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Long-term Results of Deep Brain Stimulation of the Subcallosal Cingulate for Medication-Resistant Bipolar I Depression and Rapid Cycling Bipolar II Depression
Author’s Accepted Manuscript Long Term Results of Deep Brain Stimulation of the Subcallosal Cingulate for Medication-Resistant Bipolar I Depression and Rapid Cycling Bipolar Ii DepressionDBS for type I and rapid cycling type II BD Cristina V. Torres, Elena Ezquiaga, Marta Navas, Maria Angeles García Pallero, Rafael G Sola
PII: DOI: Reference:
www.elsevier.com/locate/journal
S0006-3223(16)32476-3 http://dx.doi.org/10.1016/j.biopsych.2016.05.026 BPS12913
To appear in: Biological Psychiatry Revised date: 25 May 2016 Accepted date: 26 Cite this article as: Cristina V. Torres, Elena Ezquiaga, Marta Navas, Maria Angeles García Pallero and Rafael G Sola, Long Term Results of Deep Brain Stimulation of the Subcallosal Cingulate for Medication-Resistant Bipolar I Depression and Rapid Cycling Bipolar Ii DepressionDBS for type I and rapid cycling type II BD, Biological Psychiatry, http://dx.doi.org/10.1016/j.biopsych.2016.05.026 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
LONG TERM RESULTS OF DEEP BRAIN STIMULATION OF THE SUBCALLOSAL CINGULATE FOR MEDICATION-RESISTANT BIPOLAR I DEPRESSION AND RAPID CYCLING BIPOLAR II DEPRESSION.
Cristina V. Torres, MD, PhD, Division of Neurosurgery, Department of Surgery, University Hospital La Princesa, Madrid, Spain Elena Ezquiaga, MD, PhD, Department of Psychiatry, University Hospital La Princesa, Madrid Marta Navas, MD, Division of Neurosurgery, Department of Surgery, University Hospital La Princesa, Madrid, Spain Maria Angeles García Pallero, Division of Neurosurgery, Department of Surgery, University Hospital La Princesa, Madrid, Spain Rafael G Sola, M.D., Ph.D. Division of Neurosurgery, Department of Surgery, University Hospital La Princesa, Madrid, Spain CORRESPONDING AUTHOR INFORMATION PAGE Cristina V Torres Díaz, MD, PhD Division of Neurosurgery, University Hospital La Princesa, C/Diego de León 32, 28006, Madrid, Spain Tel: (0034) 915202200 / 17430 Fax: (0034) 914013582 Running title: DBS for type I and rapid cycling type II BD.
Key words: bipolar depression, deep brain stimulation, type I bipolar disorder, psychosurgery, rapid cycling.
Bipolar disorder, globally has a high prevalence of continuous subsyndromal symptoms or full episodes despite pharmacological treatment, and a high risk of disability, and suicide rates (1-3). A high recurrence of episodes and a rapid cycling course are among risks factors of potentially progressive and severe or even malignant outcome and a neuroprogression of deficits has been described (4, 5). In 2013, we reported a case of severe, recurrent, medication-resistant type I BD patient, who greatly benefited from DBS of the subgenual cingulum.(2) We present this patient’s long term outcome (46 months) and a new case of rapid-cycling bipolar II patient, who underwent DBS on the same area 25 months ago, and has remained euthymic since the commencement of the stimulation. The first case was a 78-year-old woman diagnosed with DSM-IV recurrent and severe type I bipolar depression, without other comorbid disorders. She was started on antidepressant medication in 1984, after recurrent depressive symptoms. She initially had a good response to antidepressants, but gradually developed episodes of mania for which lithium was introduced in 1995 with irregular compliance. Since that time, she had experienced multiple relapses of depression and manic episodes, requiring frequent admissions to the acute psychiatric unit. She tried several medications (constant lithium, valproate, and lamotrigine), antipsychotics and antidepressants, alone and in combinations, with a poor response. In 2009, she developed a severe depressive episode that persisted for two years, with mood-congruent psychotic symptoms (Cotard syndrome), despite good adherence to treatment for several years previously. She underwent a total of 42 sessions of electroconvulsive therapy (ECT), with limited
clinical response. Therefore, she underwent DBS of the subcallosal cingulated after our local ethics committee approval and signing the informed consent. At the moment of the surgery, her scores at Mini-Mental State Examination (MMSE) were 29/30. The surgical technique has been described elsewhere.(2) Stimulation was commenced 15 days after the operation, at 130 Hz, 91-μs, and 6 mA, and contacts were 3- C+ at right side and1C+ at left side, based on the postoperative MRI electrode sites. From the first month after the stimulation was started, the patient presented significant and progressive clinical response, restoring normal functionality. She began to show empathy for her family and caregivers, to autonomously perform self-care and home care tasks, and to initiate a broader social life, engaging in hobbies and pleasurable activities. These observations were supported by significant reduction in her psychometrical scores. No manic symptoms have been observed, as reflected in her scores on the Young Mania Scale (see figure). There were no complications related to the DBS. Her cognitive performance at the nine-months follow-up was unchanged (MMSE was 29/30). The parameters and medications were unchanged during her follow-up except for two occasions: At her 17 month follow up, she reported feeling sadder during her visit in clinics (no scales were performed during that visit), and her stimulation was raised to 7 mA, after which she reported having recovered. Two years after the operation, she experienced a relapse of her depression, coinciding with her right battery’s end of life. She underwent pulse generator replacement and gradually improved over the next month to her previous situation. The second case was a 59 year old man with medical history significant for alcohol dependence (abstinent for the past eleven years), diagnosed with a bipolar II syndrome 20 years ago. He had tried several medications, including, lithium, valproamide, lamotrigine, oxcarbacepine, olanzapine, quetiapine, serotonin-specific reuptake
inhibitors
(SSRI),
venlafaxine,
tranilcipromine,
trazodone,
agomelatine
and
benzodiazepines as lorazepam or ketazolam, with bad tolerance and no significant clinical response. He had needed several admissions to the psychiatric ward during his depression episodes, where he showed marked apathy, lack of initiative, and refused to get out of bed or eating food other than liquids. He performed a pharmacological suicide attempt in 2004, so electroconvulsive therapy was tried, with significant improvement, but quick relapse after the sessions. Lithium therapy was reinitiated in February 2011 with acceptable tolerance and a every month maintenance ECT was applied for 15 months, the last session in June 2011 with an improvement but persistence of subsyndromal affective symptoms. As soon as ECT was discontinued, the patient suffered continuous relapses in episodes of alternating polarity, including mixed symptomatology, without free-symptom periods, and DBS of the subgenual cingulated was proposed. Our Local Ethical Committee approved the treatment and signed consent was obtained. At the moment of the surgery, February 2014, the patient was going through a short hypomania phase. His scores at the YMS were 16 and his Minimental Scale scores were 30/30. The surgical technique was similar to the previous patient’s (see figure). Stimulation was initiated 7 days after surgery, at initial parameters of bilateral 1-C+ 6 mA, 130 Hz and 90 microseconds. He experienced a progressive improvement, when stimulation was set at 8 mA (one month after surgery). From that moment, the patient has remained euthymic. No cycles have been observed, and he has started collaborating in his family business and notably increasing his social life (Scores shown in Fig 2) At his 17 month follow-up, he suffered from pneumonia and also reported a worsening of his mood, lasting for the last three months. Both pulse generators showed low charge,
so he was admitted for a bilateral replacement. Eight mA were immediately programmed and raised to one week later. Fifteen days later, the patient reported feeling euthymic, as he has been to his last follow-up, 25 months after the DBS implantation. His MMSE remains unchanged. No changes have been made in his medication except for lorazepam, which was retired. To our knowledge, there are no previous reported experiences with DBS for type I and rapid cycling type II bipolar depression patients. We believe that our results could even reveal new prospects for treatment in the case of severe and otherwise refractory BD patients, and highlight the need for larger studies that determine whether DBS of the subcallosal cingulate is an effective and safe mood-regulation treatment for refractory BD patients.
REFERENCES 1. Kessler RC, Petukhova M, Sampson NA, Zaslavsky AM, Wittchen HU. Twelvemonth and lifetime prevalence and lifetime morbid risk of anxiety and mood disorders in the United States. Int J Methods Psychiatr Res. 2. Deep brain stimulation of the subcallosal cingulate for medication-resistant type I bipolar depression: case report. Torres CV, Ezquiaga E, Navas M, de Sola RG. Bipolar Disord. 2013 Sep;15(6):719-21. 3. Lipsman N, McIntyre RS, Giacobbe P, Torres C, Kennedy SH, Lozano AM. Neurosurgical treatment of bipolar depression: defining treatment resistance and identifying surgical targets. Bipolar Disord 2010;12(7):691-701. 4. Connolly KR, Thase ME. The clinical management of bipolar disorder: a review of evidence-based guidelines. Prim Care Companion CNS Disord 2011;13(4).
5. Ryan KA, Vederman AC, McFadden EM, Weldon AL, Kamali M, Langenecker SA, et al. Differential executive functioning performance by phase of bipolar disorder. Bipolar Disord 2012;14(5):527-36. 6. Hamani C, Mayberg H, Snyder B, Giacobbe P, Kennedy S, Lozano AM. Deep brain stimulation of the subcallosal cingulate gyrus for depression: anatomical location of active contacts in clinical responders and a suggested guideline for targeting. J Neurosurg 2009;111(6):1209-15. FINANCIAL DISCLOSURE All authors report no biomedical financial interests or potential conflicts of interest. FIGURE LEGENDS Figure: Graphs demonstrating the results of psychiatric assessment of depression, mania and functioning through the Hamilton Depression Rating Scale (HDRS), Beck Depression Inventory (BDI), Young Mania Scale (YMS) and Global Assessment of Functioning (GAF) for our first type I (top left), and for our second rapid-cycling type II bipolar patient (down left) treated with deep brain stimulation of the subcallosal cingulate. Scores are plotted against each visit: baseline; after 1.5, 3, 6, 9, 18, 42 months and after 1.5, 3, 6, 9, 18 and 25 months of DBS respectively. T1 1,5 Tesla axial (top right) and sagital (down right) magnetic resonance images (MRI) showing the correct location of the electrodes in the subgenual cingulate in our rapid-cycling type II bipolar patient.
PII: DOI: Reference:
www.elsevier.com/locate/journal
S0006-3223(16)32476-3 http://dx.doi.org/10.1016/j.biopsych.2016.05.026 BPS12913
To appear in: Biological Psychiatry Revised date: 25 May 2016 Accepted date: 26 Cite this article as: Cristina V. Torres, Elena Ezquiaga, Marta Navas, Maria Angeles García Pallero and Rafael G Sola, Long Term Results of Deep Brain Stimulation of the Subcallosal Cingulate for Medication-Resistant Bipolar I Depression and Rapid Cycling Bipolar Ii DepressionDBS for type I and rapid cycling type II BD, Biological Psychiatry, http://dx.doi.org/10.1016/j.biopsych.2016.05.026 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
LONG TERM RESULTS OF DEEP BRAIN STIMULATION OF THE SUBCALLOSAL CINGULATE FOR MEDICATION-RESISTANT BIPOLAR I DEPRESSION AND RAPID CYCLING BIPOLAR II DEPRESSION.
Cristina V. Torres, MD, PhD, Division of Neurosurgery, Department of Surgery, University Hospital La Princesa, Madrid, Spain Elena Ezquiaga, MD, PhD, Department of Psychiatry, University Hospital La Princesa, Madrid Marta Navas, MD, Division of Neurosurgery, Department of Surgery, University Hospital La Princesa, Madrid, Spain Maria Angeles García Pallero, Division of Neurosurgery, Department of Surgery, University Hospital La Princesa, Madrid, Spain Rafael G Sola, M.D., Ph.D. Division of Neurosurgery, Department of Surgery, University Hospital La Princesa, Madrid, Spain CORRESPONDING AUTHOR INFORMATION PAGE Cristina V Torres Díaz, MD, PhD Division of Neurosurgery, University Hospital La Princesa, C/Diego de León 32, 28006, Madrid, Spain Tel: (0034) 915202200 / 17430 Fax: (0034) 914013582 Running title: DBS for type I and rapid cycling type II BD.
Key words: bipolar depression, deep brain stimulation, type I bipolar disorder, psychosurgery, rapid cycling.
Bipolar disorder, globally has a high prevalence of continuous subsyndromal symptoms or full episodes despite pharmacological treatment, and a high risk of disability, and suicide rates (1-3). A high recurrence of episodes and a rapid cycling course are among risks factors of potentially progressive and severe or even malignant outcome and a neuroprogression of deficits has been described (4, 5). In 2013, we reported a case of severe, recurrent, medication-resistant type I BD patient, who greatly benefited from DBS of the subgenual cingulum.(2) We present this patient’s long term outcome (46 months) and a new case of rapid-cycling bipolar II patient, who underwent DBS on the same area 25 months ago, and has remained euthymic since the commencement of the stimulation. The first case was a 78-year-old woman diagnosed with DSM-IV recurrent and severe type I bipolar depression, without other comorbid disorders. She was started on antidepressant medication in 1984, after recurrent depressive symptoms. She initially had a good response to antidepressants, but gradually developed episodes of mania for which lithium was introduced in 1995 with irregular compliance. Since that time, she had experienced multiple relapses of depression and manic episodes, requiring frequent admissions to the acute psychiatric unit. She tried several medications (constant lithium, valproate, and lamotrigine), antipsychotics and antidepressants, alone and in combinations, with a poor response. In 2009, she developed a severe depressive episode that persisted for two years, with mood-congruent psychotic symptoms (Cotard syndrome), despite good adherence to treatment for several years previously. She underwent a total of 42 sessions of electroconvulsive therapy (ECT), with limited
clinical response. Therefore, she underwent DBS of the subcallosal cingulated after our local ethics committee approval and signing the informed consent. At the moment of the surgery, her scores at Mini-Mental State Examination (MMSE) were 29/30. The surgical technique has been described elsewhere.(2) Stimulation was commenced 15 days after the operation, at 130 Hz, 91-μs, and 6 mA, and contacts were 3- C+ at right side and1C+ at left side, based on the postoperative MRI electrode sites. From the first month after the stimulation was started, the patient presented significant and progressive clinical response, restoring normal functionality. She began to show empathy for her family and caregivers, to autonomously perform self-care and home care tasks, and to initiate a broader social life, engaging in hobbies and pleasurable activities. These observations were supported by significant reduction in her psychometrical scores. No manic symptoms have been observed, as reflected in her scores on the Young Mania Scale (see figure). There were no complications related to the DBS. Her cognitive performance at the nine-months follow-up was unchanged (MMSE was 29/30). The parameters and medications were unchanged during her follow-up except for two occasions: At her 17 month follow up, she reported feeling sadder during her visit in clinics (no scales were performed during that visit), and her stimulation was raised to 7 mA, after which she reported having recovered. Two years after the operation, she experienced a relapse of her depression, coinciding with her right battery’s end of life. She underwent pulse generator replacement and gradually improved over the next month to her previous situation. The second case was a 59 year old man with medical history significant for alcohol dependence (abstinent for the past eleven years), diagnosed with a bipolar II syndrome 20 years ago. He had tried several medications, including, lithium, valproamide, lamotrigine, oxcarbacepine, olanzapine, quetiapine, serotonin-specific reuptake
inhibitors
(SSRI),
venlafaxine,
tranilcipromine,
trazodone,
agomelatine
and
benzodiazepines as lorazepam or ketazolam, with bad tolerance and no significant clinical response. He had needed several admissions to the psychiatric ward during his depression episodes, where he showed marked apathy, lack of initiative, and refused to get out of bed or eating food other than liquids. He performed a pharmacological suicide attempt in 2004, so electroconvulsive therapy was tried, with significant improvement, but quick relapse after the sessions. Lithium therapy was reinitiated in February 2011 with acceptable tolerance and a every month maintenance ECT was applied for 15 months, the last session in June 2011 with an improvement but persistence of subsyndromal affective symptoms. As soon as ECT was discontinued, the patient suffered continuous relapses in episodes of alternating polarity, including mixed symptomatology, without free-symptom periods, and DBS of the subgenual cingulated was proposed. Our Local Ethical Committee approved the treatment and signed consent was obtained. At the moment of the surgery, February 2014, the patient was going through a short hypomania phase. His scores at the YMS were 16 and his Minimental Scale scores were 30/30. The surgical technique was similar to the previous patient’s (see figure). Stimulation was initiated 7 days after surgery, at initial parameters of bilateral 1-C+ 6 mA, 130 Hz and 90 microseconds. He experienced a progressive improvement, when stimulation was set at 8 mA (one month after surgery). From that moment, the patient has remained euthymic. No cycles have been observed, and he has started collaborating in his family business and notably increasing his social life (Scores shown in Fig 2) At his 17 month follow-up, he suffered from pneumonia and also reported a worsening of his mood, lasting for the last three months. Both pulse generators showed low charge,
so he was admitted for a bilateral replacement. Eight mA were immediately programmed and raised to one week later. Fifteen days later, the patient reported feeling euthymic, as he has been to his last follow-up, 25 months after the DBS implantation. His MMSE remains unchanged. No changes have been made in his medication except for lorazepam, which was retired. To our knowledge, there are no previous reported experiences with DBS for type I and rapid cycling type II bipolar depression patients. We believe that our results could even reveal new prospects for treatment in the case of severe and otherwise refractory BD patients, and highlight the need for larger studies that determine whether DBS of the subcallosal cingulate is an effective and safe mood-regulation treatment for refractory BD patients.
REFERENCES 1. Kessler RC, Petukhova M, Sampson NA, Zaslavsky AM, Wittchen HU. Twelvemonth and lifetime prevalence and lifetime morbid risk of anxiety and mood disorders in the United States. Int J Methods Psychiatr Res. 2. Deep brain stimulation of the subcallosal cingulate for medication-resistant type I bipolar depression: case report. Torres CV, Ezquiaga E, Navas M, de Sola RG. Bipolar Disord. 2013 Sep;15(6):719-21. 3. Lipsman N, McIntyre RS, Giacobbe P, Torres C, Kennedy SH, Lozano AM. Neurosurgical treatment of bipolar depression: defining treatment resistance and identifying surgical targets. Bipolar Disord 2010;12(7):691-701. 4. Connolly KR, Thase ME. The clinical management of bipolar disorder: a review of evidence-based guidelines. Prim Care Companion CNS Disord 2011;13(4).
5. Ryan KA, Vederman AC, McFadden EM, Weldon AL, Kamali M, Langenecker SA, et al. Differential executive functioning performance by phase of bipolar disorder. Bipolar Disord 2012;14(5):527-36. 6. Hamani C, Mayberg H, Snyder B, Giacobbe P, Kennedy S, Lozano AM. Deep brain stimulation of the subcallosal cingulate gyrus for depression: anatomical location of active contacts in clinical responders and a suggested guideline for targeting. J Neurosurg 2009;111(6):1209-15. FINANCIAL DISCLOSURE All authors report no biomedical financial interests or potential conflicts of interest. FIGURE LEGENDS Figure: Graphs demonstrating the results of psychiatric assessment of depression, mania and functioning through the Hamilton Depression Rating Scale (HDRS), Beck Depression Inventory (BDI), Young Mania Scale (YMS) and Global Assessment of Functioning (GAF) for our first type I (top left), and for our second rapid-cycling type II bipolar patient (down left) treated with deep brain stimulation of the subcallosal cingulate. Scores are plotted against each visit: baseline; after 1.5, 3, 6, 9, 18, 42 months and after 1.5, 3, 6, 9, 18 and 25 months of DBS respectively. T1 1,5 Tesla axial (top right) and sagital (down right) magnetic resonance images (MRI) showing the correct location of the electrodes in the subgenual cingulate in our rapid-cycling type II bipolar patient.