OR WAIT null SECS
© 2022 MJH Life Sciences™ and Psychiatric Times. All rights reserved.
OCD is highly comorbid and warrants consideration in difficult to treat cases. Learn more here.
SPECIAL REPORT: TREATMENT RESISTANCE
Obsessive-compulsive disorder (OCD) is characterized by repetitive thoughts, urges, and images (obsessions) and/or repetitive behaviors or mental acts aimed at reducing anxiety or distress (compulsions). OCD is thought to have a lifetime prevalence of between 1% to 3% and is a significant cause of disability worldwide.1 OCD is highly comorbid with other psychiatric disorders, which warrants consideration particularly in difficult to treat cases. First-line treatment options for OCD may include psychotherapeutic or pharmacological strategies. Specifically, selective serotonin reuptake inhibitors (SSRIs) and cognitive behavioral therapy (CBT), particularly exposure response therapy (ERP), have been shown to be effective in the treatment of OCD.2 However, many patients do not achieve a full response, often defined as a more than 35% reduction on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), with these treatment options.3,4
It is important to take consideration of clinical features, access, and tolerability when choosing between these options. Monotherapy with CBT with ERP may be recommended in patients with mild or moderate OCD. While monotherapy with an SSRI is often recommended in patients with more severe OCD, or in history of treatment response to SSRIs or comorbid depression.
The Current State of the Art and the Not Too Distant Future
Sheldon H. Preskorn, MD
Reducing Heterogeneity in Treatment-Resistant and Non–Treatment-Resistant Schizophrenia
Frederick Charles Nucifora Jr, PhD, DO, MHS
Pharmacological Management of Treatment-Resistant Anorexia Nervosa
Mary Ellen Trunko, MD; Guido K.W. Frank, MD; Terry A. Schwartz, MD; and Walter H. Kaye, MD
Case Vignette
“Melissa” is a 40-year-old female in an outpatient clinic with a history of OCD. When she first presented to clinic, she was prescribed sertraline, to which the OCD did not respond. She was switched to fluvoxamine, which was titrated to the maximum tolerated dose of 300 mg a day with partial response. She was also encouraged to begin CBT with ERP and has been consistent with treatment.
Melissa continues to endorse OCD symptoms, recounting how she spends several hours “checking the locks on my doors,” which frequently makes her late to work and appointments. She did not tolerate clomipramine or augmenting trials of risperidone or aripiprazole and is reluctant to trial any additional medications or surgery. Transcranial magnetic stimulation (TMS), which was recently approved by the Food and Drug Administration (FDA) as an adjunct to OCD, may be considered in Melissa’s case.
Initial Strategies
An inadequate treatment response with monotherapy of SSRIs or CBT may warrant combining these modalities if available and tolerable.5 An important note about SSRI trials, is that prolonged trials (8 to 12 weeks) may be needed for optimal efficacy. A meta-analysis of dose-response also suggested that higher doses are associated with greater efficacy compared to low or moderate doses although this can also be associated with greater adverse side effects.6 Clinical guidelines suggest that certain cases may warrant consideration of greater than FDA max doses of medications. Interestingly, data suggest that a lower demethylation rate of clomipramine may be associated with greater clinical outcomes, which may warrant consideration and potential augmenting with an enzyme inhibitor if a patient fails to respond to clomipramine.7
With a partial treatment response, augmenting with an antipsychotic is a common and evidence supported strategy, although only about a third of patients will respond.8 The atypical antipsychotics risperidone and aripiprazole have shown the greatest efficacy, and low doses (up to 3 mg a day of risperidone and up to 15 mg a day of aripiprazole) are typically recommended.9,10 Olanzapine and quetiapine have also been used as augmenting agents, although evidence is limited and mixed.11,12 Haloperidol also has limited supportive evidence in OCD, although it is associated with poor tolerability.13,14
Our understanding of the biological underpinnings of OCD continues to evolve, and molecular changes in glutamatergic signaling, immunological factors, as well as circuit-level dysfunction in the cortico-striato-thalamic-cortical (CSTC) tracts have been implicated in OCD. As a result, several novel options for treatment-resistant OCD are under investigation.
Glutamate
Glutamatergic dysfunction has been gaining evidence as playing a role in OCD, and numerous agents that modulate glutamatergic signaling are under investigation.15-18 One such agent is N-acetylcysteine (NAC), which effects the cystine-glutamate antiporter and can modulate glutamatergic neurotransmission. A recent systematic review and meta-analysis of 5 randomized controlled trials (RCTs) suggested that NAC administered in doses of 600 to 3000 mg a day is safe, although there are still questions regarding efficacy.19 Riluzole, which inhibits synaptic glutamate release and promotes uptake of glutamate by astrocytes has been investigated, with supportive results in early open-label studies and mixed results in subsequent controlled studies.20-22 Troriluzole, a precursor of riluzole, is now under investigation in treatment-resistant OCD. Augmenting with memantine (an N-methyl-D-aspartate receptor (NMDA-R) antagonist) has shown a benefit in open-label studies as well as subsequent RCTs.23-27 Another NMDA-R antagonist—ketamine—that has shown promise in the setting of treatment-resistant depression, has also been studied in OCD, with mixed results.28-30 There is little research on intranasal esketamine in OCD, and studies are mixed.31,32 Interestingly, there is some suggestion that CBT may enhance the effects of IV ketamine/intranasal esketamine.33,34 Lamotrigine and topiramate, both compounds capable of modulating glutamatergic signaling, have also been trialed as augmentation agents in OCD, although evidence is mixed.35
Co-agonists of the NMDA receptor and related compounds have also been investigated. Glycine, an NMDA-R co-agonist, was shown to have a modest effect on OCD symptoms, although this did not reach statistical significance and glycine was poorly tolerated.36 Compounds related to glycine have also been investigated. Rapastinel, a partial agonist at the glycine site of the NMDA-R, showed an acute positive effect on OCD symptoms in an open label trial, although these dissipated 1 week postinfusion.37 Sarcosine, a glycine transporter antagonist, showed a benefit in some OCD patients in an open-label study.38 D-cycloserine, a partial agonist at the glycine site of the NMDA-R, has mixed data, but may play an augmenting role in ERP therapy for OCD.39
Inflammation
Aberrant functioning of the immune system is thought to play a role in OCD. Specifically, autoimmune disorders have been associated with OCD in children and adults, and inflammatory markers have been found to be elevated in the brains of individuals with OCD compared to healthy controls.40,41 Given these observations, anti-inflammatory and immune modulating agents have been investigated as a possible treatment option in OCD with limited, but promising results. Celecoxib, a nonsteroidal anti-inflammatory drug, with a mechanism of cyclooxygenase-2 enzyme inhibition, has been trialed as an SSRI augmenting agent in 2 trials and demonstrated superiority to placebo.42,43 Minocycline, an antibiotic with anti-inflammatory and anti-glutamatergic properties, was shown to have a positive treatment effect when combined with fluvoxamine in a double-blind place-controlled study.44 Rituximab, an intravenously administered monoclonal antibody, is being tested in a study of treatment-resistant patients.
Interestingly, gut microbiota, which regulate and are involved in maintaining immune homeostasis, have also been found to be altered in adult OCD patients.45,46 This has led to investigation of probiotics, which may help normalize the gut microbiota as a possible treatment modality. Animal studies have shown that probiotics may confer a benefit in obsessive-compulsive-like behavior, while clinical trials in humans are still ongoing.47
Noninvasive Neurostimulation
In recent years, there has been a focus on circuit-level brain changes in psychiatric disorders, and therapeutic modulation of these brain circuits. OCD has been associated with dysregulation in the CSTC loop, and noninvasive methods of stimulation, which can potentially alter these circuits, have been investigated as treatment options.48 Repetitive transcranial magnetic stimulation (rTMS), which uses magnetic pulses to modulate neurocircuitry, has been investigated in OCD. A recent meta-analysis reported that active TMS of the dorsolateral prefrontal cortex as well as the supplementary motor area (SMA) was more effective than sham stimulation for OCD.49
A specific method of TMS developed by BrainsWay known as deep TMS, which uses an H-shaped coil capable of stimulating deeper brain structures than traditional rTMS, has also been studied targeting the anterior cingulate cortex and medial prefrontal cortex, and found to be superior to sham stimulation.50 This modality was the first TMS device to be FDA approved as an adjunct for the treatment of OCD. Since then, MagVenture has also demonstrated safety and efficacy of its coil in treating OCD when directed toward the bilateral dorsomedial prefrontal cortex, and has received FDA approval for its device as an adjunctive treatment for OCD.
New developments in TMS technology including theta burst stimulation (TBS), which may shorten the treatment time required for TMS, have also been trialed in OCD, although a randomized trial of continuous TBS for 2 weeks did not observe a significant improvement in symptoms with active stimulation versus sham.51 Another method of neurostimulation being investigated is transcranial direct current stimulation (tDCS), which involves placement of 2 electrodes on the scalp with application of weak electric current. tDCS in OCD has typically focused on targeting the SMA and orbitofrontal cortex, although results are mixed.52,53 Electroconvulsive therapy (ECT), which induces a generalized seizure and has remarkable efficacy in depression, has had some response in a limited number of case studies of OCD, although there are no RCTs that support this finding.54 Magnetic seizure therapy, which uses magnetic pulses to induce generalized seizures and is thought to be associated with less cognitive impairment than ECT, has also been investigated in an open-label pilot study of subjects with treatment-resistant OCD, although it was not found to be effective.55
Invasive Procedures
For highly refractory patients, ablative neurosurgery and deep brain stimulation (DBS) can be considered, often in addition to ongoing pharmacological treatment and CBT. Common ablative procedures and sites include anterior capsulotomy (anterior limb of internal capsule) and anterior cingulotomy (anterior cingulate gyrus and cingulum bundle).56 A systematic review of 10 studies reported a mean reduction in Y-BOCS of 57% for anterior capsulotomy and 37% for anterior cingulotomy, with adverse effects of 21.4% for capsulotomy and 5.2% for cingulotomy.57 DBS, which is a reversible alternative to ablative surgery, involves placement of implanted electrodes in the brain to directly stimulate target areas. DBS has been used in the setting of Parkinson’s disease, dystonia, and epilepsy, and received FDA approval for humanitarian use for refractory OCD in 2009.
In DBS trials for OCD, electrodes have often been implanted in the ventral capsule/ventral striatum, although other targets have included the subthalamic nucleus (STN) as well as the inferior thalamic peduncle.58 A recent systematic review of DBS for OCD reported approximately 60.6% of patients with a response of less than 35% reduction in Y-BOCS, at short-term (1.5 year) follow-up.59 Interestingly, the proportion of responders increased on longer-term (>5 year) follow-up to 70.7%. Adverse events are typically transient, although hemorrhage and infection are a small risk. While there have been no direct comparison trials of DBS versus ablative neurosurgery, a retrospective review of 20 studies found that patients undergoing capsulotomy had a greater reduction in Y-BOCS (51%) versus DBS of the VC/VS (40%) and were 9% more likely to go into remission (Y-BOCS <8).60 The review also noted similar complication rates between procedures. There is yet insufficient evidence to determine which procedure (DBS versus ablative neurosurgery) to use on an individual basis.61 Beyond these procedures, novel developments such as focused ultrasound are under investigation and may provide safer surgical options in the future.
Novel Mechanisms
Beyond the aforementioned treatment options, novel medications with unique mechanisms of action are currently under investigation for OCD, including psilocybin, nabilone, nitrous oxide, tolcapone, ondansetron, and pregabalin.35 Alternative treatments such as meditation, exercise, and acupuncture are also being investigated.48 Further data on these novel treatment options are needed.
Concluding Thoughts
While definitions of treatment-resistance vary, lack of response to SSRIs and CBT warrant next steps. With nonresponse, a switch to another serotonergic agent may be indicated. With a partial response, there is strong evidence to support the use of atypical antipsychotics as augmenting agents in OCD. Beyond this, the understanding of the pathophysiology and novel treatment options for OCD are in development.
Numerous glutamatergic agents are under investigation, data here is mixed warranting of further investigation. Medications that modulate the immune system and inflammatory response are also being studied and show promising preliminary results. Neurostimulation modalities are also being developed, initial research is supportive of TMS, and recent FDA approval of TMS as an adjunct for OCD will likely lead to an increase of use in clinical practice. Invasive surgical options including DBS and ablative procedures remain an option for treatment refractory cases who have failed numerous treatment options. Finally, medications with novel mechanisms of action and complementary treatment modalities are under investigation in OCD.
Dr Artin is a psychiatrist affiliated with the Department of Psychiatry at the University of California San Diego. Dr Sloan is a psychiatrist affiliated with the Department of Psychiatry at the University of California San Diego. Dr Daskalakis is a professor and chair of the Department of Psychiatry at the University of California San Diego.
References
1. Hirschtritt ME, Bloch MH, Mathews CA. Obsessive-compulsive disorder: advances in diagnosis and treatment. JAMA. 2017;317(13):1358-1367.
2. Koran LM, Hanna GL, Hollander E, et al; American Psychiatric Association. Practice guideline for the treatment of patients with obsessive-compulsive disorder. Am J Psychiatry. 2007;164(7 Suppl):5-53.
3. Albert U, Marazziti D, Di Salvo G, et al. A systematic review of evidence-based treatment strategies for obsessive-compulsive disorder resistant to first-line pharmacotherapy. Curr Med Chem. 2018;25(41):5647-5661.
4. Bloch MH, Green C, Kichuk SA, et al. Long-term outcome in adults with obsessive-compulsive disorder. Depress Anxiety. 2013;30(8):716-722.
5. Tundo A, Salvati L, Busto G, et al. Addition of cognitive-behavioral therapy for nonresponders to medication for obsessive-compulsive disorder: a naturalistic study. J Clin Psychiatry. 2007;68(10):1552-1556.
6. Bloch MH, McGuire J, Landeros-Weisenberger A, et al. Meta-analysis of the dose-response relationship of SSRI in obsessive-compulsive disorder. Mol Psychiatry. 2010;15(8):850-855.
7. Marcourakis R, Bernik MA, Lotufo Neto F, et al. Clomipramine demethylation rate is important on the outcome of obsessive-compulsive disorder treatment. Int Clin Psychopharmacol. 2015;30(1):43-48.
8. Thamby A, Jaisoorya TS. Antipsychotic augmentation in the treatment of obsessive-compulsive disorder. Indian J Psychiatry. 2019;61(Suppl 1):S51-S57.
9. McDougle CJ, Epperson CN, Pelton GH, et al. A double-blind, placebo-controlled study of risperidone addition in serotonin reuptake inhibitor–refractory obsessive-compulsive disorder. Arch Gen Psychiatry. 2000;57(8):794-801.
10. Albert U, Carmassi C, Cosci F, et al. Role and clinical implications of atypical antipsychotics in anxiety disorders, obsessive-compulsive disorder, trauma-related, and somatic symptom disorders: a systematized review. Int Clin Psychopharmacol. 2016;31(5):249-258.
11. Shapira NA, Ward HE, Mandoki M, et al. A double-blind, placebo-controlled trial of olanzapine addition in fluoxetine-refractory obsessive-compulsive disorder. Biol Psychiatry. 2004;55(5):553-555.
12. Kordon A, Wahl K, Koch N, et al. Quetiapine addition to serotonin reuptake inhibitors in patients with severe obsessive-compulsive disorder: a double-blind, randomized, placebo-controlled study. J Clin Psychopharmacol. 2008;28(5):550-554.
13. McDougle CJ, Goodman WK, Leckman JF, et al. Haloperidol addition in fluvoxamine-refractory obsessive-compulsive disorder. A double-blind, placebo-controlled study in patients with and without tics. Arch Gen Psychiatry. 1994;51(4):302-308.
14. McDougle CJ, Goodman WK, Price LH, et al. Neuroleptic addition in fluvoxamine-refractory obsessive-compulsive disorder. Am J Psychiatry. 1990;147(5):652-654.
15. Chakrabarty K, Bhattacharyya S, Christopher R, Khanna S. Glutamatergic dysfunction in OCD. Neuropsychopharmacology. 2005;30(9):1735-1740.
16. Starck G, Ljungberg M, Nilsson M, et al. A 1H magnetic resonance spectroscopy study in adults with obsessive compulsive disorder: relationship between metabolite concentrations and symptom severity. J Neural Transm (Vienna). 2008;115(7):1051-1062.
17. Karthik S, Sharma LP, Narayanaswamy JC. Investigating the role of glutamate in obsessive-compulsive disorder: current perspectives. Neuropsychiatr Dis Treat. 2020;16:1003-1013.
18. Marinova Z, Chuang DM, Fineberg N. Glutamate-modulating drugs as a potential therapeutic strategy in obsessive-compulsive disorder. Curr Neuropharmacol. 2017;15(7):977-995.
19. Gadallah AHA, Ebada MA, Gadallah A, et al. Efficacy and safety of N-acetylcysteine as add-on therapy in the treatment of obsessive-compulsive disorder: a systematic review and meta-analysis. Journal of Obsessive-Compulsive and Related Disorders. 2020;25:100529.
20. Pittenger C, Bloch MH, Wasylink S, et al. Riluzole augmentation in treatment-refractory obsessive-compulsive disorder: a pilot placebo-controlled trial. J Clin Psychiatry. 2015;76(8):1075-1084.
21. Emamzadehfard S, Kamaloo A, Paydary K, et al. Riluzole in augmentation of fluvoxamine for moderate to severe obsessive-compulsive disorder: randomized, double-blind, placebo-controlled study. Psychiatry Clin Neurosci. 2016;70(8):332-341.
22. Coric V, Taskiran S, Pittenger C, et al. Riluzole augmentation in treatment-resistant obsessive-compulsive disorder: an open-label trial. Biol Psychiatry. 2005;58(5):424-428.
23. Aboujaoude E, Barry JJ, Gamel N. Memantine augmentation in treatment-resistant obsessive-compulsive disorder: an open-label trial. J Clin Psychopharmacol. 2009;29(1):51-55.
24. Feusner JD, Kerwin L, Saxena S, Bystritsky A. Differential efficacy of memantine for obsessive-compulsive disorder vs. generalized anxiety disorder: an open-label trial. Psychopharmacol Bull. 2009;42(1):81-93.
25. Ghaleiha A, Entezari N, Modabbernia A, et al. Memantine add-on in moderate to severe obsessive-compulsive disorder: randomized double-blind placebo-controlled study. J Psychiatr Res. 2013;47(2):175-180.
26. Haghighi M, Jahangard L, Mohammad-Beigi H, et al. In a double-blind, randomized and placebo-controlled trial, adjuvant memantine improved symptoms in inpatients suffering from refractory obsessive-compulsive disorders (OCD). Psychopharmacology (Berl). 2013;228(4):633-640.
27. Modarresi A, Sayyah M, Razooghi S, et al. Memantine augmentation improves symptoms in serotonin reuptake inhibitor-refractory obsessive-compulsive disorder: a randomized controlled trial. Pharmacopsychiatry. 2018;51(6):263-269.
28. Rodriguez CI, Kegeles LS, Flood P, Simpson HB. Rapid resolution of obsessions after an infusion of intravenous ketamine in a patient with treatment-resistant obsessive-compulsive disorder. J Clin Psychiatry. 2011;72(4):567-569.
29. Rodriguez CI, Kegeles LS, Levinson A, et al. Randomized controlled crossover trial of ketamine in obsessive-compulsive disorder: proof-of-concept. Neuropsychopharmacology. 2013;38(12):2475-2483.
30. Bloch MH, Wasylink S, Landeros-Weisenberger A, et al. Effects of ketamine in treatment-refractory obsessive-compulsive disorder. Biol Psychiatry. 2012;72(11):964-970.
31. Rodriguez CI, Lapidus KAB, Zwerling J, et al. Challenges in testing intranasal ketamine in obsessive-compulsive disorder. J Clin Psychiatry. 2017;78(4):466-467.
32. Matteo M, Cristian P, Laura M, et al. The use of esketamine in comorbid treatment resistant depression and obsessive compulsive disorder following extensive pharmacogenomic testing: a case report. Ann Gen Psychiatry. 2021;20(1):43.
33. Adams T, Bloch M, Pittenger C. Intranasal ketamine and cognitive-behavioral therapy for treatment refractory obsessive-compulsive disorder. J Clin Psychopharmacol. 2017;37(2):269-271.
34. Rodriguez CI, Wheaton M, Zwerling J, et al. Can exposure-based CBT extend IV ketamine’s effects in obsessive-compulsive disorder? An open-label trial. J Clin Psychiatry. 2016;77(3):408-409.
35. Grassi G, Cecchelli C, Vignozzi L, Pacini S. Investigational and experimental drugs to treat obsessive-compulsive disorder. J Exp Pharmacol. 2021;12:695-706.
36. Greenberg WM, Benedict MM, Doerfer J, et al. Adjunctive glycine in the treatment of obsessive-compulsive disorder in adults. J Psychiatr Res. 2009;43(6):664-670.
37. Rodriguez CI, Zwerling J, Kalanthroff E, et al. Effect of a novel NMDA receptor modulator, rapastinel (formerly GLYX-13) in OCD: proof-of-concept. Am J Psychiatry. 2016;173(12):1239-1241.
38. Wu PL, Tang HS, Lane HY, et al. Sarcosine therapy for obsessive compulsive disorder: a prospective, open-label study. J Clin Psychopharmacol. 2011;31(3):369-374.
39. Rosenfield D, Smits JAJ, Hofmann SG, et al. Changes in dosing and dose timing of D-cycloserine explain its apparent declining efficacy for augmenting exposure therapy for anxiety-related disorders: an individual participant-data meta-analysis. J Anxiety Disord. 2019;68:102149.
40. Khandaker GM, Dantzer R, Jones PB. Immunopsychiatry: important facts. Psychol Med. 2017;47(13):2229-2237.
41. Attwells S, Setiawan E, Wilson AA, et al. Inflammation in the neurocircuitry of obsessive-compulsive disorder. JAMA Psychiatry. 2017;74(8):833-840.
42. Shalbafan M, Mohammadinejad P, Shariat SV, et al. Celecoxib as an adjuvant to fluvoxamine in moderate to severe obsessive-compulsive disorder: a double-blind, placebo-controlled, randomized trial. Pharmacopsychiatry. 2015;48(4-5):136-140.
43. Sayyah M, Boostani H, Pakseresht S, Malayeri A. A preliminary randomized double-blind clinical trial on the efficacy of celecoxib as an adjunct in the treatment of obsessive-compulsive disorder. Psychiatry Res. 2011;189(3):403-406.
44. Esalatmanesh S, Abrishami Z, Zeinoddini A, et al. Minocycline combination therapy with fluvoxamine in moderate-to-severe obsessive-compulsive disorder: a placebo-controlled, double-blind, randomized trial. Psychiatry Clin Neurosci. 2016;70(11):517-526.
45. Turna J, Grosman Kaplan K, Anglin R, et al. The gut microbiome and inflammation in obsessive-compulsive disorder patients compared to age- and sex-matched controls: a pilot study. Acta Psychiatr Scand. 2020;142(4):337-347.
46. Wu HJ, Wu E. The role of gut microbiota in immune homeostasis and autoimmunity. Gut Microbes. 2012;3(1):4-14.
47. Kantak PA, Bobrow DN, Nyby JG. Obsessive-compulsive-like behaviors in house mice are attenuated by a probiotic (Lactobacillus rhamnosus GG). Behav Pharmacol. 2014;25(1):71-79.
48. Stein DJ, Costa DLC, Lochner C, et al. Obsessive–compulsive disorder. Nat Rev Dis Primers. 2019;5(1):52.
49. Liang K, Li H, Bu X, et al. Efficacy and tolerability of repetitive transcranial magnetic stimulation for the treatment of obsessive-compulsive disorder in adults: a systematic review and network meta-analysis. Transl Psychiatry. 2021;11:332.
50. Carmi L, Tendler A, Bystritsky A, et al. Efficacy and safety of deep transcranial magnetic stimulation for obsessive-compulsive disorder: a prospective multicenter randomized double-blind placebo-controlled trial. Am J Psychiatry. 2019;176(11):931-938.
51. Liu W, Shao H, Liao J, et al. Continuous theta-burst stimulation over the right orbitofrontal cortex in treatment-resistant obsessive-compulsive disorder treatment: a randomized sham-controlled trial. Int J Gen Med. 2021;14:3109-3118.
52. Gowda SM, Narayanaswamy JC, Hazari N, et al. Efficacy of pre-supplementary motor area transcranial direct current stimulation for treatment resistant obsessive compulsive disorder: a randomized, double blinded, sham controlled trial. Brain Stimul. 2019;12(4):922-929.
53. Bation R, Mondino M, Le Camus F, et al. Transcranial direct current stimulation in patients with obsessive compulsive disorder: a randomized controlled trial. Eur Psychiatry. 2019;62:38-44.
54. Fontenelle LF, Coutinho ESF, Lins-Martins NM, et al. Electroconvulsive therapy for obsessive-compulsive disorder: a systematic review. J Clin Psychiatry. 2015;76(7):949-957.
55. Tang VM, Blumberger DM, Weissman CR, et al. A pilot study of magnetic seizure therapy for treatment-resistant obsessive-compulsive disorder. Depress Anxiety. 2021;38(2):161-171.
56. Doshi PK. Surgical treatment of obsessive compulsive disorders: current status. Indian J Psychiatry. 2009;51(3):216-221.
57. Brown LT, Mikell CB, Youngerman BE, et al. Dorsal anterior cingulotomy and anterior capsulotomy for severe, refractory obsessive-compulsive disorder: a systematic review of observational studies. J Neurosurg. 2016;124(1):77-89.
58. Bergfeld IO, Dijkstra E, Graat I, et al. Invasive and non-invasive neurostimulation for OCD. Curr Top Behav Neurosci. 2021;49:399-436.
59. Mar-Barrutia L, Real E, Segalás C, et al. Deep brain stimulation for obsessive-compulsive disorder: a systematic review of worldwide experience after 20 years. World J Psychiatry. 2021;11(9):659-680.
60. Pepper J, Hariz M, Zrinzo L. Deep brain stimulation versus anterior capsulotomy for obsessive-compulsive disorder: a review of the literature. J Neurosurg. 2015;122(5):1028-1037.
61. Fineberg NA, Hollander E, Pallanti S, et al. Clinical advances in obsessive-compulsive disorder: a position statement by the International College of Obsessive-Compulsive Spectrum Disorders. Int Clin Psychopharmacol. 2020 Jul;35(4):173-193.
Download Issue: Vol 39, Issue 1