Research paperIs deep brain stimulation effective and safe for patients with obsessive compulsive disorder and comorbid bipolar disorder?
Introduction
Obsessive compulsive disorder (OCD) is a psychiatric disorder characterized by obsessive thoughts and compulsive behaviors. Conventional treatment options for OCD are antidepressants and cognitive behavioral therapy (CBT), but an estimated 10% of patients are refractory to these treatment options (Denys, 2006). In addition, patients with OCD often have comorbid psychiatric illnesses (Brady, 2014). The prevalence of bipolar disorder (BD) in patients with OCD is estimated to be 18.4% (Amerio et al., 2015). Alternative treatments, other than CBT and medication, to manage treatment refractory OCD patients with comorbid BD are an unmet need. Although electroconvulsive therapy is effective for the treatment of BD (Perugi et al., 2017), the evidence for ECT as an effective treatment for OCD is limited (Fontenelle et al., 2015). Transcranial magnetic stimulation (TMS) is another form of treatment that has recently been proposed for OCD. However, the follow-up length of studies examining the effects of OCD are not longer than 3 months, even though the positive effects of TMS for OCD are known to be transient (Lusicic et al., 2018). For BD, TMS does not seem to be effective (Kozel, 2018).
Deep brain stimulation (DBS) involves implantation of electrodes and modulation of specific brain function. Following the first trials on DBS for OCD (Gabriels et al., 2003), several studies showed that DBS targeted at striatal areas is an effective and safe treatment option for patients with refractory OCD (Alonso et al., 2015; Denys et al., 2010). Still, most experience with DBS for OCD derives from clinical studies, excluding patients with serious comorbid symptoms (Denys et al., 2010; Mallet et al., 2008). The majority of studies excluded patients with comorbid bipolar disorder, because of the assumed risk of stimulation-induced (hypo)mania (Kohl et al., 2014; Loo et al., 2011). However, three studies examined effectiveness and safety of DBS for treatment resistant depression (TRD) and included a total of 9 patients with BD II, targeting the subcallosal cingulate (Holtzheimer, 2012), ventral capsule/ventral striatum (Malone et al., 2009) and supero-lateral branch of the medial forebrain bundle (Schlaepfer et al., 2013). DBS effectively suppressed symptoms of depression in patients with BD, while DBS caused hypomanic symptoms in only one case. Hypomanic symptoms in this patient resolved completely when stimulation was discontinued (Malone et al., 2009). In conclusion, these studies support the idea that DBS is safe for patients with BD II, but experience is still limited.
A limitation of the aforementioned studies, is that patients with BD I were excluded for treatment with DBS (Holtzheimer, 2012b; Malone et al., 2009; Schlaepfer et al., 2013). Patients with BD II have only hypomanic episodes, whereas patients with BD I have a history of at least one manic episode. To our concern, only one case-report published the results of a patients with BD I that was successfully treated with DBS of the Cg 24/25 for depressive symptoms (Torres et al., 2017). No (hypo)manic episodes occurred following DBS in this case. Nevertheless, there is still very limited evidence for the safety of DBS in patients with a (co-morbid) BD I.
Here, we present the results of 5 patients with OCD and comorbid BD I or II that received DBS of the ventral anterior limb of the internal capsule (vALIC). We examined impact of vALIC DBS on OCD and depressive symptoms, and we investigated whether DBS is safe for patients with co-morbid BD I or II, explicitly monitoring (hypo)manic symptoms.
Section snippets
Patients and procedure
Between 2005 and 2018, 5 patients suffering from treatment-refractory OCD and co-morbid BD underwent treatment with DBS targeted at the vALIC at the Amsterdam Universitair Medisch Centrum (AMC). Patients received regular treatment with DBS for clinical purposes and all consecutive patients with comorbid BD were included in the present case-series. Patients with treatment refractory and severe OCD (a minimal Yale-Brown Obsessive Compulsive Symptoms (Y-BOCS) score of 28) were included for
Results
Five patients with a comorbid diagnosis of BD type I or II were identified, and all were included in the current study. All 5 patients were female and average age was 57 (SD 9.5) years (Table 1). Three patients had a comorbid BD I and 2 patients BD II. Two patients had attempted suicide in the past. Other comorbidities included personality disorders and somatoform disorder. Patient 1, 2 and 4 were admitted at our psychiatric ward for monitoring of hypomanic symptoms during the first days or
Discussion
In this case-series, we examined safety and effectiveness of DBS for treatment-refractory OCD in patients with comorbid BD I/II. The current study is the first describing effectiveness and safety of DBS of the vALIC in patients with both OCD and comorbid BD. Our study had three important findings: 1) DBS effectively treated symptoms of OCD in 4 out of 5 patients, of which 3 patients were DBS responders; 2) DBS significantly reduced depressive symptoms to a clinically meaningful extent; 3) There
Authorship statement
All persons who meet authorship criteria are listed as authors, and all authors certify that they have participated sufficiently in the work to take public responsibility for the content, including participation in the concept, design, analysis, writing, or revision of the manuscript. Furthermore, each author certifies that this material or similar material has not been and will not be submitted to or published in any other publication before its appearance in the Journal of Affective Disorders.
Authorship contributions
Please indicate the specific contributions made by each author (list the authors’ initials followed by their surnames, e.g., Y.L. Cheung). The name of each author must appear at least once in each of the three categories below.
Declaration of Competing Interest
P.R. Schuurman acts as advisor for Medtronic and Boston. The other authors have no conflicts of interest to report. All authors have approved the final article.
Acknowledgements
All persons who have made substantial contributions to the work reported in the manuscript (e.g., technical help, writing and editing assistance, general support), but who do not meet the criteria for authorship, are named in the Acknowledgements and have given us their written permission to be named. If we have not included an Acknowledgements, then that indicates that we have not received substantial contributions from non-authors.
References (39)
- et al.
The prevalence and predictors of comorbid bipolar disorder and obsessive-compulsive disorder: a systematic review and meta-analysis
J. Affect. Disord.
(2015) Pharmacotherapy of obsessive-compulsive disorder and obsessive-compulsive spectrum disorders
Psychiatr. Clin. North Am.
(2006)Clinical repetitive transcranial magnetic stimulation for posttraumatic stress disorder, generalized anxiety disorder, and bipolar disorder
Psychiatr. Clin. North Am.
(2018)- et al.
Physical treatments for bipolar disorder: a review of electroconvulsive therapy, stereotactic surgery and other brain stimulation techniques
J. Affect. Disord.
(2011) - et al.
Subcallosal cingulate gyrus deep brain stimulation for treatment-resistant depression
Biol. Psychiatry
(2008) - et al.
Deep brain stimulation of the ventral capsule/ventral striatum for treatment-resistant depression
Biol. Psychiatry
(2009) - et al.
Rapid effects of deep brain stimulation for treatment-resistant major depression
Biol. Psychiatry
(2013) - et al.
Long-term results of deep brain stimulation of the subcallosal cingulate for medication-resistant bipolar I depression and rapid cycling bipolar ii depression
Biol. Psychiatry
(2017) - et al.
Deep brain stimulation for obsessive-compulsive disorder: a meta-analysis of treatment outcome and predictors of response
PLoS ONE
(2015) - et al.
An application of longitudinal analysis with skewed outcomes
Nurs. Res.
(2010)
Suicidal risk factors in major affective disorders
Br. J. Psychiatry
Deep brain stimulation of the ventral anterior limb of the internal capsule for treatment-resistant depression: a randomized clinical trial
JAMA Psychiatry
Obsessive-compulsive disorder and common comorbidities
J. Clin. Psychiatry
Analysis of single-case experimental count data using the linear mixed effects model: a simulation study
Behav. Res. Methods
Deep brain stimulation of the ventral ALIC is effective for refractory obsessive- compulsive disorder: a clinical cohort of 70 cases
Am. J. Psychiatry E-pub ahea
Deep brain stimulation of the nucleus accumbens for treatment-refractory obsessive-compulsive disorder
Arch. Gen. Psychiatry
Is sex important? Gender differences in bipolar disorder
Int. Rev. Psychiatry
Six-nine year follow-up of deep brain stimulation for obsessive-compulsive disorder
PLoS ONE
Electroconvulsive therapy for obsessive-compulsive disorder: a systematic review
J. Clin. Psychiatry
Cited by (6)
Anxiety in bipolar disorder: A review of publication trends
2023, Journal of Affective DisordersCitation Excerpt :Three of them are targeting anxious symptoms in general: one with deep breathing (Serafim et al., 2019), one with acupuncture (Matsuura et al., 2020), and one with deep touch pressure (Sylvia et al., 2014). The rest of the articles are about other types of medical treatments for comorbid obsessive-compulsive disorder, like deep brain stimulation (Graat et al., 2020), electroconvulsive therapy (Bulbul et al., 2013; Fontenelle et al., 2019) and advanced non-invasive brain stimulation techniques (Parlikar et al., 2019). While showing interesting results, the literature on those types of treatments is still emerging and almost all of the articles are based on case studies.
Ethical Considerations in the Implantation of Neuromodulatory Devices
2022, NeuromodulationCitation Excerpt :Conversely, FDA approval and proper medical practice are not interchangeable. Federal approval for a treatment does not indicate that the treatment is appropriate for an individual patient based on characteristics of their condition and associated comorbidities,56 Nonetheless, validated outcomes are necessary to determine the true benefits of DBS for psychiatric indications. Outcome scale and thresholds used for trials of pharmaceutical treatments should be examined in terms of their applicability to trials of NDs due to different patient populations, reference levels, and goals of treatment.
Optimizing Deep Brain Stimulation Parameters in Obsessive–Compulsive Disorder
2021, NeuromodulationCitation Excerpt :Although this cluster of symptoms is often referred to as “(hypo)mania,” we would propose to reserve this term for only those cases that meet DSM 5 criteria with regard to number of symptoms, severity and duration. Whether cases of DBS-induced increased impulsivity, euphoria, agitation and sleeping problems are associated with a pre-existing yet unrecognized comorbid bipolar spectrum disorder is not clear, although a case series in five patients with comorbid bipolar disorder found no significant changes in scores on the Young Mania Rating Scale (53). Nevertheless, we preventively admit patients with comorbid bipolar disorder during the optimization phase and start stimulation at 2.5 instead of 3.0 V.
Deep Brain Stimulation for Treatment-Resistant Mental Illness
2022, Psychiatric AnnalsDeep brain stimulation for ocd in a patient with comorbidities: Epilepsy, tics, autism, and major depressive disorder
2021, Journal of Neuropsychiatry and Clinical Neurosciences