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.

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 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.

Frequency of provider contact after FDA advisory on risk of pediatric suicidality with SSRIs.

OBJECTIVE: The Food and Drug Administration (FDA) issued a public health advisory in October 2003 on the risk of suicide in pediatric patients taking antidepressants and advised maintaining "close supervision" of such patients. In this study, the authors compared trends in the frequency of provider contacts for patients with depression before and after the advisory was issued. METHOD: Retrospective cohorts of children (N=27,370) and adults (N=193,151) with new episodes of depression treated with antidepressants were created from a national claims database of managed care plans (1998-2005). Two standards were used in measuring patient monitoring: the Health Plan Employer Data and Information Set (HEDIS) quality-of-care criterion calling for three contacts in 3 months and the FDA-recommended contact schedule totaling seven visits in 3 months. Time-series models compared postadvisory trends to the expected trend based on preadvisory measures. RESULTS: Less than 5% of all patients met FDA contact recommendations before the advisory, and the rate did not change after the advisory. A greater proportion of patients met the HEDIS contact criterion before the advisory (60% for children and 40% for adults), and the rate did not change after the advisory. A greater proportion of pediatric patients seen by a psychiatrist (80%) met the HEDIS criterion than those seen by a pediatrician (60%) or a non-pediatrician primary care physician (54%), and than adults seen by a psychiatrist (65%) or a primary care physician (37%). The proportions of pediatric patients who met the FDA recommendations did not differ by specialty. CONCLUSIONS: Contrary to expectations, the frequency of visits by patients with new episodes of depression treated with antidepressants did not increase after the October 2003 FDA advisory was issued.

Childhood characteristics associated with stage of substance use of American Indians: Family background, traumatic experiences, and childhood behaviors.

The purpose of this analysis is to examine childhood characteristics associated with stage of substance use in adulthood in two American Indian (AI) populations. Data were drawn from an epidemiologic study of two AI reservation populations for persons age 18-44 years (n=2070). We used descriptive and multivariate analysis to examine correlates of four mutually exclusive stages of substance use: lifetime abstinence (Stage 0), use of alcohol only (Stage 1A), use of marijuana/inhalants with or without alcohol (Stage 1B), and use of other illicit drugs with or without the previously listed substances (Stage 2). Problematic substance use by parents, younger age of first substance use, initiating substance use with a drug (with or without alcohol), and adolescent conduct problems were associated with higher stage substance use. Persons who experienced sexual abuse, witnessed family violence, or experienced other traumatic events before the age of 18 were more likely to be at Stage 1B than Stage 1A. These findings underscore the importance of providing effective interventions during childhood and adolescence to reduce the risk of substance use progression.

Omega-3 polyunsaturated fatty acid intake and islet autoimmunity in children at increased risk for type 1 diabetes.

CONTEXT: Cod liver oil supplements in infancy have been associated with a decreased risk of type 1 diabetes mellitus in a retrospective study. OBJECTIVE: To examine whether intakes of omega-3 and omega-6 fatty acids are associated with the development of islet autoimmunity (IA) in children. DESIGN, SETTING, AND PARTICIPANTS: A longitudinal, observational study, the Diabetes Autoimmunity Study in the Young (DAISY), conducted in Denver, Colorado, between January 1994 and November 2006, of 1770 children at increased risk for type 1 diabetes, defined as either possession of a high diabetes risk HLA genotype or having a sibling or parent with type 1 diabetes. The mean age at follow-up was 6.2 years. Islet autoimmunity was assessed in association with reported dietary intake of polyunsaturated fatty acids starting at age 1 year. A case-cohort study (N = 244) was also conducted in which risk of IA by polyunsaturated fatty acid content of erythrocyte membranes (as a percentage of total lipids) was examined. MAIN OUTCOME MEASURE: Risk of IA, defined as being positive for insulin, glutamic acid decarboxylase, or insulinoma-associated antigen-2 autoantibodies on 2 consecutive visits and still autoantibody positive or having diabetes at last follow-up visit. RESULTS: Fifty-eight children developed IA. Adjusting for HLA genotype, family history of type 1 diabetes, caloric intake, and omega-6 fatty acid intake, omega-3 fatty acid intake was inversely associated with risk of IA (hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.21-0.96; P = .04). The association was strengthened when the definition of the outcome was limited to those positive for 2 or more autoantibodies (HR, 0.23; 95% CI, 0.09-0.58; P = .002). In the case-cohort study, omega-3 fatty acid content of erythrocyte membranes was also inversely associated with IA risk (HR, 0.63; 95% CI, 0.41-0.96; P = .03). CONCLUSION: Dietary intake of omega-3 fatty acids is associated with reduced risk of IA in children at increased genetic risk for type 1 diabetes.

Spillover effects on treatment of adult depression in primary care after FDA advisory on risk of pediatric suicidality with SSRIs.

OBJECTIVE: In 2003, the U.S. Food and Drug Administration (FDA) issued a public health advisory about the risk of suicidality in pediatric patients taking selective serotonin reuptake inhibitors (SSRIs) for depression, and in 2005, the agency mandated a black box warning and medication guide indicating that pediatric and adult patients may be at risk. The authors examine the effects of this pediatric policy on treatment of adult depression in the community. METHOD: An adult cohort with newly diagnosed episodes of depression was created from a large national integrated claims database of managed care plans from October 1998 to September 2005 (N=475,838 unique episodes). Time-series analyses were used to compare the post-FDA advisory trends to the trends during the 5 years preceding the advisory. RESULTS: The rate of diagnosed depression was significantly lower after the advisory than would have been expected on the basis of the preadvisory historical trend. The average percentage of adults with new (versus recurrent) depressive episodes was 88.6% in the preadvisory period (declining at an annual rate of 1.69%), and it decreased significantly to 77.5% (declining more rapidly, at an annual rate of 7.70%). The percentage of adults with depression who did not receive an antidepressant increased from an average of 20% (declining at 0.45% annually) before the policy action to an average of 30% (increasing at an annual rate of 20.6%). The data did not show any compensatory increases in psychotherapy or prescription of atypical antipsychotics or anxiolytics. CONCLUSIONS: The FDA advisory had a significant spillover effect into community treatment for adults with depression, despite the focus of the policy on pediatric patients.

Decline in treatment of pediatric depression after FDA advisory on risk of suicidality with SSRIs.

OBJECTIVE: In October 2003, the U.S. Food and Drug Administration (FDA) issued a public health advisory about the risk of suicidality in pediatric patients taking selective serotonin reuptake inhibitors (SSRIs) for depression. This study used data from a large national pediatric cohort to examine patterns of diagnosis of depression, prescription of antidepressants, prescription of pharmacological alternatives to antidepressants, and use of psychosocial care before and after the FDA advisory was issued. METHOD: A large pediatric cohort with newly diagnosed episodes of depression was created from a national integrated claims database of managed care plans from October 1998 to September 2005 (N=65,349). Time-series models were used to compare diagnosing and prescribing trends during the 2 years after the FDA advisory and the expected trends based on data from the 5-year period preceding the advisory. RESULTS: From 1999 to 2004, pediatric diagnoses of depression increased from 3 to 5 per 1,000. After the FDA advisory was issued, the national rate decreased to 1999 levels, a significant deviation from the historical trend. Pediatricians and nonpediatrician primary care physicians accounted for the largest reductions in new diagnoses. Among patients with depression, the proportion receiving no antidepressant increased to three times the rate predicted by the preadvisory trend, and SSRI prescription fills were 58% lower than predicted by the trend. There was no evidence of a significant increase in use of treatment alternatives (psychotherapy, atypical antipsychotics, and anxiolytics). CONCLUSIONS: The FDA advisory was associated with significant reductions in aggregate rates of diagnosis and treatment of pediatric depression.

Mental health and substance abuse services to parents of children involved with child welfare: a study of racial and ethnic differences for American Indian parents.

American Indian (AI) parents of children involved with child welfare were compared to White, Black and Hispanic parents on mental health and substance abuse problems and access to treatment. Data came from the National Study of Child and Adolescent Well-Being, a longitudinal study of a nationally representative sample of children aged 0-14 years involved with child welfare. Weighted statistics provided population estimates, and multivariate logistic regression was used to predict the likelihood of caregivers receiving mental health or substance abuse services. There were significant disparities in the likelihood of receiving mental health, but not substance abuse, services. Unmet need for mental health and substance abuse treatment characterized all parents in this study. AI parents fared the worst in obtaining mental health treatment. Parents of children at home and of older children were less likely to access mental health or substance abuse treatment.

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.

What came first, major depression or substance use disorder? Clinical characteristics and substance use comparing teens in a treatment cohort.

This study utilized data on a treatment cohort from a randomized clinical trial that recruited adolescents with co-occurring major depression and substance use disorder (N=126). The purpose of this study was to compare adolescents for whom the onset of depression was first versus those for whom the onset of substance use disorder was first or in the same year as depression. Intake clinical evaluations were abstracted to yield common stressors that included childhood abuse, early loss or death, exposure to violence, and attachment problems. Tobacco, alcohol, and cannabis initiation and dependence were compared for the depression first and substance use disorder first groups, and within those groups by gender. Among the substances studied, only cannabis dependence was significantly more prevalent among those with depression first. Comparisons suggest some differences in the developmental path toward comorbid depression and substance use disorders, but remarkable similarity in measures of dependence and severity. Although small samples limited statistical significance, observed differences suggest possible avenues for prevention or intervention.

Prehospital and in-hospital mortality: a comparison of intentional and unintentional traumatic brain injuries in Colorado children.

OBJECTIVES: To describe the incidence and case-fatality rates of traumatic brain injury (TBI) in young children in Colorado, to compare these injuries based on intentionality and outcome (prehospital death, in-hospital death, or survival), and to model the association of intentionality with TBI-related mortality. METHODS: Cases were drawn from the 1994-2002 Colorado Traumatic Brain Injury Surveillance System. Incidence and case-fatality rates for intentional and unintentional TBI were calculated. We performed univariate comparisons based on the intentionality and outcome of the TBI. Multivariate logistic regression was used to estimate the association of intentionality and mortality, controlling for injury severity. RESULTS: Of the 1333 children aged 0 to 36 months with TBI, 340 had intentional and 993 had unintentional TBI. Incidence for intentional and unintentional TBI was 16.1 and 47.0 per 100,000, respectively. Children with intentional TBI had a higher case-fatality rate, in-hospital death rate, and injury severity. Intentional TBI deaths were twice as likely to occur in hospital than prehospital, whereas unintentional TBI deaths were twice as likely to occur prehospital. Intentionality was significantly associated with mortality, with the effect increasing with increasing age. CONCLUSION: Intentionality--independent of severity--raises the mortality of TBI in young children.

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.

Challenges in operationalizing the DSM-IV clinical significance criterion.

BACKGROUND: An explicit clinical significance (CS) criterion was added to many DSM-IV diagnoses in an attempt to more closely approximate the clinical diagnostic process and reduce the proportion of false positives in epidemiological studies. The American Indian Service Utilization, Psychiatric Epidemiology, Risk and Protective Factors Project (AI-SUPERPFP) offered a unique opportunity to examine the success of this effort. OBJECTIVE: To determine the impact of distress, impairment, and help-seeking reported in a lay structured interview on concordance with a clinical reappraisal. Further, to test the efficacy of 5 operationalizations of CS on the concordance and prevalence of DSM-IV lifetime disorders. DESIGN: Completed between 1997 and 2000, a cross-sectional probability sample survey with clinical reappraisal of approximately 10% of participants. SETTING: General community. PARTICIPANTS: A population-based sample of 3084 members of 2 American Indian tribal groups, who were between the ages of 15 and 54 years and resided on or near their home reservations, were randomly sampled from the tribal rolls and participated in structured psychiatric interviews. Clinical reappraisals were conducted with approximately 10% of the lay-interview participants. The response rate for the lay interview was 75%, and for the clinical reappraisal it was 72%. MAIN OUTCOMES MEASURES: The AI-SUPERPFP Composite International Diagnostic Interview (CIDI), a culturally adapted version of the CIDI, University of Michigan version. Adapted to assess DSM-IV diagnoses, questions assessing the CS criterion were inserted in all diagnostic modules. The Structured Clinical Interview for DSM-III-R (SCID) was used in the clinical reappraisal. RESULTS: Most participants who qualified as having AI-SUPERPFP CIDI lifetime disorders reported at least moderate levels of distress or impairment. Evidence of increased concordance between the CIDI and the SCID was lacking when more restrictive operationalizations of CS were used; indeed, the CIDI was very likely to underdiagnose disorders compared with the SCID (false negatives). Concomitantly, the CS operationalizations affected prevalence rates dramatically. CONCLUSION: The CS criterion, at least as operationalized to date, demonstrates little effectiveness in increasing the validity of diagnoses using lay-administered structured interviews.

Childhood physical and sexual abuse and subsequent alcohol and drug use disorders in two American-Indian tribes.

OBJECTIVE: The purpose of this study was to examine the relationship of childhood physical and sexual abuse to subsequent lifetime alcohol or drug use disorders among American Indians (AIs) by using cross-sectional and retrospective data collected from a structured epidemiological interview. METHOD: A sample of 3,084 AIs from two tribal populations-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 substance use disorders. RESULTS: Prevalence of childhood physical abuse was approximately 7% for both tribes, and childhood sexual abuse was 4%-5%, much higher for females. The Northern Plains tribe had higher prevalences of substance use disorders. Childhood physical abuse had a significant main effect in bivariate models of substance dependence, but remained significant only in the multivariate models of substance dependence for the Northern Plains tribe. Correlates of disorder were psychiatric and medical comorbidity, parental alcohol problems and adult experience of physical attacks. CONCLUSIONS: Childhood physical abuse had a stronger effect than childhood sexual abuse on lifetime substance dependence. Childhood sexual abuse, on the other hand, was more associated with lifetime substance abuse. Females more commonly experienced childhood abuse but were less likely than males to develop substance use disorders. Although additional covariates reduced the main effect on disorder, results provide clinical guidance to constellations of risk factors and expand the population at risk to include males.

Costs of childhood physical abuse: comparing inflicted and unintentional traumatic brain injuries.

OBJECTIVES: To estimate the effect of early childhood abuse (ie, inflicted injury) on medical costs of head trauma. METHODS: Abstracts of patient records were drawn from the annual 1993-2000 Colorado state-mandated hospital discharge database maintained by the Colorado Hospital Association. The 2 dependent variables were total charges (TC) and length of stay. Our key independent variable was the nature of injury, ie, inflicted or unintentional; other independent variables were age, severity level, death, and trauma designation of the hospital. Comparisons of variables between patients with inflicted and unintentional head trauma were performed using Student's t tests or chi2 statistics. Ordinary least squares regression was used to estimate the marginal and total effects of inflicted injury on TC and LOS. RESULTS: Of the 1097 head trauma patients <3 years old, 814 had unintentional and 283 had inflicted head trauma. Head trauma was defined using the Centers for Disease Control definition of traumatic brain injury. Patients with inflicted injuries were younger and had a higher average severity level and overall mortality rate than did patients with unintentional head trauma. The regression models showed that, controlling for age and severity, patients with inflicted head trauma stayed in the hospital 52% longer (2 days), and had a mean total bill 89% higher (4232 dollars more) than did patients with unintentional head trauma. CONCLUSIONS: The findings from multivariate models of TC and length of stay corroborate the simpler univariate findings of earlier studies. By focusing on the impact of those cases of child abuse that lead to a specific, severe clinical entity (traumatic brain injury), we isolated a significant economic impact of abuse on health care expenditures for injury.

Substitution in a Medicaid mental health carve-out: services and costs.

The objective is to empirically test the incentives associated with a Medicaid capitated mental health carve-out contract, whether outpatient services (less expensive, inside the contract) and residential treatment center care (costly care, outside of the contract) were substituted for inpatient psychiatric hospitalization used by children and adolescents. Data sources include Medicaid fee-for-service (FFS) claims for the non-capitated comparison sites and for residential treatment center use, and "shadow billing" encounter data for the experimental capitated managed care sites that provided public mental health services for children and adolescents with Medicaid insurance statewide in Colorado from September 1994 to June 1997. Two part least squares regression models are used to decompose services. Managed care sites are compared to sites that remained under FFS financing, before and in two post-periods after the carve-out. Principal findings show that children and adolescents who received mental health services from a capitated managed care provider were significantly less likely to receive inpatient care, and significantly more likely to receive residential treatment center care. In addition, insurance contract design contains financial incentives that affect the amount and mix of clinical care provided to clients by risk-bearing provider agencies. Findings provide evidence of cost substitution from inpatient care both inside the specialty system and outside the carve-out to other child-serving systems.