A Systematic Review of Complex Polypharmacy in Bipolar Disorder: Prevalence, Clinical Features, Adherence, and Preliminary Recommendations for Practitioners.

Objective: Extensive combination pharmacotherapy regimens for bipolar disorder have gained increasing use in routine practice in ways that outpace data from evidence-based clinical trials. The present review examined the prevalence of complex pharmacotherapy regimens in bipolar disorder patients and sought to characterize factors that most influence polypharmacy prescribing patterns.Data Sources: The authors independently systematically searched the MEDLINE, PsycINFO, and Embase databases for English-language observational/naturalistic or randomized controlled polypharmacy trials, using the keywords bipolar and polypharmacy or bipolar and combination treatment and pharmacotherapy.Study Selection: From among 3,566 publications, 49 ultimately met study inclusion criteria.Data Extraction: Information was obtained regarding prevalence rates of extensive polypharmacy as well as clinical characteristics and naturalistic outcomes for patients with simple (≤ 2) or complex (≥ 3) regimens of psychotropic agents.Results: A weighted mean percentage of 32.7% of bipolar outpatients (4,535/13,863) taking ≥ 3 psychotropic medications was identified. Factors associated with complex polypharmacy use include female sex, White race, age > 50 years, history of psychosis, greater burden of depressive illness, subtherapeutic dosing, lower treatment adherence, more extensive psychiatric comorbidity, and a greater history of suicide attempts.Conclusions: Extensive or complex combination pharmacotherapy regimens are common in many patients with bipolar disorder and often reflect greater overall illness severity. Naturalistic studies do not point to better outcomes for patients receiving more complex drug regimens, suggesting likely confounding by indication, high severity, or comorbid conditions. Formal clinical trials are needed to identify optimal drug combinations and durations when using ≥ 3 psychotropic medications to treat patients with bipolar disorder.

Psychopharmacology of COVID-19.

Background: With the rapid, global spread of severe acute respiratory syndrome coronavirus 2, hospitals have become inundated with patients suffering from coronavirus disease 2019. Consultation-liaison psychiatrists are actively involved in managing these patients and should familiarize themselves with how the virus and its proposed treatments can affect psychotropic management. The only Food and Drug Administration-approved drug to treat COVID-19 is remdesivir, and other off-label medications used include chloroquine and hydroxychloroquine, tocilizumab, lopinavir/ritonavir, favipiravir, convalescent plasma therapy, azithromycin, vitamin C, corticosteroids, interferon, and colchicine. Objective: To provide an overview of the major safety considerations relevant to clinicians who prescribe psychotropics to patients with COVID-19, both related to the illness and its proposed treatments. Methods: In this targeted review, we performed structured literature searches in PubMed to identify articles describing the impacts of COVID-19 on different organ systems, the neuropsychiatric adverse effects of treatments, and any potential drug interactions with psychotropics. The articles most relevant to this one were included. Results: COVID-19 impacts multiple organ systems, including gastrointestinal, renal, cardiovascular, pulmonary, immunological, and hematological systems. This may lead to pharmacokinetic changes that impact psychotropic medications and increase sensitivity to psychotropic-related adverse effects. In addition, several proposed treatments for COVID-19 have neuropsychiatric effects and potential interactions with commonly used psychotropics. Conclusions: Clinicians should be aware of the need to adjust existing psychotropics or avoid using certain medications in some patients with COVID-19. They should also be familiar with neuropsychiatric effects of medications being used to treat this disease. Further research is needed to identify strategies to manage psychiatric issues in this population.

Increased risk of hospital admission for mood disorders following admission for epilepsy.

OBJECTIVE: To determine if epilepsy admissions, compared to admissions for other medical causes, are associated with a higher readmission risk for mood disorders. METHODS: The Nationwide Readmissions Database is a nationally representative dataset comprising 49% of US hospitalizations in 2013. In this retrospective cohort study, we used ICD-9-CM codes to identify medical conditions. Index admissions for epilepsy (n = 58,278) were compared against index admissions for stroke (n = 215,821) and common medical causes (n = 973,078). Readmission rates (per 100,000 index admissions) for depression or bipolar disorders within 90 days from discharge for index hospitalization were calculated. Cox regression was used to test for associations between admission type (defined in 3 categories as above) and readmission for depression or bipolar disorder up to 1 year after index admission, in univariate models and adjusted for age, sex, psychiatric history, drug abuse, income quartile of patient's zip code, and index hospitalization characteristics. RESULTS: The adjusted hazard ratio (HR) for readmission for depression in the epilepsy group was elevated at 2.80 compared to the stroke group (95% confidence interval [CI] 2.39-3.27, p < 2 × 10-16), and 2.09 compared to the medical group (95% CI 1.88-2.32, p < 2 × 10-16). The adjusted HR for readmission for bipolar disorder in the epilepsy group was elevated at 5.84 compared to the stroke group (95% CI 4.56-7.48, p < 2 × 10-16), and 2.46 compared to the medical group (95% CI 2.16-2.81, p < 2 × 10-16). CONCLUSION: Admission for epilepsy was independently associated with subsequent hospital readmission for mood disorders. The magnitude of elevated risk in this population suggests that patients admitted with epilepsy may warrant targeted psychiatric screening during their hospital admission.

Increased risk of hospital admission for ICD-9-CM psychotic episodes following admission for epilepsy.

OBJECTIVE: To determine whether epilepsy admissions are associated with a higher readmission risk for psychotic episodes compared to admissions for other medical causes. METHODS: The Nationwide Readmissions Database is a nationally representative dataset from 2013. We used International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes to identify medical conditions. There were 58 278 index admissions for epilepsy, and this group was compared against admissions for stroke (n = 215 821) and common medical causes (pneumonia, urinary tract infection [UTI], congestive heart failure [CHF], and chronic obstructive pulmonary disease [COPD], n = 973 078). Readmission rates for psychotic episodes within 90 days from discharge for index hospitalizations were calculated. Cox regression was used to test for associations between admission type and readmission for psychotic episodes up to 1 year after index admission, in univariate models and adjusted for multiple medical, social, and psychiatric variables. RESULTS: Up to 90 days from index admission, there were 683/100 000 readmissions for psychotic episodes in the epilepsy group, 92/100 000 in the stroke group, and 58-206/100 000 in the medical group. The relative rate of readmission in the epilepsy group was highest in the first 30 days following index admission (311/100 000). Unadjusted hazard ratio (HR) for readmission for psychotic episodes within 1 year in the epilepsy group compared to the stroke group was 6.58 (95% confidence interval [CI] 5.69-7.61, P < 2 × 10-16 ), and 4.41 compared to the medical group (95% CI 4.00-4.85, P < 2 × 10-16 ). The fully adjusted HR for readmission in the epilepsy group remained elevated at 3.63 compared to the stroke group (95% CI 3.08-4.28, P < 2 × 10-16 ), and 1.95 compared to the medical group (95% CI 1.76-2.15, P < 2 × 10-16 ). Confounding factors most strongly associated with psychosis readmission were documented psychosis history at the time of index admission, younger age, and lower income quartile. SIGNIFICANCE: An epilepsy admission was independently associated with subsequent hospital readmission for psychotic episodes, even after adjustment for confounding variables.

Risk of readmission for suicide attempt after epilepsy hospitalization.

OBJECTIVE: The objective of this study was to examine if epilepsy admissions are associated with a higher readmission risk for suicide attempt, independent of psychiatric comorbidity, compared with index admissions for other medical causes. METHODS: The Nationwide Readmissions Database is a nationally representative dataset containing data from roughly 15 million hospital discharges. Analysis of International Classification of Disease Clinical Modification 9 (ICD-9-CM) codes in the year 2013 revealed 58,278 index admissions for epilepsy; this group was compared with admissions for stroke (N=215,821) and common medical causes (N=973,078). Ninety-day readmission rates for suicide attempts were calculated. Cox regression tested for associations between admission type and suicide attempt readmissions up to 1year following index admission. RESULTS: There were 402/100,000 readmissions for suicide attempt within 90days from index admission in the group with epilepsy; 43/100,000 in the stroke group; and between 37 and 89/100,000 in the medical group. Unadjusted hazard ratios (HR) for suicide readmissions within 1year in the group with epilepsy compared with the stroke group were 9.61 (95% confidence interval (CI): 7.69-11.90, p<2.0×10-16) and 5.02 compared with the medical group (95% CI: 4.40-5.73, p<2.0×10-16). The HR for readmission in the group with epilepsy, after adjustment for sociodemographic and psychiatric variables, were elevated at 4.91 compared with the stroke group (95% CI: 3.83-6.27, p<2.0×10-16), and 2.66 compared with the medical group (95% CI: 2.32-3.05, p<2.0×10-16). CONCLUSION: Independent of psychiatric comorbidities, epilepsy admissions may be independently associated with more than a threefold increased risk of hospital readmission for suicide in the year following index admission in comparison with patients recently hospitalized because of stroke or other common medical disorders.