Early life stress increases testosterone and corticosterone and alters stress physiology in zebra finches.

Early life stress has enduring effects on behavior and physiology. However, the effects on hormones and stress physiology remain poorly understood. In the present study, parents of zebra finches of both sexes were exposed to an increased foraging paradigm from 3 to 33days post hatching. Plasma and brains were collected from chicks at 3 developmental time points: post hatching days 25, 60 and adulthood. Plasma was assayed for testosterone (T), estradiol (E2), and corticosterone (CORT). The paraventricular nucleus of the hypothalamus was assessed for corticotrophin releasing factor (CRH) and glucocorticoid receptor (GR) expression. As expected, body mass was lower in nutritionally stressed animals compared to controls at multiple ages. Nutritionally stressed animals overall had higher levels of CORT than did control and this was particularly apparent in females at post hatching day 25. Nutritionally stressed animals also had a higher number of cells expressing CRH and GR in the paraventricular nucleus of the hypothalamus than did controls. There was an interaction, such that both measures were higher in control animals at PHD 25, but higher in NS animals by adulthood. Females, regardless of treatment, had higher circulating CORT and a higher number of cells expressing CRH than did males. Nutritionally stressed animals also had higher levels of T than did control animals, and this difference was greatest for males at post hatching day 60. There were no effects of nutritional stress on E2. These findings suggest that nutritional stress during development has long-lasting effects on testosterone and stress physiology.

Do antidepressants reduce suicide rates?

Investigators from a number of countries have linked temporal declines in the rate of completed suicide in children and adults to the increasing utilization of selective serotonin reuptake inhibitor (SSRI) antidepressants. They suggest that the relationship is causal. We undertook a thorough literature search of the rates of completed suicide using data from 1980 onwards, from the World Health Organization, the US National Center for Health Statistics, and related studies, in order to ascertain if a broad array of epidemiological evidence would or would not support a consistent association between suicide completion and SSRI utilization. The major findings were: (1) within and between countries, suicide rates vary prominently by age group; (2) national differences are marked with respect to a temporal association between rates of completed suicide and SSRI utilization; (3) in nearly half of the countries of the world, the decline in the suicide rate preceded the onset of the use of SSRIs; (4) suicide rates have fluctuated dramatically over the last century; and (5) the association between declining rates of completed suicides and increased SSRI use in the USA between 1990 and 1999 was no longer present between 2000 and 2004. We conclude that available ecological evidence does not support an inverse temporal relationship between rates of completed suicide and SSRI utilization.

Juvenile nasopharyngeal angiofibroma.

Juvenile nasopharyngeal angiofibroma is a rare yet potentially destructive vascular tumor that typically affects adolescent males. While the etiology of these tumors remains unknown, great advances have been made in their diagnosis and treatment. When juvenile nasopharyngeal angiofibroma is diagnosed at an early stage, the prognosis is generally very good, as patients can be treated with a combination of pre-operative embolization and surgical resection. Advanced juvenile nasopharyngeal angiofibroma is much more difficult to treat, since orbital and intracranial involvement are common in the natural progression of the disease. However, due to the rather innocuous presenting symptoms (commonly, nasal obstruction and epistaxis), diagnosis most often occurs in the later stages of the disease. For this reason, it is important for all physicians to have a high degree of suspicion for juvenile nasopharyngeal angiofibroma when evaluating a male adolescent with these symptoms.

Psychotropic medication in children: a study from the Netherlands.

OBJECTIVE: Although there is a global concern about the increased use of psychotropic agents in children, most research literature originates in the United States and is based on figures from the first half of the 1990s. Also, few studies document the use of various types of psychotropic agents. The objective of this study was to investigate the use of psychotropic medication in children in the Netherlands and to determine whether this corresponds with previously reported figures from the United States. METHODS: A drug utilization study based on computerized pharmacy dispensing records was conducted from 1995 to 1999 for children aged 0 to 19 years in the north of the Netherlands. RESULTS: Stimulants were the most widely used psychotropic agents among 0- to 19-year-olds (prevalence: 7.4/1000 in 1999), followed by hypnotics/anxiolytics (6.9/1000) and antidepressants (4.4/1000). Prevalence rates of stimulants increased from 1.5/1000 in 1995 to 7.4/1000 in 1999. Incidence rates, proportion of girls, and duration of stimulant treatment increased as well. Changes in prevalence rates of other psychotropic agents were much smaller than those of stimulants. Finally, the vast majority of children who were treated with psychotropic agents used only 1 agent at a time. CONCLUSION: The prevalence of stimulant use in the Netherlands is much lower than reported previously (28/1000 children in 1995) from the United States, and differences also existed with regard to the use of other psychotropic agents and combinations of psychotropic agents. However, the increase in Dutch stimulant use agrees with the previously reported 2.5-fold increase in the United States and shows that the increased use of stimulants is not limited to the United States.

Mental health services for youths in foster care and disabled youths.

OBJECTIVES: This study assessed whether mental health services for youths differ with respect to medical assistance aid category. METHODS: Computerized claims for 15,507 youths with Medicaid insurance in a populous county of a mid-Atlantic state were used to establish population-based prevalence estimates of mental disorders and psychotherapeutic treatments during 1996. RESULTS: An analysis of service claims revealed that the prevalence of mental disorders among youths enrolled in foster care (57%) was twice that of youths receiving Supplemental Security Income (SSI; 26%) and nearly 15 times that of other youths receiving other types of aid (4%). Rates of mental health service use were pronounced among foster care youths aged 6 to 14 years. Attention deficit/hyperactivity disorder, depression, and developmental disorders were the most prevalent disorders. Stimulants, antidepressants, and anticonvulsants were the most prevalent medications. CONCLUSIONS: Youths enrolled in foster care and youths receiving SSI use far more mental health services than do youths in other aid categories. Additional research should evaluate the complexity and outcomes of mental health services for youths in foster care.

Services and prevention: pharmacoepidemiology of antidepressant use.

Between 1988 and 1994, data from 3 large sites revealed a 3-5 fold increase in the prevalence of antidepressant (ATD) treatment for U.S. youths aged 2-19 years. In 1994, the ATD prevalence for youths of this age ranged from 13 per 1000 (in the HMO) to 18 per 1000 (in 2 state Medicaid systems). Males predominated in the 10-14-year-olds treated with ATDs, whereas females predominated among 15-19-year-olds. Caucasians were more than twice as likely to receive ATD therapy than their African-American counterparts. Primary care providers were the major source of ATD prescriptions for youths. The leading diagnoses in primary care were ADHD followed by depression, whereas the diagnostic order was reversed for youths who received psychiatric services. This review provides details concerning these patterns and trends in ATD treatment of youths from community-based clinical data sources. In addition, the role of these data in an expanded, comprehensive psychotropic knowledge base is discussed. Finally, the implications of an expanded knowledge base for ATD treatments are discussed in regard to generating research questions on effectiveness and safety and to improve treatment consensus within a public-health perspective.

Pemoline hepatotoxicity and postmarketing surveillance.

OBJECTIVE: To review the numerous reports of hepatotoxic adverse drug reactions (ADRs) ascribed to pemoline that were sent to the U.S. Food and Drug Administration (FDA) between 1975 and 1996 and to describe the medical community's lack of awareness of these reports. METHOD: All ADR reports from 1975 through 1996 wherein pemoline was the suspect agent were obtained from the FDA MedWatch Internet site, and some details of nine pemoline-related deaths in youths were obtained directly from the FDA. The published literature on this subject was fully reviewed. RESULTS: (1) In premarketing clinical trials with pemoline in the early 1970s, hepatic abnormalities were noted in enzyme levels (1%-3% of youths receiving maintenance treatment), during rechallenges (6 of 6), and in biopsies (2 of 2). (2) Between 1975 and 1989, 12 cases of jaundice and 6 deaths in youths ascribed to pemoline hepatotoxicity were reported to the FDA. (3) The first medical literature report of a serious ADR ascribed to pemoline was in a 1989 letter to the editor. (4) Physicians generally only became aware of serious pemoline hepatotoxicity in December 1996. (5) Pemoline use increased until 1997. CONCLUSION: Limitations in postmarketing surveillance and public reporting in the United States, particularly in the 1980s, largely accounted for delays in an appropriate response to pemoline hepatotoxicity.

Antidepressant treatment in children and adolescents: bridging the gap between efficacy and effectiveness.

This review of antidepressant treatments in children and adolescents emphasizes the gap between efficacy data derived from randomized clinical trials (RCTs) and the limited effectiveness data from community-based practices. Part one is a brief review of data from randomized, double-blind clinical trials to assess the evidence base for the major approved indications for antidepressants in youths. Part two reviews information gaps in the evidence from RCTs. Part three discusses nonexperimental evidence of the use of antidepressants, including surveys of prescription sales, physician surveys, and population-based data. Part four presents a comprehensive model for assessing the use of antidepressants in youths in the community. The model aims to answer a range of public health-oriented questions and is intended to improve treating physicians' and clinical care providers' ability to manage medications for optimal patient benefit. Suggestions are made for engaging health service providers, health insurers, academicians, advocates, and the government in building the necessary infrastructure to make effectiveness as vital as efficacy to the model of drug therapy evaluation.

Building pharmacoepidemiological capacity to monitor psychotropic drug use among children enrolled in Medicaid.

This study's objective was to develop a methodology to apply pharmacoepidemiological research toward understanding and improving psychotropic drug use among children enrolled in Medicaid. Using Kansas Medicaid data for 1995-1996, we summarized drug claims, diagnoses, and demographics for children under 20 who received at least one psychotropic drug prescription over either year. The sequence of steps needed to assure a quality improvement role is discussed. Use of key personnel in less regulatory and more clinical data applications is critical. Illustrating this approach, we found disproportionate numbers of children receiving psychotropic drugs who were young boys and larger numbers of white children receiving psychotropic prescriptions relative to their Medicaid enrollment than either African-American or Hispanic children. Medicaid agencies can expand epidemiological capacity to understand service use among segments of the population they insure as part of an overall commitment to improving quality.

Trends in the prescribing of psychotropic medications to preschoolers.

CONTEXT: Recent reports on the use of psychotropic medications for preschool-aged children with behavioral and emotional disorders warrant further examination of trends in the type and extent of drug therapy and sociodemographic correlates. OBJECTIVES: To determine the prevalence of psychotropic medication use in preschool-aged youths and to show utilization trends across a 5-year span. DESIGN: Ambulatory care prescription records from 2 state Medicaid programs and a salaried group-model health maintenance organization (HMO) were used to perform a population-based analysis of three 1-year cross-sectional data sets (for the years 1991, 1993, and 1995). SETTING AND PARTICIPANTS: From 1991 to 1995, the number of enrollees aged 2 through 4 years in a Midwestern state Medicaid (MWM) program ranged from 146,369 to 158,060; in a mid-Atlantic state Medicaid (MAM) program, from 34,842 to 54,237; and in an HMO setting in the Northwest, from 19,107 to 19,322. MAIN OUTCOME MEASURES: Total, age-specific, and gender-specific utilization prevalences per 1000 enrollees for 3 major psychotropic drug classes (stimulants, antidepressants, and neuroleptics) and 2 leading psychotherapeutic medications (methylphenidate and clonidine); rates of increased use of these drugs from 1991 to 1995, compared across the 3 sites. RESULTS: The 1995 rank order of total prevalence in preschoolers (per 1000) in the MWM program was: stimulants (12.3), 90% of which represents methylphenidate (11.1); antidepressants (3.2); clonidine (2.3); and neuroleptics (0.9). A similar rank order was observed for the MAM program, while the HMO had nearly 3 times more clonidine than antidepressant use (1.9 vs 0.7). Sizable increases in prevalence were noted between 1991 and 1995 across the 3 sites for clonidine, stimulants, and antidepressants, while neuroleptic use increased only slightly. Methylphenidate prevalence in 2- through 4-year-olds increased at each site: MWM, 3-fold; MAM, 1.7-fold; and HMO, 3.1-fold. Decreases occurred in the relative proportions of previously dominant psychotherapeutic agents in the stimulant and antidepressant classes, while increases occurred for newer, less established agents. CONCLUSIONS: In all 3 data sources, psychotropic medications prescribed for preschoolers increased dramatically between 1991 and 1995. The predominance of medications with off-label (unlabeled) indications calls for prospective community-based, multidimensional outcome studies.

Psychotherapeutic medication patterns for youths with attention-deficit/hyperactivity disorder.

OBJECTIVES: (1) To describe temporal patterns of office visits for attention-deficit/hyperactivity disorder (ADHD) and stimulant treatment for 5- to 14-year-old US youths; (2) to compare youth visits for ADHD with and without melication according to patient demographics, physician specialty, reimbursement source, and comorbid diagnoses; and (3) to compare office visits for youths with ADHD in relation to common medication patterns (stimulants alone, stimulants with other psychotherapeutic medication, and nonstimulant psychotherapeutic medications alone). DESIGN: Survey based on a national probability sample of office-based physicians in the United States. SETTING: Physician offices. PARTICIPANTS: A systematically sampled group of office-based physicians. MAIN OUTCOME MEASURES: National estimates of office visits for ADHD and psychotherapeutic drug visits for ADHD for each year and for a combined 8-year period. RESULTS: Youth visits for ADHD as a percentage of total physician visits had a 90% increase, from 1.9% in 1989 to 3.6% in 1996. Stimulant therapy within ADHD youth visits rose from 62.6% in 1989 to 76.6% in 1996. While the majority of non-ADHD youth visits were conducted by primary care physicians, one third of ADHD youth visits were managed by psychiatry and neurology specialists. Health maintenance organization insurance was the reimbursement source for 17.9% of non-ADHD youth visits but only 11.7% of ADHD youth visits. Complex medication therapy was more likely to be prescribed by psychiatrists and less likely to be related to visits with health maintenance organization reimbursement. CONCLUSIONS: National survey estimates in the 1990s confirm the substantial increase in visits for youths diagnosed as having ADHD, with more than three quarters of these visits associated with psychotherapeutic medication treatment. Physician specialty and reimbursement source variables identify distinct patient populations with a gradient in psychotherapeutic medication patterns from single-drug standard (stimulant) therapy to complex multidrug treatment regimens for which evidence-based scientific information is lacking.

Clinical and treatment characteristics of children with attention-deficit/hyperactivity disorder in psychiatric practice.

OBJECTIVE: To capture information about the clinical characteristics of, and treatments for, children with attention-deficit/hyperactivity disorder (ADHD) in psychiatric practice. METHOD: A mailed, self-administered questionnaire was sent to 81 practicing psychiatrists for them to complete on the next three consecutive patients aged 14 years and younger with ADHD seen during the 12-day study period. Information collected included the sociodemographic, clinical, and treatment characteristics of sampled patients. RESULTS: Patients in the study were predominantly white (85%), male (78%), and between 10 and 14 years old (58%). The most common ADHD subtype was combined/predominantly hyperactive (86%); 31% had no other comorbidity. Ninety-seven percent were receiving medications, with 49% receiving two or more. The single most common medication reported was methylphenidate (51% of patients) followed by clonidine (20%). Psychotropics other than psychostimulants were used in a majority of patients (55%). CONCLUSIONS: Psychiatrists, and child and adolescent psychiatrists in particular, see a more severely impaired and complex group of patients than would be expected of primary care providers. The treatment patterns of psychiatrists for these patients do not reflect the simpler treatments usually studied in clinical trials.

Prevalence variations in psychotropic treatment of children.

This study was undertaken to clarify several aspects of the estimation of prevalence of three commonly use pediatric psychotropic agents, namely, methylphenidate, desipramine, and imipramine. The study aims are threefold: (1) to show the variability of drug prevalence by comparing estimates from three data sources; (2) to show the misleading impression that can be created by reporting drug prevalence estimates based on counts of prescriptions rather than persons; (3) to show the utility of gender-by-age-specific prevalence of drug use as a marker for diagnosis. Two data sources that yield population-based prescription estimates were available: 1991 Medicaid administrative claims data for prescriptions from a mid-Atlantic state and 1991 prescription records of the northwest region of Kaiser Permanente, a staff-model health maintenance organization (HMO). Another source of data consists of the 1991 National Ambulatory Medical Care Survey, which records medication information reported during physician office visits. Data analysis consists of quantitative estimates of (1) drug prevalence from each source; (2) the ratio of prescription claims to persons; and (3) the proportion of drug use according to age and gender. Methylphenidate and desipramine prevalence had a twofold greater use among state Medicaid enrollees compared with HMO enrollees. Average claims-to-person ratios of 5:1 suggest better accuracy using persons with medication rather than prescription counts. Gender-by-age-specific prevalence rates showed that 75% of the drug use for desipramine among those less than 15 years old was found among males, whereas 75% of the desipramine use among those 15 or older was found among females, suggesting its use for the treatment of attention deficit-hyperactivity disorder among young males and for depression among older females. The variability of community physician decision making in pediatric psychopharmacology is better understood by observing drug prevalence rates from different settings. National sampling efforts should be undertaken to verify regional and setting-specific prevalence findings and to learn the reasons for their fluctuation.

Pharmacoeconomics of the new antipsychotics for the treatment of schizophrenia.

Inevitably, the greater availability of more costly antipsychotic medications has resulted in attempts to regulate the use of these agents. Early objections over the cost of treatment with clozapine or risperidone have in part been mollified by preliminary statistics on the cost effectiveness of these agents. However, this issue is complex and requires careful consideration of pharmacoeconomic principles in the development and clinical distribution of novel antipsychotics. Future cost-effectiveness studies need to consider a balance of public and private perspectives. These studies should be conducted in several settings, preferably also within the context of broader, multimodal treatment intervention strategies.

Antidepressant prescribing practices of outpatient psychiatrists.

BACKGROUND: The authors examined recent changes in the number and proportion of patients prescribed antidepressants by psychiatrists in outpatient private practice and characterized antidepressant prescription patterns by patient age, sex, race, payment source, and clinical diagnosis. METHODS: The authors analyzed physician-reported data from the 1985 and 1993-1994 National Ambulatory Medical Care Survey, focusing on visits to physicians specializing in psychiatry. Logistic regressions were used to examine associations between survey year and antidepressant prescription, adjusting for the presence of other variables. RESULTS: The proportion of outpatient psychiatric visits in which an antidepressant was prescribed increased from 23.1% (95% confidence interval [CI], 19.7%-26.5%) in 1985 to 48.6% (95% CI, 47.5%-49.7%) in 1993-1994. After controlling for several patient variables, psychiatric patients were approximately 2.3 (95% CI, 1.8-2.9) times more likely to receive an antidepressant in 1993-1994 than in 1985. In 1993-1994, selective serotonin reuptake inhibitors accounted for approximately half of the psychiatric visits with an antidepressant prescription. Increases in the rate of antidepressant prescription were particularly evident for children and young adults; whites; new patients; and patients with adjustment disorders, personality disorders, depression not otherwise specified or dysthymia, and some anxiety disorders. CONCLUSIONS: During the late 1980s and early 1990s, there was a significant increase in the prescription of antidepressants by office-based psychiatrists. This increase was greatest for patients with less severe psychiatric disorders.

Contrast-enhanced breast MRI for cancer detection using a commercially available system--a perspective.

The diagnosis and treatment of breast cancer are dependent upon early detection of the disease by physical examination and mammography. Although mammography is a relatively good and cost-effective method of early breast cancer detection, there are some inherent weaknesses associated with this imaging modality that limit its sensitivity and specificity. Contrast-enhanced MRI of the breasts provides the additional capability to answer questions raised or unanswered with conventional imaging methods. This paper reviews contrast-enhanced breast MRI interpretation guidelines and patient preselection criteria for diagnostic problem cases. Technical aspects using a commercially available three-dimensional (3D) spoiled gradient-echo technique are discussed.