A comparative analysis of antidepressants and stimulants for the treatment of adults with attention-deficit hyperactivity disorder.

BACKGROUND: Adults who identify themselves as having problems with attention and concentration will often make an office visit to request treatment with a stimulant medication, rather than an antidepressant. The uncertainty of the diagnosis and the prospect of a long-term prescription with a stimulant medication can create a dilemma for physicians. METHODS: We searched MEDLINE for any English-language studies of antidepressant or stimulant treatment of adults with attention deficits. References from relevant articles were reviewed to supplement the MEDLINE search. RESULTS: Antidepressants and stimulants seem to be equally effective for adults with attention-deficit hyperactivity disorder (ADHD). Recent controlled studies suggest that desipramine (an antidepressant) may be as effective as methylphenidate (a stimulant) for improving symptoms of adult ADHD. CONCLUSIONS: Although few good controlled studies exist, the available research suggests that certain antidepressants and stimulants are equally effective for adults with ADHD. Antidepressants may offer a safe first-line treatment for adults with ADHD.

A diagnostic aid for detecting (DSM-IV) mental disorders in primary care.

This study was designed to develop and validate a new computerized version of the Symptom Driven Diagnostic System for Primary Care (SDDS-PC) and examine its feasibility in primary care practice. One thousand and one patients (ages 18-70) coming for routine care to Kaiser-Permanente were screened on a self-administered symptom scale for major depression, alcohol and drug dependence, generalized anxiety, panic and obsessive compulsive disorders, and suicidal behavior. The screen was followed up by a brief diagnostic interview, administered by a nurse, which yielded a one-page summary of positive symptoms and a provisional computer-generated diagnosis for the physician. The physician reviewed the summary results and made a diagnosis. The nurse and physician were blind to the screen results. Patients were reinterviewed within 96 hours by a mental health professional (MHP) blind to previous results. The nurses' interviews ranged between 1.5 and 3.5 minutes for a screened positive diagnosis. Agreement between the nurse and physician diagnoses was excellent to moderate. Disagreement was usually in the direction of the physician ruling out major mental disorders in favor of subsyndromal or medical explanations. Only rarely did physicians diagnose disorders not detected by the nurse interview. Agreement between physician and MHP was moderate. Physicians using the SDDS-PC seldom made diagnoses that were not confirmed by the independent assessment of the MHP. The SDDS-PC may facilitate recognition of psychiatric disorders and minimize the physician's time in information gathering.

Obsessive-compulsive spectrum disorders in primary care: the possibilities and the pitfalls.

Although the serotonin selective reuptake inhibitors make the treatment of obsessive-compulsive spectrum disorders possible for primary care physicians, numerous obstacles to successful treatment in the primary care setting remain. Given the absence of studies of primary care patients in primary care settings, the generalizability of results from patients with obsessive-compulsive spectrum disorders in psychiatric settings is uncertain. The primary care physician must combat resistance and refusal by patients to accept psychiatric intervention. In addition, the primary care physician faces recognition problems--not only are patients reluctant to disclose such problems, but primary care physicians lack validated screening tools. The development of a new computerized compulsive-impulsive spectrum scale should assist primary care physicians in diagnosing and treating obsessive-compulsive spectrum disorders, which may occur at a rate of 10% in the primary care setting.

Psychological management by family physicians.

BACKGROUND: It is frequently assumed that primary care physicians seldom provide psychological interventions to their patients with mental health problems. This study examines self-reports of psychological interventions by family physicians. METHODS: Primary care patients (N = 937) completed a mental health screening form immediately prior to their medical visit. Results were withheld from their seven respective physicians. Following the visit, the physicians were asked to classify the range of psychological interventions they used to manage their patients' emotional problems during the visit. A structured psychiatric diagnostic interview was subsequently administered to a subgroup of the patients (n = 388). RESULTS: At least one psychological intervention was provided to nearly one fourth (24.1%) of the patients. The interventions included listening to the patient's emotional problems (22.4%), providing advice (19.0%), discussing the patient's mental disorder diagnosis (11.4%), and providing individual counseling (8.4%) or family counseling (0.6%). Two thirds (66.7%) of the patients who reported that their emotional health was poor received at least one of these psychological interventions. In a multivariate model, the likelihood of receiving a psychological intervention was higher for patients who were separated or divorced; those between 45 and 59 years of age; those with less than a college education; those who received disability payments; those who reported poor emotional health; and those who had a positive screening result for panic disorder, major depressive disorder, or obsessive-compulsive disorder. CONCLUSIONS: Primary care physicians may be far more extensively involved in providing psychological interventions than is commonly assumed.

Prevalence of mental disorders in primary care. Implications for screening.

OBJECTIVES: To determine the prevalence of five mental disorders in primary care and to identify patient groups that have a relatively high prevalence of these disorders. DESIGN: Two-stage case identification design that involves administration of a 16-item screening instrument followed by an independent diagnostic assessment. SETTING: Three family practice offices in Rhode Island. SUBJECTS: A total of 937 primary care patients completed the brief screen, 388 of whom completed the independent diagnostic assessment. PREVALENCE ESTIMATION: A Bayesian procedure was used to estimate prevalence of mental disorder from screening and assessment results. Independent assessments were based on the Structured Clinical Interview for DSM-III-R administered by a mental health professional. RESULTS: The prevalence estimates were alcohol abuse or dependence, 3.2%; generalized anxiety disorder, 2.8%; major depressive disorder, 14.1%; obsessive-compulsive disorder, 2.2%; panic disorder, 6.2%; and any of the five disorders, 22.0%. The prevalence of any of the five disorders was higher in patients returning for follow-up visits (27.9%) than in those either presenting with a new illness (21.7%) or seeking a routine physical examination (11.8%). The combined prevalence was also higher in patients with a chronic medical problem (25.8%) than in those without (16.7%). CONCLUSIONS: Patients returning for follow-up care and, to a lesser extent, those with chronic medical problems appear to be at increased risk of having a mental disorder. The practice of selectively screening new patients for mental health problems is questioned. Screening efforts in primary care should include established patients and those with chronic medical illnesses as well as new patients.

Development and validation of the SDDS-PC screen for multiple mental disorders in primary care.

OBJECTIVE: To develop, validate, and cross-validate a patient-completed screen for multiple mental disorders in primary care. DESIGN: Comparison of a patient self-report screen with an independent diagnostic assessment by mental health professionals using the Structured Clinical Interview for DSM-III-R diagnoses as criterion standard. SETTING: Three Rhode Island family practices and a South Carolina family medicine residency. SUBJECTS: In the initial validation study, 937 patients in Rhode Island were screened; 388 were interviewed. In the cross-validation study, 775 patients were screened in Rhode Island and South Carolina, and 257 were interviewed. SCREEN ITEMS: Sixty-two questions pertaining to nine mental disorders and suicidal ideation. RESULTS: A 16-item screen remained after analysis of item and scale performance. Sensitivity, specificity, and positive predictive value, respectively, were calculated for the following scales: alcohol abuse or dependence (62%, 98%, and 54%), generalized anxiety disorder (90%, 54%, and 5%), major depression (90%, 77%, and 40%), obsessive-compulsive disorder (65%, 73%, and 5%), panic disorder (78%, 80%, and 21%), and suicidal ideation (43%, 91%, and 51%). Replication in a new sample showed attenuated but acceptable operating characteristics for cross-validation. CONCLUSIONS: The Symptom-Driven Diagnostic System for Primary Care screen assesses multiple mental disorders that are common to primary care. It serves as a sensitive, valid, and patient-friendly first step in a new approach to recognizing and managing mental disorders in primary care. Finally, it aids the primary care clinician in selecting an appropriate diagnostic interview module for the disease for which the patient screened positive.

Brief diagnostic interviews (SDDS-PC) for multiple mental disorders in primary care. A pilot study.

OBJECTIVE: To pilot test the feasibility and validity of new, brief, structured, physician-administered diagnostic interviews for six mental disorders in primary care patients identified from a patient-completed screen. DESIGN: Comparison of the new diagnostic interviews with the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition, version P (SCID-P), administered independently by a mental health professional. SETTING: Three Rhode Island family practices and a South Carolina family medicine residency. SUBJECTS: Consecutive patients of either sex, aged 18 to 70 years, who were able to read and write English were eligible for screening; 775 patients completed the screen. Of these, 246 screened positive for at least one disorder and received at least one module. Of these, 158 received a SCID-P interview. RESULTS: The diagnostic interviews were found useful by all 16 participating physicians. Eighty-seven percent reported that they diagnosed a new mental problem, and 93% said that the modules clarified suspected symptoms. However, 26% thought the procedure was too time consuming, and 80% believed that reimbursement would be necessary for routine use. Detection of cases using the diagnostic modules was associated with physician intervention and with independent assessment of patient impairment. Over three quarters of the patients (76.4%) who were classified as positive by the physician interview for any of the diagnoses also tested positive on the SCID-P. Two thirds of the patients (62.7%) with at least one of the disorders (according to SCID-P) were classified by the physician interview as having a mental disorder. However, the operating characteristics varied across specific disorders and indicated a need for revisions and testing in larger samples. CONCLUSIONS: These brief physician-administered diagnostic interview modules are part of a screening and diagnostic system (Symptom-Driven Diagnostic System for Primary Care [SDDS-PC], The UpJohn Co, Kalamazoo, Mich) to detect mental disorders in primary care patients. The pilot results help establish their feasibility and validity.

The SDDS-PC: a diagnostic aid for multiple mental disorders in primary care.

The Symptom Driven Diagnostic System for Primary Care (SDDS-PC) is a new computerized clinical procedure to assist primary care physicians in diagnosing mental disorders during the course of routine practice. It has three components: (1) a 5-minute patient-administered 16-item screening questionnaire, (2) six 5-minute physician-administered diagnostic interview modules based on DSM-III-R criteria, and (3) a longitudinal tracking form. The SDDS-PC covers five disorders (major depression, panic disorder, alcohol abuse or dependence, generalized anxiety disorder, and obsessive compulsive disorder) as well as suicidal ideation. Patients who screen positive for a disorder receive the corresponding diagnostic interview module. Patients who meet mental disorder criteria on the diagnostic interview module are then followed with the longitudinal tracking form. Minor or subsyndromal conditions are also addressed at the physician's discretion. This article describes the development of SDDS-PC and summarizes results from two studies which involved comparisons between the SDDS-PC and independently administered full-length structured diagnostic interviews.

A review of unrecognized mental illness in primary care. Prevalence, natural history, and efforts to change the course.

Studies of the prevalence, natural history, and outcome of unrecognized mental illness in general medical outpatient settings were reviewed. Approximately half of the patients with a psychiatric disorder were not recognized as having a mental illness by their primary care physician. The natural history of unrecognized mental illness suggests a poorer clinical course of anxiety disorders but not for depressive disorders. Most interventions demonstrated a significant improvement in the physician's ability to identify and treat psychiatric disorders but had a minimal effect on patient symptoms and no effect on short-term health care use. Although primary care physicians do not recognize psychiatric disorders in a high percentage of patients, efforts to improve recognition may not lead to decreased patient suffering or decreased health care costs.

Are neurological abnormalities in well discordant monozygotic co-twins of schizophrenic subjects the result of perinatal trauma?

OBJECTIVE: Neurological abnormalities found in schizophrenic subjects and their healthy relatives have raised questions concerning etiology. The aim of the present study was to investigate the genetic and environmental antecedents of neurological impairment in monozygotic twins discordant for schizophrenia, with particular focus on the well discordant twins. The etiological factors of interest were history of obstetric complications, family history of psychosis, history of substance abuse, and history of postnatal cerebral trauma. METHOD: History of obstetric complications, including information from pregnancy through the neonatal period, and data on neurological "hard" and "soft" signs were obtained blindly and separately for each member of 22 monozygotic twin pairs discordant for schizophrenia and seven normal comparison monozygotic twin pairs. Clinical and family interviews provided information about background factors. RESULTS: Degree of neurological impairment in the well discordant monozygotic twins was significantly positively related to history of both neonatal and total obstetric complications. None of the three other background factors investigated was related to degree of neurological impairment in the ill or well co-twins. CONCLUSIONS: The contribution of obstetric complications to the current level of neurological impairment in well discordant co-twins suggests that the spectrum of neuroabnormality, ranging from neurological signs to schizophrenia, in monozygotic discordant twins may be the result of subtle gene-environment interaction.

Obstetric complications in histories of monozygotic twins discordant and concordant for schizophrenia.

Histories of obstetric complications (OCs) during pregnancy, labor-delivery and the neonatal period were investigated by detailed maternal report for 23 monozygotic (MZ) twin pairs discordant for schizophrenia, 10 MZ twin pairs concordant for schizophrenia and 7 normal MZ control pairs. Statistically significant differences in OC rates were found across these 3 groups. OCs being most frequent in discordant pairs and least frequent in normal control pairs. Labor complications were significantly more frequent in discordant than concordant pairs. OC rates were equivalent in sick and well discordant twins. The results provide evidence for the role of OCs in the development of schizophrenia, complications at the time of birth being especially associated with the development of schizophrenia in discordant twins.

Succinylacetone effects on renal tubular phosphate metabolism: a model for experimental renal Fanconi syndrome.

Phosphaturia is a prominent component of the renal Fanconi syndrome associated with the autosomal recessive disease, hereditary tyrosinemia. Succinylacetone (SA), the metabolic by-product of the enzyme deficiency, can be shown to produce multiple adverse effects on rat renal epithelial cell function in vitro. With the use of this compound, we have examined its interaction with Pi handling by the renal tubule cell in order to form a basis for understanding the effects of endogenously generated SA in causing phosphaturia in the genetically affected kidney. In this report we have shown complete inhibition of sodium-dependent phosphate uptake by renal brush border membrane vesicles, decreased ATP production by the SA-exposed renal tubule, and reversible inhibition of State 3 oxidation of glutamate by isolated renal mitochondria. We conclude that the phosphaturia observed in hereditary tyrosinemia results from multiple metabolic effects of SA on the renal tubule which are additive and lead to intracellular Pi depletion and diminished ATP production.

Hydrazine stress in the diabetic: ornithine decarboxylase activity.

Streptozotocin-induced diabetes of 7 weeks duration increased male Sprague-Dawley rat kidney ornithine decarboxylase activity by 4.8-fold but did not affect the liver enzyme. Hydrazine treatment of 4 hr duration stimulated equally kidney ornithine decarboxylase activities of nondiabetic and diabetic rats. Hydrazine treatment increased liver ornithine decarboxylase activity in the nondiabetic rat but did not increase it in the diabetic rat. Since hydrazine stimulates ornithine decarboxylase activity prior to polyamine and protein syntheses, we speculate that the lack of hydrazine stimulation of ornithine decarboxylase in the diabetic liver may be related in part to the unrestrained gluconeogenesis and depressed Kreb's cycle activity: the latter being required for protein synthesis.

Experimental diabetes causes mitochondrial loss and cytoplasmic enrichment of pyridoxal phosphate and aspartate aminotransferase activity.

The streptozotocin diabetic rat was selected as a model to study how insulin deficiency alters vitamin B6 utilization by focusing on pyridoxal phosphate levels and aspartate aminotransferase activities in liver tissues. Diabetes of 15 weeks' duration lowered plasma pyridoxal phosphate levels by 84%. Normal plasma pyridoxal phosphate was 480 pmole/ml. Fractionation of liver into mitochondrial and extramitochondrial compartments demonstrated that diabetes caused a 43% diminution in mitochondrial pyridoxal phosphate per gram of liver. There was no cytoplasmic change in these diabetic rats. Mitochondrial aspartate aminotransferase activity was decreased 53% per gram of diabetic liver and cytoplasmic aspartate aminotransferase activity was elevated 3.4-fold. Damage to diabetic mitochondria during preparation procedures could not account for the rise in cytoplasmic aspartate aminotransferase activity. Electrophoresis showed that in the diabetic cytoplasm both cathodal and anodal forms of the enzyme were elevated. Speculations concerning mitochondrial loss and cytoplasmic gain of enzyme activity as well as those on the reduction of plasma pyridoxal phosphate in the diabetic rat are presented.

Metabolic and mitochondrial disturbances in streptozotocin-treated Sprague-Dawley and Sherman rats.

This study provides explanation for conflicting evidence in the literature relating to changes in mitochondrial function and metabolic parameters during chemically induced diabetes. Diabetes of 3 days' duration (early ketosis) did not alter heart, kidney, or liver mitochondrial respiratory rates with glutamate or succinate even though serum glucose and triglycerides were elevated. Diabetes of 5 weeks' duration did not alter kidney or liver mitochondrial function in the fed adult rat although weight gain was depressed. The amount of kidney mitochondrial protein isolated per gram of tissue was increased by 30% in the diabetic. This increase was reversed by insulin treatment as were the other biochemical modalities measured. Superimposition of a 24-hr fast resulted in enhanced gluconeogenesis as measured by an animal weight loss of 17% within 24 hr (liver weight loss, 21%) and an elevation of serum urea nitrogen by 180% compared to fasted control. Respiratory rates of diabetic kidney mitochondria with glutamate were unaffected in the fasted animal whereas diabetic liver mitochondrial respiratory rates during succinate oxidation were reduced by 43%. Respiratory control was unchanged in the fasted diabetic rat. All the observed changes were reversed by insulin. Variation in the serum and liver metabolic indices (urea nitrogen, creatinine, glycerol, free fatty acids, free amino acids, triglycerides, and glucose) and liver mitochondrial responses to 7 weeks of chemically induced diabetes was affected by the rat strain, Sprague-Dawley versus Sherman, and rat weight, 72 g versus 222 g. Liver mitochondrial respirations in fed Sherman rats were not depressed by diabetes. Both rat strains had elevated liver free fatty acids and glutamate dehydrogenase activity in the diabetic state. Serum leucine, isoleucine, and valine were more elevated and serum lysine and arginine were more depressed in the diabetic Sprague-Dawley rat than in the Sherman rat. Conjectures on these results are presented in the text.

Localization of L-lactate dehydrogenase in mitochondria.

Relatively small but persistent amounts of L-lactate dehydrogenase (LDH) activity were found in mitochondrial preparations isolated from liver of the rat. Using a variety of cytosolic markers, it was found that essentially no cytosolic contamination was present. Respiratory velocities and respiratory control with L-lactate were somewhat lower than with glutamate, but equal or superior to those with pyruvate. Agarose gel electrophoresis showed LDH isoenzymes in mitochondria similar to that in corresponding cytosol. Subtilisin BPN', a bacterial protease, was incubated with intact mitochondria and enzyme activities were measured. Following mitochondrial disruption, the proteolytic treatment was repeated. Digitonin was also used in the fractionation of mitochondria. These techniques helped to determine the location of the LDH in the mitochondria as being mainly in the outer membrane and periplasmic space.

Influence of genetic predisposition to diabetes and obesity on mitochondrial function.

Inbred mice with the mutation diabetes C57BL/KsJ db+/db+ and the mutation obese C57BL/6J ob/ob displayed a total liver mitochondrial capacity to oxidize glutamate or succinate which was approximately eight times greater than the capacity of the C57BL/6J +/+ control mice. This increase in oxidation capacity was estimated by multiplying the observed twofold increase in each of the following components: total liver weight, the mitochondrial protein content per gram of liver, and glutamate or succinate respiration activity per milligram of liver mitochondrial protein. No significant difference in liver mitochondrial function and capacity for oxidation was observed between db+/db+ and ob/ob mutants, which indicated that these results may be primarily mediated by the genetic factors responsible for obesity and hyperphagia in these mutants, and not by the genetic traits associated with diabetes. These findings may provide a biochemical foundation in support of the thrifty gene hypothesis.

Effects of succinylacetone on methyl alpha-D-glucoside uptake by the rat renal tubule.

Succinylacetone, a catabolic end-product of tyrosine, is excreted in large quantities in urine from individuals with hereditary tyrosinemia and the Fanconi syndrome. Succinylacetone inhibits rat renal tubular concentrative uptake of the glucose transport analogue, methyl alpha-D-glucoside, in a noncompetitive and reversible fashion. This compound also depresses oxygen consumption by the rat renal tubule without fine structural damage to mitochondria. It is concluded that succinylacetone may be a useful probe in elucidation of the biochemical mechanism underlying the human Fanconi syndrome.