Invasive and noninvasive neurostimulation therapies for obsessive-compulsive and related disorders (OCRD) were systematically reviewed with the aim of assessing clinical characteristics, methodologies, neuroanatomical substrates, and varied stimulation parameters. Previous reviews have focused on a narrow scope, statistical rather than clinical significance, grouped together heterogenous protocols, and proposed inconclusive outcomes and directions. Herein, a comprehensive and transdiagnostic evaluation of all clinically relevant determinants is presented with translational clinical recommendations and novel response rates. Electroconvulsive therapy (ECT) studies were limited in number and quality but demonstrated greater efficacy than previously identified. Targeting the pre-SMA/SMA is recommended for transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS). TMS yielded superior outcomes, although polarity findings were conflicting, and refinement of frontal/cognitive control protocols may optimize outcomes. For both techniques, standardization of polarity, more treatment sessions (>20), and targeting multiple structures are encouraged. A deep brain stimulation (DBS) 'sweet spot' of the striatum for OCD was proposed, and CBT is strongly encouraged. Tourette's patients showed less variance and reliance on treatment optimization. Several DBS targets achieved consistent, rapid, and sustained clinical response. Analysis of fiber connectivity, as opposed to precise neural regions, should be implemented for target selection. Standardization of protocols is necessary to achieve translational outcomes.
Keywords: deep brain stimulation (DBS); electroconvulsive therapy (ECT); neurocircuitry; neuromodulation; neurostimulation; obsessive-compulsive disorder (OCD); transcranial direct current stimulation (tDCS); transcranial magnetic stimulation (TMS).
The pdf is here.
3.1. ECT Results
ECT involves the application of an electric charge via electrodes placed on the scalp to induce transient generalized seizures for therapeutic benefit [37]. Beyond the induction of generalized seizures, ECT does not target specific areas of the brain. Thirty-six articles were screened for eligibility, and 10 were included in the final synthesis: 6 for OCD and 4 for TS. Of the 26 articles excluded, 15 lacked a standardized outcome measure of primary symptoms; in eight, the primary diagnosis was not an OCRD or this was unclear; in a further two, both limitations were present; finally, in one investigation two neurostimulation therapies were applied. Of the included articles, OCD articles consisted of one retrospective review of medical records, four case series, and one case report, whilst TS articles consisted of four case reports. No RCT or prospective investigation of a cohort with greater than five patients was identified (across included and excluded articles), and most articles reported on a single patient. Further, clinicaltrials.gov was searched for potential RCTs that had not yet been published or identified, but no results were obtained. The final sample therefore included 46 OCD and four TS patients. Table 1 shows summary results of ECT investigations for OCD and Table 2 shows summary results of ECT investigations for TS.
3.1.1. ECT Results for OCD
The only cohort study of ECT was a retrospective review reporting a mean symptom improvement of 42% following treatment, and 35% improvement 12 months later [38]. Pooled together, the case studies for OCD revealed a response rate of 79% (11/14); within those who responded, symptom improvement of 43–95% was achieved [39–43]. Quantitative follow-up outcomes were reported in 43% of case studies (6/14 patients). In one study [41], three out of five patients were responders following treatment; only one remained a responder at 3- and 6-month follow-up, according to the clinical global impression (CGI) scale (not YBOCS). Another patient relapsed to baseline twice following consecutive cycles of ECT [42]. Depression symptoms showed clinically significant improvements of 48–62% in two investigations [38,40], and were not reported in the other articles.
3.1.2. ECT Results for TS
Improvement rates between 83–100% were reported; thus, all four patients achieved clinical response [44–47]. Qualitative follow-up outcomes were reported in three cases: all experienced complete remission with no relapse up to 8 months following treatment [44–46], yet no studies reported quantitative (i.e., YGTSS) outcomes at follow-up. Depression outcomes were not reported, despite two patients reportedly experiencing comorbid depression.
3.2. ECT Discussion
We identified variable response rates to ECT in OCD patients, with a lack of quantitative evidence of long-term efficacy. In contrast, TS patients consistently showed substantial response and remission rates, even though only four patients were reported on. The risk of bias was low for all articles (S2); the quality assessment rated no studies as good, seven as moderate, and three as poor (S3). Quality ratings were impacted by a lack of RCTs and cohort studies, poor reporting of clinical demographics and stimulation parameters, and a lack of quantitative followup. Transient effects of general fatigue and short-term memory loss were reported for some patients. OCD patients had heterogeneous symptom profiles, including obsessions of sexuality, persecution, checking, cleaning, slowness, contamination, and pathological doubt. Illness duration varied from abrupt onset of 2.5 months to 13 years, and treated individuals were between 18–47 years of age, (demographics missing for some patients). TS patients had similar complex motor and vocal tics, coprolalia, and self-injurious behaviors among other impairments; illness duration was 8–30 years, and age at ECT was between 18–36 years.
4. Conclusions
4.1. ECT
A recently published expert report on new developments in evidence-based management of OCD [240] recommends ECT only for acute treatment of comorbid conditions
(e.g., depression, psychosis). Currently, ECT is usually considered for OCD only after a
number of other treatment interventions, i.e., as a last resort, when rapid improvements
are necessary, or if a life-threatening psychiatric state is present [37]. Previous systematic
reviews of ECT for OCRD have concluded that there is a lack of unequivocal evidence to
support the efficacy of ECT. The current review found greater response rates than previous
reviews [24,26] that adopted more lenient definitions of response, and included a greater
spectrum of obsessive-compulsive conditions.
The current study identified response rates of 79% and 100% from ECT in OCD and
TS cases, respectively. Although investigations involved a small number of patients, and
there were no randomized or sham controlled investigations, the magnitude of effect was
large considering the patients’ level of severity and treatment resistance. Yet, without
randomized placebo-controlled trials, valid recommendations cannot be made. The current
review implemented stricter inclusion criteria than previous reviews, and necessitated
standardized assessments, which resulted in the inclusion of fewer articles. Pooling
together heterogeneous samples with biased methods and reporting may have previously
obscured clinical interpretations. Cohort studies with standardized assessments following
treatment and improved reporting of clinical characteristics are necessary to establish more
objective guidelines regarding the potential value of ECT in OCRD.
This is a long and exhaustive review article, the ECT part being the only one that concerns us. ECT is certainly effective for some patients with OCD or TS, with, or without, comorbid depression. But the effect is much less reliable than for mood or psychotic disorders; furthermore, since these are continuous, rather than episodic disorders, maintenance ECT would likely be necessary, but is rarely prescribed.
Those of us who have seen dramatic improvements from ECT in patients with very severe OCD know how helpful it can sometimes be. It is unfortunate that there are not better data, particularly better predictors of response, after decades of use.
I have long contended that ECT should be tried before DBS, in patients with severe, refractory OCD, since ECT is non-invasive.
The main take-home point here is that ECT may help some patients with OCD; the oft-heard clinical "wisdom" that ECT does not work for OCD is just too simplistic.
Comments
Post a Comment