Glucose-6-Phosphate Dehydrogenase Deficiency: An Actionable Risk Factor for Patients with COVID-19?

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common X-linked mutation that is more prevalent in African, Asian, Latin American and Mediterranean populations. Although most individuals are asymptomatic, exposure to certain food, drugs, or infections can trigger acute hemolytic anemia. Given the potential for coronavirus to trigger oxidative stress, unrecognized G6PD deficiency in the presence of the COVID-19 viral infection may cause hemolytic crisis and worse outcome in affected individuals. Further, since certain drugs that may be used to treat COVID-19 infection may cause hemolytic crisis in individuals with G6PD deficiency, it may be warranted to recommend adding G6PD deficiency to the list of screening elements in a COVID-19 workup for those patients where there is a high suspicion for this genetic mutation.

The use of ibuprofen to treat fever in COVID-19: A possible indirect association with worse outcome?

Fever has been reported as a common symptom occurring in COVID-19 illness. Over the counter antipyretics such as ibuprofen and acetaminophen are often taken by individuals to reduce the discomfort of fever. Recently, the safety of ibuprofen in COVID-19 patients has been questioned due to anecdotal reports of worsening symptoms in previously healthy young adults. Studies show that ibuprofen demonstrates superior efficacy in fever reduction compared to acetaminophen. As fever may have benefit in shortening the duration of viral illness, it is plausible to hypothesize that the antipyretic efficacy of ibuprofen may be hindering the benefits of a fever response when taken during the early stages of COVID-19 illness.

A New Method of Identifying Characteristics of Needing Help to Take Medications in an Older Representative Community-Dwelling Population: The Older Adults Medication Assist Scale.

OBJECTIVES: To determine the sociodemographic characteristics, health conditions, and cognitive and functional status associated with baseline prevalence and new need for help taking medication 3 years later and to construct a brief scale indicative of need for help taking medications. DESIGN: Retrospective cross-sectional and 3-year longitudinal study. SETTING: Five-county area in north-central Piedmont, North Carolina. PARTICIPANTS: Representative community-dwelling sample of black and white individuals aged 65 and older (N = 4,136). MEASUREMENTS: Information was obtained in person in participants' homes using structured questionnaires. Health conditions included sensory impairment and self-report of physician-diagnosed conditions. Cognitive status was assessed using the 10-item Short Portable Mental Status Questionnaire. Functional status was assessed using the three-item Rosow-Breslau scale, the five-item Katz activity of daily living scale, and a modified six-item Older Americans Resources and Services instrumental activities of daily living scale. RESULTS: Characteristics associated with need for help taking medications were aged 80 and older, being male, living with others, having four or more chronic conditions, and impaired cognitive or functional status (c-statistic 0.94, 77.1% sensitivity, 87.9% specificity). Predictors of new need for help with medications 3 years later included aged 75 and older at baseline, being male, and impaired cognitive and functional status (c-statistic 0.75). CONCLUSION: This brief scale can help identify persons needing help with medications and could be useful in assisting clinicians with medication management.

Folate metabolism genes, dietary folate and response to antidepressant medications in late-life depression.

OBJECTIVE: The primary aims of this study were to (i) determine whether folate metabolism genetic polymorphisms predict age of onset and occurrence of late life depression; and (ii) determine whether folate metabolism genetic polymorphisms predict response to antidepressant medications in late-life depression. METHODS: This study used the Conte Center for the Neuroscience of Depression and the Neurocognitive Outcomes of Depression in the Elderly Study database, which includes individuals aged ≥60. The folate nutrition assessment was determined by the Block Food Frequency Questionnaire. Genotype was evaluated for 15 single nucleotide polymorphisms from 10 folate metabolism genes. Logistic regression models were used to examine genetic polymorphisms and folate estimates with association with depression age of onset and remission status. RESULTS: There were 304 Caucasians in the database, 106 of these were not depressed and 198 had a diagnosis of depression. There were no significant differences between remitters and non-remitters in age, sex or estimated folate intakes. There were no folate estimates or folate metabolism gene single nucleotide polymorphisms that significantly predicted age of onset of depression or occurrence of depression. Methionine synthase reductase (MTRR) A66G (rs1801394) was significantly associated with remission status (p = 0.0077) such that those with the AA genotype were 3.2 times as likely as those with the GG genotype to be in remission (p = 0.0020). Methylenetetrahydrofolate reductase A1298C (rs1801131) achieved a borderline significance for association with remission status (p = 0.0313). CONCLUSION: The major finding from this study is that the MTRR A66G genotype predicts response to selective serotonin reuptake inhibitor antidepressants in late life depression.

Natural food folate and late-life depression.

Low folate status has been linked to depression, but findings have been inconsistent. The authors sought to examine the association between folate intake and late-life depression. This cross-sectional study included individuals age 60 and older (n = 111 depression, n = 136 comparison). Depression participants received psychiatric care. Folate and kilocalorie intakes were assessed with a Block 1998 food frequency questionnaire. Naturally occurring food folate was inversely associated with depression after controlling for age, sex, race, education, and total energy (P = 0.0047). All other folate variables including total dietary folate and folic acid were non-significant for depression. These findings may indicate that the naturally occurring form of folate is uniquely protective for depression and perhaps brain health. Alternatively, natural folate may be a surrogate for other nutrients or overall dietary quality.

Antidepressant-related adverse effects impacting treatment compliance: Results of a patient survey.

BACKGROUND: Despite the high prevalence of depression in the United States, 10 few studies have identified which adverse effects (AEs) patients are willing or unwilling to tolerate when receiving antidepressants. OBJECTIVE: The aim of this study was to identify reasons for discontinuation10 and noncompliance with antidepressant medications, the impact of AEs on compliance and quality of life (assessed using impact of AEs on activities of daily living), and patients' suggestions for improving their medication, using a patient survey. METHODS: Patients aged 18 to 65 years with mild to severe depression were 10 randomly selected by their physicians to be sent an invitation to complete the 42-question survey. Three hundred physicians nationwide assessed the severity of depression and symptoms of anxiety in each respondent, using their judgment. Patients were asked specific questions to assess reasons for discontinuation/noncompliance. Patients were also asked to rate AEs based on how difficult they were to "live with," and what 2 aspects of their antidepressant medication they would change if they could. RESULTS: In a separate, concurrent study, physicians classified 175 (50%) abdResults:0 mildly to moderately depressed and 84 (24%) as severely depressed. Ninety-one respondents (26%) were classified as having symptoms of anxiety. Two hundred seven patients (60%) indicated they had discontinued treatment with an antidepressant agent at some point in their lives, the most common reason for which was lack of efficacy (92 patients [44%]). Of the 344 patients currently being treated with an antidepressant, 75 (22%) reported noncompliance. The most common reasons for noncompliance were "have trouble remembering to take it" (19/44 patients [43%]), "gained a lot of weight" (11/41 [27%]), "unable to have an orgasm" (8/40 [20%]), and "lost interest in sex" (8/41 [20%]). The 4 AEs patients expressed as "extremely difficult to live with" were "weight gain" (104 patients [31%]), "unable to have erection" (83 [25%]), "difficulty reaching orgasm" (80 [24%]), and "tired during the day/no energy" (69 patients [21%]). The 3 most frequently cited improvements patients (n = 327) would make to their medications were better efficacy (176 patients [54%]) and eliminating AEs related to sexual desire and weight gain (112 [34%] and 105 [32%] patients, respectively). CONCLUSIONS: The findings of this survey of patients with mild to severe10 depression suggest that compliance, and hence efficacy, can be promoted by (1) understanding what patients expect and desire from the antidepressants they are prescribed and (2) prescribing antidepressants associated with low rates of weight gain, sexual dysfunction, or tiredness.

Effects of sustained-release bupropion among persons interested in reducing but not quitting smoking.

PURPOSE: To determine whether sustained-release bupropion promotes smoking reduction leading to smoking cessation among persons who wish to reduce their amount of smoking, but who are unwilling to quit or who perceive themselves as being unable to quit. METHODS: Current smokers were assigned randomly to receive either sustained-release bupropion (150 mg twice daily) or matching placebo. During an initial 6-month smoking reduction phase, those who were willing to quit entered a 7-week cessation phase, during which study medication was continued. RESULTS: Four-week continuous abstinence rates were 14% (41/295) in the bupropion group and 8% (25/299) in the placebo group (P = 0.02) during treatment. However, this benefit did not continue after treatment was stopped; subsequent continuous abstinence rates were 7% (20/295) in the bupropion group and 5% (16/299) in the placebo group (P = 0.50). Similar proportions of subjects entered the cessation phase in both treatment groups (38% [n = 113] of those in the bupropion group and 34% [n = 101] of those in the placebo group), although the time until a cessation attempt was shorter for those taking bupropion (median, 64 days vs. 118 days, P = 0.008). The extent of smoking reduction (measured by urinary cotinine concentrations) among the 327 subjects who did not enter the cessation phase was significantly greater (P <0.05) in those treated with bupropion during the reduction treatment phase, but not during the month 12 follow-up visit (P = 0.25). CONCLUSION: Sustained-release bupropion, when used in smokers initially not willing to make a cessation attempt, can help sustain smoking reduction while subjects are on active medication, reduce the time until the next cessation attempt, and increase short-term abstinence rates. However, these benefits were modest and not sustained after bupropion was discontinued.

Effect of bupropion SR on specific symptom clusters of depression: analysis of the 31-item Hamilton Rating Scale for depression.

Principal component (PC) analysis is a statistical technique that has been used to identify core depression symptoms on the Hamilton Rating Scale for Depression (HAM-D). PC analysis is also a useful method to identify unidimensional scales of the HAM-D that are more sensitive to change following antidepressant treatment. Although there have been previous PC investigations of various versions of the HAM-D, there have been no investigations of the 31-item HAM-D scale or investigations that include subjects administered bupropion SR. We performed a PC analysis on data from 910 outpatients who participated in randomized, double-blind trials evaluating bupropion SR versus placebo for major depression. The goal of our analysis was to 1) identify components (domains) of the 31-item HAM-D and 2) determine patient response to bupropion SR using the domains identified. PC analysis produced a solution comprised of 7 domains of the HAM-D that accounted for approximately 49% of the total variance. Bupropion SR demonstrated a significant reduction (p<.01, least square mean change) in symptoms over placebo on 4 domains (cognitive, retardation, fatigue/interest, and anxiety items).

Bupropion SR vs. placebo for weight loss in obese patients with depressive symptoms.

OBJECTIVE: This randomized, double-blind, placebo-controlled study evaluated the efficacy and tolerability of bupropion sustained-release (bupropion SR) in reducing weight and depressive symptoms in obese adults. RESEARCH METHODS AND PROCEDURES: Obese adults (body mass index, 30 to 44 kg/m(2)) not currently meeting criteria for major depression but with depressive symptoms (Beck Depression Inventory score 10-30) received bupropion SR 300 mg/d or placebo for 26 weeks with a 500 kcal/d-deficit diet. Patients who lost <5% of baseline weight at week 12 had bupropion SR dosage or placebo increased to 400 mg/d in a blinded fashion. RESULTS: The bupropion SR group (n = 193) lost an average of 4.4 kg (4.6% of baseline weight) vs. 1.7 kg (1.8% of baseline weight) on placebo (n = 191, p < 0.001, last-observation-carried-forward analysis). More patients in the bupropion SR group than in the placebo group (40% vs. 16% of intent-to-treat sample, 50% vs. 28% of completers, respectively) lost at least 5% of baseline weight (p < 0.05 at week 4, p < 0.001 at weeks 6 to 26). The percentage of patients reporting > or =50% decrease in depressive symptoms did not differ between groups, but depressive symptoms improved more with bupropion SR than with placebo among patients with a history of major depression (p < 0.05, weeks 4 to 26). In the sample as a whole, improvement in depressive symptoms was related to weight loss of > or =5% regardless of treatment (p < 0.0001). Bupropion SR was well-tolerated. DISCUSSION: Bupropion SR in combination with a 500 kcal/d-deficit diet facilitated weight loss. Weight loss of > or =5% may improve mood in obese patients with depressive symptoms.

Prevalence of sexual dysfunction among newer antidepressants.

BACKGROUND: Sexual dysfunction commonly occurs during antidepressant treatment. However, the reported rates of sexual dysfunction vary across antidepressants and are typically underreported in product literature. The objectives of this study were (1) to estimate the prevalence of sexual dysfunction among patients taking newer antidepressants (bupropion immediate release [IR], bupropion sustained release [SR], citalopram, fluoxetine, mirtazapine, nefazodone, paroxetine, sertraline, venlafaxine, and venlafaxine extended release [XR]) and (2) to compare physician-perceived with patient-reported prevalence rates of antidepressant-associated sexual dysfunction. METHOD: This cross-sectional, observational study was conducted in 1101 U.S. primary care clinics. Adult outpatients (4534 women and 1763 men) receiving antidepressant monotherapy were enrolled. The prevalence of sexual dysfunction was measured using the Changes in Sexual Functioning Questionnaire. RESULTS: In the overall population, bupropion IR (22%) and SR (25%) and nefazodone (28%) were associated with the lowest risk for sexual dysfunction, whereas selective serotonin reuptake inhibitor (SSRI) antidepressants, mirtazapine, and venlafaxine XR were associated with higher rates (36%-43%). In a prospectively defined subpopulation unlikely to have predisposing factors for sexual dysfunction, the prevalence of sexual dysfunction ranged from 7% to 30%, with the odds of having sexual dysfunction 4 to 6 times greater with SSRIs or venlafaxine XR than with bupropion SR. Physicians consistently underestimated the prevalence of antidepressant-associated sexual dysfunction. CONCLUSION: Ours is the first study to assess sexual dysfunction across the newer antidepressants using consistent methodology and a validated rating scale. Overall, SSRIs and venlafaxine XR were associated with higher rates of sexual dysfunction than bupropion or nefazodone. Because antidepressant-associated sexual dysfunction is considerably underestimated by physicians, greater recognition and education are imperative when prescribing antidepressant treatment.

Effect on body weight of bupropion sustained-release in patients with major depression treated for 52 weeks.

BACKGROUND: Short-term studies have demonstrated a modest weight-reducing to weight-neutral effect among patients receiving bupropion sustained-release (SR) for the treatment of depression. OBJECTIVE: This study was conducted to evaluate the long-term effects of bupropion SR on body weight in patients with depression. METHODS: This analysis was conducted within a long-term relapse-prevention study in patients with major depression. Those whose depression had responded to open-label treatment with bupropion SR were randomized to 44 weeks of double-blind treatment with bupropion SR 300 mg/d or placebo. Patients were categorized by body mass index (BMI) as follows: BMI < 22, BMI 22 to 26, BMI > or = 27, and BMI > or = 30. RESULTS: Four hundred twenty-three patients were enrolled in the double-blind phase of the study, 210 receiving bupropion SR and 213 receiving placebo. At the end of the open-label phase, the following mean weight losses were seen in the 4 BMI groups: BMI < 22, 0.5 kg; BMI 22 to 26, 1.1 kg; and BMI > or = 27 and BMI > or = 30, 1.8 kg each. At the end of double-blind treatment, mean change-from-baseline weights were as follows: BMI < 22, -0.1 kg; BMI 22 to 26, -0.6 kg; BMI > or = 27, -1.4 kg; and BMI > or = 30, -2.4 kg. The rate of change in body weight during the double-blind phase was statistically significant compared with baseline BMI (P < 0.001, analysis of covariance). CONCLUSIONS: Modest mean weight losses that increased with increasing baseline body weight were observed with long-term bupropion SR treatment. The findings of this analysis suggest that bupropion SR may be an appropriate therapeutic option in normal-weight or overweight patients with depression who are concerned about weight gain.