Since the start of the coronavirus disease 2019 (COVID-19) pandemic, COVID-19 has seriously affected not only physical health but also mental health at multiple levels [1, 2]. The prevalence of depression, anxiety, insomnia, and other stress-related disorders has been increasing dramatically and has been researched in many studies . Meanwhile, COVID-19-induced first psychotic episodes have been reported in some cases [4-14]. COVID-19-induced psychotic symptoms might have several etiologies, including psychosocial stressors , inflammatory processes, immune reactions , and the side effects of the treatment for COVID-19 . In all cases, patients presented with various psychotic symptoms, especially hallucinations and delusions [5-14], while a few cases experienced severe symptoms, including even suicidal attempts and behavior [5, 8]. Most of these cases were approached early with an appropriate intervention and obtained full recovery around 2 weeks after commencing antipsychotics.
According to the Vietnamese Ministry of Health, approximately 790,750 cases of COVID-19 and 19301 COVID-19-related deaths were reported in Vietnam by October 1, 2021 . Since August 2021, social distancing strategies have been applied in many places in Vietnam, especially in Ho Chi Minh City, where most of the infected cases were reported. In our case, the patient suffered from COVID-19 and started to exhibit psychotic symptoms during the crisis period in which most hospitals were converted into COVID-19 treatment centers with a shortage of healthcare professionals. Therefore, she could not receive appropriate psychiatric intervention. Approaching a late intervention nearly 45 days after experiencing a psychotic episode led to a steady improvement and a slow recovery.
2. CASE PRESENTATION
A 25-year-old single female real estate broker had her first AstraZeneca vaccine on August 10, 2021. On the same day, she was diagnosed with COVID-19 by a nasopharyngeal swab after her roommates observed the symptoms of the disease.
She experienced various symptoms of COVID-19 infection, including fever, nasal congestion, sore throat, rhinorrhea, cough, dysgeusia, and anosmia. In particular, she suffered from severe insomnia and told her sister that she could not sleep at all. She received a prescription for paracetamol, thymodulin, and methylprednisolone from local specialists and took these medications for 3 days.
On August 19, 2021, she tested negative for COVID-19 and had no specific symptoms other than severe insomnia.
On August 20, 2021, she showed the symptoms of delusion for the first time. She told her roommates that she was possessed by a dead male student whom she had just met.
On August 22, 2021, she attempted suicide for the first time by jumping off the second-floor balcony when she saw some healthcare professionals coming to conduct a COVID-19 test. Fortunately, she had no severe injuries and did not receive any treatment.
Three days later, she again jumped from the fifth floor and landed on the metal roof of the house next door. She was admitted to the emergency department at Nhan Dan Gia Dinh hospital with a diagnosis of multiple traumas, including subarachnoid hemorrhage, fracture in the L1-L2 vertebrae, and pelvic injuries. Internal iliac artery ligation and external fixation of the pelvis and backbone were performed. The next day, she went into a coma and recovered after one week. Then, she received pain relievers, such as nefopam and gabapentin. However, she sometimes refused to take the medications, saying that the medications tasted bitter. She was discharged 25 days after hospitalization.
On September 30, 2021, she developed a high fever of 40°C, and she was admitted to a local hospital with a diagnosis of urinary tract infection. She was discharged one day later. Her COVID-19 test was negative.
She explained her suicidal behavior to her sister; she said that she heard the voice of a dead student asking her to jump off the balcony to see a beautiful landscape. During the illness period, she had poor quality of sleep and often had desultory conversations, but she did not show aggressive behavior. She also felt guilty about hurting her relatives.
She had no history of medical illness, previous psychosis, or substance abuse. There was also no family history of mental illness.
She denied having a mental health problem and refused to consult with any psychiatrists. Therefore, on October 4, 2021, the first online interview with her sister, who had been taking care of her during the illness period, was conducted under a lockdown situation in her living place.
One day later, she agreed to have an online meeting with a doctor who could give her advice on sleep. During the interview, she lay in bed, and her movements were normal. She had a blunted affect and showed slow speech. Because of her behavior, she developed guilt feelings toward her parents. Upon thinking about her suicidal behavior, she explained that she felt depressed and wanted to die, but she denied having any hallucinatory behavior. She had a clear and accurate orientation to the person, place, and time, except for the date. She reported that she sometimes heard a very soft and unclear voice and felt very anxious about her physical health. She also felt a fear of someone coming to harm her family. She also denied having suicidality and homicidality. She said that she wanted to take medication to improve her sleep.
During the hospitalization after her second suicide attempt, a head computed tomography scan revealed subarachnoid hemorrhage. An X-ray showed fractures in the L1-L2 vertebrae and pelvis. The full blood count and biochemical profile were normal.
4. DIFFERENTIAL DIAGNOSIS
The patient’s symptoms, including a sudden onset of the first psychotic episode that lasted more than 1 month, satisfied the ICD-10 criteria for the diagnosis of an ATPD .
Delirium is a common neurological manifestation of COVID-19 . However, in this case, delirium was ruled out due to the lack of amnesia and disorientation throughout the illness episode. Moreover, the DSM-5 criteria for the diagnosis of delirium require evidence of comorbidity along with physical conditions that could contribute to the syndrome , which were absent in this case. The patient recovered from COVID-19 and experienced the first psychotic episode simultaneously.
A diagnosis of drug-induced psychosis was also excluded, even though the patient received corticosteroids a few days before the onset of psychosis. Nevertheless, she stopped taking the medications before the onset of psychotic symptoms. Typically, patients with drug-induced psychosis exhibit symptoms within 1-2 weeks of the initiation of treatment , whereas our patient developed symptoms outside of this time window.
Schizophrenia spectrum disorder should be considered during a long-term follow-up period because she is at the typical age of onset of schizophrenia spectrum disorder. Of note, the psychotic episodes can be irrelevant to COVID-19 contracting and their occurrence might be incidental. A study by Schwartz et al. revealed that the initial diagnosis was valid only in 2% and 0.5% of patients with brief psychotic disorders after a 6-month and 24-month follow-up, respectively . The rest of the patients’ initial diagnoses changed over time, particularly the diagnosis of schizophrenia spectrum disorder; 34.5% and 31.7% of patients were still diagnosed with schizophrenia spectrum disorder after a 6-month and 24-month follow-up, respectively, whereas 26.5% and 24.3% of patients were still diagnosed with schizophrenia after a 6-month and 24-month follow-up, respectively. Another study by Rusaka et al. elucidated that the diagnosis of first-episode ATPD in 70% of patients eventually converted to schizophrenia .
In addition, this case did not meet the DSM-5 criterion for the diagnosis of schizoaffective disorder . Although a few depressive symptoms were observed, they did not meet the criteria for the diagnosis of a major depressive episode.
She still experienced auditory hallucinations and suffered from insomnia, as well as other stressors and serious trauma that might trigger the next episode. Therefore, she received antipsychotics and benzodiazepines. Due to her poor adherence to treatment and the availability of antipsychotics on the market, an oral solution containing 2 mg/mL haloperidol was administered. She received 1 mg of haloperidol per day (BID) and 5 mg of diazepam once at night. After 3 days, the dose of haloperidol was increased to 2 mg/day (BID) and was kept constant for the first week of treatment.
6. OUTCOME AND FOLLOW-UP
She was followed up on every day by online interaction with her sister. Her sleep duration improved to 6 h per night, and her mood was slightly elevated. An online interview was conducted 3 days and 7 days after the start of the treatment. There was no improvement during the one week based on the scores of the Brief Psychiatric Rating Scale (BPRS), which is presented in the table below.
One week after the treatment, other than an increase in sleep, no improvement in other symptoms was observed. Due to her slow recovery, the dose of haloperidol continued to level up and reached 5 mg a day (BID) after 1 month.
Six weeks after receiving treatment, her mood and behavior were in the normal range. She denied either hallucinations or delusions. She could do some household chores and read books related to her occupation. She noted that she felt happy with her current conditions and had planned to return to her work.
She did not attend the eight-week appointment and self-discontinued the antipsychotic without any consultation from psychiatrists
The patient had a very difficult time in her life because of a late psychiatric intervention, in addition to the lockdown and quarantine strategies that were applied in many places in Vietnam. She developed a psychotic episode after contracting COVID-19, received an antipsychotic 45 days later, and showed a slow improvement, whereas other reported cases recovered quickly during two weeks of treatment [5-12, 14]. The core features of a psychotic episode are delusion, hallucination, and suicidal behavior, which are consistent with the symptoms in previously reported cases [5-14].
Importantly, the patient received the first dose of the COVID-19 vaccine and exhibited the symptoms of COVID-19 on the same day. There were several cases reported of the relationship between the first psychotic episode and the administration of the COVID-19 vaccine [24-26]. However, Reinfeld et al. did not infer that psychotic symptoms were the side effects of the vaccine and suggested that patients at risk for new-onset psychosis should be closely monitored after receiving the COVID-19 vaccine , while Grover et al. hypothesized that psychotic episodes may be related to autoimmune mechanisms . In this case, the psychotic episode could have occurred due to the concomitant COVID-19 infection and COVID-19 vaccine administration. Since the concerns were recurrently reported by cases, more research related to this field would be required for a more comprehensive conclusion.
In particular, the patient made a full recovery with oral haloperidol, which is a first-generation antipsychotic. In a similar vein, in some cases with severe symptoms and/or aggressive behavior, haloperidol was first introduced in order to obtain significant improvement [6, 7], whereas olanzapine was started to target both psychotic symptoms and sleep disturbances [8, 14]. As for reducing side-effects in maintenance treatment, most patients received second-generation antipsychotics such as risperidone [7, 9-12, 14], and aripiprazole . As these symptoms might recur, especially in the case of psychosocial stressors , and the poor prognosis of an ATPD , the present patient was considered for long-term therapy with an atypical antipsychotic. The most likely diagnosis after a longitudinal follow-up would be schizophrenia spectrum disorder, schizophrenia, bipolar disorder, or major depressive disorder [22, 23].
This case was the first reported case of COVID-19 induced psychosis in Vietnam. On the other hand, due to guarantee strategies, the patient was examined and followed-up via online interview, which may have led to some limitations on the clinical examination.
General practitioners should be aware of psychiatric symptoms in patients recently diagnosed with COVID-19 because of the potential risk of harm and poor prognosis of psychiatric symptoms. In terms of specialists, psychiatrists should be mindful of the wide range of precipitating or perpetuating factors of psychiatric presentations associated with the COVID-19 pandemic. Therefore, the conditions requiring psychiatric interventions should be recognized, and psychiatric interventions should be provided as soon as possible to prevent severe consequences and recurrences.