Updated: Nov 24, 2022
October 24, 2022
Psychiatric Times, Vol 39, Issue 10,
As the virus that causes COVID-19 illness (SARS-CoV-2) continues to mutate, we continue to see high rates of COVID-19 illness with concomitant neuropsychiatric symptoms including depressed mood, anxiety, posttraumatic stress disorder (PTSD), and other mental health problems. Medical and psychiatric comorbidity are expected to have serious long-term consequences for global public health and mental health. Although there is no evidence that natural supplements or other complementary and alternative medicine (CAM) interventions prevent or treat medical illnesses caused by SARS-CoV-2, preliminary findings suggest that select supplements and other CAM approaches (Figure1) may have beneficial effects on mental health problems associated with the pandemic. Figure. Examples of Psychological, Physical, and Nutritional Complementary Health Approaches1
Global Mental Health Impact of the COVID-19 Pandemic Millions of individuals experience depression, anxiety, and worsening or new substance use disorders (SUDs) associated with the prolonged social isolation associated of the pandemic.2 A systematic review of studies published between January 1, 2020, and January 29, 2021, estimated that an additional 53 million cases of major depressive disorder (MDD) (an increase of 27%) and an additional 76 million cases of anxiety disorders (an increase of 25%) globally.2 The mental health impact of the pandemic has been greater among women and younger individuals than among men and older individuals. Globally, additional cases of MDD and anxiety disorders attributed to the pandemic accounted for approximately 50 million disability-adjusted life years (DALYs) caused by MDD and approximately 45 million DALYs caused by anxiety disorders, representing billions in lost personal income and declines in the gross domestic product of many nations. The impact of the pandemic on the mental health of children and adolescents has been especially severe. For example, in a systematic review of studies published in English between January 1, 2020, and February 22, 2021, (N = 116 articles; total N=127,923 children and adolescents), the authors found high rates of COVID-related fear, depressed mood, and anxiety compared with pre-pandemic estimates.3 The review also found that older adolescents and girls living with chronic physical conditions were at greatest risk of experiencing negative mental health outcomes. Exercise, access to entertainment, positive family relationships, and social support were associated with better mental health outcomes. Individuals with preexisting mental health problems have reported worsening of symptoms in the context of prolonged social isolation during the pandemic. For instance, a survey of adults (N=272) conducted in the first months of the pandemic found that individuals with preexisting anxiety or depressed mood experienced symptomatic worsening somewhat higher than in the general population.4 Respondents attributed anxiety and depressed mood to prolonged social isolation from friends, family, and places of worship, and to being overwhelmed by unrelenting negative media coverage. In addition to the isolation, strategies used to reduce the spread of SARS-CoV-2 infection (ie, physical distancing and restricted travel) made it more difficult for patients to obtain treatment during the height of the pandemic. The result was that many individuals with COVID-related mental health complaints did not seek conventional care during the height of the pandemic. Although these issues were exacerbated during the height of the COVID-19 pandemic, it has not yet been determined whether individuals with mental health problems were less likely to seek care during the pandemic in general.5 Neuropsychiatric Complications of COVID-19 Research findings are revealing complex causal relationships between mental illness and COVID-19, with mental health issues grouped into 4 categories (Table 1).6 Depressed mood, anxiety disorders, and other psychiatric disorders are both risk factors for and consequences of COVID-19 infection. For example, a large cohort study of more than 60,000 cases of COVID-19 found that individuals diagnosed with any psychiatric disorder had a 65% greater risk of contracting COVID-19 compared with a matched cohort with no preexisting psychiatric disorders.7
Table 1. The 4 Categories of Mental Health Problems Related to COVID-196 Neuropsychiatric complications of SARS-CoV-2 infection are believed to be mediated by a variety of biological and environmental factors including systemic inflammation, direct viral damage to the brain, severe cytokine storm causing disruption of the integrity of the blood-brain-barrier, micro-infarcts, and thrombi in the brain, liver inflammation, impaired renal function, impaired oxygenation of the brain, viral-induced immune reactions and auto-immunity, and prolonged social isolation.8 In cases of acute illness, these factors can manifest as a multifactorial delirium.8 Delirium has been reported in approximately 30% of individuals hospitalized for management of severe COVID-19 illness.9 Older individuals are at greater risk of COVID-19-related delirium as well as acute and long-term neuropsychiatric disorders following COVID-19 illness.8 Even mild or asymptomatic infection may result in delirium, cognitive impairment, extreme fatigue, and depressed mood. A study that followed US adults for 3 months after having acute COVID-19 illness found that 18% were diagnosed with a psychiatric disorder, with one-third being newly diagnosed.10,11 Young adults, Hispanics, African Americans, and individuals with preexisting psychiatric disorders are at higher risk of worsening mental health in the aftermath of acute COVID-19 illness.12 One study found that roughly one-third of patients hospitalized for severe COVID-19 illness experienced memory loss and impaired concentration 3 months following discharge.13 One-fourth of adults admitted to ICUs with respiratory failure or shock experienced global cognitive difficulties equivalent in severity to mild Alzheimer disease 1 year following discharge.14 Similarly, there is a common complaint of persisting “brain fog” following milder COVID-19 illness.10,11 One month following acute COVID-19 illness, roughly one-third of patients report having a depressed mood, 20% to 42% report having anxiety, and as many as 20% report having obsessions or compulsions.15 Depressed mood and anxiety are reported more often by women, and those with severe COVID-19 illness, physical discomfort following acute illness, elevated inflammatory markers, and/or a history of psychiatric illness.15,16 PTSD is also common. Roughly 20% to 30% of individuals who have been hospitalized for management of severe COVID-19 symptoms have PTSD.17-20 The highest risk of PTSD is associated with younger age, female gender, ICU care, and prior history of mental illness.20 COVID-19 and PTSD share many of the same risk factors including high rates of medical comorbidities such as obesity, diabetes, metabolic syndrome, chronic pulmonary disease, cardiovascular disease, and autoimmune disease.21-23 Psychosis related to the COVID-19 pandemic has been attributed to multiple factors. A small percentage of individuals hospitalized for management of severe COVID-19 symptoms develop new-onset psychosis. There are reports of high-dose corticosteroids (used to treat severe COVID-19 illness) precipitating psychosis.24,25 The COVID-19 pandemic has resulted in a significant increase in SUDs.12 Individuals with SUDs are at higher risk of contracting COVID-19, are more likely to require hospitalization after becoming infected, and are more likely to have risk factors for severe COVID-19 illness (eg, obesity, type 2 diabetes, cancer, cardiovascular disease, and chronic liver and kidney disease).26 High prevalence rates of many psychiatric disorders call for studies on both conventional and CAM approaches aimed at reducing risk of COVID-19 infection; managing mental health problems associated with prolonged isolation; treating mental health problems that occur in the acute phase of infection; and managing mental health problems during the weeks and months following acute illness, or so-called “long COVID” (Table 227).
Table 2. Some Common Symptoms of Long COVID27 In response to the complex medical, neurologic, and psychiatric sequelae of COVID-19 illness, interdisciplinary clinics are being established in the United States to provide medical and mental health care to individuals with post-COVID syndrome.9,28 Although the subject of this review is CAM interventions, mainstream treatments including psychotropic medications and psychotherapies are also being investigated as potential treatments of mental health problems in all 4 categories of mental health issues associated with COVID-19 (Table 1).6 The Importance of Enhancing Emotional Resilience In the context of limited access to care, studies show that many individuals struggling with mental health problems related to prolonged isolation benefit from mind-body practices, exercise, and proper nutrition. These self-directed approaches have been shown to improve resilience during prolonged periods of isolation and to lessen the severity of anxiety and depression associated with the pandemic. Positive lifestyle choices may also improve overall health, reducing the risk of contracting COVID-19, or lessening severity of symptoms in individuals who contract the virus. A systematic review and meta-analysis of randomized controlled trials evaluated interventions aimed at improving mental health outcomes during and following illness caused by coronaviruses SARS-CoV-1 (SARS severe acute respiratory syndrome), Middle Eastern respiratory syndrome (MERS), and SARS-CoV-2/COVID-19.29 The authors identified studies on a range of conventional and CAM mental health interventions, most of which were done in China or the United States. Most interventions were supported by low-quality evidence (ie, expert opinions and cross-sectional studies). Most of the interventions were aimed at preventing development of PTSD. Experts recommended individual psychotherapy, hotlines, and peer support groups for individuals diagnosed with PTSD, a frequent concomitant of acute illness with H1N1 and COVID-19. Because benzodiazepines are known to worsen symptoms of PTSD, experts advised against the use of benzodiazepines to manage acute stress related to COVID-19 illness.29 Among non-pharmacologic interventions, yoga, meditation, and breathing techniques were most often recommended. However, experts cautioned that mindfulness can sometimes worsen anxiety, depressed mood, and suicidality in individuals with moderate to severe symptoms. Throughout the studies, the importance of positive lifestyle choices for maintaining good mental health in the wake of the pandemic were emphasized, including exercise, healthy eating habits, sleep hygiene, moderating alcohol consumption, and spending time with family and friends. Some experts recommended muscle relaxation and yoga to reduce anxiety and manage insomnia related to the pandemic. Despite a large body of evidence supporting the beneficial effects of spirituality and religiousness on mental health, only a few experts recommended spiritual or religious practices as coping strategies during the COVID-19 pandemic.29 Conventional Treatments of Mental Health Problems Related to COVID-19 Mainstream conventional treatments such as psychotropic medications and psychotherapy are helpful for treating mental health problems in the acute phase of COVID-19 illness and in the weeks and months following COVID-19, including during long COVID. However, to date there are no guidelines for conventional management of anxiety and depressed mood following infection with SARS-CoV-2.30 Mainstream treatments of psychiatric illness in medically ill patients may be appropriate for individuals afflicted with COVID-19. When managing psychiatric symptoms in hospitalized individuals who are acutely ill with COVID-19, use of established hospital psychiatry protocols is appropriate, including selecting psychotropics and dosages that pose the lowest risk of harm after accounting for organs that have been harmed by the virus. For example, gabapentin is an appropriate and safe treatment for anxiety only in cases where renal function is not severely impaired.8 In patients with decreased renal clearance, the dose of gabapentin should be adjusted accordingly.30 Selective serotonin reuptake inhibitors (SSRIs) are a reasonable choice for patients who complain of both depressed mood and anxiety. However, fluoxetine, paroxetine, and fluvoxamine should be avoided due to the increased risk of drug-drug interactions; and paroxetine, fluvoxamine, venlafaxine, and desvenlafaxine should be avoided due to their short half-lives and unpleasant withdrawal symptoms.8 Preliminary findings suggest that SSRIs, especially sertraline, may play an important role in managing COVID-19 infection through different mechanisms, including by ameliorating the cytokine storm syndrome, resulting in reduced levels of pro-inflammatory cytokines, increasing the number and functioning of immune cells, and possibly also through direct antiviral effects.31 Pending confirmation by future studies, sertraline and other psychotropics may emerge as important treatments of COVID-19 illness. Absence of Evidence for CAM Approaches to Prevent or Treat COVID-19 Illness Until late 2021, the absence of effective vaccines and pharmaceuticals for preventing and treating COVID-19 led to the widespread use of CAM interventions including botanicals, mindfulness, and energetic approaches.32 To date there is no evidence that supplements prevent COVID-19 illness or have antiviral effects; however, clinical trials are ongoing to investigate putative antiviral or immune enhancing properties of select natural supplements including vitamin C, vitamin D, zinc, probiotics, and NAC (N-acetylcysteine).33 Nonetheless, in less developed world regions where access to vaccines and pharmaceuticals remains limited because of availability or cost issues, millions of individuals continue to rely on CAM. Indeed, CAM approaches being used to treat COVID-19 are widely touted on social media and blogs; however, such “cures” are based on anecdotal reports often contextualized in highly politicized views of the pandemic. In fact, very few CAM interventions have been investigated in placebo- and sham-controlled studies, and there is no evidence to date that nutraceuticals or other CAM interventions kill the SARS-Co-V-2 virus, prevent COVID-19 illness, or mitigate symptoms associated with infection. In an effort to correct erroneous claims about natural supplement “cures” for COVID-19, the National Center for Complementary and Integrative Medicine (NICCM) of the National Institutes of Health has published a fact sheet on dietary supplements being hyped as preventatives or treatments of COVID-19 illness. The NCCIM site, which includes links to detailed fact sheets for consumers and health professionals, states unequivocally that “there is no scientific evidence that any of these alternative remedies can prevent or cure COVID-19.”34 The urgent global need to identify safe, effective, and affordable preventatives and treatments for COVID-19 illness has led to studies on a range of CAM approaches. An analysis of systematic reviews35 of CAM interventions in COVID-19 illness identified 24 systematic reviews (21 for traditional Chinese medicine [TCM] herbals, 2 for vitamin D, and 1 for in-home activities). It found limited evidence that some TCM herbals may slow the rate of illness progression, no evidence that vitamin D improves major health outcomes, and modest evidence that exercise, yoga, and muscle relaxation techniques may improve mental wellness. The authors cautioned that findings are limited by inclusion of only those CAM interventions for which there were enough quality studies to permit systematic reviews; and the absence of a standardized methodology for evidence mapping. A systematic review of studies on CAM interventions in patients with COVID-19 illness identified 14 studies (total N=972) and found evidence that acupuncture reduced chest pain; qigong increased physical activity and quality of life; and regular relaxation improved depressed mood, stress, anxiety, and sleep quality.36 A review of studies on self-directed CAM interventions used during the pandemic found evidence that spending time in nature (“forest bathing”) and maintaining a healthy diet, mindfulness, and regular sleep improved the immune response to the SARS-CoV-2 virus and general emotional well-being.37 CAM Approaches Being Investigated to Treat Mental Health Problems Associated With the Pandemic Because of limited or no access to vaccines and antivirals in many countries, and shortages in personnel and clinics equipped to triage individuals in the acute phase of illness and individuals with long COVID, CAM interventions—when found effective—can play an important role in preventing and recovering from COVID-19 illness by enhancing resilience, reducing depressed mood and anxiety, and improving sleep quality. Identifying promising CAM interventions is an important global public health strategy because it is likely that future pandemics also will result in widespread mental health problems in the face of limited mental health resources. Finally, it is germane to note that the desperate global search for cures has led to a veritable epidemic of unsubstantiated CAM practices that may place large populations at increased risk of illness or death. This has been especially problematic in less developed world regions such as Africa.38 Although there is presently no evidence that natural supplements prevent or treat COVID-19-related medical illness, select natural supplements are being investigated as potential treatments of mental health problems associated with the pandemic. Other CAM modalities such as mindfulness, exercise, yoga, and biofeedback are being investigated for their potential role in enhancing emotional resilience or mitigating symptom severity of depressed mood, anxiety, and other mental health problems (Table 3).
Table 3. Types of CAM Treatments Marketed for COVID-19 Mental Health Issues
Nutrition Optimal nutrition boosts immune function and plays an important role in preventing and treating moderate to severe respiratory and non-respiratory infections, and should be embraced as a preventive strategy for reducing risk of severe COVID-19 illness, particularly among older individuals in nursing homes and those with chronic medical conditions.39 For example, there is evidence that vitamins A, B complex, C, D, and E and select trace elements such as iron, zinc, selenium, magnesium, and copper have immune-boosting properties, and that dietary deficiencies of these micronutrients could interfere with immune function in response to viral infections.40 Older individuals in nursing homes are at increased risk of contracting COVID-19 and should be provided with specialized nutritional support including regular nutritional screening; dietary counseling; supplementation with essential vitamins and minerals including RDAs of vitamins A, D, E, C, B6, and B12; iron; zinc; selenium; and omega-3 PUFAs. Medically indicated malnourished older adults should be provided enteral and parenteral nutritional support.41 Poor nutrition in low-income communities and less developed countries is associated with increases in morbidity and mortality in general, and this situation has become worse in the context of the severe economic impact of the COVID-19 pandemic.42 The World Health Organization (WHO) should work with the governments of low-income countries to develop strategies to ensure access to optimal nutrition to boost immune function, especially for individuals who are severely ill.43 Exercise A multinational cross-sectional analysis done in the United Kingdom, Ireland, New Zealand, and Australia during the initial stages of lockdown found that adults who reported exercising less before or during the COVID-19 restrictions reported poorer mental health and well-being.44 This finding was consistent across all countries. Females reported more positive changes in exercise and corresponding improvements in mental health compared to males, and young adults reported more negative changes and poorer overall mental health compared to other age groups. Individuals who reported no change or a positive change in exercise starting before or during pandemic restrictions reported better mental health compared to those who reported negative changes in their exercise routine. These findings are consistent with those of a US study in which adults who did not meet recommended guidelines for regular physical activity and engaged in greater screen time reported more depressive mood symptoms and stress.45 Mindfulness and Mind-Body Practices Studies in China on individuals hospitalized for COVID-19 reported that mindfulness, relaxation, and progressive muscle relaxation reduced the severity of anxiety and depressive symptoms.46-48 An observational study conducted online in China during the early stages of the pandemic found that regular mindfulness meditation was associated with improvements in pandemic-associated depressed mood, anxiety, and stress.49 In a 10-day study conducted during the pandemic (N=64), healthy adults randomly assigned to brief daily mindfulness training experienced greater well-being and were less negatively affected by exposure to COVID-19 news compared with individuals assigned to a wait list.50 The 2 groups did not differ in other measures including negative affect, anxiety, and depressed mood. Tai chi has beneficial effects on physical and mental health, including increased aerobic capacity, improved balance, and improved sleep. There is evidence that the regular practice of tai chi may enhance immune function and improve pulmonary function in individuals with chronic obstructive pulmonary disease (COPD). The results of small non-clinical studies suggest that tai chi may reduce symptoms of anxiety and depressed mood.51 Studies have also demonstrated preventive effects of regular tai chi practice on depressed mood and anxiety.52,53 Natural Supplements A narrative review of more than 50 herbals used in traditional systems of medicine to prevent or treat medical or neuropsychiatric complications of COVID-19 illness found limited evidence from in-vitro studies and anecdotal reports for select herbals or herbal formulas.54 The authors emphasized that preclinical studies are needed to investigate mechanisms of action and confirm safety before it is appropriate to use any herbal medicines to prevent or treat COVID-related illness. They cautioned that safe medicinal uses of herbals are limited by frequent adulteration, contamination, toxicity risks, potential drug-herb interactions, and lack of standardization of many herbals. At the time of writing, no placebo-controlled studies have been published on herbals and other natural supplements as potential treatments of depressed mood, anxiety and other neuropsychiatric symptoms associated with COVID-19 illness; hence, specific treatment recommendations cannot be made. However, as previously noted, numerous clinical trials are ongoing to investigate select natural supplements including vitamin C, vitamin D, zinc, curcumin, omega-3s, probiotics, and NAC (N-acetylcysteine) for promoting immune function, reducing risk of viral infection, and reducing the severity and duration of illness.33 In parallel with these efforts, findings of placebo-controlled studies support that select natural supplements have antidepressant effects. Because effects of SARS-CoV-2 on brain function that manifest as neuropsychiatric symptoms are mediated in part by inflammation, natural supplements that have both anti-inflammatory properties and antidepressant effects (eg, vitamin D, zinc, and probiotics) should be investigated as candidates for future treatments of the medical and neuropsychiatric consequences of COVID-19 illness. Traditional Chinese Medicine Preliminary findings support the use of select TCM modalities to help reduce symptoms of depressed mood associated with COVID-19. Unfortunately, many TCM approaches used to treat depressed mood lack high quality evidence.54,55 A review of TCM interventions inpatients with COVID-19 (N=972) found evidence that acupuncture, select Chinese herbal medicine, Qigong, and other TCM traditional therapies may improve physical symptoms of COVID-19 illness, including chest pain and impaired respiratory function, as well as psychological symptoms including depressed mood, anxiety, sleep quality.36 Another study found evidence for use of a combined regimen of auriculotherapy (ie, ear acupuncture) and the Baduanjin style of Qigong for insomnia, depressed mood and anxiety associated with COVID-19.20 The evidence supporting TCM treatments for depressed mood is inconsistent with findings from some studies on acupuncture and qigong for depressed mood not associated with COVID-19 illness that reported outcomes no better than found with use of placebo.56,51 Importantly, any consideration of these modalities should include the potential for negative outcomes, and all of these factors must be discussed with patients. Biofeedback Various biofeedback approaches are widely used to manage stress and reduce anxiety. Emerging findings suggest that survivors of COVID-19 have autonomic disturbances related to cardiovascular sequelae that can deteriorate in relationship to medical and psychiatric disorders. Heart rate variability (HRV) biofeedback may provide clinically useful information about autonomic disturbances related to COVID-19 illness while potentially decreasing the deleterious impact of cardiovascular, autonomic, physical, and psychiatric sequelae.57 An ongoing clinical trial aims to determine whether HRV biofeedback reduces anxiety in individuals with long COVID.58 It has been suggested HRV biofeedback may be helpful in reducing stress in frontline health care personnel who work with COVID-19 patients; however, this has not been investigated in studies to date.59 Findings of a small study on (N=55) healthy adolescents during the COVID-19 lockdown suggest that EEG biofeedback training may significantly reduce anxiety, improve mood, and increase emotional resilience.60-62 Recommendations A well-coordinated outreach campaign at the international (ie, WHO) and national (ie, ministries of public health) levels should be aimed at both the general public and health care professionals with the goals of correcting widespread misinformation and false claims about CAM treatments and providing accurate up-to-date information on CAM interventions for enhancing emotional resilience and mitigating psychiatric illness associated with COVID-19 illness. Radical health care reforms (ie, increased reliance on self-directed interventions for enhancing wellness and emotional resilience such as mindfulness, proper nutrition, and exercise) are needed to reduce the economic impact of prolonged lockdowns during future pandemics. Low-cost mobile applications should be developed to guide the general public in positive lifestyle choices and mindfulness training.62 Large cohort studies are needed to investigate lifestyle modification approaches (eg, mindfulness, nutrition, exercise, and sleep hygiene) and identify those that optimally enhance resilience for future pandemics and other global crises. Similarly, large, multicenter, placebo-controlled studies are needed to investigate natural supplements (especially those that have both anti-inflammatory and psychoactive properties) as prospective adjunctive or monotherapy treatments of depressed mood, anxiety, and other mental health problems associated with the acute phase of COVID-19 illness and long COVID. Dr Lake is an adult psychiatrist with more than 25 years of clinical experience. He is an adjunct fellow at Western Sydney University’s National Institute of Complementary Medicine Health Research Institute in Penrith, Australia. He founded and chaired the American Psychiatric Association’s Caucus on Complementary, Alternative and Integrative Medicine from 2004 to 2010, and has chaired symposia and workshops at American Psychiatric Association conferences and other national and international conferences on complementary, alternative, and integrative mental health care. Dr Lake is the author or editor of 5 textbooks on alternative and integrative mental health care and a 10-volume series of self-help books on alternative and integrative treatments of depressed mood, anxiety, attention-deficit/hyperactivity disorder, bipolar disorder, and other mental health problems.