Innovations In Clinical Neuroscience

JAN-FEB 2017

A peer-reviewed, evidence-based journal for clinicians in the field of neuroscience

Issue link:

Contents of this Issue


Page 57 of 63

Innovations in CLINICAL NEUROSCIENCE [ V O L U M E 1 4 , N U M B E R 1 – 2 , J A N U A R Y – F E B R U A R Y 2 0 1 7 ] 58 The response to treatment was s ustained through the observation period with reduction of depressive symptoms compared to scores prior to initiation of ketamine treatment consistently ranging between 63 p ercent and 95 percent of the baseline BDI score. The clinical course for this patient followed a similar trajectory as seen with other patients who have TRD. The presence of MS did not make her more or less sensitive to the antidepressant effects of ketamine. Her antidepressant medications remained at a stable dose throughout the course of treatment. She was able to maintain a stable and non-depressed mood with this treatment and to date has had no worsening of her MS symptoms. DISCUSSION Depression is common in patients with MS, and some patients may become resistant to oral medications. 1 Generally, TRD may be defined as a failure to respond to at least two different types of oral antidepressant treatments for a period longer than four weeks at the maximum recommended dose. ECT is often used for TRD; however, based on the limited number of published cases there are still questions about its safety in patients with MS, and the long-term effects of ECT in this population are still unclear. 3 Moreover, most current treatments for TRD take several weeks to achieve clinical effect. In comparison, ketamine has a rapid onset of action. 10 Glutamatergic system plays a role in neuronal plasticity and cellular resiliency, and a growing body of evidence also suggests that it is also involved in the pathophysiology and treatment of MDD. 13,14 Ketamine, a potent selective NMDA receptor antagonist with rapid antidepressant effect even in small doses, has emerged as a promising agent for treating TRD. 10 Glutamate systems have also been associated with stroke, traumatic brain injuries, Alzheimer's disease, and amyotrophic lateral sclerosis (ALS). 9 Another NMDA receptor antagonist, riluzole, with less potency than ketamine, has been a pproved for ALS treatment, but is also used for treatment of TRD. 15 Ketamine has also been safely used to treat severe pain and allodynia in a patient with MS. 16 It was reported to h ave an anti-inflammatory effect by suppression of NF-kappaB, which is likely involved in brain neurodegenerative inflammatory diseases, such as MS, suggesting that ketamine may be neuroprotective. 17 Side effects of ketamine treatment for TRD can include transient hypertension during the infusion, anxiety, nausea or dizziness, euphoria or giddiness, pressured speech, and dissociative symptoms. Dissociation appears to be more likely when higher doses are used. Dissociation is expressed as "losing control" or being focused on an idea or thought that might be distressing. We have seen a patient with posttraumatic stress disorder who became very distressed by the repressed thoughts, which surfaced after the ketamine infusion. To avoid dissociative symptoms, we have adopted the practice of using the "ideal" body weight for dosing. This was noted after a patient, twice his ideal body weight, had profound dissociative symptoms with visual distortions. 12 Thus, starting dosing at 0.5mg/kg of ideal body weight and advancing as needed for antidepressant effect helps to mitigate dissociative symptoms. The access to treatment with ECT must also be taken into consideration when it becomes the primary antidepressant intervention. While ECT is only available in specialized centers, ketamine treatments can be done safely in an outpatient setting, infusion center, or hospital. Compared to ECT, this makes ketamine a more accessible treatment for TRD. Also, initiating treatment using an intravenous route of administration allows observation of the patient's response and interruption of treatment in case of adverse events. If a patient does well with intravenous treatments, the route of administration could be changed to intramuscular injections if such change is clinically indicated or more convenient to the patient. Parenteral use of ketamine p revents diversion or abuse and keeps the control of the medication with the treating physician. CONCLUSION I n the case described here, a patient with MS and TRD was successfully treated with intravenous ketamine for her depression over two years and had significant reduction of depressive symptoms. Thus, ketamine may be an alternative treatment to ECT for resistant depression. In particular, ketamine may have a special use in patients with MS and TRD, as ECT has the potential for side effects in this patient population. ACKNOWLEDGMENT Patient consent to publish this report was obtained. REFERENCES 1. Minden SL, Feinstein A, Kalb RC, et al. Evidence-based guideline: assessment and management of psychiatric disorders in individuals with MS: report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. 2014;82(2):174–181. 2. Little A. Treatment-resistant depression. Am Fam Physician. 2009;80(2):167–172. 3. Palm U, Ayache SS, Padberg F, Lefaucheur JP. Non-invasive brain stimulation therapy in multiple sclerosis: a review of tDCS, rTMS and ECT results. Brain Stimul. 2014;7(6):849–854. 4. Fitzsimons MG, Welch CA, Haspel KL, Gorman JM. The safety and efficacy of ECT and anesthesia in the setting of multiple sclerosis. J Psychiatr Pract. 2007;13(3):195–198. 5. Rasmussen KG, Keegan BM. Electroconvulsive therapy in patients with multiple sclerosis. J ECT. 2007;23(3):179–180. 6. Mattingly G, Baker K, Zorumski CF, Figiel GS. Multiple sclerosis and ECT: possible value of gadolinium- enhanced magnetic resonance scans for identifying high-risk patients. J Neuropsychiatry Clin Neurosci.

Articles in this issue

Archives of this issue

view archives of Innovations In Clinical Neuroscience - JAN-FEB 2017