A Case-Based Window Into Treating Acute Anxiety in COVID-19 Patients

It’s widely recognized that patients with COVID-19 may suffer from anxiety, mood dysregulation, anger and worsening of any preexisting mental illnesses. While there are currently no definitive guidelines specific to the treatment of emotional distress related to COVID-19, a new case-based review published in Cleveland Clinic Journal of Medicine’s COVID-19 Curbside Consults series offers some practical guidance in the meantime.

Case vignette

The review, “Treating Acute Anxiety in Patients with COVID-19,” details the case of a 62-year-old woman with a history of diabetes mellitus and hypertension who was admitted to a COVID-19 nursing floor upon testing positive for COVID-19 after presenting to the emergency department with worsening shortness of breath and flulike symptoms over the prior week. She had a history of diabetes mellitus and hypertension.

She was placed on supplemental oxygen, with improvement in oxygen saturation to 96%. In the setting of social distancing (no visitors, communication with family only by iPad), she exhibited several acute anxiety attacks, with episodes of chest tightness, fear and hyperventilation. A psychiatry consult was requested to help the patient manage her emotional distress.

During a virtual psychiatric interview, the patient reported worsening anxiety over the prior couple of weeks since residents in her state had been ordered to shelter in place. She said she felt isolated and scared and began experiencing insomnia, anxiety, decreased appetite and low energy at home. She reported being a lifelong generalized worrier but denied any prior psychiatric treatment. There was no evidence of confusion, mania or psychosis during the interview. She had experienced an acute panic attack in the past after a motor vehicle accident. She is a retired librarian and divorced mother of two grown children. The clinical impression was acute panic attacks and worsening of generalized anxiety disorder.

Electrocardiography showed sinus tachycardia, and the QTc interval was prolonged at 570 ms. Her respiratory rate remained elevated at 28 breaths per minute, and her oxygen saturation by pulse oximetry was 95% while she received supplemental oxygen by nasal cannula. She was awake and alert and reported feeling very stressed. There were no signs of accessory respiratory muscle use during physical exam.

In addition to medical management of her COVID-19 symptoms, she was given low-dose lorazepam, 0.5 mg intravenously every 8 hours as needed, for breakthrough panic. After a single dose, there was a subjective drop in panic symptoms and an objective decrease in respiratory rate to 20 breaths per minute. She remained awake and alert. Her oxygen saturation remained unchanged at 95% to 96% on supplemental oxygen.

She was started on gabapentin 100 mg three times daily for anxiety, along with melatonin 5 mg every night for insomnia. The gabapentin dose was increased gradually to 300 mg three times daily, with good results. Lorazepam was continued on an as-needed basis. Daily supportive psychotherapy (via cellphone) was provided. Her anxiety symptoms improved in tandem with her respiratory symptoms. She did not require admission to an intensive care unit and was discharged home with low-flow oxygen after a six-day hospital stay. Psychiatry recommended a low-dose selective serotonin reuptake inhibitor for long-term management of generalized anxiety disorder.

Takeaways from the case

The review’s authors — Cleveland Clinic psychiatrists Leo Pozuelo, MD, and Elias Khawam, MD, along with critical care medicine specialist Hassan Khouli, MD — note that research on previous viral outbreaks has revealed significant and wide-ranging psychosocial distress that impacted individuals and communities alike. They write that in the absence of firm guidelines for treatment of COVID-19-related emotional distress, their approach is based on the standard of care for managing anxiety in medically ill patients, factoring in associated medical comorbidities, drug-drug interactions and the patient’s individual needs and preexisting mental illness.

“Interventions should be implemented at the bedside to augment the patient’s own resiliency in coping with these stressful events,” they write. “A targeted combination of psychopharmacology (targeting acute anxiety and panic symptoms) and psychotherapy (relaxation techniques, breathing exercises and encouragement) is recommended.”

Pharmacotherapy considerations

They review considerations around pharmacologic management of acute anxiety in hospitalized patients with COVID-19, highlights of which are summarized below.

Benzodiazepines. Because benzodiazepines produce an immediate anxiolytic effect, they are worthy of consideration for treating anxiety and panic symptoms in the setting of mild respiratory distress. The short-acting agents alprazolam and lorazepam are preferred over their counterparts with a longer half-life, such as diazepam and chlordiazepoxide.

The authors caution, however, that benzodiazepines should be used cautiously in patients with underlying acute or chronic respiratory illness, to avoid respiratory depression and precipitation of acute respiratory failure. While anxiety-induced hyperventilation can compromise lung function, as in the case reported here, anxiety and agitation can be part of the presentation of acute respiratory decompensation, and they may be further aggravated by use of anxiolytics such as benzodiazepines. “It is important to carefully evaluate the etiology of anxiety and agitation before considering benzodiazepines,” the authors write, including assessment of mental status, use of accessory muscles of breathing, vital signs and oxygen saturation, as well as any needed laboratory or imaging studies.

The authors conclude that benzodiazepines can be used judiciously for symptom relief in anxious patients with COVID-19 infection. They recommend the lowest possible dose of alprazolam or lorazepam four times daily to achieve a uniform 24-hour effect.

“While benzodiazepines can increase the risk for delirium in critically ill patients,” they add, “a continuous infusion may be used as an alternative sedative agent in critically ill, mechanically ventilated COVID-19-infected patients to achieve light sedation with daily sedation interruption.”

Second-tier options for anxiolysis include gabapentin, an anticonvulsant GABA analogue. Although not FDA-approved for treating anxiety, gabapentin has been used in anxiety disorders and alcohol withdrawal with mild to moderate success. Another option is the FDA-approved anxiety therapy hydroxyzine, a histamine H1 receptor antagonist with a very low anticholinergic profile. Both of these options are viable when benzodiazepines are contraindicated (out of concern about respiratory depression) or benzodiazepines could aggravate the risk for delirium. Sedation is minimal with both of these medications, and there is no major respiratory depression. They are also less likely to cause delirium in the medically ill, although gabapentin requires renal monitoring in some patients and hydroxyzine increases risk of QTc interval prolongation.

Buspirone, a non-benzodiazepine therapy indicated for generalized anxiety disorder, is ineffective in acute anxiety states due to its delayed onset of effect.

Antipsychotics are not approved by the FDA for treating anxiety, but there are data supporting their efficacy. These agents can be sedating but do not suppress respiratory drive. The risk of QTc interval prolongation may be of concern when antipsychotics are combined with QTc-prolonging agents for treatment of COVID-19, such as hydroxychloroquine, chloroquine and azithromycin.

Role of psychotherapy

The authors note that psychotherapeutic techniques are valuable in managing anxiety in medically ill individuals and can empower patients to better cope with hospitalization. They recommend a supportive psychotherapy approach that includes active and empathetic listening to the patient’s concerns and fears, offering education about anxiety treatments and regularly updating the patient on the care team’s goals and objectives. Relaxation techniques and mindfulness exercises can add further value, particularly if they can be offered digitally.

The full case-based review (with references) is freely available here.