- Email: [email protected]
Transcranial Direct Current Stimulation as a Treatment for Depression in the Hemodialysis Setting
Psychosomatics 2016:]:]]]–]]] Crown Copyright & 2016 Published by Elsevier Inc. on behalf of The Academy of Psychosomatic Medicine. All rights reserved.
Case Reports
Transcranial Direct Current Stimulation as a Treatment for Depression in the Hemodialysis Setting Alison Bautovich, M.B.B.S., B.Sc. (Med), Colleen Loo, M.D., Ivor Katz, Ph.D., Donel Martin, Ph.D., Samuel Harvey, Ph.D.
Introduction It is well established that depression is more common among those with chronic physical health problems and that these patients are often challenging to diagnose and treat.1,2 Rates of depression among those with chronic kidney disease (CKD) and, in particular, those on dialysis, have been estimated to be even greater than those reported for patients with other chronic disease, with prevalence rates of approximately 20%.3,4 Depression in CKD has been shown to be associated with multiple poor outcomes, including more frequent and longer hospitalizations, decreased treatment compliance, poorer quality of life, and higher mortality rates.5-7 Unfortunately, despite these associations, rates of detection and treatment of depression in patients with CKD remain very low.8 Treating depression with antidepressant medications in patients with hemodialysis poses particular challenges.8 Although the relative activity and mode of excretion of antidepressants in this population group are well described, the choice of medication is somewhat limited. Considerations when using antidepressant medications in those on hemodialysis include increased risk of drug interactions,8,9 anticholinergic effects, including urinary retention (tricyclics),8,9 QTc prolongation (tricyclics),8,9 accumulation of toxic metabolites (venlafaxine and bupropion),9 and increased risk of bleeding (serotonin selective reuptake inhibitors).10 These problems suggest that effective nonpharmacological treatments may be of particular use in this patient population. Although there are other promising nonpharmacological treatments for depression, including psychotherapy, the focus of this case report is on the use of brain stimulation, and in particular, transcranial direct current stimulation (tDCS). Psychosomatics ]:], ] 2016
tDCS is a noninvasive form of brain stimulation in which a low-amplitude direct current is passed into the cerebral cortex through scalp electrodes. The currents used are relatively weak (1–3 mA, compared with 800– 900 mA in electroconvulsive therapy (ECT)), and the patient can remain awake and alert during treatment sessions, with no anesthetic being required. Rather than inducing action potentials such as in ECT and transcranial magnetic stimulation (TMS), tDCS primarily works by modulating the spontaneous neuronal network activity.11,12 These neuromodulatory effects have made tDCS of interest in the treatment of neurologic and psychiatric disease. The fact that tDCS does not induce action potentials is an important difference, particularly for those with CKD, in whom electrolyte disturbance, polypharmacy, metabolic derangements, and frequent comorbidities can make the use of ECT problematic. tDCS has been explored as a potential treatment for depression for several decades. However, there has been a surge in interest in tDCS since 2000, possibly as a result of commercial tDCS machines becoming more readily available. Although the methodology, study
Received July 27, 2015; revised November 8, 2015; accepted November 19, 2015. From School of Psychiatry, University of New South Wales, Sydney, Australia (AB, CKL, SBH); NSW Institute of Psychiatry, Westmead, Australia (AB); Department of Psychiatry, St George Hospital, Kogarah, Australia (AB, CKL, SH); Department of Renal Medicine, St George Hospital, Kogarah, Australia (IK); Black Dog Institute, Sydney, Australia (CKL, DM, SBH); Faculty of Medicine, University of New South Wales, Sydney, Australia (IK); Prince of Wales Hospital, Randwick, Australia (AB). Send correspondence and reprint requests to Alison Bautovich, M.B.B.S., B.Sc. (Med), School of Psychiatry, University of New South Wales, Black Dog Institute Building, Hospital Road, Randwick NSW 2031, Australia; e-mail: [email protected] Crown Copyright & 2016 Published by Elsevier Inc. on behalf of The Academy of Psychosomatic Medicine. All rights reserved.
www.psychosomaticsjournal.org
1
Case Reports design, and stimulus parameters differ among studies, most recent studies, including this case report, have focused on excitatory (anodal) stimulation of the left dorsolateral prefrontal cortex. tDCS has been shown to be a promising treatment for depression, with a recent meta-analysis13 finding an effective size within the same range found for antidepressant medication.14 Given the challenges of treating depression in those with CKD, particularly those requiring hemodialysis, tDCS has the potential to be a safe and efficacious treatment. In this case report, we describe the successful administration of tDCS to a patient with chronic renal failure treated with hemodialysis. This patient was treated as part of an open-labeled pilot study (HREC approval ref: 12/267 (HREC/13/POWH/132) which aimed to demonstrate the feasibility and acceptability of using brain stimulation in the unique setting of a hemodialysis unit. In all, 45 patients with hemodialysis at St George Hospital, a large teaching hospital in Sydney, Australia, were screened for depression by a clinician. Of these 45 patients, 6 were diagnosed with depression on clinical interview using DSM IV criteria and standardized measures; 2 patients subsequently agreed to a trial of tDCS treatment, although 1 decided not to proceed following the first treatment because of a change in social circumstances that were unrelated to the tDCS treatment. The following case report describes the remaining patient who received tDCS as a treatment for depression for a 6-week period. This case is reported because of the novelty of using brain stimulation in this patient population, as well as the potential for tDCS to be a major treatment advance for those with depression in the setting of chronic comorbid physical health problems. Case Report Mr. A, a 77-year-old man with end-stage kidney disease secondary to glomerulonephritis, had been treated with hemodialysis for 7 years. He described several months history of depressive symptoms, including sleep disturbance, low energy, low mood, decreased motivation, and ruminating thoughts regarding past events and regrets. He also described negative views of the future and had fleeting suicidal thoughts, although he denied wanting to harm himself. He had no previous psychiatric history, specifically he 2
www.psychosomaticsjournal.org
denied any history of depression or psychotropic medication use. There was no known family history of any psychiatric illness. He had multiple comorbidities including hypertension, dyslipidemia, gout, and a previous stroke that had resulted in a left homonymous hemianopia and disequilibrium. The stroke had occurred over 2 years before the tDCS study and was not thought to be related to the onset of depression. Mr. A was taking multiple medications, including gabapentin, pantoprazole, pravastatin, allopurinol, clopidogrel, latanoprost eye drops, metoprolol, and fish oil. He continued to live with his wife, who was also his caregiver. Mr. A received hemodialysis 3 times per week. An assessment battery was completed before any treatment (baseline) and at completion of treatment (6 weeks). This battery involved standardized measures of (1) mood—self-rated Beck Depression Inventory (BDI) and the clinician-rated Montgomery and Asberg Depression Rating Scale (MADRS), (2) cognitive function—Montreal Cognitive Assessment (MOCA), and (3) quality of life—SF-36. The SF-36 provides separate normative scores for the effect of both physical and mental health symptoms on functioning. During the tDCS treatment course, subsequent mood assessments using the BDI and the MADRS were then completed on a weekly and fortnightly basis, respectively. tDCS was administered at 2.5 mA for 30 minutes with each session for a period of 6 weeks (18 sessions total), with each session taking place during Mr. A's hemodialysis sessions. tDCS was stopped following the completion of the 18 treatment sessions with no taper period. tDCS was delivered using an Eldith DCstimulator (NeuroConn, Germany) with the anode placed over the left dorsolateral prefrontal cortex (F3 on the EEG 10/20 system) and the cathode positioned over F8. Mr. A completed an adverse event assessment at the end of each tDCS session. Mood outcome measures were then repeated at 1 month following completion of tDCS treatment.
Results Both clinician-rated (MADRS) and patient-rated (BDI) measures of mood improved throughout the study as shown in the Figure. Actual scores for BDI were 22 (baseline) and 11 (completion), and for MADRS 20 (baseline) and 7 (completion). These Psychosomatics ]:], ] 2016
Bautovich et al. FIGURE.
Mood Outcome Measures Before, During, and After Treatment Using tDCS. *MADRS and BDI Scores Shown on Same Scale. The MADRS is a ClinicianRated Scale Validated for use in Depression That Produces a Total Score Between 0 and 60. The Following Cutoffs Have Been Suggested: Severe Depression, 31; Moderate, 25; Mild, 15; and Remission Less Than 7. The Beck Depression Inventory (BDI) is One of the Most Validated and Widely Used Self-Report Depression Measures Available. It has a Generally Agreed Cutoff Score to Define Clinically Significant Depression in the General Population of 11 or more. However, Attempts to Define a Valid Cutoff Score to Use Among Patients With CKD/End Stage Kidney Disease Have Resulted in Recommendations Ranging From 11–17. (Color version of figure is available online.)
25 20 Symptom score *
15 10 5
MADRS BDI
0
measures were also reflected in clinician interview, with the patient meeting criteria for remission of the major depressive episode both at the end of the treatment course and at 1-month follow-up. Both physical (SF-36 physical health component score; baseline: 35.6, completion: 32.4) and mental health functioning (SF-36 mental health component score; baseline: 37.8, completion: 29.3) aspects of quality of life also improved. Assessment of cognition at the completion of treatment revealed no significant changes (MOCA baseline 21/25 and MOCA completion 22/25). The tDCS treatments were well tolerated, with the only side effect reported being a mild skin tingling or burning sensation at the beginning of each treatment session, consistent with previous reports of tDCS.15 Additionally, the tDCS did not appear to have any negative effect on hemodialysis adequacy, as measured by Kt/V, urea reduction ratios, fluid gain between dialysis sessions, and biochemical and hematological testing. At the completion of the study, consideration was given to further treatment, including antidepressant medication or psychotherapy or both. However, given the improvement in the patient's depressive symptoms, such treatments were declined at this time. The Psychosomatics ]:], ] 2016
patient was referred back to his renal physician and family doctor with the knowledge that these treatments could be considered in the future should the need arise.
Discussion This case report demonstrates that tDCS can be successfully administered to a patient with multiple medical comorbidities in a hemodialysis unit. Although there are obvious limitations in the conclusions that can be drawn regarding efficacy, given that there were no major changes in the patient that would explain the improvement in their previously persistent depressive symptoms, it appears that tDCS was beneficial in the treatment of depression in this case. Importantly, administering tDCS in this unique setting was shown to be both feasible and well tolerated. Although there are case reports of excellent response to ECT in patients with CKD and severe depression refractory to antidepressant medication,16 special precautions are required in such patients. These include the need to control abrupt increases in blood pressure, adequate muscle relaxation to prevent strong contractions and the subsequent risk of fractures in an osteopenic patient,16 careful management of potassium levels that are further increased by succinyl choline,17 a muscle relaxant commonly administered during ECT, and attention to ECT dose levels, ideally established by individual seizure threshold titration, as the latter may be altered by acidosis and hypocalcaemia.18 tDCS does not require such precautions and is a safe and easily administered treatment. Furthermore, the fact that tDCS is portable, low in cost, well tolerated, and has a favorable side effect profile19 makes it very suitable for the general hospital or dialysis unit setting. However, using tDCS in the hemodialysis setting poses some challenges. Having patients so close together and in need of regular nursing review created difficult, but not unsolvable, problems relating to privacy and confidentiality. Patients are often prone during hemodialysis, which also made the positioning of the electrodes somewhat difficult. The logistics of working within the dialysis treatment setting also had to be carefully planned through frequent consultation www.psychosomaticsjournal.org
3
Case Reports with nursing staff. To this end, tDCS was administered in the middle 1–2 hours of the hemodialysis session, so as to minimize any complications during the connecting and disconnecting to the dialysis machine. However, the fact that tDCS could be administered during hemodialysis sessions, without any need for extra appointments or time spent at the hospital, was a major benefit. Although the evidence base for the use of tDCS in the treatment of depression is growing, to date, most studies have excluded participants with major physical health problems. To our knowledge, there is only one study looking at the use of tDCS for the treatment of depression in those with chronic physical illness. This was a pilot study in 10 HIV-infected persons,20 with results suggesting that tDCS was a welltolerated and seemingly efficacious treatment among this group. Before our report, there have been no studies describing the use of tDCS for the treatment of depression in renal patients. Although the results from this case report need further study and evaluation in larger randomized trials, based on our report tDCS can be considered to be a promising alternative treatment for depression among those with CKD or, potentially, other chronic physical illness. Among
selected patients it appears to be feasible and generally well tolerated. Conflicts of Interest and Source of Funding A.B. received support from the New South Wales Institute of Psychiatry and the Royal Australian and New Zealand College of Psychiatrists for the submitted work; C.L. received financial support from the Stanley Medical Research Foundation to fund research into tDCS treatment in depression and honoraria from Astra-Zeneca for speaking at an ECT conference; I.K. received payments as a consultant for National Renal Care and has received Grants from, and sits on the Chronic Kidney Disease Advisory Panel for Amgen; and C.L. had tDCS equipment donated from Soterix as part of other ongoing research; IK is a member of the Kidney Health Australia (KHA) Advisory Committee and Chronic Kidney Disease Surveillance Group. Acknowledgments: Special thanks to Emily O'Keefe who assisted in the administration of tDCS. The authors would also like to thank all of the nursing staff and renal physicians at St George Hospital and in particular, Sarah Lee, for her support and help in coordinating this project.
References 1. Rayner L, Price A, Evans A, Valsraj K, Higginson IJ, Hotopf M: Antidepressants for depression in physically ill people. Cochrane Database Syst Rev 2010(3):CD007503, Available from: http://dx.doi.org/10.1002/14651858.CD00 7503.pub2 2. Harvey SB, Ismail K: Psychiatric aspects of chronic physical disease. Medicine 2008; 36:471–474 3. Palmer S, Vecchio M, Craig JC, Tonelli M, Johnson DW, Nicolucci A, et al: Prevalence of depression in chronic kidney disease: systematic review and metaanalysis of observational studies. Kidney Int 2013; 84(1): 170–191 4. Bautovich A, Katz I, Smith M, Loo CK, Harvey SB: Depression and chronic kidney disease: a review for clinicians. Aust N Z J Psychiatry 2014; 48(6): 530–541 5. Hedayati SS, Minhajuddin AT, Afshar M, Toto RD, Trivedi MH, Rush AJ: Association between major depressive episodes in patients with chronic kidney disease and initiation of dialysis, hospitalization, or death. J Am Med Assoc 2010; 303(19):1946–1953 6. Chilcot J, Davenport A, Wellsted D, Firth J, Farrington K: An association between depressive symptoms and survival
4
www.psychosomaticsjournal.org
7.
8.
9.
10.
11.
12.
in incident dialysis patients. Nephrol Dial Transplant 2011; 26(5):1628–1634 Palmer SC, Vecchio M, Craig JC, Tonelli M, Johnson DW, Nicolucci A, et al: Association between depression and death in people with CKD: a meta-analysis of cohort studies. Am J Kidney Dis 2013; 62(3):493–505 Hedayati SS, Finkelstein FO: Epidemiology, diagnosis, and management of depression in patients with CKD. Am J Kidney Dis 2009; 54(4):741–752 Cohen LM, Tessier EG, Germain MJ, Levy NB: Update on psychotropic medication use in renal disease. Psychosomatics 2004; 45(1):34–48 Yuan Y, Tsoi K, Hunt RH: Selective serotonin reuptake inhibitors and risk of upper GI bleeding: confusion or confounding? Am J Med 2006; 119(9):719–727 Brunoni AR, Ferrucci R, Fregni F, Boggio PS, Priori A: Transcranial direct current stimulation for the treatment of major depressive disorder: a summary of preclinical, clinical and translational findings. Prog Neuropsychopharmacol Biol Psychiatry 2012; 39(1):9–16 Arul-Anandam AP, Loo C: Transcranial direct current stimulation: a new tool for the treatment of depression? J Affect Disord 2009; 117(3):137–145
Psychosomatics ]:], ] 2016
Bautovich et al. 13. Kalu UG, Sexton CE, Loo CK, Ebmeier KP: Transcranial direct current stimulation in the treatment of major depression: a meta-analysis. Psychol Med 2012; 42(9): 1791–1800 14. Nitsche MA, Boggio PS, Fregni F, Pascual-Leone A: Treatment of depression with transcranial direct current stimulation (tDCS): a review. Exp Neurol 2009; 219(1):14–19 15. Loo CK, Alonzo A, Martin D, Mitchell PB, Galvez V, Sachdev P: Transcranial direct current stimulation for depression: 3-week, randomised, sham-controlled trial. Br J Psychiatry 2012; 200(1):52–59 16. Williams S, Ostroff R: Chronic renal failure, hemodialysis, and electroconvulsive therapy: a case report. J ECT 2005; 21(1):41–42
Psychosomatics ]:], ] 2016
17. Horton WA, Fergusson NV: Hyperkalaemia and cardiac arrest after the use of suxamethonium in intensive care. Anaesthesia 1988; 43(10):890–891 18. Varghese ST, Sagar R, Jhanjee S: Chronic renal failure and electroconvulsive therapy. Indian J Med Sci 2006; 60(3): 114–115 19. Berlim MT, Van den Eynde F, Daskalakis ZJ: Clinical utility of transcranial direct current stimulation (tDCS) for treating major depression: a systematic review and meta-analysis of randomized, double-blind and shamcontrolled trials. J Psychiatr Res 2013; 47(1):1–7 20. Knotkova H, Rosedale M, Strauss SM, Horne J, Soto E, Cruciani RA, et al: Using transcranial direct current stimulation to treat depression in HIV-infected persons: the outcomes of a feasibility study. Front Psychiatry 2012; 3:59
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5
Case Reports
Transcranial Direct Current Stimulation as a Treatment for Depression in the Hemodialysis Setting Alison Bautovich, M.B.B.S., B.Sc. (Med), Colleen Loo, M.D., Ivor Katz, Ph.D., Donel Martin, Ph.D., Samuel Harvey, Ph.D.
Introduction It is well established that depression is more common among those with chronic physical health problems and that these patients are often challenging to diagnose and treat.1,2 Rates of depression among those with chronic kidney disease (CKD) and, in particular, those on dialysis, have been estimated to be even greater than those reported for patients with other chronic disease, with prevalence rates of approximately 20%.3,4 Depression in CKD has been shown to be associated with multiple poor outcomes, including more frequent and longer hospitalizations, decreased treatment compliance, poorer quality of life, and higher mortality rates.5-7 Unfortunately, despite these associations, rates of detection and treatment of depression in patients with CKD remain very low.8 Treating depression with antidepressant medications in patients with hemodialysis poses particular challenges.8 Although the relative activity and mode of excretion of antidepressants in this population group are well described, the choice of medication is somewhat limited. Considerations when using antidepressant medications in those on hemodialysis include increased risk of drug interactions,8,9 anticholinergic effects, including urinary retention (tricyclics),8,9 QTc prolongation (tricyclics),8,9 accumulation of toxic metabolites (venlafaxine and bupropion),9 and increased risk of bleeding (serotonin selective reuptake inhibitors).10 These problems suggest that effective nonpharmacological treatments may be of particular use in this patient population. Although there are other promising nonpharmacological treatments for depression, including psychotherapy, the focus of this case report is on the use of brain stimulation, and in particular, transcranial direct current stimulation (tDCS). Psychosomatics ]:], ] 2016
tDCS is a noninvasive form of brain stimulation in which a low-amplitude direct current is passed into the cerebral cortex through scalp electrodes. The currents used are relatively weak (1–3 mA, compared with 800– 900 mA in electroconvulsive therapy (ECT)), and the patient can remain awake and alert during treatment sessions, with no anesthetic being required. Rather than inducing action potentials such as in ECT and transcranial magnetic stimulation (TMS), tDCS primarily works by modulating the spontaneous neuronal network activity.11,12 These neuromodulatory effects have made tDCS of interest in the treatment of neurologic and psychiatric disease. The fact that tDCS does not induce action potentials is an important difference, particularly for those with CKD, in whom electrolyte disturbance, polypharmacy, metabolic derangements, and frequent comorbidities can make the use of ECT problematic. tDCS has been explored as a potential treatment for depression for several decades. However, there has been a surge in interest in tDCS since 2000, possibly as a result of commercial tDCS machines becoming more readily available. Although the methodology, study
Received July 27, 2015; revised November 8, 2015; accepted November 19, 2015. From School of Psychiatry, University of New South Wales, Sydney, Australia (AB, CKL, SBH); NSW Institute of Psychiatry, Westmead, Australia (AB); Department of Psychiatry, St George Hospital, Kogarah, Australia (AB, CKL, SH); Department of Renal Medicine, St George Hospital, Kogarah, Australia (IK); Black Dog Institute, Sydney, Australia (CKL, DM, SBH); Faculty of Medicine, University of New South Wales, Sydney, Australia (IK); Prince of Wales Hospital, Randwick, Australia (AB). Send correspondence and reprint requests to Alison Bautovich, M.B.B.S., B.Sc. (Med), School of Psychiatry, University of New South Wales, Black Dog Institute Building, Hospital Road, Randwick NSW 2031, Australia; e-mail: [email protected] Crown Copyright & 2016 Published by Elsevier Inc. on behalf of The Academy of Psychosomatic Medicine. All rights reserved.
www.psychosomaticsjournal.org
1
Case Reports design, and stimulus parameters differ among studies, most recent studies, including this case report, have focused on excitatory (anodal) stimulation of the left dorsolateral prefrontal cortex. tDCS has been shown to be a promising treatment for depression, with a recent meta-analysis13 finding an effective size within the same range found for antidepressant medication.14 Given the challenges of treating depression in those with CKD, particularly those requiring hemodialysis, tDCS has the potential to be a safe and efficacious treatment. In this case report, we describe the successful administration of tDCS to a patient with chronic renal failure treated with hemodialysis. This patient was treated as part of an open-labeled pilot study (HREC approval ref: 12/267 (HREC/13/POWH/132) which aimed to demonstrate the feasibility and acceptability of using brain stimulation in the unique setting of a hemodialysis unit. In all, 45 patients with hemodialysis at St George Hospital, a large teaching hospital in Sydney, Australia, were screened for depression by a clinician. Of these 45 patients, 6 were diagnosed with depression on clinical interview using DSM IV criteria and standardized measures; 2 patients subsequently agreed to a trial of tDCS treatment, although 1 decided not to proceed following the first treatment because of a change in social circumstances that were unrelated to the tDCS treatment. The following case report describes the remaining patient who received tDCS as a treatment for depression for a 6-week period. This case is reported because of the novelty of using brain stimulation in this patient population, as well as the potential for tDCS to be a major treatment advance for those with depression in the setting of chronic comorbid physical health problems. Case Report Mr. A, a 77-year-old man with end-stage kidney disease secondary to glomerulonephritis, had been treated with hemodialysis for 7 years. He described several months history of depressive symptoms, including sleep disturbance, low energy, low mood, decreased motivation, and ruminating thoughts regarding past events and regrets. He also described negative views of the future and had fleeting suicidal thoughts, although he denied wanting to harm himself. He had no previous psychiatric history, specifically he 2
www.psychosomaticsjournal.org
denied any history of depression or psychotropic medication use. There was no known family history of any psychiatric illness. He had multiple comorbidities including hypertension, dyslipidemia, gout, and a previous stroke that had resulted in a left homonymous hemianopia and disequilibrium. The stroke had occurred over 2 years before the tDCS study and was not thought to be related to the onset of depression. Mr. A was taking multiple medications, including gabapentin, pantoprazole, pravastatin, allopurinol, clopidogrel, latanoprost eye drops, metoprolol, and fish oil. He continued to live with his wife, who was also his caregiver. Mr. A received hemodialysis 3 times per week. An assessment battery was completed before any treatment (baseline) and at completion of treatment (6 weeks). This battery involved standardized measures of (1) mood—self-rated Beck Depression Inventory (BDI) and the clinician-rated Montgomery and Asberg Depression Rating Scale (MADRS), (2) cognitive function—Montreal Cognitive Assessment (MOCA), and (3) quality of life—SF-36. The SF-36 provides separate normative scores for the effect of both physical and mental health symptoms on functioning. During the tDCS treatment course, subsequent mood assessments using the BDI and the MADRS were then completed on a weekly and fortnightly basis, respectively. tDCS was administered at 2.5 mA for 30 minutes with each session for a period of 6 weeks (18 sessions total), with each session taking place during Mr. A's hemodialysis sessions. tDCS was stopped following the completion of the 18 treatment sessions with no taper period. tDCS was delivered using an Eldith DCstimulator (NeuroConn, Germany) with the anode placed over the left dorsolateral prefrontal cortex (F3 on the EEG 10/20 system) and the cathode positioned over F8. Mr. A completed an adverse event assessment at the end of each tDCS session. Mood outcome measures were then repeated at 1 month following completion of tDCS treatment.
Results Both clinician-rated (MADRS) and patient-rated (BDI) measures of mood improved throughout the study as shown in the Figure. Actual scores for BDI were 22 (baseline) and 11 (completion), and for MADRS 20 (baseline) and 7 (completion). These Psychosomatics ]:], ] 2016
Bautovich et al. FIGURE.
Mood Outcome Measures Before, During, and After Treatment Using tDCS. *MADRS and BDI Scores Shown on Same Scale. The MADRS is a ClinicianRated Scale Validated for use in Depression That Produces a Total Score Between 0 and 60. The Following Cutoffs Have Been Suggested: Severe Depression, 31; Moderate, 25; Mild, 15; and Remission Less Than 7. The Beck Depression Inventory (BDI) is One of the Most Validated and Widely Used Self-Report Depression Measures Available. It has a Generally Agreed Cutoff Score to Define Clinically Significant Depression in the General Population of 11 or more. However, Attempts to Define a Valid Cutoff Score to Use Among Patients With CKD/End Stage Kidney Disease Have Resulted in Recommendations Ranging From 11–17. (Color version of figure is available online.)
25 20 Symptom score *
15 10 5
MADRS BDI
0
measures were also reflected in clinician interview, with the patient meeting criteria for remission of the major depressive episode both at the end of the treatment course and at 1-month follow-up. Both physical (SF-36 physical health component score; baseline: 35.6, completion: 32.4) and mental health functioning (SF-36 mental health component score; baseline: 37.8, completion: 29.3) aspects of quality of life also improved. Assessment of cognition at the completion of treatment revealed no significant changes (MOCA baseline 21/25 and MOCA completion 22/25). The tDCS treatments were well tolerated, with the only side effect reported being a mild skin tingling or burning sensation at the beginning of each treatment session, consistent with previous reports of tDCS.15 Additionally, the tDCS did not appear to have any negative effect on hemodialysis adequacy, as measured by Kt/V, urea reduction ratios, fluid gain between dialysis sessions, and biochemical and hematological testing. At the completion of the study, consideration was given to further treatment, including antidepressant medication or psychotherapy or both. However, given the improvement in the patient's depressive symptoms, such treatments were declined at this time. The Psychosomatics ]:], ] 2016
patient was referred back to his renal physician and family doctor with the knowledge that these treatments could be considered in the future should the need arise.
Discussion This case report demonstrates that tDCS can be successfully administered to a patient with multiple medical comorbidities in a hemodialysis unit. Although there are obvious limitations in the conclusions that can be drawn regarding efficacy, given that there were no major changes in the patient that would explain the improvement in their previously persistent depressive symptoms, it appears that tDCS was beneficial in the treatment of depression in this case. Importantly, administering tDCS in this unique setting was shown to be both feasible and well tolerated. Although there are case reports of excellent response to ECT in patients with CKD and severe depression refractory to antidepressant medication,16 special precautions are required in such patients. These include the need to control abrupt increases in blood pressure, adequate muscle relaxation to prevent strong contractions and the subsequent risk of fractures in an osteopenic patient,16 careful management of potassium levels that are further increased by succinyl choline,17 a muscle relaxant commonly administered during ECT, and attention to ECT dose levels, ideally established by individual seizure threshold titration, as the latter may be altered by acidosis and hypocalcaemia.18 tDCS does not require such precautions and is a safe and easily administered treatment. Furthermore, the fact that tDCS is portable, low in cost, well tolerated, and has a favorable side effect profile19 makes it very suitable for the general hospital or dialysis unit setting. However, using tDCS in the hemodialysis setting poses some challenges. Having patients so close together and in need of regular nursing review created difficult, but not unsolvable, problems relating to privacy and confidentiality. Patients are often prone during hemodialysis, which also made the positioning of the electrodes somewhat difficult. The logistics of working within the dialysis treatment setting also had to be carefully planned through frequent consultation www.psychosomaticsjournal.org
3
Case Reports with nursing staff. To this end, tDCS was administered in the middle 1–2 hours of the hemodialysis session, so as to minimize any complications during the connecting and disconnecting to the dialysis machine. However, the fact that tDCS could be administered during hemodialysis sessions, without any need for extra appointments or time spent at the hospital, was a major benefit. Although the evidence base for the use of tDCS in the treatment of depression is growing, to date, most studies have excluded participants with major physical health problems. To our knowledge, there is only one study looking at the use of tDCS for the treatment of depression in those with chronic physical illness. This was a pilot study in 10 HIV-infected persons,20 with results suggesting that tDCS was a welltolerated and seemingly efficacious treatment among this group. Before our report, there have been no studies describing the use of tDCS for the treatment of depression in renal patients. Although the results from this case report need further study and evaluation in larger randomized trials, based on our report tDCS can be considered to be a promising alternative treatment for depression among those with CKD or, potentially, other chronic physical illness. Among
selected patients it appears to be feasible and generally well tolerated. Conflicts of Interest and Source of Funding A.B. received support from the New South Wales Institute of Psychiatry and the Royal Australian and New Zealand College of Psychiatrists for the submitted work; C.L. received financial support from the Stanley Medical Research Foundation to fund research into tDCS treatment in depression and honoraria from Astra-Zeneca for speaking at an ECT conference; I.K. received payments as a consultant for National Renal Care and has received Grants from, and sits on the Chronic Kidney Disease Advisory Panel for Amgen; and C.L. had tDCS equipment donated from Soterix as part of other ongoing research; IK is a member of the Kidney Health Australia (KHA) Advisory Committee and Chronic Kidney Disease Surveillance Group. Acknowledgments: Special thanks to Emily O'Keefe who assisted in the administration of tDCS. The authors would also like to thank all of the nursing staff and renal physicians at St George Hospital and in particular, Sarah Lee, for her support and help in coordinating this project.
References 1. Rayner L, Price A, Evans A, Valsraj K, Higginson IJ, Hotopf M: Antidepressants for depression in physically ill people. Cochrane Database Syst Rev 2010(3):CD007503, Available from: http://dx.doi.org/10.1002/14651858.CD00 7503.pub2 2. Harvey SB, Ismail K: Psychiatric aspects of chronic physical disease. Medicine 2008; 36:471–474 3. Palmer S, Vecchio M, Craig JC, Tonelli M, Johnson DW, Nicolucci A, et al: Prevalence of depression in chronic kidney disease: systematic review and metaanalysis of observational studies. Kidney Int 2013; 84(1): 170–191 4. Bautovich A, Katz I, Smith M, Loo CK, Harvey SB: Depression and chronic kidney disease: a review for clinicians. Aust N Z J Psychiatry 2014; 48(6): 530–541 5. Hedayati SS, Minhajuddin AT, Afshar M, Toto RD, Trivedi MH, Rush AJ: Association between major depressive episodes in patients with chronic kidney disease and initiation of dialysis, hospitalization, or death. J Am Med Assoc 2010; 303(19):1946–1953 6. Chilcot J, Davenport A, Wellsted D, Firth J, Farrington K: An association between depressive symptoms and survival
4
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7.
8.
9.
10.
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12.
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