Women's issues in mood disorders

Since the introduction of antidepressants in the 1950s, it was assumed for the next several decades that there were no special reasons to look at the application of these medications to women. In the past half-century, particularly in the past decade, since the advent of the selective serotonin re-uptake inhibitors (SSRI), a series of specific foci have developed. Firstly, there appear to be differences in the degree of response to particular antidepressants between the genders. Secondly, there is data concerning hormonal effects of particular relevance to women, i.e. prolactin, which separates out among the antidepressants. Also of concern to women are the potential teratogenic effects of these medications, which impact on their use during pregnancy. Finally, there are certain diagnostic syndromes that are particularly relevant to women: premenstrual dysphoric disorder (PMDD); postpartum depression (PPD) and perimenopausal depression (PMD). It appears that the SSRIs may be more effective, relative to the older tricyclic antidepressants (TCA), in women than in men. The SSRIs have shown to be effective in treating these disorders, with the possibility of intermittent luteal phase treatment of PMDD. Non-antidepressant (AD) approaches have generally been found to be less effective. In the first trimester of pregnancy, there is data available supporting the safe use of SSRIs, particularly those first released, i.e. fluoxetine and sertraline. Finally, all SSRIs, with the exception of sertraline, can increase the risk of hyperprolactinaemia. This can lead to a variety of complications including amenorrhea and osteoporosis. This effect of sertraline, due to its unique profile in blocking re-uptake of dopamine, extends itself into additional relative benefits for sleep and memory. The issues associated for women with bipolar disorder are dealt with in terms of both increased risk of relapse during pregnancy and postpartum periods, as well as the relative risk of use of lithium and mood stabilizers in pregnancy and lactation.     

Personality disorders predict relapse in alcoholic patients

This prospective study examines the association of DSM-III-R Axis II comorbidity with (time to) relapse since the end of treatment in a sample of 105 outpatient and 82 inpatient alcoholics. Furthermore, this study addresses the role of motivation for change, time in program, and working alliance in the mechanism underlying the association between Axis II and relapse. We found that Axis II comorbidity in alcoholics is a robust predictor of relapse following treatment, while the effect is strongest in outpatients with low motivation for change and/or short time in program. Motivation for change and time in program did not mediate the association of Axis II with relapse. We also found poor working alliance to be related to personality pathology among inpatients, and from our findings it can be hypothesised that poor working alliance is part of the mechanism underlying the observed impact of Axis II on treatment outcome in outpatients. A preliminary model of the role of personality pathology in the mechanism of relapse is proposed.     

Statistical issues in quality-of-life assessment

In recent years, the assessment of drug effects on quality of life (QOL) has become very popular in clinical trials. QOL assessment quantifies the ability of a person to function normally in society. It may be used to distinguish between therapies that appear to be equally efficacious and equally safe. QOL is usually assessed by a QOL instrument, which consists of a number of questions. A QOL instrument is a very subjective tool that usually has a large variation. To ensure the accuracy and reliability of QOL assessment in clinical trials, the adopted QOL instrument should be validated. Some statistical tests are proposed for validation of a QOL instrument in terms of validity, reliability, test-retest reproducibility, responsiveness, and sensitivity. Some statistical issues regarding the validation of utility analysis and calibration for QOL against life events and /or disease status will also be discussed.     

Co-occurring disorders in substance abuse treatment: issues and prospects

This article explores the epidemiology of co-occurring disorders (CODs) with an emphasis on the implications of study findings for the functioning and potential of substance abuse treatment. Severity of disorder is discussed as an issue that may have particular significance for the selection of specialized as opposed to traditional substance abuse treatment forms. Exploration is made, as well, of the resources currently available to substance abuse treatment, especially the human resources available, and the implications of resource availability for undertaking initiatives specific to COD. Findings from standard and enhanced treatment for comorbid individuals are examined in an effort to clarify areas of need for specialized and typical treatment personnel. Issues are raised for consideration by the clinical research and treatment provider communities in terms of assessment and diagnosis, manpower and training, and response to the challenge of relapse in this population.     

Personality disorders and alcoholism treatment outcome

The relationship existing between personality disorders (classified according to DSM III) and alcohol treatment outcome was evaluated in 404 alcoholics admitted to the Psychiatric Clinic of the University of Trieste, Italy. One quarter of the subjects had personality disorders, mainly of the 'antisocial', 'dependent', and 'borderline' subtypes. Alcohol abuse was specifically related to 'antisocial' personalities. Marked differences in treatment outcome among personality disorders were found. Group therapy for alcoholism was not beneficial to 'antisocial' personalities; it was most useful among 'dependent' subjects.     

Personality disorders in opiate addicts show prognostic specificity

Early studies examining the relationship of personality disorders to opiate addiction attempted to define an "addictive personality." Later research found that personality disorders in opiate addicts were common but heterogeneous. We examined whether different comorbid personality disorders have prognostic specificity. Rates of depression and alcoholism as well as assessments of specific problems were measured in a 2.5-year follow-up of 150 treated opioid addicts. Using DSM-III criteria, we found that borderline personality disorder predicted more depressive disorders and alcoholism at follow-up; yet greater recovery from these disorders was seen. Borderline patients had more severe psychiatric problems as measured by the Addiction Severity Index. Other ASI outcomes differed by personality disorder; antisocial addicts had more legal problems, and narcissistic addicts had more medical problems. These results suggest that treatment for opiate addicts be tailored to the specific needs of the patients, which can be predicted, in part, by their comorbid personality disorder diagnosis.     

Methodological issues in drug assessment research

Increased sensitivity to methodological issues in drug assessment research is needed in light of challenges to research design, conduct, and outcomes. Major issues presented include (a) the nature and adequacy of placebo controls, (b) problems in maintaining the integrity of “blind” conditions, and (c) the potential design-compromising effects of informed consent. The necessity of true matching placebos, particularly concerning physical/perceptual characteristics and the ability to produce transitory changes in subjects, was stressed. Though the double-blind condition has conceptual integrity, the operation of drug and placebo side effects and associated guess bias may confound research results. Use of a triple-blind condition and addition of a drug-disguised group is suggested. Last, the issue of informed consent and its implications for the integrity of drug research is a problem deserving more attention.     

New issues in cancer risk assessment

When a nonlinear dose-response at low doses can be justified, an acceptable daily intake for a carcinogen can be obtained by dividing a benchmark dose, associated with a low incidence of tumors in animals, by uncertainty factors to account for animal-to-human extrapolation, human variability, and risk reduction from a low observed adverse-effect level. This approach can utilize mechanistic information to justify smaller uncertainty factors than typical default values of 10. If a nonlinear dose-response cannot be justified, traditional linear extrapolation from the benchmark dose to zero sometimes gives similar results. This suggests a unified risk-assessment procedure based on uncertainty factors. The issue of cross-species extrapolation based on the risk relative to background risks, rather than excess risk, is examined. The relative risk approach reduces the estimates of cancer risk in humans based on common rodent tumors, such as the liver in some strains of mice.     

Neurocognitive parameters should be incorporated in the Minnesota Multiphasic Personality Inventory-2 assessment of patients with alcohol use disorders

Introduction and Aims. Treatment planning for alcohol use disorder (AUD) patients is often preceded by the assessment of psychopathology and personality with the Minnesota Multiphasic Personality Inventory‐2 (MMPI‐2). However, during periods of abstinence, cognitive impairments (e.g. attention, memory and executive dysfunctions) related to neurological and somatic pathology may affect level and pattern of MMPI‐2 scale scores, resulting in clinical misinterpretation. Design and Methods. A re‐analysis of the data of the Egger et al. study is conducted in order to examine the clinical significance of the MMPI‐2 profiles of 222 AUD patients (mean age 42.2 ± 9.6 years; 76.6% men) by using neurologically relevant item correction procedures. Hierarchical cluster analyses of neurologically relevant item‐corrected solutions were compared to the original MMPI‐2 profile. Results. Impulsiveness and psychopathic deviation were identified as a common denominator. Discussion and Conclusions. Uncorrected MMPI‐2 assessment in AUD tends to overstress psychopathology and to overlook disinhibitory traits in early abstinence, caused by chronic alcoholism.[Walvoort SJW, Wester AJ, Egger JIM. Neurocognitive parameters should be incorporated in the Minnesota Multiphasic Personality Inventory‐2 assessment of patients with alcohol use disorders. Drug Alcohol Rev 2012;31:550–557]     

Personality assessment of substance-dependent patients in a therapeutic community

The design and implementation of a personality assessment system for severely substance-dependent men in a therapeutic community (TC) are described. The system was designed from a treatment utility perspective (Hayes, Nelson, & Jarrett, 1987) and uses the Personality Research Form E (Jackson, 1984) to provide each patient with feedback (a) describing his normal personality traits, (b) predicting his probable pattern of adjustment to the treatment setting, and (c) prescribing specific actions he can take to address potentially problematic behaviors. Discussing the results with the patient helps him cope with the TC. Reviewing the assessment results with the staff promotes their empathy for the patient as a person whose behavior can be understood as an interaction of his personality with the specific demands of the TC rather than seeing the patient in exclusively pathological terms. Specific suggestions for behavior change guide both the patient and the staff and are potentially useful in various treatment settings.     

Human milk biomonitoring data: interpretation and risk assessment issues

Biomonitoring data can, under certain conditions, be used to describe potential risks to human health (for example, blood lead levels used to determine children's neurodevelopmental risk). At present, there are very few chemical exposures at low levels for which sufficient data exist to state with confidence the link between levels of environmental chemicals in a person's body and his or her risk of adverse health effects. Human milk biomonitoring presents additional complications. Human milk can be used to obtain information on both the levels of environmental chemicals in the mother and her infant's exposure to an environmental chemical. However, in terms of the health of the mother, there are little to no extant data that can be used to link levels of most environmental chemicals in human milk to a particular health outcome in the mother. This is because, traditionally, risks are estimated based on dose, rather than on levels of environmental chemicals in the body, and the relationship between dose and human tissue levels is complex. On the other hand, for the infant, some information on dose is available because the infant is exposed to environmental chemicals in milk as a "dose" from which risk estimates can be derived. However, the traditional risk assessment approach is not designed to consider the benefits to the infant associated with breastfeeding and is complicated by the relatively short-term exposures to the infant from breastfeeding. A further complexity derives from the addition of in utero exposures, which complicates interpretation of epidemiological research on health outcomes of breastfeeding infants. Thus, the concept of "risk assessment" as it applies to human milk biomonitoring is not straightforward, and methodologies for undertaking this type of assessment have not yet been fully developed. This article describes the deliberations of the panel convened for the Technical Workshop on Human Milk Surveillance and Biomonitoring for Environmental Chemicals in the United States, held at the Hershey Medical Center, Pennsylvania State College of Medicine, on several issues related to risk assessment and human milk biomonitoring. Discussion of these topics and the thoughts and conclusions of the panel are described in this article.     

Critical issues in adolescent substance use assessment.

Despite advances in methodology and instrumentation, the assessment of adolescent drug and alcohol involvement remains a complex clinical and practical process. It requires the careful and skillful implementation of procedures across a wide range of service systems and providers. While the literature identifies and provides information on singular aspects of the assessment of adolescents, few sources furnish an integrated overview of the key issues necessary for appropriate and accountable assessment. Consequently, this paper synthesizes theoretical, research, and clinical issues into a practical framework that can be used by clinical and research staff making assessment decisions. Issues discussed have been informed by the literature and by our collective experience during the 8-year development and testing of the Comprehensive Adolescent Severity Inventory (CASI).     

Personality disorders in early adolescence and the development of later substance use disorders in the general population

Assessments of personality disorder (PD) and conduct disorder (CD) in a random community sample at mean age 13 were employed to predict subsequent substance abuse disorder (SUD), trajectories of symptoms of abuse or dependence on alcohol, marijuana, or other illicit substances, and hazard of initiating marijuana use over the subsequent decade. Personality disorders and conduct disorder were associated with diagnoses and symptoms of SUDs in every model and their effects were independent of correlated family risks, participant sex, and other Axis I disorders. Specific elevated PD symptoms in early adolescence were also associated with differential trajectories of already initiated SUD symptoms as well as elevated risk for future onset of SUD symptoms. For several models the greatest of these effects were shown for borderline PD and for conduct disorder, the predecessor of adult antisocial PD. Passive-aggressive PD also showed independent elevation effects on substance use symptoms for alcohol and marijuana. Analyses over 30 years suggest that Cluster B PD (borderline, histrionic, narcissistic) are independent risks for development of SUD and warrant clinical attention.