Our patient “Ms. S.” is a 33-year-old woman with a history of severe and enduring anorexia nervosa (SE-AN), gastroparesis, epilepsy, major depressive disorder, generalized anxiety disorder (GAD), and post-traumatic stress disorder (PTSD) who was admitted to the hospital with severe malnutrition. At the time of her admission, she had a body mass index (BMI) of 13 kg/m2 (indicating extreme underweight status), and had restricted her caloric intake to 100 kcal per day due to stomach pain and fear of losing control while eating.
Ms. S has an extensive psychiatric history. Her anorexia nervosa symptoms started at age 13. She attended specialized treatment for anorexia nervosa starting in her teen years. She had modest treatment success at several points in time, notably during her early twenties, a period of time during which she completed schooling and pursued a professional career. In her mid- to late- twenties she again became symptomatic of her eating disorder and received intensive and highly specialized treatments for eating disorders, including several residential eating disorder treatment programs. She had a history of medical sequelae of severe malnutrition, including gastroparesis and slow-transit constipation. She has required admission to medical units numerous times for monitored refeeding, and has developed electrolyte abnormalities and extreme bradycardia. During several of these admissions she was found to engage in extreme avoidance of the consumption of calories. She had a history of concealing food to falsely elevate calorie counts, and tampered with medical devices that delivered calories, such as naso-gastric tube connections. At times, she would have episodes of behavioral dysregulation, including removing therapeutic lines, attempting impulsively to leave the hospital against medical advice.
In addition to the SE-AN, Ms. S has suffered from depression and anxiety since her late teenage years. She has had numerous psychiatric hospitalizations and several prior suicide attempts. She has a history of non-suicidal self-injurious behavior. Her last suicide attempt was by wrist cutting, requiring sutures by a hand surgeon, approximately two months prior to this admission. For treatment of her depression and anxiety she has failed numerous medication trials, including selective serotonin reuptake inhibitor and serotonin and norepinephrine reuptaie inhibitor antidepressants, typical and atypical antipsychotics, anti-epileptic mood stabilizers, psycho-stimulants, and lithium. She failed three previous full courses of electroconvulsive therapy. The patient had had one prior trial of ketamine more than ten years prior; however, the details of this trial are not known and it seems she did not finish a full ketamine course. She has a history of trauma, including sexual trauma in early adulthood. She has engaged in psychotherapy both during hospitalizations and as an outpatient, in various modalities including cognitive-behavioral therapy, dialectical-behavior therapy, and acceptance and commitment therapy.
Ms. S has a history of numerous medical hospitalizations due to her malnourishment. She had been discharged from our hospital one month prior to this presentation, but had been unable to maintain the weight she had gained during the previous hospitalization. At the time of this hospital admission, she was afebrile, with bradycardia (52 beats per minute) and hypotension (blood pressure 88/45). Labs were significant for leukopenia (white blood cell count 2.8 k/mm3) and anemia (Hemoglobin 10.7 g/dL); electrolytes, liver function tests and coagulation studies were normal. Her home medications were restarted, which included Klonopin 1mg in the morning and 1.5mg in the evening, Ativan 2mg three times daily with meals, Reglan 10 mg three times a day with meals, Pyridostigmine 90 mg three times daily, Seroquel 200 mg two times daily, Trazodone 100mg three times daily plus 300mg at bedtime, and Gabapentin 600 mg three times daily. Chest x-ray showed clear lungs and electrocardiogram (EKG) showed sinus bradycardia. A few days after admission, the patient was transferred to the medical intensive care unit for management of hypotension; she was given a 1-liter bolus of normal saline and 1-liter of lactated ringers; she was briefly treated with levophed, and was then transferred back to the floors after blood pressure was stabilized.
The psychiatry team was consulted upon admission for assistance with managing Ms. S’s disordered eating behaviors and mood and anxiety disorder symptoms; psychiatry followed her throughout her admission. On assessment, Ms. S was quite symptomatic of SE-AN with severe and entrenched eating disorder cognitions: panic at the thought of consuming calories, preoccupied with thoughts of food and rigid rules around eating in order to influence weight, intense fear of losing control over eating, shame when seeing her body in the mirror. In response to her fears about eating and weight, she fixated on her anxiolytic medications and attempted to negotiate with providers for higher doses of her medications; she recognized that in the past higher doses had yielded sedation but not true anxiolysis. She complained of severe depression, in spite of a robust regimen of antidepressant medications. Themes of her depression included sadness, loss of interest, feeling slowed down, seeing self as a failure and causing problems for others, and self-dislike. She had suicidal ideation without acute intent or plan. She felt absolutely unmotivated to challenge her anxious and eating-disorder based cognitions - the psychiatric consultants formulated that her depression created such profound symptoms that rendered behavioral treatment of her SE-AN and GAD prohibitively difficult. She scored 42 on the Beck Depression Inventory (BDI) and 26 on the Quick Inventory of Depressive Symptomatology. Since the patient had tried multiple medications and interventions for her MDD without adequate therapeutic benefit, she was considered to have TRD and alternative options were explored. The patient was willing to try ketamine to address her depression with the hope that it would ameliorate her distress and enhance collaboration in the care of her eating disorder. She provided written informed consent to undergo ketamine treatments. She was medically cleared for ketamine infusion therapy by her primary internal medicine team.
Ms. S received seven ketamine infusions over 3 weeks. She initially received 0.5mg/kg IV ketamine over 40 minutes; the dose was increased up to 1 mg/kg based on tolerability and response. The infusions were performed in the operating room staging area, with an anesthesiologist available throughout the infusion. Her heart rate, respiratory rate, and oxygen saturation were monitored continuously, and her blood pressure was measured every 15 minutes. She was assessed throughout treatment for adverse effects. Her vital signs were monitored every 30 minutes for 2 hours after the infusion, and she was kept on constant cardiac telemetry while on the medical-surgical floors. She experienced only mild side effects of nausea and dissociation during the treatments. She had one short episode of a tachyarrhythmia (heart rate of 110) on telemetry after her third treatment, which spontaneously resolved. Subsequent EKG tracing was unremarkable. Additionally, she had a drop in her blood oxygenation to 90% during treatment 6, when she received a 1mg/kg dose. She briefly required oxygen, 2 liters per minute via nasal cannula.
During each session, Ms. S engaged in acceptance and commitment therapy (ACT) with the attending psychiatrist (CD-B). ACT is a “third-wave” psychotherapy based on the premise that unpleasant emotions are a fundamental part of human life; and that accepting rather than eliminating these experiences reduces the suffering caused by them. In ACT, patients are taught skills for dealing with their internal experiences that increase their cognitive flexibility [16]. During ketamine-assisted psychotherapy sessions, Ms. S was observed to be open to sharing her thoughts and feelings, thought about her future dreams and stated goals, expressed that she could give up rules and control in regards to her eating, could process her thoughts and feelings with more flexibility, allowed herself to eat more calorie-dense foods than usual, and ate a scone with the provider at the last session. BDI Scores were obtained after each session (see Figure 1).
After an initial 35% drop in her BDI, there was some variability in her depression severity scores. Of note, on treatment day three, her nutritional intake was transitioned from total parenteral nutrition (TPN) to an oral nutritional supplement (Ensure). This caused her a great deal of distress, and we believe that this is reflected in her elevated BDI score. However, with continued ketamine infusions, the patient’s final BDI Score had decreased to 17. The patient no longer had suicidal ideation at the end of the treatment.
The patient was transitioned from TPN to oral nutritional supplement and then to a regular oral diet. On the day of discharge, her BMI was 14.8, representing a nearly 4-kilogram weight gain over 4 weeks. She was given instructions to follow up with gastroenterology and psychiatry as well as a ketamine clinic as an outpatient, with a recommendation to pursue maintenance outpatient ketamine infusions.
The patient was contacted in order to provide consent to publish this case report, and she provided an update. She had been unable to follow up with an outpatient ketamine clinic. She has been hospitalized twice since the events of this case report for continued stomach pain. She has been doing well psychologically, and denies symptoms of depression. She expresses further interest in trying ketamine again given its positive effects.