Brain Stimulation xxx (2014) 1e2
Contents lists available at ScienceDirect
Brain Stimulation journal homepage: www.brainstimjrnl.com
Letter to the Editor
Treatment of Depression in a Patient With Epilepsy To the Editor: Repetitive transcranial magnetic stimulation (rTMS) is becoming a commonly used treatment tool in the management of patients with mood disorders including depression [1]. The most significant safety consideration with the provision of rTMS treatment is that there is a documented incidence of rTMS induced seizures in both healthy individuals engaged in experimental protocols and in patients undergoing rTMS treatment [2]. For this reason, a history of epilepsy or seizures is typically considered a contraindication for engaging in rTMS treatment. Here we report a case history of the successful treatment of a patient with a documented history of epilepsy who underwent rTMS treatment for depression. Mr AA was a 57-year-old married man on a disability pension who presented initially with a long history of recurrent and treatment refractory depression. He first presented with depression in his early 40s and this progressed in severity over several years to the point where approximately 10 years prior to presentation he permanently ceased employment. Over the course of a period of approximately 15 years he underwent treatment with a long series of antidepressants including paroxetine, fluoxetine, sertraline, escitalopram, citalopram, venlafaxine, duloxetine and mirtazapine. None of these produced a remission of his depressive symptoms. Approximately 18 months prior to presentation he underwent a course of 18 ECT treatments (a mixture of uni and bilateral) which improved his mood transiently but lead to no sustained response. At presentation, Mr AA was tearful, described low mood, anhedonia, substantial social anxiety, a reduction in concentration, energy and motivation and significant hopelessness. He had some transient suicidal ideation but no current plans or intent. There was no history of episodes of mania or mood elevation. There was a period of excessive alcohol consumption for approximately 6 months but he had ceased drinking any alcohol three months prior to presentation. Mr AA had a documented history of epilepsy which was diagnosed at age 26. He experienced 1e2 grand mal seizures per year for a number of years until eventually stabilized on a combination of Sodium Valproate and Lamotrigine. At the time of presentation he had experienced no seizures for 11 years. Mr AA was taking sodium valproate (100 mg/day), lamotrigine (300 mg/day), aripiprazole (5 mg/day), duloxetine (60 mg/day) and clonazepam (0.5 mg nocte as required). Based on the severity of Mr AA’s depression and his failure to respond to multiple courses of medication and a significant course of ECT, a decision was made to proceed with rTMS despite his history of epilepsy. He was fully informed of the increased risks associated with his history and gave informed consent. To minimize the 1935-861X/$ e see front matter Ó 2014 Elsevier Inc. All rights reserved.
risk of seizure induction, rTMS was provided with low-frequency stimulation: one continuous 20 min train applied at 1 Hz to the right dorsolateral prefrontal cortex daily for 20 consecutive weekdays. Stimulation was localized 6 cm anterior to the optimal site for stimulation of the right abductor pollicis brevis muscle. Stimulation was provided at 120% of the resting motor threshold (assessed as the minimum stimulation intensity producing three or more visible muscle twitches out of five stimulations). Mr AA underwent a planned course of 20 treatments of rTMS over a four-week period of time. This had a substantial positive impact on his mood and social anxiety, with an almost complete resolution of his depressive symptoms. There was a reduction in his score on the Inventory of Depressive Symptomatology from 52 to 19, and on the Beck Anxiety Inventory from 16 to 3. He experienced no seizures during treatment or any abnormal motor or other neurological activity. Depression is a disorder that commonly occurs in patients with epilepsy with substantial negative consequences for quality of life [3]. Historically, there has been clinical reluctance to treat patients with depression and epilepsy with antidepressant medications due to somewhat unfounded concerns about potential pro-convulsive effects of these medications [4]. rTMS is a new and extremely helpful antidepressant treatment strategy which is also likely to be substantially restricted in use in patients with epilepsy. However, the risk of inducing seizures with rTMS in this patient group may be substantially lower than might otherwise be believed. No seizures were reported in a series of studies utilizing low frequency (1 Hz) rTMS for the treatment of patients with epilepsy (see review in Ref. [2]), with a review reporting a per patient risk of seizure induction of 1.4% with all types of rTMS utilized in studies until that time [5]. It appears quite likely that the risk of seizure induction is related to rTMS stimulation intensity with low-frequency stimulation, as we utilized in this case, far less likely to induce a seizure due to the reduction of cortical excitability generally produced with this type of stimulation [6]. However, low-frequency stimulation does not always produce a reduction in cortical excitability and it should not always be assumed that there is negligible risk associated with this type of approach. It is worthy of note that a number of studies have found no difference in efficacy between high frequency left and low frequency right sided rTMS (for example Refs. [7,8]). In summary, depression is a common clinical problem occurring in patients with epilepsy and may remain resistant to standard antidepressant approaches. rTMS should generally be avoided in patients with a history of epilepsy, but there may be exceptions where carefully administered rTMS can be a successful and life altering treatment. The administration of rTMS under these circumstances requires a careful balancing of risks and potential benefits and the provision of informed consent. Lowfrequency right prefrontal stimulation is a sensible first choice treatment approach.
2
Letter to the Editor / Brain Stimulation xxx (2014) 1e2
PBF is supported by an NHMRC Practitioner Fellowship (606907).PBF has received equipment for research from MagVenture A/S, Medtronic Ltd, Cervel Neurotech and Brainsway Ltd and funding for research from Cervel Neurotech.
Paul B. Fitzgerald* Monash Alfred Psychiatry Research Centre (MAPrc), The Alfred and Monash University Central Clinical School, Level 4, 607 St Kilda Road, Melbourne, Victoria 3004, Australia author. Tel.: þ61 3 9076 6552; fax: þ61 3 9076 6588. E-mail address: paul.fi[email protected]
* Corresponding
Received 21 February 2014 Available online xxx
http://dx.doi.org/10.1016/j.brs.2014.03.003
References [1] Fitzgerald PB, Daskalakis ZJ. The effects of repetitive transcranial magnetic stimulation in the treatment of depression. Expert Rev Med Devices 2011 Jan;8(1): 85e95. [2] Rossi S, Hallett M, Rossini PM, Pascual-Leone A. Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. Clin Neurophysiol 2009 Dec;120(12):2008e39. [3] Kanner AM. Epilepsy and mood disorders. Epilepsia 2007;48(Suppl. 9):20e2. [4] Kondziella D, Asztely F. Don’t be afraid to treat depression in patients with epilepsy! Acta Neurol Scand 2009 Feb;119(2):75e80. [5] Bae EH, Schrader LM, Machii K, et al. Safety and tolerability of repetitive transcranial magnetic stimulation in patients with epilepsy: a review of the literature. Epilepsy Behav 2007 Jun;10(4):521e8. [6] Fitzgerald PB, Fountain S, Daskalakis ZJ. A comprehensive review of the effects of rTMS on motor cortical excitability and inhibition. Clin Neurophysiol 2006 Dec;117(12):2584e96. [7] Isenberg K, Downs D, Pierce K, et al. Low frequency rTMS stimulation of the right frontal cortex is as effective as high frequency rTMS stimulation of the left frontal cortex for antidepressant-free, treatment-resistant depressed patients. Ann Clin Psychiatry 2005 Jul-Sep;17(3):153e9. [8] Fitzgerald PB, Brown T, Marston NAU, Daskalakis ZJ, Kulkarni J. A double-blind placebo controlled trial of transcranial magnetic stimulation in the treatment of depression. Arch Gen Psychiatry 2003;60:1002e8.
Contents lists available at ScienceDirect
Brain Stimulation journal homepage: www.brainstimjrnl.com
Letter to the Editor
Treatment of Depression in a Patient With Epilepsy To the Editor: Repetitive transcranial magnetic stimulation (rTMS) is becoming a commonly used treatment tool in the management of patients with mood disorders including depression [1]. The most significant safety consideration with the provision of rTMS treatment is that there is a documented incidence of rTMS induced seizures in both healthy individuals engaged in experimental protocols and in patients undergoing rTMS treatment [2]. For this reason, a history of epilepsy or seizures is typically considered a contraindication for engaging in rTMS treatment. Here we report a case history of the successful treatment of a patient with a documented history of epilepsy who underwent rTMS treatment for depression. Mr AA was a 57-year-old married man on a disability pension who presented initially with a long history of recurrent and treatment refractory depression. He first presented with depression in his early 40s and this progressed in severity over several years to the point where approximately 10 years prior to presentation he permanently ceased employment. Over the course of a period of approximately 15 years he underwent treatment with a long series of antidepressants including paroxetine, fluoxetine, sertraline, escitalopram, citalopram, venlafaxine, duloxetine and mirtazapine. None of these produced a remission of his depressive symptoms. Approximately 18 months prior to presentation he underwent a course of 18 ECT treatments (a mixture of uni and bilateral) which improved his mood transiently but lead to no sustained response. At presentation, Mr AA was tearful, described low mood, anhedonia, substantial social anxiety, a reduction in concentration, energy and motivation and significant hopelessness. He had some transient suicidal ideation but no current plans or intent. There was no history of episodes of mania or mood elevation. There was a period of excessive alcohol consumption for approximately 6 months but he had ceased drinking any alcohol three months prior to presentation. Mr AA had a documented history of epilepsy which was diagnosed at age 26. He experienced 1e2 grand mal seizures per year for a number of years until eventually stabilized on a combination of Sodium Valproate and Lamotrigine. At the time of presentation he had experienced no seizures for 11 years. Mr AA was taking sodium valproate (100 mg/day), lamotrigine (300 mg/day), aripiprazole (5 mg/day), duloxetine (60 mg/day) and clonazepam (0.5 mg nocte as required). Based on the severity of Mr AA’s depression and his failure to respond to multiple courses of medication and a significant course of ECT, a decision was made to proceed with rTMS despite his history of epilepsy. He was fully informed of the increased risks associated with his history and gave informed consent. To minimize the 1935-861X/$ e see front matter Ó 2014 Elsevier Inc. All rights reserved.
risk of seizure induction, rTMS was provided with low-frequency stimulation: one continuous 20 min train applied at 1 Hz to the right dorsolateral prefrontal cortex daily for 20 consecutive weekdays. Stimulation was localized 6 cm anterior to the optimal site for stimulation of the right abductor pollicis brevis muscle. Stimulation was provided at 120% of the resting motor threshold (assessed as the minimum stimulation intensity producing three or more visible muscle twitches out of five stimulations). Mr AA underwent a planned course of 20 treatments of rTMS over a four-week period of time. This had a substantial positive impact on his mood and social anxiety, with an almost complete resolution of his depressive symptoms. There was a reduction in his score on the Inventory of Depressive Symptomatology from 52 to 19, and on the Beck Anxiety Inventory from 16 to 3. He experienced no seizures during treatment or any abnormal motor or other neurological activity. Depression is a disorder that commonly occurs in patients with epilepsy with substantial negative consequences for quality of life [3]. Historically, there has been clinical reluctance to treat patients with depression and epilepsy with antidepressant medications due to somewhat unfounded concerns about potential pro-convulsive effects of these medications [4]. rTMS is a new and extremely helpful antidepressant treatment strategy which is also likely to be substantially restricted in use in patients with epilepsy. However, the risk of inducing seizures with rTMS in this patient group may be substantially lower than might otherwise be believed. No seizures were reported in a series of studies utilizing low frequency (1 Hz) rTMS for the treatment of patients with epilepsy (see review in Ref. [2]), with a review reporting a per patient risk of seizure induction of 1.4% with all types of rTMS utilized in studies until that time [5]. It appears quite likely that the risk of seizure induction is related to rTMS stimulation intensity with low-frequency stimulation, as we utilized in this case, far less likely to induce a seizure due to the reduction of cortical excitability generally produced with this type of stimulation [6]. However, low-frequency stimulation does not always produce a reduction in cortical excitability and it should not always be assumed that there is negligible risk associated with this type of approach. It is worthy of note that a number of studies have found no difference in efficacy between high frequency left and low frequency right sided rTMS (for example Refs. [7,8]). In summary, depression is a common clinical problem occurring in patients with epilepsy and may remain resistant to standard antidepressant approaches. rTMS should generally be avoided in patients with a history of epilepsy, but there may be exceptions where carefully administered rTMS can be a successful and life altering treatment. The administration of rTMS under these circumstances requires a careful balancing of risks and potential benefits and the provision of informed consent. Lowfrequency right prefrontal stimulation is a sensible first choice treatment approach.
2
Letter to the Editor / Brain Stimulation xxx (2014) 1e2
PBF is supported by an NHMRC Practitioner Fellowship (606907).PBF has received equipment for research from MagVenture A/S, Medtronic Ltd, Cervel Neurotech and Brainsway Ltd and funding for research from Cervel Neurotech.
Paul B. Fitzgerald* Monash Alfred Psychiatry Research Centre (MAPrc), The Alfred and Monash University Central Clinical School, Level 4, 607 St Kilda Road, Melbourne, Victoria 3004, Australia author. Tel.: þ61 3 9076 6552; fax: þ61 3 9076 6588. E-mail address: paul.fi[email protected]
* Corresponding
Received 21 February 2014 Available online xxx
http://dx.doi.org/10.1016/j.brs.2014.03.003
References [1] Fitzgerald PB, Daskalakis ZJ. The effects of repetitive transcranial magnetic stimulation in the treatment of depression. Expert Rev Med Devices 2011 Jan;8(1): 85e95. [2] Rossi S, Hallett M, Rossini PM, Pascual-Leone A. Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. Clin Neurophysiol 2009 Dec;120(12):2008e39. [3] Kanner AM. Epilepsy and mood disorders. Epilepsia 2007;48(Suppl. 9):20e2. [4] Kondziella D, Asztely F. Don’t be afraid to treat depression in patients with epilepsy! Acta Neurol Scand 2009 Feb;119(2):75e80. [5] Bae EH, Schrader LM, Machii K, et al. Safety and tolerability of repetitive transcranial magnetic stimulation in patients with epilepsy: a review of the literature. Epilepsy Behav 2007 Jun;10(4):521e8. [6] Fitzgerald PB, Fountain S, Daskalakis ZJ. A comprehensive review of the effects of rTMS on motor cortical excitability and inhibition. Clin Neurophysiol 2006 Dec;117(12):2584e96. [7] Isenberg K, Downs D, Pierce K, et al. Low frequency rTMS stimulation of the right frontal cortex is as effective as high frequency rTMS stimulation of the left frontal cortex for antidepressant-free, treatment-resistant depressed patients. Ann Clin Psychiatry 2005 Jul-Sep;17(3):153e9. [8] Fitzgerald PB, Brown T, Marston NAU, Daskalakis ZJ, Kulkarni J. A double-blind placebo controlled trial of transcranial magnetic stimulation in the treatment of depression. Arch Gen Psychiatry 2003;60:1002e8.
