Abstract
Chief Complaint and Presenting Problem
R. was a 17
History of Present Illness
Parents report that before the onset of illness, R. had been a healthy and fully functional adolescent with friends and activities. R. had moved to the United States ∼1.5 months before onset of illness from a South American country. One week before his presentation to the ED, he began to express paranoid thoughts, believing his 10-year-old sister was being “preyed upon” by her physical education teacher. R. also believed that a certain priest the family had met was trying to kill them all. Parents report he had been aggressive for about a month; however, his aggression had worsened recently, particularly toward father.
Parents reported R. had command type auditory hallucinations telling him to kill his father because of “lots of lies.” R. denied any plan or intent to harm anyone including his father. He repeatedly demonstrated disorganized behavior such as attempting to elope from home, undressing himself inappropriately in the presence of others, brushing his teeth excessively each time after eating, taking long showers more than three times a day, and drinking excessive fluids. During this time, R started to become withdrawn, and was reportedly sleeping <4 hours per night due to auditory hallucinations. There were no acute stressors identified before onset of his symptoms, other than stress related to their recent immigration.
In addition to his psychotic symptoms, R. reported feeling sad and withdrawn for inability to go to school in the United States. He reported believing he “can't achieve anything here.” He denied other depressive symptoms, suicidal ideation, intent, or plan. He also denied any illicit substance use.
Psychiatric History
There was no psychiatric history. Parents reportedly spoke to a doctor in their native country through telehealth 3 days before presentation, who recommended risperidone 0.5 mg two times daily for psychosis. Parents reported R.'s behavior and symptoms showed no improvement.
Developmental History
R was the first child of his family. Mother reportedly had regular prenatal care and denied any substance use during pregnancy. At 32 weeks' gestation, mother had premature labor contractions and required administration of isoxsuprine. At the time, there were no signs of early rupture of membranes. Intrauterine growth continued within normal limits until delivery. However, mother had prolonged labor for which she required induction of labor during delivery. Nevertheless, R was born at term through vaginal delivery without any other complications.
Birth weight was 3700 g at birth. At birth, R had torticollis that was successfully treated with massage therapy.
Mother reported that R met all developmental milestones on time.
Educational History
R was a high functioning student in school. He was in honor classes during his education and had successfully graduated high school with excellent grades.
Social History
R was born and raised by his parents in South America. He was an avid athlete, involved in tennis and swimming. He and his family moved to the United States ∼1.5 months before onset of illness; he was living in maternal aunt and uncle's house with his family and maternal grandmother. R. shared a room with both parents and a sister who was 10 years old.
Family History
Paternal uncle was diagnosed with schizophrenia and was on unknown medications. Paternal grandfather died by suicide.
Medical History
Medical history was notable for healthy growth and development. There was no history of sleep problems or nutritional deficiencies. R had no history of seizures, head injury, or loss of consciousness.
Mental Status Examination
On the initial mental status examination, R was awake, alert, and oriented to all three spheres. He was noted to have a tall and thin body habitus and dressed in a hospital gown. He presented with appropriate grooming and hygiene. He was calm and superficially engaged in the interview, often needing questions to be repeated in Spanish. He had intense eye contact with minimal blinking. Speech was monotonous, soft, and scarce that required prompting. Mood was euthymic, and affect was flat. Thought process was prominent for loose associations with tangential thinking and thought blocking. Thought content was illogical at times with paranoid-persecutory delusions, thought insertion, and thought broadcasting.
He reported command type auditory hallucinations and was observed responding to internal stimuli. No other sign of perceptual disturbance was noted. R denied suicidal ideation, but endorsed homicidal ideations on admission. He was easily distracted during the interview, was not able to maintain an appropriate level of attention and concentration. His memory was not tested officially; however, it was grossly intact. He exhibited poor insight and judgment.
Formulation
In summary, R was a 17-year-old Hispanic adolescent boy with acute onset psychosis that began upon immigration to the United States. Primary target symptoms included paranoid delusions, command-auditory hallucinations, disorganized behavior, and negative symptoms including affect blunting and social isolation. Family history of schizophrenia and completed suicide were predisposing factors. His recent relocation from South America to the United States was the primary predisposing factor. Perpetuating factors included inadequate psychiatric treatment, low socioeconomic status, and inability to continue school in the United States. Engagement in the offered treatment and family support were his protective factors.
Multiaxial Diagnoses
Treatment Course
R was hospitalized for 10 days for the management of psychosis. The hospital course was complicated by catatonia and akathisia.
Initially, R.'s risperidone was increased to 1 mg twice daily to target psychotic symptoms. Oral daily dose of diphenhydramine 50 mg was also initiated to target insomnia and prevent extrapyramidal syndrome symptoms. However, he continued to be paranoid, believing that there were cameras watching him and people were following him. He was observed to be disorganized and excited, pacing around the unit, and walking into rooms of other patients. R. at one point placed his hands around the neck of another patient. For these reasons, he required frequent intramuscular injections with olanzapine 5 mg and diphenhydramine 50 mg in the first few days of his admission.
R. continued to report auditory hallucinations commanding him to “do it” or “close your eyes,” or “be quiet.” Risperidone dose was gradually increased to 1 mg in the morning and 2 mg at bedtimes. A few days after admission, he developed catatonia with staring episodes, frequent echolalia, occasional mannerisms such as touching faces of staff and violating personal space, moderate rigidity, moderate refusal to eat or drink, intermittent motor excitement, perseverance, and frequent impulsivity. Bush-Francis Catatonia Rating Scale score was 15 at the time. R. also reported an internal feeling of restlessness, seen continuously pacing, anxious, and engaging in inappropriate behavior that suggested akathisia. Lorazepam 2 mg was administered intramuscularly as a challenge, which observably improved his symptoms.
Lorazepam 0.5 mg twice daily was subsequently started to target both catatonia and akathisia. Catatonia symptoms showed gradual improvement; however, paranoid persecutory delusions, command-type auditory hallucinations, and akathisia persisted into day 4 of admission. Risperidone was increased to 2 mg twice daily dose for psychotic symptoms and propranolol 10 mg twice daily dose was added for augmentation of akathisia treatment. Lorazepam was continued at 0.5 mg twice daily dose as it appeared to be helping the catatonia and diphenhydramine was continued at 50 mg at bedtime for insomnia. In the following 2 days, catatonia and akathisia symptoms completely resolved; however, psychotic symptoms persisted, for which risperidone was increased to 2 mg in the morning and 3 mg at bedtime.
After day 7 of admission, R became more cooperative. He was more linear and observed with significant improvement in his psychotic symptoms (paranoid-persecutory delusions, command-type auditory hallucinations, and disorganized behavior). Catatonia and akathisia symptoms remained under control. Lorazepam was discontinued carefully and gradually the following 3 days, and he was psychiatrically stable enough for discharge back home on risperidone 2 mg in the morning and 3 mg at bedtime, diphenhydramine 50 mg at bedtime, and propranolol 10 mg twice daily doses.
Discussion
Schizophreniform disorder is characterized by symptoms of psychosis lasting <6 months and closely related to schizophrenia. According to the American Psychiatric Association, two-thirds of individuals with schizophreniform disorder will eventually receive a diagnosis of schizophrenia or schizoaffective disorder (Torres, 2020). Schizophrenia is a complex brain condition defined by positive symptoms (e.g., hallucinations and delusions) and negative symptoms (e.g., alogia, flattened affect, and social withdrawal) (Gogtay et al., 2011).
It typically onsets during late adolescence and early adulthood. Early-onset schizophrenia begins between the ages of 13–18 years and is associated with a worse prognosis. In addition, onset in 50%–60% of these cases can be characterized by marked deterioration from previous level of functioning (Androutsos, 2012). Given an early onset, R. demonstrated positive and negative symptoms as well as rapid deterioration in functioning with added catatonic features described above.
Both genetic and environmental factors influence the development of psychosis. For example, there is higher familial predisposition and genetic loading in cases of childhood schizophrenia in comparison with adult onset (Androutsos, 2012). Such was R's case, as he had a family history of schizophrenia. In terms of environmental factors, R.'s first psychotic break occurred within the context of migrating from South America to the United States. Studies have shown that younger age of migration is associated with greater incidence of psychosis (Veling et al., 2011).
Migration during childhood is among the strongest risk factors for first onset psychosis, as this is a vulnerable period in which significant stressors may affect neurodevelopment (Kirkbride et al., 2017). Adversities, such as change of cultural context, psychosocial stressors, and underlying circumstances for immigration (e.g., economic or refugees/asylum seekers) experienced by immigrants may precipitate onset of psychosis. A phenomenological study found in immigrants that 70% of psychotic breaks occurred after migration that was likely due to stressors related to adapting to a new culture, language, and people in an unaccustomed environment (Pallaveshi et al., 2017).
Psychosis in adolescents is typically treated with antipsychotics. Studies have shown similar efficacy between first- (FGA) and second-generation antipsychotics (SGA) (Pillay et al., 2017) in the treatment, with the exception of clozapine that has superiority in treatment-resistant patients (Lee et al., 2020). The decision to use risperidone, a SGA, was made for R. given its evidence in the pediatric population (Hrdlicka and Dudova, 2007), and potentially more favorable side effect profile than an FGA (Pillay et al., 2018).
Risperidone has demonstrated efficacy in adolescent patients at doses between 1 and 6 mg daily. Doses higher than 6 mg daily have not been studied with adolescents (Klykylo et al., 2014). R.'s dose of risperidone was raised to 5 mg daily. In a study of adolescent schizophrenia comparing low-dose range risperidone (0.15–0.6 mg/day) and high-dose range risperidone (1.5–6.0 mg/day), the higher dose range showed greater efficacy in treatment both statistically and clinically (Haas et al., 2009). Although the literature suggests that doses >3 mg may have no additional benefit and a greater adverse effect burden (Klykylo et al., 2014), R.'s psychotic symptoms persisted at the lower dose.
In a review of optimal dosing and long-term effects of risperidone, it was recommended that patients with first episode schizophrenia risperidone should initially be treated with 4 mg/day or less and then slowly increased depending on clinical response (Kim and Kim, 2003). After increasing to 5 mg/day, R.'s psychotic symptoms significantly improved so that he was stable for discharge. A case series of early onset schizophrenia reported that several patients experienced improvement in functionality and reduction of positive and negative symptoms at 6-month follow-up on risperidone doses of 4–5 mg/day (Quintana and Keshavan, 1995).
Catatonia is rare in adolescents, with a frequency of 0.6% of the inpatient population (Cohen et al., 1999), but is commonly associated with schizophrenia (Cohen et al., 2005) and it carries greater morbidity and mortality (Cornic et al., 2009). Prompt diagnosis and treatment is essential. Lorazepam challenge is a means of diagnosing catatonia (Sienaert et al., 2014). R.'s diagnosis of catatonia was confirmed after improvement of his echolalia, impulsivity, refusal to eat or drink, and mannerisms after intramuscular lorazepam 2 mg.
The first-line treatment of catatonia is benzodiazepines (Raffin et al., 2015). We effectively treated R's catatonia with lorazepam; it has established efficacy secondary to its presumptive role in mitigating GABAergic dysfunction in the basal ganglia (Rasmussen et al., 2016). Benzodiazepines work through allosteric modulation of GABA-A receptors, thereby correcting deficiency of GABAergic function (Sienaert et al., 2014). A naturalistic cohort study in adolescents demonstrated that benzodiazepine treatment resulted in improvement in 65% of cases; there was no correlation between dose and efficacy (Raffin et al., 2015).
Low-dose lorazepam was given for R. as it is also the most reported benzodiazepine for catatonia treatment (Zaman et al., 2019). Clonazepam and diazepam have also been used in the pediatric population (Valerstain et al., 2023) Longer acting benzodiazepines at higher doses may be required to adequately treat catatonia due to the putative baseline cortical hyperplasticity in children (Smith et al., 2023).
Electroconvulsive therapy or other pharmacological approaches can also be used to treat catatonia if there is contraindication or poor response to benzodiazepines (Rasmussen et al., 2016). A retrospective analysis showed that valproic acid, N-methyl-D-aspartate receptor antagonists, and SGA were safe and effective in treating pediatric catatonia (Smith et al., 2023). These treatments are likely effective because in addition to GABA dysfunction, pathophysiology of catatonia also implicates glutamate, serotonin, and dopamine pathway disruption (Burrow et al., 2023).
Given that R.'s presentation was complicated by catatonia, and risperidone was continued, a decision whether to discontinue antipsychotics due to the associated risk of worsening catatonia or precipitating neuroleptic malignant syndrome or malignant catatonia was necessary. (Sienaert et al., 2014). The risk of catatonia seems to be higher with FGAs due to higher D2 blockade and potential for extrapyramidal symptoms (Sienaert et al., 2014). However, although some may suggest that antipsychotics are ineffective, other studies indicate that SGAs may be beneficial in catatonia (Burrow et al., 2023), possibly due to the 5HT-2 antagonist activity that may stimulate dopamine release in the prefrontal cortex (Sienaert et al., 2014).
There have also been multiple case reports that describe how risperidone in combination with a lorazepam taper has been used successfully in several cases of benzodiazepine-resistant catatonia in psychosis in young patients (Aboraya et al., 2009; Grenier et al., 2011).
Akathisia is a neuropsychiatric syndrome that commonly occurs as an early adverse effect of antipsychotics and presents as psychomotor restlessness usually involving the lower extremities (Pringsheim et al., 2018). Patients often report feeling the urge to move and demonstrate an inability to sit still. Some patients may describe the feeling of restlessness while not engaging in actual movement (Patel and Marwaha, 2023). Akathisia, one of the most common extrapyramidal symptoms, is thought to occur as a result of neurotransmitter imbalance in the nucleus accumbens (Patel and Marwaha, 2023). Early identification of akathisia is important in youth due to the high risk of morbidity and risk of suicidal ideation if left untreated (Patel and Marwaha, 2023).
An initial management step for akathisia is to lower the dose of the precipitating medication or to switch to an antipsychotic with a lower risk of extrapyramidal symptoms (Patel and Marwaha, 2023). Reduction of R.'s dose of antipsychotic or switching medications was not an option due to the risk of worsening his psychotic symptoms. Beta-blockers such as propranolol, or benzodiazepines such as lorazepam have been historically used for treatment. However, propranolol is more efficacious than lorazepam (Adler et al., 1985; Sharma et al., 2005).
It is also the most studied for akathisia and does not have the added risk of dependence, which makes it suitable for long-term use (Pringsheim et al., 2018). Unless the patient has pre-existing congestive heart failure or asthma (in which case benztropine would be more appropriate), propranolol is considered as first-line treatment of akathisia (Patel and Marwaha, 2023). In addition, recent studies may indicate that low-dose mirtazapine may be as effective as propranolol (Poyurovsky and Weizman, 2018; Pringsheim et al., 2018). R.'s akathisia was treated successfully with 10 mg propranolol twice and resolved completely within 2 days.
In summary, R.'s case offers insight into the role genetics and environment play in the early onset of psychosis. It also illustrates the complexity of his clinical picture, given psychosis with catatonia and akathisia, highlighting the importance of early recognition and treatment to improve outcomes. R.'s response is illustrative of the concept that targeted pharmacotherapy can be effective and safe in youth, SGAs can be effectively used to treat early onset psychosis, benzodiazepines offer safe and effective treatment of comorbid catatonia, and propranolol can be effective in addressing akathisia.
Footnotes
Disclosures
B.J.C. is on the scientific advisory board of the Tourette Association of America, medical advisory board of Galen Mental Health, and received honoraria from the American Academy of Child and Adolescent Psychiatry, Partners Healthcare, Harvard Medical School/Psychiatry Academy, grant support from Florida Children's Medical Services, and research support from Emalex, NIMH, and Zynerba. She is on the national advisory board of Skyland Trail and was former cochair of the medical advisory board of the Tourette Association of America (TAA), a nonpaid position. R.I., D.O., G.H., and Y.B. have no disclosures.