Reversible Lacosamide Interference in Electroconvulsive Therapy: A Case Report

Case history

Ms. M is a 64-year-old female with a psychiatric history of schizoaffective disorder, bipolar type, and malignant catatonia, receiving biweekly maintenance electroconvulsive therapy (ECT). Her medical history includes hypertension, Parkinson’s disease, a reported seizure disorder, thyroid disease, hyperparathyroidism, gastroesophageal reflux disease, aortic valve replacement, and iron deficiency anemia.

She was transferred to our academic tertiary care center from an outside hospital for ECT to treat presumed malignant catatonia. Psychoactive medications restarted at the time of her admission included carbidopa-levodopa 10–100 mg twice daily, lorazepam 2 mg by mouth every 8 hours, and lacosamide 200 mg twice daily. An EEG obtained at the outside hospital showed diffuse background slowing, consistent with mild global encephalopathy.

Symptomatology

At the outside hospital, Ms. M presented with abnormal vital signs (T 100.8°F, BP 157/95, RR 26, pulse 126), and catatonic features including rigidity, grasp reflex, mutism, glabellar reflex, and gegenhalten resistance. Lorazepam administration resulted in decreased rigidity and partial responsiveness. Upon admission, she had an unkempt appearance, head tilted to the right, bilateral hand tremor, abnormal orofacial movements, was non-verbal and non-responsive to commands. Her initial Bush Francis Catatonia Rating Scale (BFCRS) score was 22.

Diagnosis

The working diagnosis was malignant catatonia, based on the patient’s presentation and partial response to lorazepam. Psychiatry was consulted shortly after admission to assist with management. The BFCRS score and clinical signs supported the diagnosis. EEG results indicated mild global encephalopathy.

Treatment

Ms. M began ECT the day after admission. The first five treatments were unilateral; treatments six through seventeen were bilateral. Despite appropriate escalation in stimulus, the first six treatments over 13 days showed little response (electrographic seizure duration 23.8 ± 13.0 seconds), with an average BFCRS score of 16.8 ± 1.2. During the first month, lacosamide was continued at 200 mg twice daily, lorazepam was increased to 6 mg three times daily, and amantadine was titrated to 200 mg/day over three weeks. Mental status and catatonia symptoms showed minimal improvement.

When a hold was placed on lacosamide, the patient demonstrated longer electrographic seizure durations and gradual improvement in catatonia symptoms. Over the next nine treatments, her BFCRS score decreased to 3. She began to engage in conversation, follow commands, and track gaze. Mental status improved, with better hygiene, alertness, normalized speech, and orientation to self and location.

Given the level of contractures and deconditioning from severity and duration of catatonia, she required physical, occupational, and speech therapy. She was discharged to a rehabilitation facility to continue rebuilding her strength, with plans to follow up with outpatient psychiatry for medication management and biweekly ECT.

Written consent was obtained from the patient to publish this case report.

Discussion

We present a case in which a patient with an otherwise successful history of ECT treatments experienced poor seizure quality in response to lacosamide. This case highlights the complicated interplay between anti-seizure medication (ASM) pharmacodynamics and concurrent ECT treatment. In the presence of lacosamide, electrographic seizure duration, convulsion duration, and clinical response were significantly diminished, but a hold on lacosamide restored these findings to adequate lengths of time (Figure 1) corresponding with objective improvements on the BFCRS. However, there is evidence to suggest that ASMs with different mechanisms of action may not present a significant inhibitory effect on adequate seizure generation. For instance, a randomized controlled trial found that both valproic acid and carbamazepine may both be administered without diminishing the clinical effects of ECT.¹ Although the mechanism of valproic acid is thought to be diverse and is less well understood, carbamazepine is similar to lacosamide in that they both act on voltage gated sodium channels (VGSCs).² Carbamazepine, however, solely stabilizes the fast inactivation state of the VGSCs while lacosamide preferentially enhances slow inactivation, making it distinct among ASMs.^3,4 Fast inactivation occurs on the scale of milliseconds after a single action potential, while slow inactivation works in response to repeated or prolonged stimulation. Slow inactivation decreases the number of channels available to propagate an action potential and thus decreases the excitability of a membrane as stimuli are continually administered.⁵ Therefore, it is plausible that lacosamide could have an exaggerated adverse effect on ECT outcomes as it prevents the rapid repolarization of neuronal membranes more longitudinally compared to other ASMs.

Figure 1.

Convulsive and Electrographic Durations Before and After Lacosamide Discontinuation, with 95% Confidence Intervals. There was a Statistically Significant Increase in Both Durations After Lacosamide Discontinuation (p < 0.01)

ECT can make a profound difference in the quality of life and morbidity of a catatonic patient, and it is therefore of the utmost importance to critically assess any medications that may impede a successful course of treatment. While recent findings have suggested that ASMs may not be universally contraindicated during ECT, it is important to understand the nuances of drug mechanisms when electing to either continue or hold a drug in the context of ECT. For our patient, we suspect lacosamide hindered ECT success. Further research, including controlled studies and mechanistic investigations, is needed to determine whether this effect is specific to lacosamide’s pharmacodynamics or an idiosyncratic patient response.

Conflicts of Interest

There are no conflicts of interest to disclose.