Dramatic and persistent relief from chronic suicidality, emotional disturbances, and trauma symptomatology with oral ketamine and memantine in refractory depression with complex PTSD

Dear Editor, Ketamine is used off-label for indications ranging from depression to chronic pain. We know of no report of the successful use of oral ketamine, administered without psychotherapy, for complex posttraumatic stress disorder (cPTSD).[1,2] We describe a patient with chronic depression and cPTSD who failed >30 previous interventions but had dramatic and persistent relief from chronic suicidality and PTSD symptoms with 3 once-daily oral ketamine sessions. CASE REPORT A 27-year-old woman presented with longstanding depression with suicidal ideation, anxiety with panic, sleep and appetite disturbance, and disturbed interpersonal and occupational functioning. The suicidal urges began at the age of 11 years in a background of repeated violence, longstanding emotional neglect and invalidation, and later sexual abuse. Trauma-related symptoms included increased autonomic arousal, derealization, and flashbacks. Her suicidal ideation was chronic and present even in the absence of stress; she had multiple emergency room visits and hospitalizations related to suicidality and self-harm. Across years, under different teams in different parts of India, she was treated with but failed to tolerate or benefit from adequate doses of drugs prescribed for adequate durations, singly and in combinations; these included fluoxetine, sertraline, paroxetine, escitalopram, vortioxetine, venlafaxine, bupropion, mirtazapine, lamotrigine, lithium, venlafaxine, agomelatine, buspirone, alprazolam, clonazepam, pregabalin, modafinil, atomoxetine, aripiprazole, haloperidol, risperidone, olanzapine, quetiapine, clozapine, and prazosin. She underwent cognitive behavioral therapy, dialectical behavior therapy, mentalization-based therapy, and psychodynamic therapy, delivered by trained therapists, with little benefit. Repetitive transcranial magnetic stimulation and neurofeedback were unsuccessful. At presentation, she was on no treatments for a year. She was diagnosed with chronic recurrent depressive disorder and cPTSD (ICD-11). The number of previous depressive episodes was undocumented partly because they had not been recognized as such, partly because of chronicity, and partly because of overlap with cPTSD symptoms and suicidality; however, periods of euthymia were recognized. Because persistent suicidal ideation was her predominant and most distressing symptom, she was offered a trial of ketamine. Despite a body-mass index of 43, in three consecutive once-daily outpatient sessions she was treated with a fixed dose of 150 mg of oral racemic ketamine (Ketapil; Psychotropics India Ltd) in 100 mL of water, sipped across 10 min.[3] During the first session, she experienced derealization, tactile hallucinations, dizziness, and amplified negative thoughts, followed by an hour-long crying episode. In the next sessions, she was asked to listen to a recording of her own voice expressing positive affirmations; despite dissociative symptoms, there was no crying. In explanation, in the institute at which protocols were developed,[3] patients are encouraged to converse with caregivers, review happy memories in conversation, review happy photographs and videos, or do whatever allows them to experience positive thoughts during the session. She preferred to record her voice and listen to it. By 1 week, her Hamilton Rating Scale for Depression score gradually dropped from 22 to 9. There was marked reduction in suicidality, depression, re-experiencing, anxiety, hypervigilance, derealization, and intrusive thoughts. She described “feeling normal for the first time” and being able to focus on tasks without intrusive suicidal thoughts. Her cognition improved; she was also able to experience positive emotions. She was started on bupropion 300 mg/d and memantine 10 mg/d to maintain treatment gains. She also began weekly trauma therapy. At a 5-month follow-up, she reports sustained relief from urges to self-harm and continued improvement in mood, cognition, and cPTSD symptoms. DISCUSSION We describe, for the first time in literature, the successful use of oral ketamine, delivered without psychotherapy, for the attenuation of chronic suicidality and a range of debilitating symptoms associated with 16 years of depression and cPTSD, refractory to an impressive array of drugs, psychological interventions, and somatic interventions. The benefits were subsequently maintained with bupropion and memantine. The patient would have been saved from years of suffering and impairment had a therapeutic trial of ketamine been offered earlier. Ketamine, with or without psychotherapy, is effective in patients with PTSD[4,5]; whereas clinical experience suggests that ketamine, combined with psychotherapy, may benefit cPTSD,[1,2] clinical trial data are lacking. Our report therefore encourages exploration of ketamine as an early rather than late treatment for depression and cPTSD, especially when suicidality is present.[3] Our patient had failed bupropion earlier but improved with a bupropion-memantine combination. Weak evidence supports add-on memantine for civilian PTSD[6]; there is no evidence, yet, for memantine in cPTSD. Our report, therefore, also encourages the exploration of memantine in the maintenance therapy of cPTSD. Declaration of patient consent The authors certify that they have obtained written informed consent from the patient for the publication of this report. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.