Electroconvulsive Therapy (ECT) for Refractory Psychiatric Symptoms in Huntington’s Disease: A Case Series and Review of the Literature

Case 1

Patient 1 is a 45-year-old right-handed Hispanic female with HD diagnosed after presenting with three years of gradual mood, cognitive, and motor decline with worsening chorea. Family history was significant for multiple paternal family members with undiagnosed abnormal movements. Patient’s genetic testing confirmed 44 CAG repeats in the HTT gene. At the time of her initial evaluation she had cognitive impairment, depression, and required assistance performing high-level activities of daily living. Her index Unified Huntington’s Disease Rating Scale (UHDRS) motor score was 49. She was initially unable to tolerate olanzapine due to akathisia. She was subsequently transitioned to tetrabenazine and propranolol for motor symptoms and escitalopram and clonazepam for depression, anxiety, and insomnia. Escitalopram was later switched to nortriptyline due to persistent depression, irritability, and emotional lability.

Unfortunately, nineteen months after the patient’s diagnosis, her daughter unexpectedly died leading to worsening depressive symptoms and self-injurious behavior with precipitous clinical decline into severe major depressive disorder with psychotic features and suicidality. She required two inpatient admissions for suicidal ideation and attempt. During her last admission, her symptoms were resistant to maximum medication adjustment with both antipsychotics and antidepressants. At twenty months post-HD diagnosis, she was deemed unsafe for discharge to a facility or home due to the severity and refractory nature of her symptom, and she was therefore offered ECT. ECT was performed under anesthesia using a Thymatron IV with bitemporal electrode placement. Her settings were pulse width 0.50 seconds and a charge dose of 40%. This produced electroencephalographic seizures ranging from twenty-five to forty-eight seconds. She was noted to have a marked early response with improvement in depressive symptoms and resolution of psychotic features and suicidal ideation after the fifth session. She was able to be discharged home safely with family. Her medications at discharge were quetiapine 200 mg BID, amantadine 300 mg daily, and sertraline 150 mg daily.

The patient was initially continued on maintenance outpatient ECT therapy after discharge. Her mood symptoms were initially stable as an outpatient, and she was noted to be laughing and pleasant during clinic visits. Due to family concerns about cognitive changes, maintenance ECT was held, and she subsequently had a brief relapse of recurrent intrusive thoughts, anxiety, and passive suicidal ideation. She was promptly restarted on maintenance ECT therapy with resolution of suicidality and no recurrence of psychotic features. Her cognitive exam is unchanged from her index evaluation, now thirty-seven months after HD diagnosis. She has received a total of twenty-nine ECT sessions.

Case 2

Patient 2 is a 52-year-old right-handed White male who first presented with one year of chorea, mood fluctuations, and mild dementia. His father had presumed HD, and the patient had genetic testing confirming 42 CAG repeats in the HTT gene. He presented with depressive symptoms including situational distress regarding his diagnosis, difficulty sleeping, anxious rumination, low appetite, and hypersensitivity to sounds. His index Montreal Cognitive Assessment (MoCA) score was 17/30 and initial UHDRS motor score was 27. His previous neurologist started him on tetrabenazine for motor symptoms. Mood symptoms transiently improved after stopping tetrabenazine but soon returned. He was then started on olanzapine for mood and chorea.

About six months after diagnosis, the patient endorsed “mental pain and depression” along with passive suicidal ideation that occurred in response to being confronted with the loss of his prior abilities and independence. Olanzapine was decreased and lithium was started for both antidepressant and anti-suicidal effect. He developed increased fear, paranoia, anxiety, and insomnia that improved mildly after decreasing the lithium dose and adding a benzodiazepine. Medication optimization was limited by sedation, non-compliance, and inadequate effectiveness. About ten months after diagnosis, he required two inpatient psychiatry admissions for progressive depressive symptoms. After discharge, he was re-assessed in clinic where he reported marked lethargy, forgetfulness, and severe depression with active suicidal ideation with plan of drowning. He was voluntarily admitted to inpatient psychiatry. Though his suicidality resolved with increased venlafaxine dose to 150 mg daily, he was still depressed and interested in trying ECT due to his recent precipitous decline requiring multiple hospital admissions. At twelve months after initial diagnosis of HD, the patient was initiated on ECT with right unilateral electrode placement. His settings were pulse width 0.25 ms, frequency range of 10– 70 Hz, and charge dose range of 5– 25%. Electrographic seizure length ranged from thirty to seventy-five seconds.

The patient underwent six total ECT sessions with resolution of his depression and hopelessness leading to a successful, safe discharge. He was subsequently continued on venlafaxine monotherapy for mood and continued on twice monthly maintenance ECT without recurrence of suicidality or major depression. He had mild worsening in chorea with UHDRS motor score of 31 increased from index score 27, so olanzapine was increased to 5 mg BID. He continued to see improvements in depression and anxiety with continued resolution of suicidality at nine months post-ECT initiation after twenty-seven total sessions scheduled every 2-3 weeks. He also endorsed gradual improvement in cognitive and motor function that he attributed to ECT treatments.

Case 3

Patient 3 is a 38-year-old right-handed White male who was diagnosed with HD after presenting at age 31 with abnormal movements, twitching, and frequent blinking. His mother and maternal grandmother had HD. The patient had 46 CAG repeats in the HTT gene. He started to have slowly progressive forgetfulness in the year following diagnosis. Neuropsychiatric testing revealed impaired executive functioning, mild memory deficits, and anxiety without initial signs of depression. He was started initially on amantadine and later baclofen. He began having increased irritability three years after diagnosis and was started on fluoxetine which was reportedly ineffective. He developed increased irritability, paranoia, intense delusions, hyper-religiosity, and suicidal/homicidal ideations. He was trialed on numerous psychiatric medications including oxcarbazepine, haloperidol, olanzapine, aripiprazole, carbamazepine, clozapine, and lithium with no significant control of his refractory psychosis, which led to multiple inpatient psychiatry hospitalizations. He moved into a skilled nursing facility (SNF) four years after diagnosis and had progressively worsening agitation and impulsivity.

At six years after diagnosis he was admitted to the hospital from the SNF with increased agitation, combativeness, destructiveness, attempted elopement, and suicidal ideation. On admission, his medication list included lithium, amantadine, baclofen, clozapine, gabapentin, and chlorpromazine. Motor symptoms were well-controlled. Despite multiple medication adjustments for psychosis, the patient had continued agitation, delusions, and combativeness. He also had visual hallucinations of insects on his food and was refusing to eat. Given his refractory psychosis and suicidal ideation, the patient was started on ECT three months into the hospitalization. He had sessions three times a week with improvement in agitation, frequency of suicidal ideation, self-injurious behaviors, and intensity of delusions. All sessions had bilateral electrode placement (except eight sessions with right unilateral placement), with settings of 0.25– 1.0 ms pulse width, 40– 140 Hz frequency, and charge dose of 100% (except for two sessions performed at 50% due to delirium that was later attributed to medications, especially benzodiazepines). The patient had a total of forty-one ECT treatments, and electroencephalographic seizure length ranged from twenty-one to eighty-four seconds. When attempting to decrease ECT frequency to twice weekly, the patient’s symptoms would worsen, especially self-injurious behavior and agitation. Patient was continued on ECT three times a week for 3.5 months. The decision was made to decrease the frequency to twice per week and taper off over another month given that the frequent ECT schedule, although showing some effect, was not a sustainable plan after discharge. The patient had some worsening of symptoms after discontinuing ECT, but mood and psychosis were improved compared to admission.

He was ultimately discharged on clozapine, chlorpromazine, diazepam, and gabapentin. At his outpatient follow-up psychiatry appointment 2.5 weeks after discharge, patient had hyper-religiousity, delusions, and auditory hallucinations, stable from discharge. Although he had stable homicidal ideation and suicidal ideation without a plan, the patient had no reported behavioral problems, and he was able to be managed safely at his nursing home.

Case 4

Patient 4 is a 52-year-old right-handed White male with a history of depression, anxiety, and pre-manifest HD. Family history was notable for mother, maternal grandfather, maternal aunt, maternal first-cousin, and maternal great-aunt with HD. At age 45, he had genetic testing confirming 39 CAG repeats in the HTT gene. He endorsed a lifetime of fluctuating depression and anxiety which worsened around the time of HD gene confirmation that also coincided with his mother’s death and graduate school stressors. He was initially trialed on sertraline by his primary care doctor and later switched to bupropion, escitalopram, and clonazepam. He established care with the movement disorders clinic and neuropsychiatry at age 50 and did not have motor or cognitive symptoms or signs at that time. Over the next 8– 12 months, the patient developed worsening depression, increased emotional lability, insomnia, and passive suicidal ideation requiring increased doses of current medications and the initiation of lithium. He was later started on levothyroxine for lithium-induced hypothyroidism. The patient’s depressive symptoms were eventually resistant to dose escalation and supportive psychotherapy, so he was voluntarily admitted for ECT, now seven years after initial HD gene confirmation, and still without motor manifestations. On admission, patient endorsed lack of energy, disturbed sleep, psychomotor retardation, lack of motivation, and depression without current suicidal ideation.

He received a total of seven ECT sessions, scheduled three times a week. Lithium was discontinued on admission given concern that it could contribute to delirium with ECT. The patient had improvement in mood starting after the first session. He tolerated ECT well except for one session where he expressed that he had experienced anesthetic awareness between the period of induction of muscle paralysis and the initiation of the seizure. The patient found this quite disturbing. All sessions had right unilateral electrode placement with settings of 0.25 ms pulse width, 40 Hz frequency (except 10 Hz with initial session), and 25– 50% charge dose (except the initial session which was done with 5% charge). Electroencephalographic seizure length ranged from twenty-one to forty-two seconds. After seven inpatient ECT sessions, the patient reported improved mood, motivation, and energy. He had less anhedonia and denied suicidal ideation. On the day of discharge, he described his mood as “great” and scaled it as a 7/10 compared to 3-4/10 on admission. On discharge, he was continued on bupropion, escitalopram, clonazepam, and levothyroxine. Lithium was discontinued, and trazadone was added for sleep. The patient was discharged home with a plan to continue outpatient maintenance ECT twice a week, and the patient had good adherence to this plan. However, due to a second reported experience of anesthetic awareness during an outpatient ECT session, the patient refused to continue with the maintenance ECT. He is being maintained on medications, without return of suicidal ideation.

Among our cases, all patients presented with depression on admission with three of the four experiencing suicidal ideation refractory to medication. Two of the four patients also presented with refractory psychosis. Two patients received bilateral electrode placement during ECT while the other two received right unilateral. Patient 3 had a prolonged hospitalization and ECT course due to highly resistant symptoms and difficulty weaning ECT frequency. After ECT course, all patients had improvements in mood and suicidal ideation. Both patients who presented with co-existing psychosis had added improvement in psychotic symptoms. While not an intended outcome, one patient also reported additional subjective improvement in motor function. ECT was overall well tolerated in all of our patients. One patient experienced two episodes of anesthetic awareness although this was likely due to insufficient anesthesia and not an effect of ECT. Three of the four patients were continued on outpatient maintenance ECT following discharge.

When combining the information from past literature and this case series, the number of ECT sessions per admission ranged from 4 to 41 with an average of 10 sessions. Of the total 23 hospitalizations for ECT, thirteen had right unilateral electrode placement, four had bilateral electrode placement, and two had a combination of right unilateral and bilateral. Electrode placement was not recorded in four of the 23 cases. The pulse frequency ranged from 10– 90 Hz with the majority raging from 40– 90 Hz. The pulse width ranged from 0.25– 2 milliseconds. The seizure duration measured by EEG ranged from 5– 84 seconds with the majority ranging from 20– 60 seconds. Thirty-five percent of patients continued maintenance ECT after hospital discharge.