necessarily captured by routinely used clinician-administered or self-report measures. For example, another interesting, and challenging, phenomenon is that sometimes patients report guilt, shame, and/or frustration that their symptoms improved so dramatically in such a brief period. They feel something must be wrong with them if they can feel so much better, if it is this “easy.” Some patients report they unintentionally “blunt” the clinical benefit of ketamine because they are worried about when it will end and are “waiting for the other shoe to drop.”
A clear informed consent process is paramount, for both research and clinical settings. Ideally, the participant’s mental health care provider should be involved early, and patients should be encouraged to discuss the pros and cons of ketamine with family members or other close confidants. Overall, we have found that patients are glad they participated and are willing to seek out alternative routes for additional doses, either through research or clinical settings, or to explore other treatment options. We have not had patients who reported seeking out illegal means of obtaining ketamine.
Dr Averill is Clinical Research Psychologist, Clinical Neuroscience Division, Veterans Affairs National Center for PTSD, West Haven, CT; Associate Research Scientist, Department of Psychiatry, Yale School of Medicine, New Haven, CT; and Clinical Director, Emerge Research Program, Department of Psychiatry, Yale School of Medicine. Mr Averill is Neuroimaging & Technology Manager, Emerge Research Program, Clinical Neuroscience Division, Veterans Affairs National Center for PTSD, West Haven, CT and Department of Psychiatry, Yale University School of Medicine. Dr Abdallah is Assistant Professor of Psychiatry, Yale University School of Medicine, and Director of Neuroimaging, Clinical Neuroscience Division, Veterans Affairs National Center for PTSD.
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