Pharmacogenomics guided versus standard antidepressant treatment in a community pharmacy setting: A randomized controlled trial.

The literature on pharmacogenomics as a tool to support antidepressant precision is burgeoning. Recently, a more active role has been argued for pharmacists in pharmacogenomic testing, with both pharmacists and family physicians perceiving pharmacist-led testing as a valuable method by which to scale this innovation for depression treatment. In this prospective, single-blind randomized controlled design, we evaluated the impact of pharmacogenomics guided versus standard antidepressant treatment of depression and anxiety, implemented in three large community pharmacies. Participants were 213 outpatients diagnosed with major depressive disorder and/or generalized anxiety disorder, randomized to receive pharmacogenomics guided (n = 105) or standard antidepressant treatment (n = 108); participants were blinded to the study. Patient reported outcomes of depression, anxiety, disability, and treatment satisfaction were assessed at months 0, 1, 3, and 6. Hypotheses were investigated using mixed effect models on the full data. All clinical outcomes improved significantly. The primary outcome (depression) and two secondary outcomes (generalized anxiety and disability) exhibited significant time by group interactions indicating that they improved for participants who received pharmacogenomics guided treatment more so than they did for participants who received standard treatment. Treatment satisfaction improved similarly for both groups. Results contribute to a growing body of work evaluating the impact of pharmacogenomics testing to inform antidepressant medication treatment for depression and anxiety, and provides important initial evidence for the role of pharmacists in care delivery. Pharmacogenomic testing may be a valuable tool to allow pharmacists to more effectively collaborate in facilitating clinical treatment decisions. ClinicalTrials.gov registration: (NCT03591224).

A multidimensional investigation of anxiety sensitivity and depression outcomes in cognitive-behavioral group therapy.

We examined how anxiety sensitivity - the fear of symptoms of anxiety due to their perceived harmful effects - and gender are associated with treatment trajectory and outcomes in a large outpatient sample (N = 278) who received 14-weeks of cognitive-behavioral group therapy (CBGT) for depression. Three dimensions of anxiety sensitivity (cognitive, physical, and social concerns) and depression were assessed at pre-treatment, and the latter was assessed weekly during treatment. Latent growth curve models supported a link between cognitive concerns (fears of losing control over thoughts) and greater improvement in depression near the end of treatment (i.e., weeks 10-14); gender did not moderate trajectory. Gender (i.e., identifying as a woman) and greater physical concerns (fears of physical consequences of arousal symptoms) were associated with completion of < 8 sessions. Results suggest that those with more cognitive concerns might require greater time in treatment and/or benefit most from the focus on maladaptive assumptions and core beliefs in later CBGT sessions. Future research, including investigation of intervening variables, may elucidate the mechanisms through which greater physical concerns and gender are associated with treatment non-completion. Results supported differential associations of anxiety sensitivity dimensions with depression treatment outcomes, though further research attention is needed.

Brief interventions for problem gambling: A meta-analysis.

BACKGROUND: Brief interventions have been increasingly investigated to promote early intervention in gambling problems; an accurate estimate of the impact of these interventions is required to justify their widespread implementation. The goal of the current investigation was to evaluate the efficacy of in-person brief interventions for reducing gambling behaviour and/or problems, by quantifying the aggregate effect size associated with these interventions in the published literature to date. METHODS: Randomized controlled trials including the following design features were identified via systematic review: an adult sample experiencing problems associated with gambling; an in-person individual psychosocial intervention of brief duration (≤3 sessions); a control/comparison group; and an outcome related to gambling behaviour and/or problems. RESULTS: Five records compared brief interventions to assessment only control; using a random effect model, brief interventions were associated with a small but statistically significant reduction in gambling behaviour across short-term follow-up periods versus assessment only control (g = -.19, 95% CI [-.37, -.01]). Aggregate effect sizes for gambling problems and long-term follow-up periods were not statistically significant. Five records compared brief interventions to longer active interventions; there was no significant difference between brief interventions and longer active interventions. CONCLUSIONS: Results supported the efficacy of brief interventions for problem gambling compared to inactive control in the reduction of gambling behaviour; no differences were found across brief versus longer interventions for both gambling behaviour and problems. While these findings must be interpreted in the context of the limited number of studies and small magnitude of the combined effect sizes, the current meta-analysis supports the further investigation of the public health impact of these cost-effective interventions.

The role of outcome expectancy in therapeutic change across psychotherapy versus pharmacotherapy for depression.

BACKGROUND: Patient outcome expectancy - the belief that treatment will lead to an improvement in symptoms - is linked to favourable therapeutic outcomes in major depressive disorder (MDD). The present study extends this literature by investigating the temporal dynamics of expectancy, and by exploring whether expectancy during treatment is linked to differential outcomes across treatment modalities, for both optimistic versus pessimistic expectancy. METHODS: A total of 104 patients with MDD were randomized to receive either cognitive behavioral therapy (CBT) or pharmacotherapy for 16 weeks. Outcome expectancy was measured throughout treatment using the Depression Change Expectancy Scale (DCES). Depression severity was measured using both the Hamilton Depression Rating Scale and Beck Depression Inventory-II. RESULTS: Latent growth curve models supported improvement in expectancy across both treatments. Cross-lagged panel models revealed that both higher optimistic and lower pessimistic expectancy at mid-treatment predicted greater treatment response in pharmacotherapy. For CBT, the associative patterns between expectancy and depression differed as a function of expectancy type; higher optimistic expectancy at pre-treatment and lower pessimistic expectancy at mid-treatment predicted greater treatment response. LIMITATIONS: The sample size limited statistical power and the complexity of models that could be explored. CONCLUSIONS: Results suggest that outcome expectancy improved during treatment for depression. Whether outcome expectancy represents a specific mechanism for the reduction of depression warrants further investigation.

A Preliminary Investigation of the Effect of Acute Alcohol on Dopamine Transmission as Assessed by [11 C]-(+)-PHNO.

BACKGROUND: Previous positron emission tomography (PET) studies exploring the effect of acute alcohol on dopamine (DA) levels have yielded inconsistent results, with only some studies suggesting increased synaptic DA levels after an alcohol challenge. The D2 /D3 agonist radiotracer, [11 C]-(+)-propyl-hexahydro-naphtho-oxazin ([11 C]-(+)-PHNO), has greater sensitivity to synaptic DA fluctuation than previously used antagonist radiotracers and is in principle more suitable for imaging alcohol-induced changes in DA. Its high affinity for the D3 receptor also enables measuring changes in D3 -rich brain areas which have previously been unexplored. The aim of this study was to investigate whether alcohol reduces [11 C]-(+)-PHNO binding in the striatum and in D3 -rich extra-striatal areas. METHODS: Eight healthy drinkers underwent 2 [11 C]-(+)-PHNO PET scans following alcohol and placebo in a randomized, single-blind, crossover design. [11 C]-(+)-PHNO binding in the striatum and in the extra-striatal regions were compared between the 2 scans. RESULTS: Acute alcohol administration did not significantly reduce [11 C]-(+)-PHNO binding in either the limbic striatum (d = 0.64), associative striatum (d < 0.20), or the sensorimotor striatum (d < 0.15). Similarly, there were no changes in binding in the D3 -rich areas of the ventral pallidum (d = 0.53), substantia nigra (d < 0.15), or globus pallidus (d < 0.15). However, greater percent change in [11 C]-(+)-PHNO binding (ΔBPND ) between scans was related to lower blood alcohol levels. CONCLUSIONS: Using the agonist radiotracer, [11 C]-(+)-PHNO, our preliminary findings suggest that alcohol is not associated with robust changes in tracer binding in striatal or extra-striatal regions. However, we found that changes in [11 C]-(+)-PHNO binding following alcohol are dependent on blood alcohol levels suggesting that increases in DA may occur at lower stimulating doses. The effect of lower doses of alcohol on DA warrants further investigation in a larger study.

Investigating the effects of norepinephrine α1 receptor blockade on dopamine levels: A pilot PET study with [11 C]-(+)-PHNO in controls.

Interest in a role for norepinephrine (NE) in substance use disorders has increased over recent years. In particular, its interaction with dopamine (DA) is of importance. In this study, positron emission tomography (PET) was used to explore the impact of prazosin (an alpha 1 NE antagonist) on DA levels. Healthy volunteers were administered prazosin for approximately 4 weeks at the daily dose of 15 mg to reach steady state. Participants were scanned with PET imaging and the [11 C]-(+)-PHNO tracer at baseline (before prazosin), at steady state, and after a wash out period. Prazosin administration was associated with an increase of [11 C]-(+)-PHNO binding potential in the dorsal caudate relative to baseline, which corresponds to a decrease in DA levels. This study is the first to demonstrate interactions between DA and NE in healthy humans.

A review of positron emission tomography studies exploring the dopaminergic system in substance use with a focus on tobacco as a co-variate.

With the evolving sensitivity of positron emission tomography (PET) and the emergence of novel radiotracers, greater insight has been gained into the dopaminergic system as it relates to substance use. In this review, we summarize PET investigations from the last ten years that explore the dopaminergic system in tobacco, alcohol, stimulant, opiates, and cannabis addiction. In light of the prevalence of substance co-use, this review will also explore the effect of tobacco and other substance abuse co-morbidity on the dopaminergic system across study samples in the reviewed literature. In non-dependence, increased DA transmission following acute stimulant administration is a robust and consistent observation but is less detectable following acute alcohol and tobacco, where it likely represents a conditioned effect mediating reward expectation. Chronic drug exposure is generally associated with a hypo-functioning pre-synaptic dopamine system and lower D2/D3 receptor availability relative to healthy controls. Emerging evidence also shows that stimulant use disorders in particular may also be associated with greater D3 receptor availability relative to controls. A defined role for the dopaminergic system in cannabis and opiate use is yet to be elucidated. Future work is also needed to delineate the potential interactive effects of acute and chronic tobacco and substance co-use on the dopaminergic system.

Effect of provision of an integrated neonatal survival kit and early cognitive stimulation package by community health workers on developmental outcomes of infants in Kwale County, Kenya: study protocol for a cluster randomized trial.

BACKGROUND: Each year, more than 200 million children under the age of 5 years, almost all in low- and middle-income countries (LMICs), fail to achieve their developmental potential. Risk factors for compromised development often coexist and include inadequate cognitive stimulation, poverty, nutritional deficiencies, infection and complications of being born low birthweight and/or premature. Moreover, many of these risk factors are closely associated with newborn morbidity and mortality. As compromised development has significant implications on human capital, inexpensive and scalable interventions are urgently needed to promote neurodevelopment and reduce risk factors for impaired development. METHOD/DESIGN: This cluster randomized trial aims at evaluating the impact of volunteer community health workers delivering either an integrated neonatal survival kit, an early stimulation package, or a combination of both interventions, to pregnant women during their third trimester of pregnancy, compared to the current standard of care in Kwale County, Kenya. The neonatal survival kit comprises a clean delivery kit (sterile blade, cord clamp, clean plastic sheet, surgical gloves and hand soap), sunflower oil emollient, chlorhexidine, ThermoSpot(TM), Mylar infant sleeve, and a reusable instant heater. Community health workers are also equipped with a portable hand-held electric scale. The early cognitive stimulation package focuses on enhancing caregiver practices by teaching caregivers three key messages that comprise combining a gentle touch with making eye contact and talking to children, responsive feeding and caregiving, and singing. The primary outcome measure is child development at 12 months of age assessed with the Protocol for Child Monitoring (Infant and Toddler version). The main secondary outcome is newborn mortality. DISCUSSION: This study will provide evidence on effectiveness of delivering an innovative neonatal survival kit and/or early stimulation package to pregnant women in Kwale County, Kenya. Study findings will help inform policy on the most appropriate interventions for promoting healthy brain development and reduction of newborn morbidity and mortality in Kenya and other similar settings. TRIAL REGISTRATION: ClinicalTrial.gov NCT02208960 (August 1, 2014).

Risk factors for medication nonadherence in older adults with cognitive impairment who live alone.

OBJECTIVE: The aim of this study was to prospectively examine the influence of cognitive, medical, behavioral, and social risk factors on medication nonadherence in community-dwelling older adults with cognitive impairment. METHODS: A sample of 339 elderly participants with cognitive impairment, who lived alone and took at least one medication, underwent baseline assessment which included the five subscales of the Dementia Rating Scale (DRS), number of medications, retrospective medication nonadherence, amount of formal and informal assistance, functional impairment, depression, perception of social resources, comorbidity, and alcohol consumption. The outcome was medication nonadherence during the 12-month prospective period as reported by the participants' primary care physicians and caregivers at three-month intervals. RESULTS: Fifty-nine participants (17.4%) had, at least, one report of medication nonadherence. Logistic regression analyses indicated for every point increase on the DRS Conceptualization subscale (OR = 1.14; 95% CI = 1.02-1.27), there was a 14% increase in the odds of nonadherence. For every point increase on the DRS Memory subscale (OR = 0.89; 95% CI = 0.81-0.97) and DRS Initiation/Perseveration subscale (OR = 0.93; 95% CI = 0.87-1.00), there was an 11% decrease and 7% decrease in the odds, respectively. Having at least one previous occurrence of medication nonadherence (OR = 2.61; 95% CI = 1.18-5.62) and taking at least four medications (OR = 2.58; 95% CI = 1.31-5.29), both increased the odds by over 2.5-fold. CONCLUSIONS: Our unique finding that better conceptualization predicted nonadherence has important implications for healthcare providers' approaches to improve adherence in older adults with cognitive impairment. Replication in future studies is warranted.