|Year : 2019 | Volume
| Issue : 3 | Page : 129-131
Treatment of nonsuicidal self-injury disorder with oral ketamine
Brigitte C Vanle1, Mitchell Fuller2, Gabriella Hangiandreou2, Stuart Silverman3
1 Medical College of Wisconsin-Central Wisconsin, Wausau, WI; Cedars-Sinai Medical Center, Los Angeles, California, USA
2 Medical College of Wisconsin-Central Wisconsin, Wausau, WI, USA
3 Cedars-Sinai Medical Center, Los Angeles, California, USA
|Date of Submission||05-Sep-2019|
|Date of Acceptance||22-Oct-2019|
|Date of Web Publication||29-Nov-2019|
Dr. Brigitte C Vanle
Medical College of Wisconsin-Central Wisconsin, 333 Pine Ridge Blvd, Wausau, WI 54401
Source of Support: None, Conflict of Interest: None
Nonsuicidal self-injury disorder (NSSID) is the deliberate alteration or destruction of body tissue without conscious suicidal intent and for purposes not socially sanctioned. NSSID can cause significant morbidity and mortality, and despite being recognized as a clinical entity for many years, clear pharmacological guidelines on how to effectively treat these symptoms do not yet exist. Given the dearth of evidence regarding effective medication treatment of this condition, we present a case where remission of nonsuicidal self-injury was achieved through the use of oral ketamine.
Keywords: Ketamine, nonsuicidal self-injury, nonsuicidal self-injury disorder, self-mutilation, treatment-resistant
|How to cite this article:|
Vanle BC, Fuller M, Hangiandreou G, Silverman S. Treatment of nonsuicidal self-injury disorder with oral ketamine. Heart Mind 2019;3:129-31
| Introduction|| |
Nonsuicidal self-injury disorder (NSSID) is the intentional, nonsocially sanctioned, self-injurious behavior with the expectation to provide relief from interpersonal problems or unpleasant thoughts. The disorder is defined by the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) as 5 or more days within a year of self-injurious behavior, with the purpose to receive emotional relief [Figure 1]. Historically, the terms “self-mutilation” and NSSID have been used interchangeably, which are difficult to treat and cause significant morbidity and mortality.
|Figure 1: Diagnostic and Statistical Manual of Mental Disorders, 5th Edition criteria for nonsuicidal self-injury disorder|
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The nonmedication interventions to address NSSID include dialectical behavior therapy, emotion regulation group therapy, manual-assisted cognitive therapy, and dynamic deconstructive psychotherapy. However, medication treatment of NSSID has not been well-studied, and there are no Food and Drug Administration-approved medications for this disorder. There is some benefit with atypical antipsychotics and naltrexone in adults' comorbid with Borderline Personality Disorder. Unfortunately, the use of atypical antipsychotics in this population is limited, given significant side effects, such as excess weight gain, hyperlipidemia, and impaired glucose metabolism. Similarly, naltrexone is only considered in cases of extreme, chronic, and dangerous NSSID (i.e., cutting to the bone and recurrent infections secondary to self-injurious behaviors). Although selective serotonin reuptake inhibitors are widely used, it remains unclear whether they are useful in nondepressed NSSID patients. Given the dearth of evidence regarding effective treatment of this highly impairing condition, we describe the first case of NSSI who achieved remission with oral ketamine.
| Case Report|| |
A 52-year-old male presented to a rheumatoid outpatient clinic for a chief complaint of fibromyalgia-related pain and depression. He rated his fibromyalgia pain on the visual analog scale (VAS) a 10/10. At the time of the visit, the patient's pain medications included Lyrica 225 mg BID, morphine 90 mg ER qd, and hydromorphone 8 mg BID. In addition to these symptoms, the patient endorsed a long history of nonsuicidal self-injury (NSSI). The depressive and anxiety symptoms had previously been treated by the patient's psychiatrist with clonazepam 0.5 mg and duloxetine 60 mg. However, the patient had failed trials with Lexapro, Seroquel, and CBT to treat anxiety, depression, and NSSID. The patient's NSSI started in high school and had self-induced damage over fifty times to the arms, thighs, and head. The patient met DSM criteria [Figure 1] as patient reported performing self-injury to manage emotional pain and a compelling need to prove their own existence, yet was not diagnosed with obsessive-compulsive disorder. The patient's symptoms were further defined by the completion of the subjective NSSI assessment tool.
Family history included both parents who had depression and attempted suicide. Social history included being single and never married. The patient had a Bachelor of Arts degree and worked in advertising, but had lost his job. He has been disabled since. At the time of visit, to better control the chief complaints of continued pain and depression, the only change to the treatment plan was starting oral ketamine 3 mg TID. When re-evaluated 1 month later, the patient stated a reduction in pain and depressive symptoms. In addition, an unexpected finding was that the patient had completely stopped NSSI after the 1st week of ketamine dose. To improve symptoms, the ketamine dose was gradually titrated to the current dose of 75 mg TID. A summary of the titrated ketamine dose is shown in [Figure 2].
At 5-month follow-up and treatment with ketamine, the patient stated a further significant reduction in pain (VAS 4/10). As a result, the patient's opioid dose of morphine ER 90 mg QD decreased to 60 mg QD but continued hydromorphone. Lyrica was stopped but continued duloxetine for added pain management. The patient remained asymptomatic and did not engage in NSSI.
Two years later, access to oral ketamine stopped for 50 days, due to unavailability from the distributor, the patient was forced to taper off of ketamine, and NSSI returned on day 3. When oral ketamine was stopped, the patient reported increased pain, increased depressive symptoms and had poor sleep. When oral ketamine became available again, the patient's self-mutilation behaviors immediately disappeared; depressive symptoms, malaise, headache, and sleep improved. Since restarting oral ketamine, the patient has not had an incidence of NSSI. The patient gave informed consent for publication considerations.
| Discussion|| |
Current use of oral ketamine
The use of the oral route of ketamine for mood disorders is uncommon. Two factors contribute to this: Low oral bioavailability and compounding unavailability at pharmacies. However, there are four case studies and an open-label trial documenting the effects of oral ketamine among patients with treatment-resistant depression. In all cases, oral ketamine was compounded by a pharmacy and generally mixed with cherry syrup. One case study treated unipolar and bipolar depression patients with 1.25 mg/kg oral S-ketamine as a 2-week add-on treatment, half of the patients responded early and permanently maintained remission. This dose at 1.25 mg is approximately 85 mg/day for a 150 lb/68-kg patient, and is roughly one-third of the permanent dose we utilized (225 mg/day). However, we titrated to this maximum dose across 9 months.
Two studies dosed patients with treatment-resistant depression at 0.5 mg/kg ketamine as augmentation to antidepressants. After only 24 h from the first dose, depressive symptoms significantly reduced as measured by the standardized Montgomery-Asberg Depression Rating Scale, scores decreased from 36 to 1–17. Repeated oral treatments were given every 2–3 weeks between 1 and 3 mg/kg dose to maintain remission and a reduction in HAM-D depression scores by 37%–45%. A palliative study was open-label of daily ketamine (0.5 mg/kg) for 28 days on antidepressant-naïve hospice patients. The time of response was 3 days for anxiety and 14 days for depression. All patients who had finished the trial had decreased depression scores by at least 30%. There were also improvements in pain, anxiety, and depressive symptoms in a hospice patient with daily 40 mg oral ketamine. In summary, there is a wide variety of dosing strategies, as these studies dosed according to body weight and used nontitrated and relatively lower daily ketamine dose than what was used in our case study. We started with a very low dose (3 mg TID) to avoid potential side effects and enhance tolerability and slowly titrated the oral ketamine dose to sustain the therapeutic effects. However, dosing for oral ketamine has not been standardized yet.
This case report describes a patient whose NSSID, depression, and chronic pain symptoms were effectively treated with oral ketamine. In the afore-mentioned studies, patients took oral ketamine at home, with daily dosing every few weeks for maintenance. Generally, oral ketamine is compounded and mixed with a sweet cherry syrup, to mask the bitter flavor. Meta-analyses of intravenous (IV) route of ketamine have reported high response and high remission rates for treating depression. However, the disadvantages of IV ketamine include the limited access and inefficient maintenance, forcing patients to return to outpatient clinics for IV delivery, and paying out of pocket. Utilizing oral ketamine has advantages, given that it circumvents the need for IV administration and costly visits, as most ketamine clinics charge 1000 dollars per infusion. Therefore, standardized use of oral ketamine could be a potential alternative to IV ketamine. There is little evidence for acute and chronic side effects of oral ketamine; however, current evidence is limited.
Although there is a significant concern of side effects and potential cognitive deficits with chronic use of ketamine, there is little evidence to support or refute chronic effects. The studies cited report an improvement in cognition and mental state, which may be an indirect effect of improving depressive symptoms. It should also be noted that most of the reported cases involved patients in hospice and palliative settings. Although the use of oral ketamine is not commonly described in practice or in literature, it may be a promising therapeutic for treating depression and as described in this case report, for NSSID.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Self-Injury ISftSo. Definition of Non-Suicidal Self-Injury. Self-Injury ISftSo; 2007.
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders: DSM-5. Arlington, VA: American Psychiatric Association; 2013.
Turner BJ, Austin SB, Chapman AL. Treating nonsuicidal self-injury: A systematic review of psychological and pharmacological interventions. Can J Psychiatry 2014;59:576-85.
Whitlock J, Exner-Cortens D, Purington A. Assessment of nonsuicidal self-injury: development and initial validation of the Non-Suicidal Self-Injury-Assessment Tool (NSSI-AT). Psychological assessment 2014; 26:935-46.
Paslakis G, Gilles M, Meyer-Lindenberg A, Deuschle M. Oral administration of the NMDA receptor antagonist S-ketamine as add-on therapy of depression: A case series. Pharmacopsychiatry 2010;43:33-5.
De Gioannis A, De Leo D. Oral ketamine augmentation for chronic suicidality in treatment-resistant depression. Aust N
Z J Psychiatry 2014;48:686.
Irwin SA, Iglewicz A. Oral ketamine for the rapid treatment of depression and anxiety in patients receiving hospice care. J Palliat Med 2010;13:903-8.
Irwin SA, Iglewicz A, Nelesen RA, Lo JY, Carr CH, Romero SD, et al.
Daily oral ketamine for the treatment of depression and anxiety in patients receiving hospice care: A 28-day open-label proof-of-concept trial. J Palliat Med 2013;16:958-65.
McNulty JP, Hahn K. Compounded oral ketamine. Int J Pharm Compd 2012;16:364-8.
Xu Y, Hackett M, Carter G, Loo C, Gálvez V, Glozier N, et al.
Effects of low-dose and very low-dose ketamine among patients with major depression: A systematic review and meta-analysis. Int J Neuropsychopharmacol 2016;19. pii: pyv124.
[Figure 1], [Figure 2]
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