Effects of SSRIs on peripheral inflammatory cytokines in patients with Generalized Anxiety Disorder.

BACKGROUND: Extensive research into psychoneuroimmunology has led to substantial advances in our understanding of the reciprocal interactions between the central nervous system and the immune system in neuropsychiatric disorders. To date, inflammation has been implicated in the pathogenesis of depression and anxiety. The immunomodulating effects of antidepressants on depression have been reported, however, there is no evidence of the similar effects of antidepressants on anxiety. The aim of the study was to investigate the effects of selective serotonin reuptake inhibitors (SSRIs) on peripheral inflammatory cytokines in patients with first episode generalized anxiety disorder (GAD). METHODS: A prospective cohort design was employed: 42 patients with first episode GAD were treated with either escitalopram or sertraline for 12 weeks. Anxiety was measured by the Generalized Anxiety Disorder Scale and the State Trait Anxiety Inventory, serum pro-inflammatory cytokine levels were measured by the enzyme-linked immunosorbent assay (ELISA), and CRP determined by an immunoturbidimetric method before and after SSRIs treatment RESULTS: Baseline levels of anxiety and pro-inflammatory cytokines including IL-1α, IL-6, IL-8, IL-12, IFN-γ, and CRP were significantly reduced after treatment of SSRIs (p < 0.05 in all cases). In addition, the change of anxiety measures co-vary with the change of peripheral cytokine levels (p < 0.05 in all cases). The regression model revealed that log transformed baseline levels of CRP and IL-6 predicted treatment response (p < 0.05 in both cases). CONCLUSIONS: This study is the first to investigate the effects of SSRIs on pro-inflammatory cytokines in patients with first episode GAD. The findings indicate moderate acute anti-inflammatory effects of SSRIs in GAD, and suggest that these anti-inflammatory effects may underlie anxiolytic effects of SSRIs. The study also indicates that serum levels of CRP and IL-6 may predict treatment response. However, data from randomized controlled trials is warranted to confirm these findings.

Yogic Breathing Instruction in Patients with Treatment-Resistant Generalized Anxiety Disorder: Pilot Study.

AIM: This study aims to evaluate the feasibility and effects of instruction in yogic breathing techniques (Pranayama) in patients with treatment-resistant generalized anxiety disorder (GAD) in UK secondary mental health services settings. MATERIALS AND METHODS: Participants were adult primary or secondary care patients with a primary diagnosis of GAD (with or without comorbidity) and persistent anxiety symptoms of at least moderate intensity, despite prior treatment with two or more medications of proven efficacy. Patients participated in group-delivered yogic breathing training and practice for 12 weeks. Structured assessments were performed at baseline, after 1, 2, and 6 weeks of instruction, and at end-point. Participants also completed the antisaccade (emotional variant) task and startle response task at baseline and end-point. RESULTS: At baseline, participating patients (n = 9) had moderate-to-severe anxiety symptoms and mild-to-moderate depressive symptoms, they attended 84% of offered sessions and provided positive feedback on the content and delivery of treatment. Symptom severity reduced significantly from baseline to end-point. There were greater errors on negative trials compared to neutral trials in the antisaccade task at baseline, and a significant reduction in antisaccade errors for negative stimuli as compared to neutral stimuli between baseline and end-point: but there were no significant differences in either mean heart rate or startle response between baseline and end-point. LIMITATIONS: The absence of a control group and small sample size. CONCLUSION: Yogic breathing techniques proved simple to learn and may be beneficial in reducing anxiety and depressive symptoms in patients with treatment-resistant GAD. Yogic breathing had no effect on autonomic arousal, but the reduction in errors to negative stimuli in the antisaccade task suggests an improvement in attention control during the intervention accompanying the reduction in symptoms.

Evaluating psychological interventions in a novel experimental human model of anxiety.

Inhalation of 7.5% carbon dioxide increases anxiety and autonomic arousal and provides a novel experimental model of anxiety with which to evaluate pharmacological and psychological treatments for anxiety. To date several psychotropic drugs including benzodiazepines, SSRIs and SNRIs have been evaluated using the 7.5% CO2 model; however, it has yet to be used to evaluate psychological interventions. We compared the effects of two core psychological components of mindfulness-meditation (open monitoring and focused attention) against general relaxation, on subjective, autonomic and neuropsychological outcomes in the 7.5% CO2 experimental model. 32 healthy screened adults were randomized to complete 10 min of guided open monitoring, focused attention or relaxation, immediately before inhaling 7.5% CO2 for 20 min. During CO2-challenge participants completed an eye-tracking measure of attention control and selective attention. Measures of subjective anxiety, blood pressure and heart rate were taken at baseline and immediately following intervention and CO2-challenge. OM and FA practice reduced subjective feelings of anxiety during 20-min inhalation of 7.5% CO2 compared to relaxation control. OM practice produced a strong anxiolytic effect, whereas the effect of FA was more modest. Anxiolytic OM and FA effects occurred in the absence of group differences in autonomic arousal and eye-movement measures of attention. Our findings are consistent with neuropsychological models of mindfulness-meditation that propose OM and FA activate prefrontal mechanisms that support emotion regulation during periods of anxiety and physiological hyper-arousal. Our findings complement those from pharmacological treatment studies, further supporting the use of CO2 challenge to evaluate future therapeutic interventions for anxiety.

Clinical effectiveness of interventions for treatment-resistant anxiety in older people: a systematic review.

BACKGROUND: Anxiety and related disorders include generalised anxiety disorder, obsessive-compulsive disorder, panic disorder, post-traumatic stress disorder and phobic disorders (intense fear of an object or situation). These disorders share the psychological and physical symptoms of anxiety, but each disorder has its own set of characteristic symptoms. Anxiety disorders can be difficult to recognise, particularly in older people (those aged over 65 years). Older people tend to be more reluctant to discuss mental health issues and there is the perception that older people are generally more worried than younger adults. It is estimated that between 3 and 14 out of every 100 older people have an anxiety disorder. Despite treatment, some people will continue to have symptoms of anxiety. People are generally considered to be 'resistant' or 'refractory' to treatment if they have an inadequate response or do not respond to their first treatment. Older adults with an anxiety disorder find it difficult to manage their day-to-day lives and are at an increased risk of comorbid depression, falls, physical and functional disability, and loneliness. OBJECTIVE: To evaluate the effectiveness of pharmacological, psychological and alternative therapies in older adults with an anxiety disorder who have not responded, or have responded inadequately, to treatment. DATA SOURCES: Electronic databases (MEDLINE, MEDLINE In-Process and Other Non-Indexed citations, EMBASE, The Cochrane Library databases, PsycINFO and Web of Science) were searched from inception to September 2013. Bibliographies of relevant systematic reviews were hand-searched to identify additional potentially relevant studies. ClinicalTrials.gov was searched for ongoing and planned studies. REVIEW METHODS: A systematic review of the clinical effectiveness of treatments for treatment-resistant anxiety in older adults was carried out. RESULTS: No randomised controlled trial or prospective comparative observational study was identified meeting the prespecified inclusion criteria. Therefore, it was not possible to draw any conclusions on clinical effectiveness. LIMITATIONS: As no study was identified in older adults, there is uncertainty as to which treatments are clinically effective for older adults with an anxiety disorder who have not responded to prior treatment. The comprehensive methods implemented to carry out this review are a key strength of the research presented. However, this review highlights the extreme lack of research in this area, identifying no comparative studies, which is a marked limitation. CONCLUSIONS: Specific studies evaluating interventions in older adults with an anxiety disorder who have not responded to first-line treatment are needed to address the lack of evidence. The lack of evidence in this area means that older adults are perhaps receiving inappropriate treatment or are not receiving a particular treatment because there is limited evidence to support its use. At this time there is scope to develop guidance on service provision and, as a consequence, to advance the standard of care received by older adults with a treatment-resistant anxiety disorder in primary and secondary care. Evaluation of the relative clinical effectiveness and acceptability of pharmacological and psychological treatment in older adults with an anxiety disorder that has not responded to first-line treatment is key future research to inform decision-making of clinicians and patients. An important consideration would be the enrolment of older adults who would be representative of older adults in general, i.e. those with multiple comorbid physical and mental disorders who might require polypharmacy. STUDY REGISTRATION: The protocol for the systematic review is registered on PROSPERO (registration number CRD42013005612). FUNDING: The National Institute for Health Research Health Technology Assessment programme.

The effect of focused attention and open monitoring meditation on attention network function in healthy volunteers.

Mindfulness meditation techniques are increasingly popular both as a life-style choice and therapeutic adjunct for a range of mental and physical health conditions. However, little is known about the mechanisms through which mindfulness meditation and its constituent practices might produce positive change in cognition and emotion. Our study directly compared the effects of Focused Attention (FA) and Open-Monitoring (OM) meditation on alerting, orienting and executive attention network function in healthy individuals. Participants were randomized to three intervention groups: open-focused meditation, focused attention, and relaxation control. Participants completed an emotional variant of the Attention Network Test (ANT) at baseline and post-intervention. OM and FA practice improved executive attention, with no change observed in the relaxation control group. Improvements in executive attention occurred in the absence of change in subjective/self-report mood and cognitive function. Baseline levels of dispositional/trait mindfulness were positively correlated with executive control in the ANT at baseline. Our results suggest that mindfulness meditation might usefully target deficits in executive attention that characterise mood and anxiety disorders.

Potential neuroimmunological targets in the treatment of anxiety disorders.

In the translation of psychoneuroimmunology research into clinical practice, one critical step is to identify biomarkers for improved diagnosis and targeting of interventions. Inflammatory markers deserve special attention due to their crucial role linking various health conditions and disorders. In this chapter, we discuss the pivotal roles of cytokines in signalling to the brain and leading to behavioural changes. This is followed by a review of recent research findings into neuroimmunology of depression, and immunomodulating effects of antidepressants. The rest of the chapter focuses on neuroinflammatory hypothesis in anxiety disorders, and provides an overview of current research evidence on inflammatory responses in anxious state and anxiety disorders. Research suggestions are recommended, including study design, risk factors, medication effects, and measurement strategies. Clinical and pharmacotherapeutic implications and future research directions are also discussed in the final section.

A neuroimmunological perspective on anxiety disorders.

OBJECTIVE: Research into psychoneuroimmunology has led to substantial advances in our understanding of the reciprocal interactions between the central nervous system and the immune system in neuropsychiatric disorders. To date, the presence of inflammatory responses and the crucial role of cytokines in major depression have been addressed in numerous studies. However, neuroinflammatory hypotheses in anxiety disorders have been studied less extensively than in major depression. There is a high research need for better understanding of both the heterogeneous role of specific cytokines in the control of anxious states and in different anxiety disorders and of the immunomodulating effects of antidepressants on anxiety. METHODS: Relevant literature was identified through a search of MEDLINE via PubMed. We discuss recent research on neuroimmunology in anxiety and make methodological recommendations for future investigation of neuroinflammatory hypotheses in anxiety disorders. RESULTS: Some accumulating evidence has indicated modulatory effects of cytokines on neuronal communication and anxiety; however, research has not revealed consistent reproducible findings. CONCLUSIONS: The availability of inflammatory biomarkers may provide an opportunity to identify patients via specific pathophysiological processes and to monitor therapeutic responses within relevant pathways. Further understanding of the neuroimmunological mechanisms to untangle the reciprocal associations between inflammation and anxiety is warranted.

Defensive startle response to emotional social cues in social anxiety.

Potentiation of fear-related defense behaviours coordinated by the amygdala in response to environmental threat characterizes several anxiety disorders. We compared eye-blink startle responses to startle probes delivered during the presentation of emotional and neutral social cues in high and low generalized social anxiety. Socially anxious individuals exhibited larger startle responses to emotional (positive and negative) relative to neutral social cues, compared to non-anxious individuals.

Structured relaxation in the treatment of akathisia: case series.

PURPOSE: Akathisia remains a common side effect especially from antipsychotic medication. If the condition is diagnosed the management options are limited. SUBJECTS/METHODOLOGY: We tested a structured relaxation program on nine patients with a diagnosis of schizophrenia suffering from akathisia. All patients were rated on Barnes Akathisia Scale (BAS) before the relaxation program, immediately after and again one week later. RESULTS: The mean BAS score was before the relaxation 3.3 which reduced to 1.4 immediately after to finally 1.0 a week later. A Wilcoxon signed ranks test revealed a significant reduction in BAS score from baseline to endpoint (P = 0.026; Z = -2.232) and a highly significant reduction from baseline to follow-up (P = 0.008; Z = -2.636). DISCUSSION: Although the study has a number of limitations the relaxation program appears to be a promising alternative to traditional treatment of akathisia. The patients appreciated the relaxation session but none of them managed to carry it out on their own without professional encouragement. The findings in this case series warrant further investigation with larger numbers of patients.

Sexual dysfunction associated with antidepressant drugs.

The term 'sexual dysfunction' describes a disturbance in sexual desire and the psychophysiological changes that characterise the normal sexual response cycle, and cause marked personal distress and interpersonal difficulty. Epidemiological studies indicate that sexual dysfunction is common in the general population, but more common in depressed individuals in community settings and clinical samples. Most antidepressant drugs have adverse effects on sexual function, but accurate identification of the incidence of treatment-emergent dysfunction has proved troublesome. Futhermore, investigations of sexual dysfunction associated with antidepressants have one or more methodological flaws. There may be some advantages for bupropion, moclobemide, nefazodone and reboxetine over other antidepressants. Many approaches have been adopted for management of patients with sexual dysfunction associated with antidepressant treatment, including waiting for the problem to resolve, behavioural strategies to modify sexual technique, individual and couple psychotherapy, delaying the intake of antidepressants until after sexual activity, reduction in daily dosage, 'drug holidays', use of adjuvant treatments, and switching to a different antidepressant.