Psychotic Symptoms After SARS-CoV-2 Infection.

ABSTRACT: This case series reports three middle-aged male patients with no prior history of psychiatric disorders who developed psychotic symptoms with manic characteristics after COVID-19 infection. They presented mystic and paranoid delusions associated with euphoria, logorrheic, insomnia, and bizarre behaviors. Two of them required psychiatric hospitalization and one received corticosteroids. Treatment with antipsychotic medication improved their symptoms in a few weeks. This case series reports the new-onset psychosis probably due to COVID-19 infection. Pathogenetic speculation about the probable causes of COVID-19 psychosis, such as inflammatory reaction and corticosteroid use, was done. Moreover, other probable causes of manic psychosis, such as late-onset bipolar disorder, were also considered and ruled out. There is a need for more research to determine the causality between psychotic symptoms and COVID-19 infection.

Bipolar type I diagnosis after a manic episode secondary to SARS-CoV-2 infection: A case report.

RATIONALE: Our objective is to provide awareness about psychotic vulnerability in patients infected with SARS-CoV-2 and to better understand the role of steroid withdrawal in manic episodes, especially with its common usage in respiratory disease caused by SARS-CoV-2. PATIENT CONCERNS: We present the case of a patient who was hospitalized twice after discontinuing steroid therapy for SARS-CoV-2 infection and presented with a manic episode despite not having a psychiatric history. DIAGNOSIS: The patient tested positive on a polymerase chain reaction test for SARS-CoV-2 and developed pneumonia. Other organic differential diagnoses such as encephalitis were also investigated and excluded. Manic episodes were diagnosed according to DSM-V criteria. Subsequently, the patient was diagnosed with type I bipolar disorder. INTERVENTIONS: According to the protocols, supplemental oxygen therapy, prophylactic enoxaparin and intravenous (IV) steroids were administered. Steroid dosage was gradually reduced under supervision. During the acute mania, antipsychotics and benzodiazepines were administered. OUTCOMES: After discharge, the patient was admitted to the psychiatric consultation service. He first received mood stabilizer therapy and then received supportive psychotherapy. LESSONS: Psychotic symptoms commonly occur after the discontinuation of high-dose steroid therapy; however, controlled tapering may prevent these side effects. Only a few cases have reported concomitant SARS-CoV-2 infection and manic episodes, often with an apparent relationship with steroid withdrawal syndrome. In this case, we considered psychotic vulnerability a condition that is often underestimated. In consideration of the SARS-CoV-2 pandemic, the case may represent an underlying trigger for psychotic decompensation, which, in concert with neuroinflammation, may induce a manic episode.

Effectiveness of electroconvulsive therapy in acute management of delirious mania in COVID-19 positive woman in second trimester pregnancy.

Delirious mania has been described as a state of acute excitement, fluctuating sensorium, affective and catatonic symptoms. Electroconvulsive therapy (ECT) despite being an effective treatment modality in such cases, has been under-utilised during pregnancy, mainly due to safety concerns. Here, we report the effectiveness of ECT in acute management of delirious mania in a 24 weeks pregnant woman who also tested COVID-19 positive during hospitalisation. Patient presented with three weeks history of acute manic excitement with period of altered sensorium and catatonic symptoms with no response to trials of two antipsychotic agents. After organic causes ruled out, patient was planned for ECT while ongoing antipsychotic was continued. After the first ECT session, patient tested positive for COVID-19, though asymptomatic and had to be shifted to COVID-19 isolation facility. Complete resolution of psychiatric symptoms occurred after fifth ECT. All five ECT sessions, including those in COVID-19 isolation facility were carried out under supervision of a multidisciplinary team. None of the ECT sessions had any major adverse event. Symptom remission sustained even following ECT discontinuation. No neonatal or maternal adverse effects observed after an uneventful delivery at 35 weeks. Both mother and child continued to maintain well in follow-up period of one year on oral olanzapine. In this unusual concurrent presentation of mania, delirium and catatonic symptoms during second trimester pregnancy, we highlighted the effectiveness and safety of ECT as a viable treatment modality. Additionally, management challenges posed by patient testing COVID-19 positive and then, administering ECT in COVID-19 isolation facility using personal protective equipment by multidisciplinary team has been highlighted.

Antiviral, immunomodulatory, and neuroprotective effect of lithium.

Currently, in psychiatry, lithium is a drug of choice as a mood stabilizer in the maintenance treatment of bipolar disorder for the prevention of manic and depressive recurrences. The second most important psychiatric use of lithium is probably increasing the efficacy of antidepressants in treatment-resistant depression. In addition to its mood-stabilizing properties, lithium exerts antisuicidal, antiviral, immunomodulatory, and neuroprotective effects. The goal of the review is to describe the experimental and clinical studies on the last three properties of lithium. Antiviral effects of lithium pertain mostly to DNA viruses, especially herpes viruses. The therapeutic effects of lithium in systemic and topical administration on labial and genital herpes were demonstrated in clinical studies. There is also some evidence, mostly in experimental studies, that lithium possesses antiviral activity against RNA viruses, including coronaviruses. The immunomodulatory effect of lithium can mitigate "low-grade inflammatory" conditions in bipolar illness. The neuroprotective properties of lithium make this ion a plausible candidate for the prevention and treatment of neurodegenerative disorders. A favorable effect of lithium was shown in experimental models of neurodegenerative disorders. On the clinical level, some preventive action against dementia and moderately therapeutic activity in Alzheimer's disease, and mild cognitive impairment were observed. Despite promising results of lithium obtained in animal models of Huntington's disease and amyotrophic lateral sclerosis, they have not been confirmed in clinical studies. A suggestion for common mechanisms of antiviral, immunomodulatory, and neuroprotective effects of lithium is advanced.

Association between serum lithium level and incidence of COVID-19 infection.

An antiviral effect of lithium has been proposed, but never investigated for coronavirus disease 2019 (COVID-19). Using electronic health records of 26 554 patients with documented serum lithium levels during the pandemic, we show that the 6-month COVID-19 infection incidence was lower among matched patients with 'therapeutic' (0.50-1.00) versus 'subtherapeutic' (0.05-0.50) lithium levels (hazard ratio (HR) = 0.82, 95% CI 0.69-0.97, P = 0.017) and among patients with 'therapeutic' lithium levels versus matched patients using valproate (HR = 0.79, 95% CI 0.67-0.92, P = 0.0023). Lower rates of infection were observed for both new COVID-19 diagnoses and positive polymerase chain reaction tests, regardless of underlying psychiatric diagnosis and vaccination status.

Lamotrigine may Increase Risk of Arrythmias.

The Food and Drug Administration (FDA) is advising health care practitioners that lamotrigine (Lamictal), used in managing seizures and bipolar disorder, may increase the risk of serious and potentially lethal arrythmias.The risk is greater if the patient has underlying cardiac disease or is taking medications that affect heart conduction.The FDA is requiring in vitro studies of other sodium channel blockers to determine if this risk is a class effect or unique to lamotrigine.

Effect of medication therapy combined with transcranial direct current stimulation on depression and response inhibition of patients with bipolar disorder type I: a clinical trial.

OBJECTIVE: Bipolar Disorder (BD) is one of the most common mental disorders associated with depressive symptoms and impairment in executive functions such as response inhibition. This study aimed to investigate the effectiveness of medication therapy combined with Transcranial Direct Current Stimulation (tDCS) on depression and response inhibition of patients with BD. METHOD: This is a double-blinded randomized clinical trial with pretest, posttest, and follow-up design. Participants were 30 patients with BD randomly assigned to two groups of Medication+tDCS (n = 15, receiving medications plus tDCS with 2 mA intensity over dorsolateral prefrontal cortex for 10 days, two sessions per day each for 20 min) and Medication (n = 15, receiving mood stabilizers including 2-5 tables of 300 mg (mg) lithium, 200 mg sodium valproate, and 200 mg carbamazepine two times per day). Pretest, posttest and 3-month follow-up assessments were the 21-item Hamilton Depression Rating Scale (HDRS) and a Go/No-Go test. Collected data were analyzed in SPSS v.20 software. RESULTS: The mean HDRS score in both groups was reduced after both interventional techniques, where the group received combined therapy showed more reduction (P < 0.01), although their effects were not maintained after 3 months. In examining response inhibition variable, only the combined therapy could reduce the commission error of patients under a go/no-go task (p < 0.05), but its effect was not maintained after 3 months. There was no significant difference in the group received medication therapy alone. CONCLUSION: Medication in combination with tDCS can reduce the depressive symptoms and improve the response inhibition ability of people with BD. TRIAL REGISTRATION: This study was registred by Iranian Registry of Clinical Trials (Parallel, ID: IRCT20191229045931N1 , Registration date: 24/08/2020).

Delirious mania in a patient with COVID-19 pneumonia.

Delirious mania (the coexistence of delirium and mania) is described in the literature but not recognised in standard nosologies. We report a woman in her late 30s, with no psychiatric history, who presented with concurrent symptoms of mania and delirium. She was diagnosed with COVID-19 pneumonia (positive reverse transcription-PCR test). There was no history of substance misuse or concurrent medical illness. CT head scan was normal as were blood investigations, other than elevated inflammatory markers. She received standard treatment for COVID-19 pneumonia and lorazepam and quetiapine to treat her neuropsychiatric symptoms. She made a full recovery after 9 days. She was apyrexial with normal oxygen saturation throughout her illness. The case shows that severe neuropsychiatric symptoms can complicate otherwise mild COVID-19 pneumonia with neuroinflammation being a possible mechanism. A diagnosis of delirious mania appears to better capture the complexity of the presentation than a diagnosis of mania or delirium alone.

Lithium toxicity at therapeutic doses as a fallout of COVID-19 infection: a case series and possible mechanisms.

Lithium, a mood stabilizer used in the treatment of bipolar disorder is known for its anti-inflammatory properties with the discussion of its potential use in COVID-19 infection. The SARS-CoV-2 virus causing COVID-19 infection is known to enter the target cells through angiotensin converting enzyme-2 receptors present in abundance in the lung and renal tissue. Recent research supports the evidence for direct renal injury by viral proteins. Here we report two patients with bipolar disorder presenting with lithium toxicity in the presence of COVID-19 infection. Two patients with bipolar disorder, maintaining remission on lithium prophylaxis, presented to the psychiatric emergency with recent-onset fever and altered sensorium. Both the patient's investigations revealed lithium toxicity, elevated serum creatinine, urea and inflammatory markers. Hypernatremia, hyperkalaemia, and hyperchloremia were seen in one patient. Lithium and other psychotropic medications were stopped immediately, and COVID-19 treatment was initiated. Patient with clinical signs of lithium toxicity, hypernatremia, hyperkalaemia, and hyperchloremia developed ventricular tachycardia. He survived and regained consciousness after 2 weeks of aggressive conservative management. However, another patient died of acute respiratory failure on day 3. Possible direct infection of the kidney by SARS-CoV-2 viral proteins can manifest with acute kidney injury and lithium toxicity among patients on long-term lithium therapy. Health professionals treating COVID-19 infection among individuals on lithium therapy should be aware of the possibility of lithium toxicity in the background of renal injury.

Study protocol for a randomised placebo-controlled trial of pramipexole in addition to mood stabilisers for patients with treatment resistant bipolar depression (the PAX-BD study).

BACKGROUND: Treatment Resistant Bipolar Depression (TRBD) is a major contributor to the burden of disease associated with Bipolar Disorder (BD). Treatment options for people experiencing bipolar depression are limited to three interventions listed by National Institute for Health and Care: lamotrigine, quetiapine and olanzapine, of which the latter two are often not well tolerated. The majority of depressed people with BD are therefore prescribed antidepressants despite limited efficacy. This demonstrates an unmet need for additional interventions. Pramipexole has been shown to improve mood symptoms in animal models of depression, in people with Parkinson's Disease and two proof of principle trials of pramipexole for people with BD who are currently depressed. METHODS: The PAX-BD study, funded by the United Kingdom (UK) National Institute for Health Research, aims to extend previous findings by assessing the efficacy, safety and health economic impact of pramipexole in addition to mood stabilisers for patients with TRBD. A randomised, double-blind, placebo controlled design is conducted in a naturalistic UK National Health Service setting. An internal pilot study to examine feasibility and acceptability of the study design is included. Participants with TRBD are screened from National Health Service secondary care services in up to 40 mental health trusts in the UK, with the aim of recruiting approximately 414 participants into a pre-randomisation phase to achieve a target of 290 randomised participants. Primary safety and efficacy measures are at 12 weeks following randomisation, with follow up of participants to 52 weeks. The primary outcome is depressive symptoms as measured by Quick Inventory for Depressive Symptomatology - Self Report. Secondary outcomes include changes in anxiety, manic symptoms, tolerability, acceptability, quality of life and cost-effectiveness. Outcome measures are collected remotely using self-report tools implemented online, and observer-rated assessments conducted via telephone. ANCOVA will be used to examine the difference in rating scale scores between treatment arms, and dependent on compliance in completion of weekly self-report measures. A mixed effects linear regression model may also be used to account for repeated measures. TRIAL REGISTRATION: ISRCTN72151939. Registered on 28 August 2019, http://www.isrctn.com/ISRCTN72151939 Protocol Version: 04-FEB-2021, Version 9.0.

Severe mental illness is associated with increased mortality and severe course of COVID-19.

OBJECTIVE: Psychiatric disorders have been associated with unfavourable outcome following respiratory infections. Whether this also applies to coronavirus disease 2019 (COVID-19) has been scarcely investigated. METHODS: Using the Danish administrative databases, we identified all patients with a positive real-time reverse transcription-polymerase chain reaction test for COVID-19 in Denmark up to and including 2 January 2021. Multivariable cox regression was used to calculate 30-day absolute risk and average risk ratio (ARR) for the composite end point of death from any cause and severe COVID-19 associated with psychiatric disorders, defined using both hospital diagnoses and redemption of psychotropic drugs. RESULTS: We included 144,321 patients with COVID-19. Compared with patients without psychiatric disorders, the standardized ARR of the composite outcome was significantly increased for patients with severe mental illness including schizophrenia spectrum disorders 2.43 (95% confidence interval [CI], 1.79-3.07), bipolar disorder 2.11 (95% CI, 1.25-2.97), unipolar depression 1.70 (95% CI, 1.38-2.02), and for patients who redeemed psychotropic drugs 1.70 (95% CI, 1.48-1.92). No association was found for patients with other psychiatric disorders 1.13 (95% CI, 0.86-1.38). Similar results were seen with the outcomes of death or severe COVID-19. Among the different psychiatric subgroups, patients with schizophrenia spectrum disorders had the highest 30-day absolute risk for the composite outcome 3.1% (95% CI, 2.3-3.9%), death 1.2% (95% CI, 0.4-2.0%) and severe COVID-19 2.7% (95% CI, 1.9-3.6%). CONCLUSION: Schizophrenia spectrum disorders, bipolar disorder, unipolar depression and psychotropic drug redemption are associated with unfavourable outcomes in patients with COVID-19.

Management challenges in patients with comorbid COVID-19 associated delirium and serious mental illness - A case series.

BACKGROUND: There is still a lot unknown about the novel Coronavirus Disease 19 (COVID-19) and its effects in humans. This pandemic has posed several challenging clinical situations to healthcare providers. OBJECTIVE: We hope to highlight the distinctive challenges that COVID-19 presents in patients with serious mental illness and what steps primary medical teams can take to co-manage these patients with the psychiatry consultants. METHODS: We present a retrospective chart review of four patients who were on psychotropic polypharmacy and admitted to our hospital from the same long-term psychiatric facility with COVID-19 delirium and other associated medical complications. RESULTS: We illustrate how the primary medical teams and psychiatrists collaborated in clinical diagnosis, treatment, and management. CONCLUSIONS: Patients with serious mental illness and COVID-19 infection require active collaboration between primary medical teams and psychiatrists for diagnostic clarification, reduction of psychotropic polypharmacy to avoid adverse effects and drug-drug interactions, prevention of psychiatric decompensation, and active management of agitation while balancing staff and patient safety concerns.