Psychological advocacy towards healing (PATH): A randomized controlled trial of a psychological intervention in a domestic violence service setting.

BACKGROUND: Experience of domestic violence and abuse (DVA) is associated with mental illness. Advocacy has little effect on mental health outcomes of female DVA survivors and there is uncertainty about the effectiveness of psychological interventions for this population. OBJECTIVE: To test effectiveness of a psychological intervention delivered by advocates to DVA survivors. DESIGN, MASKING, SETTING, PARTICIPANTS: Pragmatic parallel group individually randomized controlled trial of normal DVA advocacy vs. advocacy + psychological intervention. Statistician and researchers blinded to group assignment. Setting: specialist DVA agencies; two UK cities. Participants: Women aged 16 years and older accessing DVA services. INTERVENTION: Eight specialist psychological advocacy (SPA) sessions with two follow up sessions. MEASUREMENTS: Primary outcomes at 12 months: depression symptoms (PHQ-9) and psychological distress (CORE-OM). Primary analysis: intention to treat linear (logistic) regression model for continuous (binary) outcomes. RESULTS: 263 women recruited (78 in shelter/refuge, 185 in community), 2 withdrew (1 community, control group; 1 intervention, refuge group), 1 was excluded from the study for protocol violation (community, control group), 130 in intervention and 130 in control groups. Recruitment ended June 2013. 12-month follow up: 64%. At 12-month follow up greater improvement in mental health of women in the intervention group. Difference in average CORE-OM score between intervention and control groups: -3.3 points (95% CI -5.5 to -1.2). Difference in average PHQ-9 score between intervention and control group: -2.2 (95% CI -4.1 to -0.3). At 12 months, 35% of the intervention group and 55% of the control group were above the CORE-OM -2clinical threshold (OR 0.32, 95% CI 0.16 to 0.64); 29% of the intervention group and 46% of the control group were above the PHQ-9 clinical threshold (OR 0.41, 95% CI 0.21 to 0.81). LIMITATIONS: 64% retention at 12 months. CONCLUSIONS: An eight-session psychological intervention delivered by DVA advocates produced clinically relevant improvement in mental health outcomes compared with normal advocacy care. TRIAL REGISTRATION: ISRCTN registry ISRCTN58561170 Original Research 3675/3750.

Assessing for domestic violence in sexual health environments: a qualitative study.

OBJECTIVES: Domestic violence and abuse (DVA) is a major clinical challenge and public health issue. Sexual health services are an important potential site of DVA intervention. The Assessing for Domestic Violence in Sexual Health Environments (ADViSE) intervention aimed to improve identification and management of DVA in sexual healthcare settings and is a modified version of the Identification and Referral to Improve Safety (IRIS) general practice programme. Our qualitative evaluation aimed to explore the experiences of staff participating in an IRIS ADViSE pilot. METHODS: Interviews were conducted with 17 sexual health clinic staff and DVA advocate workers. Interviews were audio recorded, transcribed, anonymised and analysed thematically. RESULTS: Staff prioritised enquiring about DVA and tailored their style of enquiry to the perceived characteristics of patients, current workload and individual clinical judgements. Responding to disclosures of abuse was divided between perceived low-risk cases (with quick onwards referral) and high-risk cases (requiring deployment of institution safeguarding procedures), which were viewed as time consuming and could create tensions with patients. Ongoing training and feedback, commissioner recognition, adequate service-level agreements and reimbursements are required to ensure sustainability and wider implementation of IRIS ADViSE. CONCLUSIONS: Challenges of delivering and sustaining IRIS ADViSE included the varied styles of enquiry, as well as tensions and additional time pressure arising from disclosure of abuse. These can be overcome by modifying initial training, providing regular updates and stronger recognition (and resources) at policy and commissioning levels.

Effects of 7.5% carbon dioxide inhalation on anxiety and mood in cigarette smokers.

Cigarette smoking is associated with elevated risk of anxiety and mood disorder. Using the 7.5% carbon dioxide (CO2) inhalation model of anxiety induction, we examined the effects of smoking status and abstinence from smoking on anxiety responses. Physiological and subjective responses to CO2 and medical air were compared in smokers and non-smokers (Experiment One) and in overnight abstinent and non-abstinent smokers (Experiment Two). CO2 induced greater increases in blood pressure in non-smokers compared with smokers (ps < 0.043), and greater increases in anxiety (p = 0.005) and negative affect (p = 0.054) in non-abstinent compared with abstinent smokers. CO2 increased physiological and subjective indices of anxiety. There were differences across smoking groups indicating that the CO2 inhalation model is a useful tool for examining the relationship between smoking and anxiety. The findings suggested that both acute smoking and acute abstinence may protect against anxious responding. Further investigation is needed in long-term heavy smokers.

Changes in cardiovascular function after venlafaxine but not pregabalin in healthy volunteers: a double-blind, placebo-controlled study of orthostatic challenge, blood pressure and heart rate.

It is generally thought that venlafaxine raises blood pressure at higher doses; however, some studies have found no effect or a decrease in blood pressure. The aim of this study was to evaluate the cardiovascular (CV) effects of 3 weeks of dosing with venlafaxine, pregabalin and placebo on young healthy adults. Fifty-four participants, of mean age 23.1 years (sd 4.68), 29 male, were randomised into three parallel groups. Each group received one of the three drugs, dosed incrementally over a 3-week period to reach daily doses of 150 mg/day venlafaxine and 200 mg/day pregabalin. Blood pressure sphygmomanometer measurements, heart rate measurements, and orthostatic challenges recorded continuously beat-to-beat were performed weekly over this period and 5 days after treatment cessation. Results showed resting systolic blood pressure (SBP) and resting and standing diastolic blood pressure (DBP) and heart rate (HR) were significantly raised by venlafaxine compared with the pregabalin and placebo groups. SBP drop on standing was larger, the resulting overshoot was smaller, and recovery was slower on venlafaxine. HR recovery was significantly impaired by venlafaxine. CV changes were observed after only 1 week of dosing at 112.5 mg/day. These effects of venlafaxine are likely to be due to its action of noradrenergic reuptake inhibition.

Evaluation of the effects of venlafaxine and pregabalin on the carbon dioxide inhalation models of Generalised Anxiety Disorder and panic.

Previous studies have shown that subjective and objective symptoms of anxiety induced by 7.5% CO(2) inhalation can be attenuated by anxiolytics such as lorazepam and, to a lesser extent, paroxetine. Venlafaxine and pregabalin, two other licensed treatments for Generalised Anxiety Disorder, were used to further investigate the 7.5% and 35% CO(2) models of anxiety in healthy volunteers. Fifty-four participants were randomised to receive either placebo, venlafaxine or pregabalin. Study treatments were dosed incrementally over a three week period, to reach daily doses of 150 mg venlafaxine and 200mg pregabalin by the CO(2) challenge test day. Participants inhaled air 7.5% CO(2) for 20 minutes (single-blind presentation), and a non-blinded single vital capacity of 35% CO(2). Subjective ratings were recorded before and after each inhalation. Both 7.5% and 35% CO(2) inhalations produced the expected effects of increased ratings of symptoms of panic and anxiety, with increased blood pressure and heart rate. No significant treatment effects were found, although there were trends towards a reduction in feeling tense and nervous by both drugs compared with placebo during the 7.5% CO(2) challenge, and a reduction in alertness generally in the venlafaxine group compared with the pregabalin group. In contrast with the clear anxiolytic effects of benzodiazepines reported in several previous CO(2) studies, these findings suggest that the anxiogenic effects of CO(2) challenges are not significantly influenced by these serotonergic and GABAergic anxiolytics. This may be due to a lack of sensitivity of the CO(2) challenges in healthy volunteers to these drug types.

The effect of a clinically effective and non-effective dose of lorazepam on 7.5% CO2-induced anxiety.

Symptoms of anxiety induced by 7.5% CO2 inhalation can be attenuated by acute administration of GABA(A) receptor anxiolytics such as lorazepam and alprazolam. This study investigated if these effects are dose-related, by comparing a 0.5 mg dose (considered non-clinically effective) and a 2 mg dose of lorazepam (clinically effective) on 7.5% CO2 inhalation. Eighteen healthy males (mean age 20.6 years, SD 1.29), judged physically and mentally fit, attended three visits, each one week apart, to take each treatment in a randomised double-blind crossover design. Drugs were given 60 min prior to 20 min air inhalation, followed by 20 min 7.5% CO2 inhalation. The order of gas presentation was single blind. Subjective ratings using visual analogue scales (VAS) and questionnaires were recorded before and after each inhalation. Blood pressure (BP), heart rate (HR), respiration rate (RR) and expired CO2 were recorded during each inhalation. Inhalation of 7.5% CO2 significantly raised BP, HR, RR and expired CO2. Ratings of feeling like leaving the room were significantly lower on 2 mg compared with 0.5 mg and placebo, and dose-dependent trends were seen in scores for VAS fearful, anxious, stressed, tense, and worried. Results may be indicative of dose-dependent effects of lorazepam in a CO2 model of anxiety.

The effects of 7.5% carbon dioxide inhalation on task performance in healthy volunteers.

Studies have shown that anxiety can positively or negatively affect performance with respect to focusing of attention or distractibility, subjective workload and effort (Humphreys and Revelle, 1984). The inhalation of carbon dioxide (CO(2)) is associated with physiological and psychological effects of anxiety (Bailey et al., 2005) but its effects on performance have rarely been reported. The studies reported here looked at the effects of CO(2) inhalation on physiological and subjective measures and performance on two tasks. Eight healthy male participants completed a tracking task with a reaction time component, and 12 healthy participants (six male) completed a complex target identification task. Tasks were performed during 20-min inhalations of 7.5% CO(2)/21% O(2)/71.5% N(2) mixture or medical air. Continuous heart rate and blood pressure measures were taken, in addition to subjective measures of mood and workload. In comparison with air, CO(2) increased heart rate and blood pressure, increased subjective scores of panic, anxiety, fear, and tension, and reduced subjective scores of relaxation and happiness. Attention was focussed when inhaling CO(2) during the simple task, and central demand was greater when inhaling CO(2) during the complex task. Therefore, inhalation of 7.5% CO(2) produces effects on task performance which are consistent with anxiety.

Validating the inhalation of 7.5% CO(2) in healthy volunteers as a human experimental medicine: a model of generalized anxiety disorder (GAD).

Anxiety is a complex phenomenon that can represent contextually different experiences to individuals. The experimental modelling in healthy volunteers of clinical anxiety experienced by patients is challenging. Furthermore, defining when and why anxiety (which is adaptive) becomes an anxiety disorder (and hence maladaptive) is the subject of much of the published literature. Observations from animal studies can be helpful in deriving mechanistic models, but gathering evidence from patients and reverse translating this to healthy volunteers and thence back to laboratory models is a more powerful approach and is likely to more closely model the clinical disorder. Thus the development and validation of a robust healthy volunteer model of anxiety may help to bridge the gap between the laboratory and the clinic and provide 'proof of concept' in screening for novel drug treatments. This review considers these concepts and outlines evidence from a validated healthy volunteer model of generalized anxiety disorder (GAD) following the inhalation of 7.5% CO(2).

Effects of 7.5% CO(2) inhalation on allocation of spatial attention to facial cues of emotional expression.

Increased vigilance to threat-related stimuli is thought to be a core cognitive feature of anxiety. We sought to investigate the cognitive impact of experimentally induced anxiety, by means of a 7.5% CO(2) challenge, which acts as an unconditioned anxiogenic stimulus, on attentional bias for positive and negative facial cues of emotional expression in the dot-probe task. In two experiments we found robust physiological and subjective effects of the CO(2) inhalation consistent with the claim that the procedure reliably induces anxiety. Data from the dot-probe task demonstrated an attentional bias to emotional facial expressions compared with neutral faces regardless of valence (happy, angry, and fearful). These attentional effects, however, were entirely inconsistent in terms of their relationship with induced anxiety. We conclude that the previously reported poor reliability of this task is the most parsimonious explanation for our conflicting findings and that future research should develop a more reliable paradigm for measuring attentional bias in this field.

Preliminary evidence of anxiolytic effects of the CRF(1) receptor antagonist R317573 in the 7.5% CO(2) proof-of-concept experimental model of human anxiety.

We have validated the use of prolonged inhalation of 7.5% carbon dioxide (CO(2)) as a human model of anxiety and have shown that drugs from two prototypical classes of anxiolytics, benzodiazepines and a serotonin reuptake inhibitor, attenuate CO(2)-induced symptoms (Bailey et al., 2007a). Preclinical evidence suggests that drugs acting at the corticotropin-releasing factor (CRF) system may be useful for the treatment of depression, anxiety, and other stress-related disorders (Valdez, 2006), hence we have now examined the effects of a CRF(1) receptor antagonist in the 7.5% CO(2) model. In a randomized double-blind, placebo-controlled, study in 32 healthy participants we examined the effects of 7 days of treatment with the CRF(1) receptor antagonist, R317573, at a dose that shows a favourable safety profile and is comparable with those effective in preclinical models (40 mg). On day 8, eight of the placebo-treated group received lorazepam (LZP) 2 mg as a positive control. All participants underwent 20 min inhalation of 7.5% CO(2)-enriched air. Subjective reports of peak gas effects were assessed using visual analogue scales and questionnaires. The mean age of participants was 26 years, and 13 were male. The peak effects of CO(2) were expressed as a difference from baseline scores obtained while breathing air alone. Compared with placebo (PLAC), both drug groups showed a decrease in all subjective symptoms, total score on the panic symptom inventory (CRF 11 [2.6], PLAC 16.4 [3.1], LZP 2.9 [3.0]) and a generalized anxiety disorder symptom scale (CRF 2.2 [1.5], PLAC 8.2 [2.2], LZP 1.1 [1.5]). We have shown that a drug that acts to inhibit the CRF(1) receptor shows efficacy in the 7.5% CO(2) model of anxiety in healthy participants.