It is Electric! Electroconvulsive Therapy for Refractory Central Pain and Comorbid Psychiatric Disease

Introduction

Central pain syndromes are a complex, diverse group of clinical conditions that are poorly understood. In the general healthcare community, this often leads to refractory suffering in the patients carrying these diagnoses. The presentation of these syndromes can be idiosyncratic and fraught with vague, subjective patient descriptions without objective physical findings, and they often occur, causally or not, with psychiatric disorders such as major depressive disorder. Owing to a variety of diagnostic criteria, they tend to be difficult to diagnose, making definitive management of these conditions problematic. Furthermore, these syndromes often prove resistant to many pharmacologic interventions.

Electroconvulsive therapy (ECT) is a particularly effective treatment for medically refractory major depressive disorder. ¹ It also exhibits concurrent analgesic properties independent of its effects on mood.^2,3 As such, ECT has shown efficacy in small studies on chronic multifactorial pain conditions including those with suspected central pain mechanisms.^2,4–6 Herein, we present a patient with progressive, debilitating central pain, refractory to multimodal pharmacologic and nonpharmacologic therapies, but that ultimately responded to ECT.

Case Description

PA was a 47-year-old woman diagnosed with Huntington disease in 1997. Her first symptoms were depression, risky behaviors, and obsessive-compulsive symptoms. They were medically managed with little success for many years in conjunction with cognitive-behavioral therapy. She later took medication to suppress chorea.

As the course of her disease evolved, she developed widespread pain. She described it at various times as her skin being “lit on fire,” “stabbed,” “squeezed like a boa constrictor,” or itching unbearably. These symptoms led to attempted treatment with a wide variety of neuroleptic medications for suspected akathisia. Her disease burden worsened with the onset of descriptors of pain in the axial lumbar spine, buttocks, abdomen, knees, and appendicular long bones. Numerous medical evaluations took place to identify an organic etiology for her pain without success. These symptoms worsened, despite trials with neuropathic agents, including duloxetine, tricyclic antidepressants, and pregabalin. Her persistent untreated condition led to significant functional debility.

Confounding the picture, she had cognitive decline and psychotic delusions about the cause of her pain. She had very frequent medication adjustments, all at high doses. She started treatment with tricyclic antidepressants, selective serotonin reuptake inhibitors, and serotonin—norepinephrine reuptake inhibitors, with little to no relief of her whole-body pain. Nonsteroidal anti-inflammatory agents, long- and short-acting narcotics, and muscle relaxants were also minimally efficacious.

Her clinical state deteriorated to such a point wherein she was hospitalized, confined to her bed, and unable to tolerate even the lightest touch from caregivers due to severe pain, all accompanied by behavioral outbursts and constant screaming. An interdisciplinary team comprising physicians from neurology, psychiatry, anesthesia pain medicine, and palliative care assumed care. Attempts at identifying a single cause of pain were replaced by recognizing this presentation of “total pain,” with clear psychiatric, central, and existential components. A trial of ECT was offered to attempt to treat the psychotic depression with hopes that associated analgesia would result as all standard treatments had been ineffective.

She underwent a course of three sequential ECT treatments during her hospitalization, leading to dramatically decreased pain levels. She did experience transient, post-ECT somnolence, as well as slowing of cognition and movement while awake, side effects that she and her caregivers deemed acceptable given the relief of suffering voiced by PA and observed by her team. By the time of discharge, her pain scores were reduced and her level of physical functioning had significantly increased. Her opioid and nonopioid analgesic regimen was pared down significantly compared with her admission regimen and she was an active participant in physical and occupational therapy. With this significant functional improvement, PA was discharged to her home with minimal pain symptoms.

Unfortunately, she developed a recurrence of her diffuse pain symptoms three months after the first course of ECT. She subsequently underwent a second successful course of ECT in the hospital setting. She was started on maintenance ECT, and a rate of roughly one treatment a month provided persistent pain suppression.

Discussion

Central pain is often used as an umbrella term to encompass a variety of neuropathic pain symptoms thought to be caused by aberrant pain signaling and processing in the brain and spinal cord. ⁷ These aberrant processes can reflect discrete, anatomically focal cell injury, but can also demonstrate poorly localized patterns of cell and tissue injury with a wide range of immunologic and inflammatory responses. Recent hypotheses speculate that these syndromes arise from injury to thalamic sensory neural tissue, causing an increased response to all sensory stimuli, both noxious and non-noxious. ⁸ Common organic causes include vascular lesions, MS, TBI, spinal cord trauma, tumors, abscesses, meningitis, and Parkinsonism. ⁹

Huntington's disease is an autosomal dominant neurodegenerative disorder caused by a series of trinucleotide repeats on chromosome 4, leading to the expression of the abnormal Huntingtin protein. This abnormal protein leads to cerebral degeneration in the caudate nucleus, putamen, substantia nigra, hippocampus, cerebellum, hypothalamus, and thalamus. ¹⁰ Progressive motor dysfunction and choreiform movement disorders are common in patients with Huntington disease, and many of these patients experience debilitating cognitive decline. An estimated 33–76% of patients have simultaneous psychiatric disorders. ¹¹ In the case of PA, her severe depression and psychotic delusions occurred concurrently and likely as a causal factor of her expression of pain.

Therapies for central pain syndromes are broad and of variable efficacy. Current guidelines recommend therapies with typical analgesic agents, such as NSAIDs, opioids, and acetaminophen, as well as atypical analgesics, such as tricyclic antidepressants, fluvoxamines, anticonvulsants, local anesthetics, and N-methyl-D-aspartate receptor (NMDA) antagonists.^12,13 For those patients who experience simultaneous psychiatric mood disorders, such as major depressive disorder, ECT may be a reasonable last resort for salvage therapy.^2,6,14 Mechanistically, ECT releases monoamine neurotransmitters, most notably dopamine and serotonin. ¹⁵ PET imaging shows decreased metabolic activity in the frontal and cingulate cortex immediately after treatment. ¹⁶ Previous studies have shown that these altered plasma levels of neurotransmitters after ECT therapy are likely responsible for decreased central pain transmission, which may decrease both pain and depressive symptoms.^17,18

There are few studies that have evaluated ECT therapy in the treatment of chronic pain syndromes. The first case in the literature dates to 1946 in a 55-year-old man with depression and phantom limb pain. ⁵ Several cases followed in the 1950s.^4,6,19 The largest study to date comprises 21 patients with chronic pain, in which 19 of the 21 patients experienced significant improvement in their pain symptoms after ECT. ³ Despite this lack of evidence, ECT has a favorable safety profile and can be considered in the therapeutic armamentarium for patients who have exhausted standard treatment regimens who continue to have suffering in the setting of central pain syndromes and coexisting mood disorders.