Case Presentation
Ms. P, a 19-year-old woman with no past psychiatric history or family psychiatric history, was voluntarily admitted to a freestanding for-profit psychiatric hospital with a chief complaint of "I need to mellow down." The history of the present illness, obtained primarily through the patient's sister, revealed 48 hours of pressured, often nonsensical speech, absent sleep, almost continuous dancing, brief spontaneous crying spells, auditory hallucinations, and the delusion that her stepfather impregnated her. The initial admission workup revealed a negative urine drug screen and pregnancy test and unremarkable CBC and chemistry panel. Ms. P was given an admission diagnosis of bipolar disorder, manic with psychosis, and was started on ziprasidone, 60 mg b.i.d., and lorazepam, 1 mg b.i.d. Two days into the hospitalization, she spiked a fever of 38.2°C and was not eating, talking, or moving. She was transferred to a local medical emergency department, where the evaluation included a lumbar puncture and head CT scan; results for both were normal, and the patient was returned to the psychiatric hospital. The fever, immobility, and food refusal persisted over the next 2 days while Ms. P was given trials of olanzapine, 10 mg orally and 5 mg i.m.; haloperidol, 5 mg i.m.; and aripiprazole, 10 mg orally. At this time, she was medically admitted to the community hospital.
In the hospital, Ms. P's heart rate ranged from 120 to 150, her respiratory rate was 30–40, and laboratory workup revealed a creatine phosphokinase level of 4,600 U/liter (normal range, 35–274 U/liter) and metabolic acidosis. An EEG displayed no epileptiform activity, and a repeat head CT scan was also read as normal. The patient remained mute and immobile, with no food or fluid intake. A nasogastric tube and an intravenous line were placed, and a dose of amantadine was administered through the tube. Ms. P. developed hives and was treated with methylprednisolone for a presumed allergic reaction. Her mental status remained unchanged, prompting her transfer to a tertiary care hospital 13 days after her original admission.
At the hospital, Ms. P was admitted to the neurology service and received admission diagnoses of acute parkinsonism with hypoxia, neuroleptic malignant syndrome, and catatonia. She was found to be nonverbal and rigid, with posturing and waxy flexibility. She had a skin rash on her left thigh. Her heart rate remained in the range of 125–150, her respiratory rate in the range of 25–35, and her temperature 38.5°C. Her pulse oximetry reading was 97% on 2 liters/minute of oxygen.
Results of a more extensive workup included negative findings from a hepatitis panel and tests for HIV, antinuclear antibody, vancomycin-resistant enterococci, thyroid-stimulating hormone, and methicillin-resistant Staphylococcus aureus. A repeat EEG revealed no seizure pattern and no abnormalities in background rhythm, findings of a body CT scan were normal, and echocardiography showed normal left and right ventricular size and function and no significant valvular regurgitation. CSF analysis was negative for fungus. A ventilation/perfusion scan was negative for pulmonary embolus. Abnormal findings included a WBC count of 21,000 (normal range, 4.8–10.8×103; differential not performed), an albumin level of 2.5 g/dl (normal range, 3.5–5.5 g/dl), serum protein electrophoresis with increased a2 globulin, and central line culture revealing gram-positive cocci.
Prescribed medications consisted of vancomycin and ciprofloxacin for the infection in addition to lansoprazole, metoclopramide, enoxaparin, metoprolol, and bromocriptine. All medications, fluids, and feedings were administered via intravenous line or nasogastric tube.
A psychiatry consultation was requested and obtained the day after admission. The evaluation led to a diagnosis of bipolar disorder with catatonic decompensation, and treatment recommendations were for intravenous lorazepam, elimination of metoclopramide, and the pursuit of emergency guardianship for ECT.
The lorazepam was titrated up to 6 mg t.i.d. without any notable improvement in mental status but with a slight reduction in rigidity. Despite bedside physical therapy and nursing care interventions, Ms. P developed contractures in her left hand and bilateral foot drop.
Twenty days into Ms. P's hospitalization, a guardianship hearing was held at City Hall Orphan's Court. It was determined that Ms. P's 22-year-old sister was the family member best able to serve as a temporary emergency guardian. The guardianship order was written to cover any and all medical treatments, including ECT. Informed consent for ECT was obtained from the guardian, and the first treatment was administered 2 days later.
ECT treatment was performed in the hospital recovery room following standardized procedure. ECT was administered using a MECTA spECTrum 5000Q device (MECTA Corporation, Portland, Ore.) with bitemporal electrode placement, brief pulse currents, and initial energy settings at 20% of the device's maximum. At the time of initial monitoring, Ms. P's pulse was 143. Metoprolol, 5 mg i.v., was administered before treatment, lowering her pulse to 105. Based on her body weight, methohexital, 40 mg, and succinylcholine, 30 mg, were administered before treatment. The treatment produced a 28-second modified generalized seizure. Within 10 seconds of the seizure termination, Ms. P developed torsade de pointes, a form of ventricular tachycardia in which QRS morphology varies. A code was immediately initiated; Ms. P received synchronized DC cardioversion with 120 J and regained a rapid sinus rhythm. She was subsequently intubated and transferred to the medical intensive care unit. After extubation several hours later, it was noted that Ms. P was tracking with her eyes and for the first time spoke several words.
Ms. P remained in the medical intensive care unit for 24 hours. Cardiology consultation and additional testing were unable to ascertain the etiology of her acute life-threatening rhythm disturbance. Several pharmacologic recommendations were offered if Ms. P were to undergo further ECT. At this time, multiple conversations were held with her sister, addressing the potential risks and benefits of continuing the ECT treatment course. The treatment team was unable to delineate any additional treatment options for the malignant catatonia, which, left untreated, is associated with high morbidity and mortality. There had been a glimmer of initial response to ECT, but there was now an associated risk of reintroducing the life-threatening arrhythmia with future treatment. Ultimately, the guardian chose to continue the ECT, viewing it as the best hope to "get my sister back."
Ms. P received eight additional ECT treatments with robustly positive results. The pharmacologic regimen for all subsequent treatments included pretreatment with 5 mg i.v. of metoprolol and 1 g i.v. of magnesium and then 40 mg i.v. of methohexital and 15 mg i.v. of rocuronium, a nondepolarizing, fast-onset neuromuscular blocking agent, for treatment. Neostygmine, 1.5 mg i.v., was administered after treatment to reverse the rocuronium, and glycopyrrolate, 0.2 mg i.v., was given to prevent neostygmine-induced extreme bradycardia. There was no recurrence of posttreatment rhythm disturbances. By the conclusion of these treatments, Ms. P was eating and drinking adequately to meet her dietary requirements, engaging in daily physical therapy, and communicating appropriately with the treatment team, her family, and her friends. Mental status examination revealed no mood symptoms, perceptual disturbances, or thought disorder. Lithium carbonate pharmacotherapy was initiated at the conclusion of ECT, with dose titration to a blood level of 0.8 mEq/liter. By day 52 of her hospitalization, supplemental oxygen, intravenous lines, and the nasogastric tube were removed, and Ms. P was adequately stabilized medically and psychiatrically for discharge to a rehabilitation hospital.
Ms. P remained psychiatrically stable on lithium during her 21-day rehabilitation stay. By discharge, only mild left foot drop persisted. At 3-month follow-up, Ms. P reported that she was living with her boyfriend, that her ambulation was almost back to normal, and that she had resumed her usual activities.
Treatment of Catatonia
When correctly identified, catatonia can be rapidly and effectively treated. Given multiple potential etiologies and subtypes, it is not surprising that published studies of catatonia treatment overwhelmingly consist of case series and open prospective trials. The etiology, severity, and pattern of catatonic features do not appear to affect treatment outcome. The long-term prognosis appears to be most closely linked to successful treatment of the underlying condition (
6).
Treatment of catatonia is a team effort best accomplished in the hospital setting. All patients require attentive nursing care to ensure adequate hydration, nutrition, mobilization, and skin care. Critically ill patients with malignant catatonia or neuroleptic malignant syndrome, such as Ms. P, urgently require treatment to reverse hyperthermia, maintain stable blood pressure and cardiac rhythm, ensure adequate oxygenation, and avoid renal failure.
Although intravenous amobarbital has long been considered useful in the treatment of catatonic mutism, only one double-blind randomized controlled trial, published over 15 years ago, found that amobarbital was superior to saline (
8). Despite the absence of controlled studies, benzodiazepine treatment has become the standard of care. Nonmalignant forms of catatonia usually respond to parenteral lorazepam, at 6–20 mg/day. The medication is often administered 30–60 minutes before meals to elicit a transient period of increased responsiveness to maintain adequate food intake and hydration. Dosing is usually initiated at 3–4 mg/day and can be rapidly increased to achieve symptom resolution. Some investigators believe that ECT should be initiated by the fifth day after inadequate response to lorazepam. In malignant catatonia, further delaying ECT is associated with increased mortality (
4). In Ms. P's case, delays in obtaining the emergency guardianship precluded earlier ECT.
Two rapid catatonia treatment challenge tests have emerged in the literature. The lorazepam challenge consists of administering 1 mg of lorazepam intravenously and waiting up to 5 minutes for a response; if there is no response, an additional 1 mg i.v. of lorazepam is administered. The zolpidem challenge consists of administering 10 mg of zolpidem orally or through a nasogastric tube to achieve a plasma concentration between 80 and 150 ng/liter within 30 minutes of ingestion. Response usually occurs within 30 minutes and lasts 3 hours (
9). A positive response generally predicts a more sustained response to a subsequent lorazepam trial. Nonresponse to these challenge tests does not preclude future lorazepam response, although higher doses are often necessary and concurrent preparation for ECT should be initiated.
In addition to lorazepam, a number of case reports suggest that atypical antipsychotics may relieve the motor as well as the nonspecific signs and symptoms of catatonia (
10,
11). Discontinuation of antipsychotic medications, especially high-potency agents, is generally an initial treatment recommendation, particularly in cases of malignant catatonia or neuroleptic malignant syndrome. While all antipsychotics can induce neuroleptic malignant syndrome, a number of case reports suggest that atypical antipsychotics, including risperidone, olanzapine, and ziprasidone, can be effective in short- and long-term treatment of catatonia (
10,
11).
The belief that neuroleptic malignant syndrome is an idiosyncratic response to acute dopamine blockade led to the pharmacologic treatment strategy of using pre- and postsynaptic dopamine receptor agonists in conjunction with the muscle relaxant dantrolene sodium. Generally, intravenous treatment with dantrolene is initiated for the first 48 hours, with the addition of amantadine and/or bromocriptine for absent or incomplete response. Concerns about this approach include delayed response, the risk of liver toxicity at higher doses of dantrolene, and the risk of aggravating psychosis with bromocriptine (
4).
Case series and open prospective trials suggest that ECT is a highly effective treatment for all forms of catatonia, including malignant catatonia and neuroleptic malignant syndrome. The literature also supports the use of ECT for malignant catatonia in children, pregnant women, elderly persons, and medically compromised patients (
12,
13). APA treatment guidelines (
14) state that ECT is probably the most effective treatment for catatonic syndromes regardless of etiology. They further suggest that ECT should be considered in patients with schizophrenia and prominent catatonic features as well as in patients with bipolar disorder with catatonic features not responsive to benzodiazepines.
Bitemporal electrode placement with brief pulse currents with initial energy at half the patient's age is recommended (
4). The decision to use higher-than-recommended energy settings in Ms. P's case was based on the anticonvulsive effects of the acute benzodiazepine treatment. Treatment can be administered daily in malignant catatonia or neuroleptic malignant syndrome until significant symptom resolution is achieved. Even in cases of rapid dramatic response to ECT, courses of at least six treatments are recommended to mitigate the possibility of rapid relapse (
4). Treatment modifications for patients with very high seizure thresholds after high-dose benzodiazepine treatment can include use of etomidate anesthesia and the benzodiazepine antagonist flumazenil. Catatonic patients have never been included in ECT treatment trials, so recommendations regarding electrode placement, energy settings, treatment frequency, and number of treatments to prevent relapse are not evidence based.