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Expert opinion in bipolar disorder: Impact of COVID-19 on outcomes and treatment of bipolar disorder

Published:March 19, 2021DOI:https://doi.org/10.1016/j.pmip.2021.100074

      Abstract

      Bipolar disorder is a common mental illness with a high burden of disability and comorbidity including highly prevalent medical conditions that increase risk for severe COVID-19 illness. Moreover, increased vulnerability to stress, routine and lifestyle disruption in people living with bipolar disorder is well-established. Although data examining the impact of COVID-19 disease and the resulting pandemic on those with bipolar disorder are limited, the present paper aims to discuss existing research at the intersection of COVID-19 and mental health with the goal of considering potential impacts of COVID-19 on outcomes and treatment of bipolar disorder.

      Keywords

      1. Introduction

      Bipolar disorder is a common mental illness with significant morbidity and mortality (Yatham et al., 2018) that by some estimates is considered to be the 6th leading cause of disability globally [
      • Yatham L.N.
      • Kennedy S.H.
      • Parikh S.V.
      • et al.
      Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder.
      ,
      • Lopez A.D.
      The global burden of disease, 1990–2020.
      ]. It is associated with the highest rate of suicide of any illness, occurring in ~15% of affected individuals [
      • Strakowski S.M.
      Bipolar disorder.
      ]. Independent of suicide, rates of all-cause mortality are elevated at virtually every age [
      • Kessing L.V.
      • Vradi E.
      • McIntyre R.S.
      • et al.
      Causes of decreased life expectancy over the life span in bipolar disorder.
      ]. The defining feature of bipolar disorder is the occurrence of manic or hypomanic episodes, although most of the illness course is typically characterized by recurring episodes of depression [
      • Carvalho A.F.
      • Firth J.
      • Vieta E.
      Bipolar disorder.
      ].
      Given these considerations, people with bipolar disorder may be at increased risk for poor outcomes in response to epidemics or pandemics. In a little over one year’s time, SARS-CoV-2 infections have caused an incalculable toll of suffering, death and illness, and the resulting COVID-19 pandemic has disrupted the routines and livelihoods of billions of people worldwide. Although data examining the impact of COVID-19 disease and the resulting pandemic on those with bipolar disorder are limited, in this review we discuss existing research at the intersection of COVID-19 and mental health with the goal of considering potential impacts of COVID-19 on outcomes and treatment of bipolar disorder.

      2. Stress and other risk factors for mood episodes during COVID-19

      Many studies documenting the distress caused by the COVID-19 pandemic are ongoing and rapidly emerging. Shanahan et al.’s longitudinal cohort study of young adults ages 20–22 – an age group associated with the onset of bipolar symptoms as well as important professional, educational and social transitions – demonstrated COVID-19-related lifestyle and economic disruption were strongly associated with emotional distress [
      • Shanahan L.
      • Steinhoff A.
      • Bechtiger L.
      • et al.
      Emotional distress in young adults during the COVID-19 pandemic: evidence of risk and resilience from a longitudinal cohort study.
      ]. Stressful life events and general stress are core components or triggers of bipolar depressive episodes and may also precipitate episodes of mania or hypomania [
      • Proudfoot J.
      • Whitton A.
      • Parker G.
      • et al.
      Triggers of mania and depression in young adults with bipolar disorder.
      ,
      • Proudfoot J.
      • Doran J.
      • Manicavasagar V.
      • et al.
      The precipitants of manic/hypomanic episodes in the context of bipolar disorder: a review.
      ]. Disruption of daily routines, decreased exercise, and use of substances such as alcohol and marijuana have also been identified as triggers common to both depressive and manic episodes [
      • Proudfoot J.
      • Whitton A.
      • Parker G.
      • et al.
      Triggers of mania and depression in young adults with bipolar disorder.
      ,
      • Frank E.
      • Gonzalez J.M.
      • Fagiolini A.
      The importance of routine for preventing recurrence in bipolar disorder.
      ]. Moreover as discussed subsequently, individuals with bipolar disorder are at elevated risk for developing substance use disorders. Sleep disruption, a consequence of life disruption and stress, also may increase the risk of mood episodes in individuals with bipolar disorder (Strakowski, 2014).
      Data on the status and outcomes of people with bipolar disorder during the COVID-19 pandemic remain sparse; however, it is reasonable to infer that for many people living with bipolar disorder, the secondary consequences of the pandemic have increased their vulnerability to a mood episode and other negative outcomes. One Australian population-based cohort study, the COLLATE Project [
      • Van Rheenen T.E.
      • Meyer D.
      • Neill E.
      • et al.
      Mental health status of individuals with a mood-disorder during the COVID-19 pandemic in Australia: initial results from the COLLATE project.
      ], surveyed adults 18 years or older in April 2020 with 1292 respondents self-reporting a mood disorder (bipolar or a depressive disorder) and 3167 respondents without a reported mental disorder. The study then compared COVID-19 related lifestyle changes, primary concerns and psychological distress among groups. Findings indicated heightened psychological distress in the mood disorder group compared to the group reporting no mental disorder with further elevated levels of stress and depression in respondents with bipolar disorder compared to those with a depressive disorder. Consistent with previous studies demonstrating increased rates of post-traumatic stress disorder (PTSD) in a bipolar disorder cohort after a collective trauma such as the terrorist attacks on September 11, 2001 [
      • Pollack M.H.
      • Simon N.M.
      • Fagiolini A.
      • et al.
      Persistent posttraumatic stress disorder following September 11 in patients with bipolar disorder.
      ], the bipolar disorder group in COLLATE, then, appears to be particularly vulnerable to the disruption of the pandemic.

      3. Psychiatric comorbidities in bipolar disorder and COVID-19

      The COVID-19 pandemic also created increases in psychiatric morbidity overall including, but not limited to, anxiety and substance use, which research suggests may be a consequence of an increase in interoceptive awareness of or behavioral immune system (BIS) activation as well as economic distress and social isolation [
      • McKay D.
      • Asmundson G.J.G.
      COVID-19 stress and substance use: current issues and future preparations.
      ]. A recent meta-analysis [
      • Cénat J.M.
      • Blais-Rochette C.
      • Kokou-Kpolou C.K.
      • et al.
      Prevalence of symptoms of depression, anxiety, insomnia, posttraumatic stress disorder, and psychological distress among populations affected by the COVID-19 pandemic: a systematic review and meta-analysis.
      ] found that the prevalence of anxiety in 68 independent samples of populations affected by COVID-19 was four times higher than compared with recent prevalence data on common mental health disorders from the World Health Organization (WHO). Results also showed significantly higher rates of insomnia and psychological distress in COVID-19 affected populations compared with the general population. As noted, sleep disruption may be particularly risky for people with bipolar disorder who appear to have inherent dysregulation of circadian rhythms.
      The high prevalence of psychiatric comorbidities in those with bipolar disorder at baseline potentiates an increase in risk of destabilization during the COVID-19 pandemic. Lifetime prevalence of substance use disorders in those with bipolar disorder is estimated to be around 50% [
      • Regier D.A.
      • Farmer M.E.
      • Rae D.S.
      • et al.
      Comorbidity of mental disorders with alcohol and other drug abuse. Results from the Epidemiologic Catchment Area (ECA) Study.
      ]. Furthermore, research examining substance use disorders impact on illness course in people with bipolar disorder has consistently shown them to negatively effect outcomes [
      • Cerullo M.A.
      • Strakowski S.M.
      The prevalence and significance of substance use disorders in bipolar type I and II disorder.
      ]. Similarly, anxiety symptoms and syndromes have been found to be common among people with bipolar disorder with a prevalence estimates as high as 50% [
      • Vázquez G.H.
      • Baldessarini R.J.
      • Tondo L.
      Co-occurrence of anxiety and bipolar disorders: clinical and therapeutic overview.
      ]. Anxiety disorders in bipolar disorder are associated with increased likelihood of suicide attempts and deaths [
      • Yatham L.N.
      • Kennedy S.H.
      • Parikh S.V.
      • et al.
      Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder.
      ].

      4. Suicide

      Since the onset of the COVID-19 pandemic psychiatric experts have been concerned that rates of suicide may increase as a result of many of the secondary consequences of the pandemic (summarized in Table 1), as well as evidence of increased rates of suicide in previous epidemics, such as SARS in 2003. Moreover, the United States was demonstrating alarming increases in rates of suicide in young people prior to the pandemic, providing a substrate for an even worse catastrophe [
      • Hedegaard H.
      • Curtin S.C.
      • Warner M.
      Increase in suicide mortality in the United States.
      ]. Although studies are ongoing, some recent data suggest no rise in suicide rates among high income countries so far, although there is a more mixed picture among low income countries [
      • John A.
      • Pirkis J.
      • Gunnell D.
      • et al.
      Trends in suicide during the covid-19 pandemic.
      ]. Regardless, although a clear trend of increased suicides in the general population has not yet been demonstrated to date, the pandemic is not over and an overlap of risk factors associated with suicide in bipolar disorder and the secondary psychosocial consequences of the COVID-19 pandemic is a serious concern (Table 1). At baseline, suicide among people living with bipolar disorder is highly prevalent, and as noted, it is one of the leading causes of death among those with a diagnosis [
      • Yatham L.N.
      • Kennedy S.H.
      • Parikh S.V.
      • et al.
      Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder.
      ]. Suicide rates in bipolar disorder vary between studies but a recent systematic review [
      • Plans L.
      • Barrot C.
      • Nieto E.
      • et al.
      Association between completed suicide and bipolar disorder: a systematic review of the literature.
      ] demonstrated rates are approximately 20–30 times higher than in the general population.
      Table 1Similarities between risk factors associated with suicide in bipolar disorder and the secondary consequences of the COVID-19 pandemic.
      Risk factors associated with increased likelihood of suicide in bipolar disorder
      Ref. [1].
      Secondary consequences of the COVID-19 pandemic amongst the general population
      Ref. [12].
      Current depressive or mixed episodeIncreased rates of depression
      Comorbid substance use disorderIncreased rates of substance use
      Comorbid anxiety disorder
      Comorbid anxiety disorder is the only psychiatric comorbidity associated with increased likelihood of suicide attempt and death by suicide in bipolar disorder.
      Increased rates of anxiety
      Comorbid eating disorderIncreased economic disruption
      Occupational problemsIncreased social isolation
      Bereavement
      Social Isolation
      a Ref.
      • Yatham L.N.
      • Kennedy S.H.
      • Parikh S.V.
      • et al.
      Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder.
      .
      b Ref.
      • McKay D.
      • Asmundson G.J.G.
      COVID-19 stress and substance use: current issues and future preparations.
      .
      * Comorbid anxiety disorder is the only psychiatric comorbidity associated with increased likelihood of suicide attempt and death by suicide in bipolar disorder.

      5. Psychiatric manifestations of COVID-19

      To our knowledge there are no published reports examining the psychiatric sequelae of COVID-19 in a homogenous bipolar cohort; however a growing number of case reports [
      • Ferrando S.J.
      • Klepacz L.
      • Lynch S.
      • et al.
      COVID-19 psychosis: a potential new neuropsychiatric condition triggered by novel coronavirus infection and the inflammatory response?.
      ,
      • Noone R.
      • Cabassa J.A.
      • Gardner L.
      • et al.
      Letter to the Editor: New onset psychosis and mania following COVID-19 infection.
      ,
      • Correa-Palacio A.F.
      • Hernandez-Huerta D.
      • Gómez-Arnau J.
      • et al.
      Affective psychosis after COVID-19 infection in a previously healthy patient: a case report.
      ] suggest that COVID-19 infection may be associated with psychiatric symptoms including psychosis, mood alterations and suicide even in those with no prior psychiatric history or no other significant medical problems. It remains unclear and often difficult to assess whether these psychiatric symptoms are a direct result of CNS viral infection, the associated immunological and inflammatory responses, commonly used treatments such as corticosteroids or, at times, a result of increased psychosocial stress co-occurring with severe disease [
      • Keyhanian K.
      • Umeton R.P.
      • Mohit B.
      • et al.
      SARS-CoV-2 and nervous system: from pathogenesis to clinical manifestation.
      ]. The direct neurobiological impacts and stress may also precipitate new psychiatric illnesses in people who are at risk, e.g., through a family history of illness. Bipolar disorder is highly familial (Strakowski, 2014), so family members of a proband with bipolar disorder might also be at risk. To date, whether this risk has been realized in the pandemic is unknown.

      6. Medical comorbidity in bipolar disorder and increased risk for severe COVID-19 illness

      Compared with the general population and most other psychiatric conditions, bipolar disorder is associated with a significantly increased prevalence of cardiovascular disease [
      • Weiner M.
      • Warren L.
      • Fiedorowicz J.G.
      Cardiovascular morbidity and mortality in bipolar disorder.
      ], a finding consistent across studies and linked to multiple mediators including lifestyle, medications (particularly antipsychotics) and pathophysiology of the illness itself [
      • Goldstein B.I.
      • Baune B.T.
      • Bond D.J.
      • et al.
      Call to action regarding the vascular-bipolar link: a report from the Vascular Task Force of the International Society for Bipolar Disorders.
      ]. Large epidemiological studies also have also demonstrated cardiovascular disease to be the most consistent cause of excess mortality in people with bipolar disorder with an increased mortality risk up to 2.5-fold higher than the general population [
      • Roshanaei-Moghaddam B.
      • Katon W.
      Premature mortality from general medical illnesses among persons with bipolar disorder: a review.
      ]. Smoking among people with bipolar disorder has also been found to up to 3.5 times more common than the general population [
      • Goldstein B.I.
      • Baune B.T.
      • Bond D.J.
      • et al.
      Call to action regarding the vascular-bipolar link: a report from the Vascular Task Force of the International Society for Bipolar Disorders.
      ]. These medical disorders put people with bipolar disorder at an increased risk for severe COVID-19 illness (Fig. 1, [
      • CDC
      COVID-19: people at increased risk – people with certain medical conditions.
      ]). Consequently, more than ever, assessment for – as well as prevention and treatment of – associated cardiovascular and metabolic disease is essential in the management of bipolar disorder.
      Figure thumbnail gr1
      Fig. 1Overlap between prevalent medical conditions in bipolar disorder and risk factors for severe Covid-19 illness.

      7. Role of telepsychiatry on clinical care and outcomes during COVID-19

      A growing body of research supports the safe and effective use of telepsychiatry in a wide range of clinical settings [
      • Seidel R.W.
      • Kilgus M.D.
      Agreement between telepsychiatry assessment and face-to-face assessment for Emergency Department psychiatry patients.
      ,
      • Bashshur R.L.
      • Shannon G.W.
      • Bashshur N.
      • et al.
      The empirical evidence for telemedicine interventions in mental disorders.
      ,
      • Bauer M.S.
      • Krawczyk L.
      • Miller C.J.
      • et al.
      Team-based telecare for bipolar disorder.
      ] and has demonstrated strong, consistent evidence in support of its feasibility, acceptance by users, lower cost, and clinical outcomes across various mental health diagnoses [
      • Bashshur R.L.
      • Shannon G.W.
      • Bashshur N.
      • et al.
      The empirical evidence for telemedicine interventions in mental disorders.
      ]. Telepsychiatry and clinical videoconference has been shown to extend the reach of collaborative care models in the treatment of bipolar disorder [
      • Bauer M.S.
      • Krawczyk L.
      • Miller C.J.
      • et al.
      Team-based telecare for bipolar disorder.
      ] and has the potential to improve access to evidence-based care [
      • Miller C.J.
      Telemental health via videoconferencing: a promising method for improving access to evidence-based mental health care for bipolar disorder.
      ]. Delivering telepsychiatric care presents numerous transdiagnostic challenges, most notably, the need to address behavioral emergencies such as a suicidal patient [
      • Turvey C.
      • Coleman M.
      • Dennison O.
      • et al.
      ATA practice guidelines for video-based online mental health services.
      ]; however there are also special telepsychiatric considerations relevant to the treatment of bipolar disorder such as the challenge of accurately assessing speech rate, voice prosody, psychomotor agitation and psychotic symptoms such as paranoia and hallucinations [
      • Burgess C.
      • Miller C.J.
      • Franz A.
      • et al.
      Practical lessons learned for assessing and treating bipolar disorder via telehealth modalities during the COVID-19 pandemic.
      ].

      8. Challenges to treatment of bipolar disorder during COVID-19 and evidence-based recommendations for care

      COVID-19-associated social and financial stressors as well as the disease itself pose many challenges to providing safe and effective clinical care for those living with mental illness. As discussed previously, people living with bipolar disorder are particularly vulnerable to pandemic-related disruption, yet for those in need of higher levels of care, job loss, loss of health insurance, decreased availability of childcare, and remote-schooling at home create barriers that may prevent them receiving such care. Inpatient psychiatric facilities are also not well-equipped for infection prevention and management of patients with active SARS-CoV-2 infections [
      • Li L.
      Challenges and priorities in responding to COVID-19 in inpatient psychiatry.
      ]. Evidenced-based, clinical recommendations for care of patients with bipolar disorder during the COVID-19 pandemic were recently published [
      • Hernández-Gómez A.
      • Andrade-González N.
      • Lahera G.
      • et al.
      Recommendations for the care of patients with bipolar disorder during the COVID-19 pandemic.
      ] and included assessment guidelines, evidence-based treatment interventions such as the use of Interpersonal Social Rhythm Therapy (IPSRT) to promote maintenance of healthy habits and routine, and a description of the risk of drug-drug-interaction between psychotropics used for bipolar disorder and treatments for COVID-19. These recommendations will likely evolve as we learn more about COVID-19 and its intersection with mental health.

      9. Conclusion

      The COVID-19 pandemic presents many challenges to the health and treatment of those living with bipolar disorder – an illness with a high burden of disability and comorbidity at baseline including highly prevalent medical conditions that increase risk for severe COVID-19 disease. Evidence demonstrating the COVID-19 pandemic’s toll on mental health is growing, and although contemporary studies examining the pandemic’s effects on outcomes in bipolar disorder are limited, the increased vulnerability to stress, daily routine and lifestyle disruption in this population is well-established. Increased use of telepsychiatry can provide an effective way of increasing access to mental health care, but many challenges remain to provide treatment for patients with bipolar disorder at all levels of care during the COVID-19 pandemic. Mental health providers treating this population may benefit from a review of emerging COVID-19-specific treatment recommendations [
      • Burgess C.
      • Miller C.J.
      • Franz A.
      • et al.
      Practical lessons learned for assessing and treating bipolar disorder via telehealth modalities during the COVID-19 pandemic.
      ,
      • Hernández-Gómez A.
      • Andrade-González N.
      • Lahera G.
      • et al.
      Recommendations for the care of patients with bipolar disorder during the COVID-19 pandemic.
      ] to help deliver effective care for and promote the ongoing stability of people with bipolar disorder.

      Funding

      This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

      Declaration of Competing Interest

      The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: David Spelber, MD has no conflicting or competing interests to disclose. Stephen M. Strakowski, MD serves as chair of Data and Safety Monitoring Boards for Sunovion and has grants to University of Texas from Janssen Pharmaceuticals.

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