Abstract
Chief Complaint and Presenting Problem
B. was a 16-year-old adolescent boy in 11th grade in special education, with a history of schizophrenia and two past psychiatric admissions, referred for symptoms of catatonia.
History of Present Illness
Mother reported that B. experienced the onset of symptoms in eighth grade, when he began to show decreased focus and struggled with schoolwork. His behavior became oppositional, soon progressing to school refusal. B. was referred for inpatient psychiatric admission in ninth grade for oppositional behavior and poor concentration. He was not started on medication and did not follow-up with outpatient treatment after discharge. A second admission occurred during 10th grade for psychotic symptoms.
B. was diagnosed with schizophrenia and discharged on olanzapine and benztropine. B. continued with outpatient treatment. Mother reported that despite good treatment response to olanzapine, for unclear reasons it was discontinued, and B. was started on aripiprazole 5 mg daily. Four days before his emergency department (ED) presentation, his aripiprazole dose was increased to 10 mg qday.
Mother reported that over the week leading to B.'s third admission to the hospital, he had developed severe insomnia and had stopped talking. He was taken to his primary care provider and B. had been taken to the pediatrician the past fall for insomnia and bizarre behavior over the course of 1 week. He was mute during the visit, prompting the pediatrician to order basic blood work that was unremarkable. The following day, he continued to exhibit bizarre behavior; he was pacing, sweating, and complaining of chest pain. He seemed anxious and paranoid, and refused to let his parents take him to the hospital. He was eventually taken to the ED by emergency medical services, requiring the use of 200 mg of intramuscular ketamine en route to the ED due to aggression.
In the ED, B. appeared withdrawn and seemed to be responding to internal stimuli. He endorsed auditory hallucinations of voices telling him to “find the crayons” or “eat vegetables and good things will happen” as well as visual hallucinations of “colors and crayons.” He was also religiously preoccupied, repeatedly saying “I love you God.” An electrocardiogram showed sinus tachycardia with a heart rate of 138 (likely attributable to the ketamine), which was resolved with the administration of intravenous fluids. Medical work-up included abdominal and chest X-ray, as well as head computed tomography (CT) scan without contrast, which were unrevealing, and basic laboratories showing nonspecific abnormalities, such as mild leukocytosis. Urine toxicology was negative.
B. was medically cleared and was admitted to an inpatient psychiatric unit in a private hospital. Upon arrival to the unit, B. was uncooperative with staff, physically pushing away team members who approached him. As he remained nonverbal and poorly responsive to staff for 2 days, he was transferred to an academic medical center to complete further medical work-up. He was admitted to a medical floor and was followed closely by psychiatry.
On arrival, at the medical floor B. was completely mute, hardly ambulating, with poor intake by mouth and seemed paranoid. A diagnosis of catatonia was made, and B. was started on lorazepam (unknown starting dose) while discontinuing his prescribed medication of aripiprazole. Concurrently with lorazepam, B. underwent an extensive medical work-up, including complete blood count, comprehensive metabolic panel, thyroid-stimulating hormone, free thyroxine, liver function tests, creatine phosphokinase, urinalysis, urine drug screen, lead, ceruloplasmin, prolactin, porphobilinogen, HIV, rapid plasma reagin, antinuclear antibodies, folate, B6, and B12; magnetic resonance imaging (MRI) of the brain, abdomen, and pelvis; chest CT; ultrasonography of the scrotum; lumbar puncture and cerebrospinal fluid (CSF) analysis including culture and autoimmune encephalitis panel; video electroencephalogram; tests for metabolic/genetic syndromes, including Fragile X, serum amino acids, urine organic acids, and arylsulfatase A leukocytes; and single nucleotide polymorphism microarray. All test results were within normal limits. In addition, tests for coronavirus disease-19 (COVID-19) were sent on several occasions. B. was negative for COVID-19 with the exception of one test that was thought to be a false positive. Lorazepam was titrated up to 2.5 mg q4h (for a total daily dose of 15 mg) over a period of 10 days, with partial response. B. began to ambulate more, was slightly more verbal, and his by mouth (PO) intake improved. However, his symptoms did not completely resolve, and mother, who was at B.'s bedside throughout his admission, reported that he was still quite different from his baseline. Lorazepam was gradually reduced to 1 mg q8h, and quetiapine was started at 50 mg bid.
Consequently, B.'s condition worsened. He had reverted to his previous state of not eating and not speaking. Mother did not consent to restarting lorazepam, as she felt it was unhelpful. Quetiapine was then switched to olanzapine 2.5 mg qday. Given exacerbation in symptoms and no significant improvement despite multiple medication trials, a repeat CSF autoimmune encephalitis panel was sent, and a repeat brain MRI was done. B. was started on intravenous immunoglobulin and methylprednisolone while awaiting the results of testing for a possible autoimmune encephalitis; the CSF panel eventually came back negative. At that point, B. was started on diazepam that was titrated up to 10 mg q6h (for a total daily dose of 40 mg).
Three weeks into his hospital admission, B.'s PO intake continued to deteriorate, and a nasogastric tube was placed to ensure adequate feeding. Over a month after he had been admitted to the hospital, given no significant improvement in his condition, the family agreed to consider electroconvulsive therapy (ECT), and B. was transferred to another large academic center where ECT was available.
Psychiatric History
B. had experienced two prior psychiatric hospitalizations since eighth grade and a diagnosis of schizophrenia had been made.
Developmental History
There were no prenatal or perinatal complications, and B. met all developmental milestones on time. Birth weight was not available.
Educational History
B. was an 11th grade student with an individualized educational plan for emotional disturbance. Before high school, he was reported to be an honors student.
Social History
B. lived with his biological parents. Before onset of illness, mother reported B. had enjoyed playing basketball and listening to music. In middle school, B. suffered from bullying by his peers.
There was no reported history of abuse, neglect, or child protective services involvement.
Family History
A paternal half-brother (34 years old) was diagnosed with bipolar disorder; there was no other family history reported of psychiatric disorders or suicide.
Medical History
B. had no significant medical history and no known drug allergies. He denied any history of alcohol, marijuana, and all other substance use.
Mental Status Examination
On initial evaluation, B. was markedly impaired, and many components of the mental status examination could not be completed. He was mostly immobile, constantly mumbling, and not responding to his name. He did not make eye contact, answer any questions, or follow directions.
The Bush–Francis Catatonia Rating Scale (BFCRS) score was 20.
Hospital Course
B. was admitted to a medical floor and evaluated by child and adolescent psychiatry. Despite initial consideration of ECT, mother remained hesitant about the treatment and strongly preferred to attempt other pharmacological interventions. After careful review of all available information, under a working diagnosis of catatonia associated with a primary psychotic disorder, a decision was made to start treatment with high-dose olanzapine.
Olanzapine was titrated up to 20 mg daily, while simultaneously tapering off diazepam, as it did not seem to have any beneficial effects and closely monitoring vital signs. B.'s condition quickly improved, as noted by both mother and the medical team. On day 3 of treatment with high-dose olanzapine, B. was more redirectable and intermittently communicative. On day 4, he was observed asking mother to open a soda can for him, and his BFCRS score was down to 12. On day 5, B. pulled out his nasogastric tube, and began eating. Benztropine 0.5 mg bid was added to address akathisia and sialorrhea, with good effect. On day 7, B. was still pacing, but was able to engage in interviews more meaningfully. BFCRS score was 7. Laboratories showed a mild elevation of liver transaminases that were declining within a couple of days (aspartate transaminase 50 → 33; alanine transaminase 92 → 79). Throughout his entire admission, B.'s vital signs were stable, and there was no concern for malignant catatonia or neuroleptic malignant syndrome (NMS).
When the diazepam taper was completed, B. was transferred to the inpatient psychiatry unit. On the unit, olanzapine was continued at the same dose with maintained improvement. B.'s speech became more fluent, and his responses more appropriate. His internal preoccupation appeared to resolve, and his thought process became increasingly organized. The family was offered a referral to a partial hospitalization treatment program, but parents declined, instead opting to take B. home with outpatient psychiatric follow-up.
Brief Formulation
B. was a 16-year-old adolescent boy with a history of schizophrenia who presented with symptoms consistent with catatonia. An extensive medical and neurological diagnostic evaluation confirmed that the catatonia was secondary to his primary psychotic disorder.
From a biological perspective, B. had a genetic predisposition to develop a psychiatric condition, given a family history positive for a half-brother with bipolar disorder. An additional biological factor that might have contributed was his recent treatment with aripiprazole, which appeared to be less effective than olanzapine and may have precipitated his catatonic state.
From a psychological perspective, B.'s recent decline in cognitive function and academic performance might have prompted psychological anguish leading to psychiatric decompensation. B.'s past academic achievement had been highly praised by his family, and his recent challenges with concentration in the context of this family dynamic may have resulted in higher levels of psychological distress. This might have also created an aversion to academic work and social engagement. Furthermore, B.'s relationship with mother seemed enmeshed at times; mother never left his bedside throughout his hospital stay, and often spoke for B., which may have perpetuated his poor communication with the treatment team even as he was beginning to improve.
From a social perspective, the social isolation and remote academic learning environment in the context of the COVID-19 pandemic might have also contributed to his psychiatric decompensation.
B.'s strengths included a high level of functioning before his psychotic illness and a supportive family.
Multi-Axial Diagnoses
Axis I: Schizophrenia, unspecified, with catatonia
Axis II: Deferred
Axis III: None
Axis IV: Cognitive and educational difficulties likely secondary to primary psychotic illness
Axis V: Global Assessment of Functioning: 8
Discussion
B.'s case is an excellent example of the challenges of evaluation and treatment of catatonia in adolescents. Catatonia is a syndrome that involves abnormal motor activity and behavior, with markedly decreased responsiveness to the environment. Although the majority of cases are associated with a mental disorder (Abrams and Taylor 1976), up to 25% of cases present in the context of a medical/neurological condition, such as anti-N-methyl-
To meet diagnostic criteria for catatonia, patients need to exhibit three or more of the following symptoms: stupor, catalepsy, waxy flexibility, mutism, negativism, posturing, mannerism, stereotypy, agitation, grimacing, echolalia, and echopraxia. It is estimated that catatonia is present in ∼10%–18% of the adult psychiatric inpatient population (Pommepuy and Januel 2002; Beach et al. 2017); however, literature suggests that the numbers in child and adolescent inpatient psychiatric units are much lower, <1% (Cohen et al. 1999, 2005).
Patients often present with refusal to eat or drink, and may require a nasogastric tube to prevent malnutrition, as was the case with B. It is important not to miss “malignant catatonia,” in the differential diagnosis, a life-threatening condition similar to NMS, with serious medical complications including dehydration, acute renal failure, autonomic instability, hyperthermia, and altered consciousness (Philbrick and Rummans 1994; Ghaziuddin et al. 2017).
The clinical presentation of catatonia and NMS is quite similar and, although the underlying neurobiology of catatonia is not fully understood, like NMS, it is thought to result from dysregulation of the GABAergic, glutamatergic (Rasmussen et al. 2016), and potentially dopaminergic, neurotransmitter systems (Ghaziuddin et al. 2017).
If an adolescent is suspected to have catatonia, screening can be done using one of several rating scales, including the widely used BFCRS (Bush et al. 1996), which was utilized for B. Once the diagnosis has been made, the etiology should be elucidated, and treatment should be initiated quickly, given the potential medical and psychiatric sequelae of catatonia. Benzodiazepines, which exert their effects through GABAA receptor agonism, are considered first-line treatment as they are effective and widely available. Benzodiazepines should be started immediately if catatonia is suspected while the diagnostic work-up of the underlying etiology is underway. Among the benzodiazepines, lorazepam is the most studied for treatment of catatonia (Hawkins et al. 1995). If treatment with lorazepam fails, ECT should be considered next, with a reported response rate of 80%–100% in adolescents (Consoli et al. 2010).
Although successful treatment of catatonia with benzodiazepines is well documented, some studies propose that it may not be as effective for all patient groups. Specifically, it has been reported that patients with schizophrenia are the least likely to respond to benzodiazepines (Ungvari et al. 1999; Rosebush and Mazurek 2010). Thus, although the treatment algorithm recommends ECT as the next step if benzodiazepines are ineffective at high doses, alternatives to benzodiazepines might be considered in cases of catatonia due to schizophrenia-spectrum illnesses. The extant literature does support the use of alternative agents for patients who do not respond sufficiently to benzodiazepines, and/or for whom ECT is unavailable or unappealing. Some of the agents identified include antiepileptic drugs, NMDA-R antagonists, and atypical antipsychotics (Beach et al. 2017).
Clinicians routinely avoid the use of antipsychotics in the treatment of catatonia. Owing to D2 dopamine receptor blockade, typical antipsychotics have potential to worsen catatonia, and may increase the risk of malignant catatonia or NMS. However, atypical antipsychotics block 5-HT2A receptors, resulting in higher levels of dopamine and have a lower affinity to D2 receptors, and are thus less likely to aggravate the underlying catatonic condition (Seeman and Tallerico 1998; Matsui-Sakata et al. 2005). Several atypical neuroleptics, including aripiprazole, clozapine, risperidone, ziprasidone, and olanzapine, were reported to be effective in case reports, mostly in patients with schizophrenia-spectrum illness, with or without the concomitant use of benzodiazepines (Van Den Eede et al. 2005; Beach et al. 2017). Specifically, olanzapine has been found to be effective in the treatment of nonmalignant catatonia, in doses ranging from 2.5 to 45 mg/day (Delbello et al. 2000; Cassidy et al. 2001; Tan et al. 2006; Babington and Spiegel 2007; Guzman et al. 2008).
In B.'s case, numerous factors were taken into consideration in choosing olanzapine as the next step in treatment. These factors include the reported insufficient improvement on benzodiazepines; mother's preference to exhaust psychopharmacological interventions before ECT; a history of beneficial response to olanzapine; and a clinical presentation consistent with a primary psychotic disorder underlying the catatonic symptoms, with an extensive neurological and medical work-up that ruled out other etiologies. Furthermore, B. was admitted to a medical floor where he could be monitored closely for potential symptoms of malignant catatonia or NMS.
In conclusion, this is a challenging case that illustrates successful treatment of catatonia with an atypical antipsychotic, despite potential risks. This case adds to the growing body of literature suggesting that in adolescents who present with nonmalignant catatonia associated with a primary psychotic disorder and who do not show sufficient improvement with benzodiazepines, atypical antipsychotics may be an effective alternative to ECT.
Footnotes
Acknowledgment
We acknowledge the editorial assistance from Maria Cruz, BA.
Disclosures
No competing financial interests exist.