Pharmacogenomics--can genetics help in the care of psychiatric patients?

Psychiatric patients demonstrate varied responses to treatment. Consequently, treatment strategies are trial-and-error, which has a negative effect on prognosis and compliance. The aim of pharmacogenomic research is to enable customised drug treatment by identifying variations within multiple candidate genes (those encoding drug-targeted neurotransmitter receptors, transporters and metabolic enzymes) that are likely to confer the inter-individual differences in drug response and development of drug-induced side effects. Pharmacogenetic and pharmacogenomic research to date has identified genetic polymorphisms of dopamine (DA) and serotonin (5-HT) receptor subtypes, the serotonin transporter (5-HTT) and metabolic enzymes (cytochrome P450 [CYP] family) as important contributors to the variability in response to psychiatric drugs and the development of drug-induced side effects such as tardive dyskinesia and weight gain. It is anticipated that technological and methodological advances will provide further candidate genes and refine association analyses of existing candidates, enabling pharmacogenomic research to move towards future treatment regimes that are catered to the individual.     

Does adding psychotherapy to pharmacotherapy improve social functioning in the treatment of outpatient depression?

The existence of an overall association between severity of depression and level of social functioning is well documented. To increase the probability of a long-term recovery, a normal level of social functioning is essential. It is currently unknown whether combined therapy has a better outcome than pharmacotherapy with regard to social functioning. In a 6-month randomized clinical trial in outpatients with major depression, all patients studied had a baseline score of at least 14 points on the 17-item Hamilton Depression Rating Scale (HDRS). The two conditions consist of pharmacotherapy (PhT) (N=84) and combined therapy (CoT), pharmacotherapy plus 16 sessions of short psychodynamic supportive psychotherapy (N=83). Efficacy was assessed using the 17-item HDRS, the Clinical Global Impression (CGI) Severity and Improvement scales, the Depression subscale of the Symptom Checklist-90 (SCL-90), the Quality of Life Depression Scale (QLDS), more the Groningen Social Disability Schedule (GSDS). Severity of depression decreased significantly (on the SCL-90 Depression subscale and the QLDS) more in the CoT condition. A larger improvement in social functioning was demonstrated for remitted patients than for nonremitted patients. The number of dimensions of social functioning that had improved significantly was higher in CoT than in PhT. There was a moderate advantage of the CoT condition on both depressive symptoms and level of social functioning in comparison with PhT. We also found a positive association between depression severity and level of social functioning.     

Observation of treatment of depression in primary care setting in first week - what happens in first week of treatment with antidepressants?

Depression is frequently diagnosed and treated by general practicioners. In observational study we investigated the influence of the severity of depressive and anxiety symptoms on the frequency of patients' questions about mental disorder and their tendency to misinterpret the signs and symptoms of depression as side effects of medication. In 60 public health centers across Slovenia a total of 422 patients with depression treated with paroxetine were included. After one week of treatment one quarter of patients reported adverse effects and 15% of these patients misinterpreted signs of depression and anxiety for adverse effects. These patients tend to be more anxious and more depressed at the beginning of treatment. Half of them could not accept the explanation of their misinterpretation. A total of 55% patients had additional questions about illness at the second visit and these patients were also more anxious and more depressed at the beginning of treatment.     

Health care providers’ perspectives of medication adherence in the treatment of depression: a qualitative study

Purpose

Non-adherence to antidepressant medications is a significant barrier to the successful treatment of depression. The purpose of this study was to explore the perspectives of health care providers on antidepressant medication non-adherence in clinical practice.

Methods

Individual semi-structured interviews were conducted with a purposive sample of 31 health care providers from a range of disciplines and settings in the state of New South Wales, Australia. Interviews focused on medication adherence issues in depression and participants’ strategies in addressing them. Interviews were audio recorded, transcribed verbatim and thematically content analyzed using a constant comparison approach.

Results

Participants acknowledged medication non-adherence to be a complex problem in depression, and attributed this problem to patient, medication and environmental-specific issues. Five approaches in addressing non-adherence were reported: patient education, building partnerships with patients, pharmacological management, developing behavioural skills and building supportive networks. Challenges to the management of non-adherence were lack of time and skills, assessment of medication adherence, transition period immediately post-discharge and conflicts in views between providers.

Conclusion

Participants were able to identify issues and strategies in addressing antidepressant non-adherence; however, barriers were also identified that could impact on providers’ ability to address this issue effectively. More research is needed to develop effective multidisciplinary strategies that take into account providers’ perspectives in improving adherence to antidepressant medications.     

Does the community care?

This article seeks to direct attention towards the need to educate the community to care for mentally handicapped people prior to the establishment of further community care systems. It is argued that mentally handicapped people living in the community are isolated in terms of both social contacts and occupation; and that certain assumptions are made, without supportive evidence, about the community's willingness to care.     

Does personality disorder decrease the likelihood of remission in early-onset chronic depression?

Background

The impact of personality disorders (PD) on the course of depression has been gaining interest among clinical researchers over the past decade. Recent observational studies have found that PD was associated with impaired social functioning and reduced likelihood of depression recovery. Elevated rates of PD have been noted in early-onset and chronic forms subtypes of depression. However, scant data exist regarding the link between PD and outcome for this depression subtype.

Methods

The National Epidemiological Survey on Alcohol and Related Conditions database was analyzed. This survey included 43 093 respondents, 18 years and older, conducted in 2001 through 2002. Logistic regression was used to identify demographic and clinical predictors of remission in early-onset chronic depression.

Results

The absence of PD, having more years of education, and being married considerably improved the likelihood of remission. Paranoid personality disorder and obsessive-compulsive disorder were the only specific PD found to be associated with a reduced probability of remission.

Limitations

Depression remission status may have biased the recollection of PD symptoms. Borderline personality disorder, narcissistic personality disorder, and schizotypal personality disorder were not assessed.

Conclusions

This study suggests that PD are significant predictors of remission in early-onset chronic depression.     

Can enhanced acute-phase treatment of depression improve long-term outcomes? A report of randomized trials in primary care

OBJECTIVE: The authors' goal was to determine whether improved outcomes from enhanced acute-phase (3-month) treatment for depression in primary care persisted. METHOD: They conducted a 19-month follow-up assessment of 156 patients with major depression in the Collaborative Care intervention trials, which had found greater improvements in treatment adherence and depressive symptoms at 4 and 7 months for patients given enhanced acute-phase treatment than for patients given routine treatment in a primary care setting. Sixty-three of the 116 patients who completed the follow-up assessment had received enhanced treatment, and 53 had received routine treatment in primary care. The Inventory for Depressive Symptomatology and the Hopkins Symptom Checklist were used to measure depressive symptoms. Automated pharmacy data and self-reports were used to assess adherence to and adequacy of pharmacotherapy. RESULTS: At 19 months, the patients who had received enhanced acute-phase treatment did not differ from those who had received routine primary care treatment in clinical outcomes or quality of pharmacotherapy. CONCLUSIONS: Even though enhanced acute-phase treatment of depression in primary care resulted in better treatment adherence and better clinical outcomes at 4 and 7 months, these improvements failed to persist over the following year. Continued enhancement of depression treatment may be needed to ensure better long-term results.     

Does the clinical course of depression determine improvement in symptoms and quality of life?

Clinical course factors characterizing individuals' history with depression may be helpful in predicting treatment-related change in quality of life (QOL). Such factors have been studied in relation to symptomatic change with mixed results. This 9-week single-blind treatment trial using reboxetine (1 week placebo lead-in) evaluated the impact of age of onset, history of antidepressant treatment, duration of index episode, number of past episodes, and the presence of precipitating stress on depressed individuals' treatment response. We found that QOL did not normalize along with clinical remission in all areas. Using multivariate analysis, we found that age of onset, history with antidepressants, and the presence of identifiable precipitating stress were all significant predictors of QOL change (controlling for symptomatic change); some factors also predicted symptomatic improvement. Our results support the trend of distinguishing between treatment-related change in QOL and symptomatic change and suggest clinical course factors as promising predictors of QOL.     

Does the presence of anxiety affect the validity of a screening test for depression in the elderly?

INTRODUCTION: Depression in the elderly is frequently detected by screening instruments and often accompanied by anxiety. We set out to study if anxiety will affect the ability to detect depression by a screening instrument. OBJECTIVE: To validate the short Zung depression rating scale in Israeli elderly and to study the affect of anxiety on its validity. DESIGN: The short Zung was validated against a psychiatric evaluation, in a geriatric inpatient and outpatient service. The overall validity was determined, as well as for subgroups of sufferers and non-sufferers of anxiety. SETTING: An urban geriatric service in Israel. PATIENTS: 150 medical inpatients and outpatients, aged 70 years and older.MEASURES: Psychiatric evaluation of modified Anxiety Disorders Interview Schedule for DSM-IV as criterion standard for anxiety and depression and short Zung instrument for depression. RESULTS: By criterion validity, 60% suffered from depression. The overall validity of the short Zung was high (sensitivity 71.1%, specificity 88.3%, PPV 90.1%, NPV 67.1%). The validity for those not suffering from anxiety was good (sensitivity 71.1%, specificity 90.2%, PPV 84.4%, NPV 80.7%). In those with anxiety, sensitivity, specificity and PPV were high (71.2%, 77.8%, 94.9% respectively), although the specificity was less than in non-suffers. However major difference was in the NPV rate being much lower (31.8%). CONCLUSION: The short Zung, an easily administered instrument for detecting depression, is also valid in the Israeli elderly. However, anxiety limits the usefulness of this instrument in correctly ruling out depression. The clinician must be aware, therefore, that those suffering from anxiety may score negatively for depression on a screening instrument, such as the short Zung.     

Should the treatment of depression in the Netherlands be changed after the STAR*D study?

The main results of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study are discussed in order to find out whether the results should lead to changes in the way in which depression is treated in the Netherlands. The outcomes of the STAR*D study are not sufficient justification for altering the current recommendations about the successive steps to be taken according to the Dutch multidisciplinary guideline for the treatment of depression.     

Glucocorticoid inhibition in the treatment of depression: can we think outside the endocrine hypothalamus?

Background: Major depressive disorder affects a substantial percentage of the U.S. population, and can be highly debilitating. Selective serotonin reuptake inhibitors are commonly prescribed to treat depression, but may not be as effective for more severe or persistent depression. Methods: The authors review data concerning the effects of corticosteroid synthesis inhibitors (CSIs) in the management of depressive disorders, present a hypothesis as to their possible mechanisms of action based on recent data suggesting synergistic effects of glucocorticoids on extrahypothalamic corticotropin‐releasing hormone (CRH), and consider alternative hypotheses. Published reports evaluating the efficacy of CSIs in treating depression are reviewed and presented in light of recent findings regarding actions of glucocorticoids on the central CRH system. Results: Results from open label and double‐blind studies by several groups have indicated that CSIs may be efficacious or of adjunctive value in some patients with depression, including those refractory to other agents; however, there is a need for more controlled studies. Several lines of data suggest that the mechanism of action of these agents may not be solely a function of inhibition of adrenal cortisol production. Conclusions: The authors propose that CSIs may be efficacious in part by reducing glucocorticoid enhancement of CRH action in neurons of the central nucleus of the amygdala and other structures outside the endocrine hypothalamus. Possible effects of systemically administered CSIs on glucocorticoid receptor regulation, neuroactive steroids, and classical monoamine systems are also discussed. We conclude that available clinical data suggest a potential role for CSIs in the management of depressive disorders, especially major depression with psychotic features. Depression and Anxiety, 2009. © 2009 Wiley‐Liss, Inc.     

Do health professionals' attitudes interfere with the treatment of depression?

Might the attitudes of health care professionals help to explain why most persons with a depressive disorder do not receive adequate care? To assess this question, the authors surveyed the faculty and staff of a midwestern university. One hundred percent of the social workers who responded found psychotherapy or counseling to be extremely or quite effective in treating persons with a major depressive episode, compared to 55% of the psychologists and 31% of the psychiatrists. For medication, the corresponding figures were 88% of psychiatrists, 64% of psychologists, and 46% of social workers. Many respondents noted problems with interprofessional communication, while most psychiatrists felt that individuals treated by two or more professionals for their depression usually receive poorer care. If future studies indicate that nonmedical therapists who view antidepressants as relatively ineffective are less likely to refer depressed clients for medication evaluation, these findings might help to explain why many depressed individuals who could benefit from medication do not receive it. Concerns about interprofessional communication, as well as psychiatrists' beliefs about the quality of care received by persons treated by more than one professional, might also explain why joint treatment occurs less often than would be desirable. The authors discuss some of the implications that these findings may have for the education of health care professionals.