Relapse in bipolar disorder in hospitalized patients with COVID-19: A case series and key recommendations.

COVID-19 has adversely affected the lives of people with bipolar disorder (BD). We have reported three patients with BD, who suffered from relapse after being diagnosed with COVID-19. Patient X is a 54-year-old man who developed manic episode, while Y is a 63-year-old man and Z is a 52-year-old woman who developed severe depression after being hospitalized for COVID-19. In this case series, three patients with BD who developed manic or depressive episodes during COVID-19 infection have been described. Adequate liaison between consultation-liaison psychiatrist and primary medical team was done. Rational pharmacotherapy along with psychosocial interventions led to favorable outcomes in all three cases. Copyright:

INTRODUCTION

The COVID-19 pandemic has caused an unprecedented disruption worldwide. This disruption is likely to affect the lives of people with mental illness more adversely, especially those with bipolar disorder (BD), as they are most affected by the alteration in biological and social rhythm. The diagnosis of COVID-19 and subsequent hospitalization, psychological distress, and neuropsychiatric manifestations of the illness can lead to relapse in BD. New-onset manic symptoms in patients with COVID-19 have been documented in a few case reports.[12] Here, we present a case series of three patients with BD, who suffered from a relapse after being diagnosed with COVID-19. In addition, we have discussed a few recommendations for the management of hospitalized patients with BD and COVID-19.

CASE REPORTS

Case 1

X, a 58-year-old man with BD, diabetes, and COVID-19 pneumonia (reverse transcription–polymerase chain reaction [RT-PCR] positive), was admitted due to fever, cough, and breathlessness. He had 20 episodes of depression and mania in the last 25 years. He was maintaining well on sodium valproate 1500 mg/d and chlorpromazine 100 mg/d for the last 3 months. After admission, parenteral amoxicillin, dexamethasone 18 mg/d, and remdesivir 600 mg (over 5 days) were administered. On day 2 of admission, he appeared excessively cheerful and overtalkative. He displayed disinhibited behavior like undressing inside the ward. His sleep reduced to 4–5 h/night, and he reported multiple grandiose ideas. After 1 week, his physical condition improved, but behavioral disturbances persisted. On mental status examination (MSE), he was oriented, had increased psychomotor activity, increased volume of speech, exalted mood, prolixity of thought, ideas of grandiosity, and poor insight. On investigation, inflammatory markers were raised [Table 1]. He was diagnosed as BD, current episode mania without psychotic symptoms. Chlorpromazine was stopped, and haloperidol 10 mg was started. Sodium valproate 1500 mg was continued. Gradually, his sleep improved; psychomotor activity and behavior returned to normalcy. Within 7 days, Young Mania Rating Scale score reduced from 26 to 6 and he was subsequently discharged. In follow-up consultations, he was found to be maintaining well after 4 weeks of discharge.

Table 1

Inflammatory markers of three cases

Laboratory tests (normal value)	X	Y	Z
D-dimer (<0.50 mcg/mL)	1.01	6.85
hsCRP (<1.0 mg/L)	176.79		14.39
LDH (140-280 U/L)	445	566
Ferritin (20-250 ng/mL)	1263	1879
IL-6 (5-15 pg/mL)	9.7	3.1

IL6 – Interleukin 6; LDH – Lactate dehydrogenase; hsCRP – High sensitive C reactive protein

Case 2

Y, a 63-year-old man with hypertension, epilepsy, BD, and COVID-19 (RT-PCR positive), was admitted due to fever and dyspnea for 2 days. He had 25 episodes of mania and depression in the last 25 years. The last episode (mania) was 1.5 years ago. He was on sodium valproate 600 mg/d and quetiapine 25 mg/d. After admission, he was started on parenteral antibiotics (linezolid, piperacillin + tazobactam), dexamethasone 18 mg/d, and remdesivir (600 mg over 5 days). Although his clinical condition was improving, he started reporting persistent and pervasive low mood, anhedonia, fatigue, decreased sleep and appetite, ideas of hopelessness, and guilt for the 3rd day of admission. Over the next 2–3 days, he communicated death wishes and pleaded that he must be administered a lethal dose of medications. On MSE, he was tearful, had decreased psychomotor activity, sad affect, ideas of hopelessness, death wishes, decreased attention span, and impaired personal judgment. Upon investigations, serum lactate dehydrogenase, D-dimer, and ferritin levels were raised [Table 1]. Diagnosis of BD, current episode severe depression without psychotic symptoms, was made (based on severity; however, duration was <2 weeks). Supportive sessions were held. Quetiapine was hiked to 100 mg/d, and sodium valproate 600 mg/d was continued. Within 1 week, his mood improved and Hamilton Depression Rating Scale (HDRS) score improved from 25 to 6 and he was subsequently discharged. In follow-up telepsychiatric consultations, he was found to be maintaining well after 4 weeks of discharge.

Case 3

Z, a 52-year-old woman, known case of BD and interstitial lung disease, was admitted after being diagnosed with COVID-19 by RT-PCR. She had BD for 13 years, and the last episode (severe depression) was 10 months back. She was maintaining well on sodium valproate 800 mg/d and lurasidone 40 mg/d. On the 2nd week of admission, she developed persistent and pervasive sadness, excessive tiredness, and decreased interest in activities. Her interaction with others reduced, and she reported decreased sleep and appetite. She was often irritable and refused to take food and medications. She expressed pessimistic views regarding her health and suicidal ideation. On MSE, she was tearful, had reduced psychomotor activity, ideas of hopelessness, and helplessness. Investigations revealed raised serum C-reactive protein levels [Table 1]. On reviewing the medications, we found that lurasidone had been inadvertently discontinued after admission. We made a diagnosis of BD, current episode severe depression without psychotic symptoms, and lurasidone up to 40 mg/d was restarted. Supportive sessions were taken. Gradually, she improved, and HDRS score reduced from 24 to 8 in 10 days. Regular telepsychiatry consultations were done after discharge, and she maintained well after 3 months of discharge.

DISCUSSION

This case series points toward a possible association between relapse in BD and COVID-19. Patient X developed manic symptoms, while Y and Z developed depressive symptoms after being diagnosed with COVID-19. There are multiple explanations for relapse in BD in COVID-19 patients. First of all, as seen in all three index cases, COVID-19 is associated with production of a high amount of pro-inflammatory factors.[3] This pro-inflammatory state leads to relapse in patients with BD.[45] Second, iatrogenic factors, such as administration of corticosteroids and antibiotics, might also lead to relapse in BD, as they have been reported to induce manic and depressive episodes.[67] Third, stress due to diagnosis of COVID-19, isolation, and hospitalization can also lead to relapse in BD. Onset of manic symptoms due to stress associated with COVID-19 pandemic has been reported.[89] Finally, inadvertent discontinuation of medications during hospitalization, as seen in patient Z, could lead to relapse.

As hospitalized patients with COVID-19 and BD are more prone to suffer from relapse, liaison with psychiatry should be done for all patients with BD. In addition, patients should be encouraged to follow an activity schedule, tailored as per their clinical condition, to minimize disruption of their daily rhythms. While using psychotropic agents, interaction of these medications with corticosteroids, remdesivir, and antimicrobials should be kept in mind.[10] Follow-up should be planned (either in-person or telepsychiatry) and patients should be helped to cope with interpersonal and financial losses.

To conclude, manic and depressive episodes in hospitalized COVID-19 patients present many challenges, often leading to overutilization of resources and poor outcomes. However, adopting a flexible approach with these patients along with prompt liaison with psychiatrists, may lead to better therapeutic outcomes. Well-designed studies should be conducted to assess the effectiveness of different pharmacological and nonpharmacological interventions for the prevention and management of relapse of BD in patients with COVID-19.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the legal guardian has given his consent for images and other clinical information to be reported in the journal. The guardian understands that names and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.