Heather D. Orton

Persisting Decline in Depression Treatment After FDA Warnings

CONTEXT In October 2003 the Food and Drug Administration (FDA) issued a Public Health Advisory about the risk of suicidality for pediatric patients taking antidepressants; a boxed warning, package insert, and medication guide were implemented in February 2005. The warning was extended to young adults aged 18 to 24 years in May 2007. Immediately following the 2003 advisory, unintended declines in case finding and non-selective serotonin reuptake inhibitor substitute treatment were shown for pediatric patients, and spillover effects were seen in adult patients, who were not targeted by the warnings. OBJECTIVE To determine whether the unintended declines in depression care persisted for pediatric, young adult, and adult patients. DESIGN Time series analyses. SETTING Ambulatory care settings nationally. Patients Pediatric, young adult, and adult cohorts of patients with new episodes of depression (n = 91 748, 70 311, and 630 748 episodes, respectively). INTERVENTIONS Post-FDA advisory trends were compared with expected trends based on preadvisory patterns using a national integrated managed care claims database from July 1999 through June 2007. MAIN OUTCOME MEASURES Depression diagnosis; antidepressant, antipsychotic, and anxiolytic prescriptions; and psychotherapy visits. RESULTS Changes in pediatric depression care were similar to changes for adults. National diagnosis rates of depression returned to 1999 levels for pediatric patients and below 2004 levels for adults. Primary care providers continued significant reductions in new diagnoses of depression (44% lower for pediatric, 37% lower for young adults, 29% for adults); diagnoses by mental health providers who were not psychiatrists increased. Numbers of prescriptions of anxiolytic and atypical antipsychotic medications did not significantly change from preadvisory trends. Psychotherapy increased significantly for adult, though not pediatric, cases. Selective serotonin reuptake inhibitor use decreased in all cohorts; serotonin-norepinephrine reuptake inhibitor increased for adults. CONCLUSIONS Diagnosing decreases persist. Substitute care did not compensate in pediatric and young adult groups, and spillover to adults continued, suggesting that unintended effects are nontransitory, substantial, and diffuse in a large national population. Policy actions are required to counter the unintended consequences of reduced depression treatment.

Childhood physical and sexual abuse and subsequent depressive and anxiety disorders for two American Indian tribes

BACKGROUND This study examined the relationship of childhood abuse, both physical and sexual, with subsequent lifetime depressive and anxiety disorders--depression or dysthymia, post-traumatic stress disorder (PTSD), and panic or generalized anxiety disorder (GAD)--among American Indians (AIs). METHOD Three thousand and eighty-four AIs from two tribes--Southwest and Northern Plains--participated in a large-scale, community-based study. Participants were asked about traumatic events and family history, and were administered standard diagnostic measures of depressive/anxiety disorders. RESULTS Prevalence of childhood physical abuse was approximately 7% for both tribes. The Southwest tribe had higher prevalence of depressive and anxiety disorders, with rates of PTSD being the highest. Childhood physical abuse was significant in bivariate models of depressive/anxiety disorders, and remained so in the multivariate models. CONCLUSIONS Childhood physical abuse was a significant predictor of all disorder groups for males in both tribes except for panic/GAD for the Northern Plains tribe in multivariate models; females showed a more varied pattern. Childhood sexual abuse did not significantly differ for males and females, and was an independent predictor of PTSD for both tribes, controlling for childhood physical abuse and other factors, and was significant for the other disorder groups only in the Southwest. Additional covariates that increased the odds of depressive/anxiety disorder, were adult physical or sexual victimization, chronic illness, lifetime alcohol or drug disorder, and parental problems with depression, alcohol, or violence. Results provided empirical evidence of childhood and later life risk factors and expanded the population at risk to include males.

Antidepressant discontinuation and risk of suicide attempt: a retrospective, nested case-control study.

OBJECTIVE Prior efforts to assess the impact of antidepressant use on risk of suicide attempt focused on antidepressant initiation or duration of use. Gaps remain in understanding risks associated with antidepressant discontinuation in the context of the drug regimen. We assessed the effects of antidepressant discontinuation on the risk of suicide attempt. METHOD We report a nested case-control study of suicide attempt with at least 12 months of prior observation. A retrospective cohort of 2.4 million patients with depression (ICD-9 codes 296.2, 296.3, 300.4, and 311), aged 5-89 years, was created using standard Healthcare Effectiveness Data and Information Set (HEDIS) criteria; from this cohort, cases (n = 10,456) and controls (n = 41,815) were selected for study. Data were from a large, national, longitudinal, integrated claims database of managed care enrollees in the United States from calendar years 1999 through 2006. RESULTS Compared to controls, cases were more likely to have used antidepressants, to have had multiple antidepressants, and to have had prior depressive episodes and inpatient stays that involved depression. After adjusting for confounding due to depression severity, comorbidities, and other medications, antidepressant use showed a protective effect for suicide attempt (OR = 0.62, P < .001). Compared to prior therapy, antidepressant discontinuation had a significant risk for suicide attempt (OR = 1.61, P < .05). Antidepressant initiation had the highest risk for suicide attempt (OR = 3.42, P < .05), followed by titration (titration up, OR = 2.62; down, OR = 2.19; P < .05). CONCLUSIONS Substantial confounding exists in examining the link between antidepressant use and suicide attempt, specifically regarding those factors associated with characteristics of depression. Antidepressant discontinuation showed a significant risk for suicide attempt, as did the period of an abbreviated trial, that is, stopping before a therapeutic regimen of 56 days had been reached. The highest risk was associated with initiation, a finding consistent with other studies, closely followed by periods of dosing changes and discontinuation. Patients should be closely monitored during these periods.

Comparison between omega-3 and omega-6 polyunsaturated fatty acid intakes as assessed by a food frequency questionnaire and erythrocyte membrane fatty acid composition in young children

Objective:We conducted a dietary validation study in youth aged 1–11 years by comparing dietary intake of omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) as assessed by a parent-completed semiquantitative food frequency questionnaire (FFQ) over time to erythrocyte membrane composition of the same fatty acids.Design:The study population included youth aged 1–11 years who were participants in the Diabetes Autoimmunity Study in the Young (DAISY), a longitudinal study in Denver, Colorado that is following a cohort of youth at risk for developing type I diabetes. Four hundred and four children who had erythrocyte membrane fatty acid data matched to an FFQ corresponding to the same time frame for a total of 917 visits (matches) were included. PUFA intake was expressed both as g/day (adjusted for total energy) and as percent of total fat intake. We used mixed models to test the association and calculate the correlation between the erythrocyte membrane estimates and PUFA intake using all records of data for each youth.Results:Intakes of total omega-3 fatty acids (β=0.52, P<0.0001, ρ=0.23) and marine PUFAs (β=1.62, P<0.0001, ρ=0.42), as a percent of total fat in the diet, were associated with percent of omega-3 and marine PUFAs in the erythrocyte membrane. Intakes of omega-6 PUFAs (β=0.04, P=0.418, ρ=0.05) and arachidonic acid (β=0.31, P=0.774, ρ=0.01) were not associated.Conclusions:In these young children, an FFQ using parental report provided estimates of average long-term intakes of marine PUFAs that correlated well with their erythrocyte cell membrane fatty acid status.

Alcohol, Drug, and Mental Health Specialty Treatment Services and Race/ Ethnicity: A National Study of Children and Families Involved With Child Welfare

We used data on a national sample of children involved with child welfare systems to compare American Indian caregivers with White, Black, and Hispanic caregivers in their need for, and receipt of, specialty alcohol, drug, and mental health treatment. American Indian caregivers were significantly less likely to receive services than were Hispanic caregivers (P<.05) but not significantly less likely than were White or Black caregivers. Child placement, child age, and caregiver psychiatric comorbidity were significantly associated with service receipt.

Childhood abuse and later parenting outcomes in two American Indian tribes

OBJECTIVES To examine the relationship of childhood physical and sexual abuse with reported parenting satisfaction and parenting role impairment later in life among American Indians (AIs). METHODS AIs from Southwest and Northern Plains tribes who participated in a large-scale community-based study (n=3,084) were asked about traumatic events and family history; those with children were asked questions about their parenting experiences. Regression models estimated the relationships between childhood abuse and parenting satisfaction or parenting role impairment, and tested for mediation by depression or substance use disorders. RESULTS Lifetime substance use disorder fully mediated the relationship between childhood physical abuse and both parenting satisfaction and parenting role impairment in the Northern Plains tribe. There was only partial mediation between childhood sexual abuse and parenting role impairment in the Southwest. In both tribes, lifetime depression did not meet the criteria for mediation of the relationship between childhood abuse and the two parenting outcomes. Instrumental and perceived social support significantly enhanced parenting satisfaction; negative social support reduced satisfaction and increased the likelihood of parenting role impairment. Exposure to parental violence while growing up had deleterious effects on parenting outcomes. Mothers and fathers did not differ significantly in the relation of childhood abuse experience and later parenting outcomes. CONCLUSIONS Strong effects of social support and mediation of substance abuse disorders in the Northern Plains offer direct ways in which childhood victims of abuse could be helped to avoid negative attributes of parenting that could put their own children at risk. PRACTICE IMPLICATIONS Mothers were not significantly different from fathers in the relation of abusive childhood experiences and later parenting outcomes, indicating both are candidates for interventions. Strong effects of social support offer avenues for interventions to parents. The prevalence of substance use disorders and their role as a mediator of two parenting outcomes in the Northern Plains should focus special attention on substance use treatment, especially among those who experienced childhood victimization. These factors offer direct ways in which childhood victims of abuse can be helped to avoid negative attributes of parenting that could put their own children at risk of violence.

The Association of Panic Disorder, Posttraumatic Stress Disorder, and Major Depression With Smoking in American Indians

INTRODUCTION Rates of cigarette smoking are disproportionately high among American Indian populations, although regional differences exist in smoking prevalence. Previous research has noted that anxiety and depression are associated with higher rates of cigarette use. We asked whether lifetime panic disorder, posttraumatic stress disorder, and major depression were related to lifetime cigarette smoking in two geographically distinct American Indian tribes. METHODS Data were collected in 1997-1999 from 1506 Northern Plains and 1268 Southwest tribal members; data were analyzed in 2009. Regression analyses examined the association between lifetime anxiety and depressive disorders and odds of lifetime smoking status after controlling for sociodemographic variables and alcohol use disorders. Institutional and tribal approvals were obtained for all study procedures, and all participants provided informed consent. RESULTS Odds of smoking were two times higher in Southwest participants with panic disorder and major depression, and 1.7 times higher in those with posttraumatic stress disorder, after controlling for sociodemographic variables. After accounting for alcohol use disorders, only major depression remained significantly associated with smoking. In the Northern Plains, psychiatric disorders were not associated with smoking. Increasing psychiatric comorbidity was significantly linked to increased smoking odds in both tribes, especially in the Southwest. CONCLUSIONS This study is the first to examine the association between psychiatric conditions and lifetime smoking in two large, geographically diverse community samples of American Indians. While the direction of the relationship between nicotine use and psychiatric disorders cannot be determined, understanding unique social, environmental, and cultural differences that contribute to the tobacco-psychiatric disorder relationship may help guide tribe-specific commercial tobacco control strategies.

LIBBY ET AL. RESPOND

We welcome the opportunity to continue the dialogue on studying American Indians’ experiences with child welfare systems. While Thompson agrees on the importance of such disparities research and a focus on caregivers, he raises an interesting question about the appropriate reference group for racial/ethnic comparisons. Our decision to use American Indian care-givers as the reference group was hypothesis driven. We were investigating whether disparities exist for American Indian caregivers compared with others in the United States; in the interest of space, we did not report all possible contrasts. However, an interested reader could have examined all comparisons by looking at the results shown in Table 2 of our article. For example, dividing the odds ratio for Whites (2.32) by the odds ratio for Blacks (1.39) results in an odds ratio of 1.67, which is identical to the odds ratio that would have been obtained for the White subgroup if the model had been estimated with Blacks as the reference group. Standard errors, however, cannot be obtained from the table. Our choice of reference group was also reasonable statistically. We agree that a reference group should be sufficiently large to allow for reasonably precise estimates, as ours did (160/968 unweighted; 20163/308958 weighted). The fact that our estimate for a contrasted subgroup (Hispanics) was statistically significant is evidence that the American Indian group was large enough to act as the reference group. It is also important to note that changing the reference group does not change the parameter estimates for any other variables in the model or the overall test of the model (here the F statistic). Regardless of the reference group, the precision of parameter estimates for small subgroups may be compromised, as evidenced by standard errors; in our case these were slightly larger for American Indians and Hispanics (proportionally smaller subgroups) than for Whites and Blacks. The issue is thus not which subgroup is the reference group, but small subgroups in general. Our assertion that “Hispanic caregivers fared the best”1(p630) referred to the fact that, as shown in Table 1, Hispanic caregivers received more assessments and service referrals and had higher rates of prior service receipt than White, Black, and American Indian caregivers. It is time for disparities research to move beyond rote comparisons with Whites. Rather, we should concentrate on considering and proposing hypotheses to be tested.