ABCB1 polymorphism predicts escitalopram dose needed for remission in major depression

The ATP-binding cassette family of transporter proteins, subfamily B (MDR/TAP), member 1 (ABCB1) (P-glycoprotein) transporter is a key component of the blood–brain barrier. Many antidepressants are subject to ABCB1 efflux. Functional polymorphisms of ABCB1 may influence central nervous system bioavailability of antidepressants subject to efflux. Single-nucleotide polymorphisms (SNPs) at rs1045642 (C3435T) of ABCB1 have been associated with efflux pump efficiency. This may explain part of the interindividual variation in antidepressant dose needed to remit. Individuals (N=113) with DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) major depressive disorder (MDD) were treated with escitalopram (ESC) or venlafaxine (VEN) over 8 weeks. The17-item Hamilton Depression Rating Scale was assessed serially, blind to genotype. SNP rs1045642 of ABCB1 along with two SNPs previously reported to be in linkage disequilibrium with it (rs2032582 and rs1128503) were genotyped. Demographic features, clinical features, P450 metabolizer status and 5-HTTLPR (serotonin-transporter-linked promoter region) genotype were controlled for. Carriers of rs1045642 TT needed on average 11 mg of ESC to remit, whereas TC and CC carriers required 24 and 19 mg, respectively (P=0.0001). This equates to a 2.0- (95% confidence interval=1.5–3.4; P<0.001) fold greater ESC dose needed to remit for C carriers compared with TT carriers at rs1045642. Of VEN-treated subjects carrying TT genotype at rs1045642, 73.3% remitted compared with 12.5% for CC genotype (odds ratio=6.69; 95% confidence interval=1.72–25.9, P=0.006). These data suggest that antidepressant dose needed to remit can be predicted by an ABCB1 SNP. This has the potential clinical translation implications for dose selection and remission from MDD.

Cumulative morbidity and prognostic staging of illness in the systematic treatment enhancement program for Bipolar Disorder (STEP-BD)

Objective: Staging models may provide heuristic utility for intervention selection in psychiatry. Although a few proposals have been put forth, there is a need for empirical validation if they are to be adopted. Using data from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD), we tested a previously elaborated hypothesis on the utility of using the number of previous episodes as a relevant prognostic variable for staging in bipolar disorder.

Methods: This report utilizes data from the multisite, prospective, open-label study ‘Standard Care Pathways’ and the subset of patients with acute depressive episodes who participated in the randomized trial of adjunctive antidepressant treatment. Outpatients meeting DSM-IV diagnostic criteria for bipolar disorder (n = 3345) were included. For the randomized pathway, patients met criteria for an acute depressive episode (n = 376). The number of previous episodes was categorized as less than 5, 5–10 and more than 10. We used disability at baseline, number of days well in the first year and longitudinal scores of depressive and manic symptoms, quality of life and functioning as validators of models constructed a priori.

Results: Patients with multiple previous episodes had consistently poorer cross-sectional and prospective outcomes. Functioning and quality of life were worse, disability more common, and symptoms more chronic and severe. There was no significant effect for staging with regard to antidepressant response in the randomized trial.

Conclusions: These findings confirm that bipolar disorder can be staged with prognostic validity. Stages can be used to stratify subjects in clinical trials and develop specific treatments.

Managing panic disorder in general practice

BACKGROUND: Panic disorder (PD) is common in the community and contributes to significant distress and decreased quality of life for people who suffer from it. Most people with PD will present in the first instance to their general practitioner or hospital emergency department for assistance, often with a focus on somatic symptoms and concerns.

OBJECTIVE: This article aims to assist the GP to manage this group of patients by providing an outline of aetiology, approaches to assessment, and common management strategies.

DISCUSSION Although GPs have an important role to play in ruling out any causal organic basis for panic symptoms, the diagnosis of PD can usually be made as a positive diagnosis on the basis of careful history taking. Thorough and empathic education is a vital step in management. The prognosis for PD can be improved by lifestyle changes, specific psychological techniques, and the judicious use of pharmacotherapy.

Assessing and managing old age psychiatric disorders in community practice

A shortage of specialised facilities means that general practitioners have a prominent role in community care of the elderly with mental illness.

Characterization of the improvement in depressive symptoms following Bariatric surgery

Background : The Beck Depression Inventory (BDI) has been frequently employed as a measure of depression in studies of obesity, with the majority of studies reporting an improvement in scores following weight loss. Given the potential similarity in obesity-related and depressive symptoms, it is uncertain whether all components of depression would improve equally with weight loss.

Method : The study included obese patients who had undergone laparoscopic adjustable gastric banding (LAGB) surgery and had completed BDIs at baseline and 1 year after surgery. Two groups of patients were included, a general background group (N = 191, mean age = 41 ± 9, mean BMI = 43 ± 8) and a group identified as experiencing elevated depressive symptoms based on BDI scores ≥23 (EDS group; (N = 67, mean age = 40 ± 9, mean BMI = 45 ± 7).

Results : Overall, BDI scores fell for both groups, background group at baseline 17 ± 9–8 ± 7 at 1 year and for the EDS group at baseline 30 ± 5–14 ± 10 at 1 year. Patient scores on the negative self-attitude subscale were significantly greater than the two other subscales and showed the greatest improvement 1 year following LAGB. Preexisting antidepressant therapy had little or no association on the BDI scores or on its change following weight loss.

Conclusion : High rates of depression are continually reported in obesity, as is a remarkable decrease in depressive symptoms following weight loss. Negative attitudes towards one’s self appears to be driving elevated BDI scores rather than the overlap in physical symptoms between obesity and depression.

The relationship between excessive daytime sleepiness and depressive and anxiety disorders in women

Objective: Excessive daytime sleepiness (EDS) is a common clinical symptom that affects women more than men. However, the association of excessive sleepiness with depressive and anxiety disorders in the broader population is unclear. The aim of this study was, therefore, to examine the association between excessive daytime sleepiness as measured by the Epworth Sleepiness Scale, and depressive and anxiety disorders in a population-based sample of women.

Methods: Using the Structured Clinical Interview for DSM-IV Disorders (Non-Patient) (SCID-I/NP), 944 women aged 20–97 years (median 49 years, IQR 33–65 years) were assessed for depressive and anxiety disorders as part of the Geelong Osteoporosis Study. EDS was assessed using the Epworth Sleepiness Scale (ESS, cut-off > 10). Lifestyle factors were documented by self-report, height and weight were measured, and socioeconomic status categorised according to the Index of Relative Socio-Economic Advantage and Disadvantage.

Results: Overall, 125 (13.2%) of the women were identified with EDS. EDS was associated with an increased likelihood for both current (OR = 2.11, 95% CI 1.10–4.06) and lifetime history (OR = 1.95, 95% CI 1.28–2.97) of depressive disorders, but not anxiety disorders, independent of age and alcohol consumption. These findings were not explained by antidepressant or sedative use, body mass index, physical activity, smoking, or socioeconomic status.

Conclusions: These results suggest that excessive daytime sleepiness is associated with current and lifetime depressive, but not anxiety disorders. Clinically, this highlights the need to take into account the possible bidirectional relationship between depressive disorders and excessive sleepiness when assessing mental health issues in patients with EDS.

Treatment response for acute depression is not associated with number of previous episodes: lack of evidence for a clinical staging model for major depressive disorder

Mental illness has been observed to follow a neuroprogressive course, commencing with prodrome, then onset, recurrence and finally chronic illness. In bipolar disorder and schizophrenia responsiveness to treatment mirrors these stages of illness progression, with greater response to treatment in the earlier stages of illness and greater treatment resistance in chronic late stage illness.

Using data from 5627 participants in 15 controlled trials of duloxetine, comparator arm (paroxetine, venlafaxine, escitalopram) or placebo for the treatment of an acute depressive episode, the relationship between treatment response and number of previous depressive episodes was determined. Data was dichotomised for comparisons between participants who had >3 previous episodes (n=1697) or ≤3 previous episodes (n=3930), and additionally for no previous episodes (n=1381) or at least one previous episode (n=4246). Analyses were conducted by study arm for each clinical trial, and results were then pooled.

There was no significant difference between treatment response and number of previous depressive episodes. This unexpected finding suggests that treatments to reduce symptoms of depression during acute illness do not lose efficacy for patients with a longer history of illness.

Screening, referral and treatment for depression in patients with coronary heart disease: a consensus statement from the National Heart Foundation of Australia

In 2003, the National Heart Foundation of Australia position statement on “stress” and heart disease found that depression was an important risk factor for coronary heart disease (CHD). This 2013 statement updates the evidence on depression (mild, moderate and severe) in patients with CHD, and provides guidance for health professionals on screening and treatment for depression in patients with CHD.

The prevalence of depression is high in patients with CHD and it has a significant impact on the patient’s quality of life and adherence to therapy, and an independent effect on prognosis. Rates of major depressive disorder of around 15% have been reported in patients after myocardial infarction or coronary artery bypass grafting.

To provide the best possible care, it is important to recognise depression in patients with CHD. Routine screening for depression in all patients with CHD is indicated at first presentation, and again at the next follow-up appointment. A follow-up screen should occur 2–3 months after a CHD event. Screening should then be considered on a yearly basis, as for any other major risk factor for CHD.

A simple tool for initial screening, such as the Patient Health Questionnaire-2 (PHQ-2) or the short-form Cardiac Depression Scale (CDS), can be incorporated into usual clinical practice with minimum interference, and may increase uptake of screening.

Patients with positive screening results may need further evaluation. Appropriate treatment should be commenced, and the patient monitored. If screening is followed by comprehensive care, depression outcomes are likely to be improved.

Patients with CHD and depression respond to cognitive behaviour therapy, collaborative care, exercise and some drug therapies in a similar way to the general population. However, tricyclic antidepressant drugs may worsen CHD outcomes and should be avoided.

Coordination of care between health care providers is essential for optimal outcomes for patients. The benefits of treating depression include improved quality of life, improved adherence to other therapies and, potentially, improved CHD outcomes.

Hyponatraemia: an audit of aged psychiatry patients taking SSRIs and SNRIs

Objective: 

Escitalopram efficacy in depression a cross-ethnicity examination of the serotonin transporter promoter polymorphism

Current evidence suggests that polymorphism in the serotonin transporter gene (5-HTTLPR) predicts antidepressant efficacy in whites but less so in Asians. However, it is not clear whether this effect can be observed for specific types of antidepressant drugs. White (n = 47) and Korean (n = 118) participants with major depressive disorder were treated with escitalopram and assessed over 8 weeks. Among those with the l/l but not l/s or s/s genotypes, whites had greater depression score reductions, response rates, and remission rates compared with Koreans. Our results suggest that 5-HTTLPR predicts escitalopram efficacy in an ethnicity-dependent manner.