Concomitant Anticonvulsants With Bitemporal Electroconvulsive Therapy: A Randomized Controlled Trial With Clinical and Neurobiological Application.
BACKGROUND
Electroconvulsive therapy (ECT) is an effective treatment for major affective disorders. The combined use of ECT and anticonvulsant mood stabilizers is a common clinical scenario. There is dearth of systematic studies on the use of this combination with regard to clinical or cognitive outcomes.


OBJECTIVE
We aimed to compare clinical improvement and cognitive adverse effects between patients who received only ECT versus those who received ECT and anticonvulsants. We hypothesized that improvement would be fastest in patients who received only ECT.


METHODS
We conducted a randomized controlled trial in which patients prescribed ECT while being treated with anticonvulsants were randomized into 3 groups: full-dose (FD), half-dose (HD), and stop anticonvulsant. A blind rater assessed clinical improvement in patients using rating scales [Young's Mania Rating Scale (YMRS) and Clinical Global Impression] for clinical improvement and cognitive adverse effects (Postgraduate Institute memory scale). Analysis was done using mixed-effects modeling to delineate differences in clinical and cognitive outcomes across the 3 arms of the study over the course of ECT.


RESULTS
Of the 54 patients recruited, 36 patients went into treatment allocation arms per the initial randomization plan. The main anticonvulsants prescribed were sodium valproate and carbamazepine. Patients in the 3 groups were comparable on clinical features. The most common diagnosis was bipolar affective disorder-with current episode of mania. Overall, there was no difference across the 3 groups in final clinical outcome scores (YMRS and Clinical Global Impression) when analyzed as intention to treat (ITT) or "as treated." In both analyses, group × time interaction was significant when comparing trend of YMRS scores between the FD anticonvulsant group and the HD group from baseline to last ECT (P = 0.0435 in ITT and P = 0.0055 in as treated). Patients in the FD group improved faster than those in the HD group. There were no differences across the 3 groups with regard to their cognitive adverse effects in the ITT analysis; "as-treated analysis" showed the HD patients to have performed poorly on some domains. Seizure parameters showed no significant difference across the 3 groups.


CONCLUSIONS
This is a preliminary prospective study examining whether coprescription of anticonvulsants with ECT affected clinical or cognitive outcomes. The most important takeaway point from this study is the significant reduction in YMRS scores when ECT was given with FD anticonvulsant compared with halving the dose (HD) of anticonvulsant. This difference was shown in both ITT and as-treated analysis. There is a need for more prospective studies to examine this clinical question.
From the *Department of Psychiatry and Behavioral Sciences, Duke University Medical Center Durham, NC; †Department of Psychiatry National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India; and ‡Goulburn Valley Area Mental Health Service (GVAMHS), Shepparton, VIC, Australia.
Gopalkumar
G
Rakesh
Jagadisha
J
Thirthalli
Channaveerachari Naveen
CN
Kumar
Kesavan
K
Muralidharan
Vivek H
VH
Phutane
Bangalore N
BN
Gangadhar
D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000523:psychology / Q000628:therapy; D003072:Cognition Disorders / Q000453:epidemiology / Q000209:etiology / Q000523:psychology; D003865:Major Depressive Disorder; D004565:Electroconvulsive Therapy / Q000009:adverse effects / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008568:Memory; D008875:Middle Aged; D009483:Neuropsychological Tests; D011569:Psychiatric Status Rating Scales; D016896:Treatment Outcome; D055815:Young Adult
D000927:Anticonvulsants