Effects of celecoxib augmentation of antidepressant or anxiolytic treatment on affective symptoms and inflammatory markers in patients with anxiety disorders: exploratory study.

Prolonged stress has been associated with elevated levels of circulating proinflammatory cytokines. Cyclo-oxygenase-2 inhibitors such as celecoxib exert anti-inflammatory effects and may enhance the response to antidepressant drug treatment in patients with depressive disorders, but their effect on anxiety symptoms in patients with anxiety disorders is uncertain. Patients with a primary diagnosis of an anxiety disorder, with stabilised symptoms, underwent either 6 weeks of celecoxib augmentation of continued treatment (n = 18) or continued 'treatment as usual' (n = 9). Assessments included the Warwick-Edinburgh mental well-being Scale (WEMWEBS), Hospital Anxiety and Depression Scale (HADS), Oxford questionnaire of emotional side effects of antidepressants (OQUESA) and Clinical Global Impression of Illness Severity (CGI-S). Venous blood samples were collected for assays of inflammatory cytokines. Patients who underwent celecoxib augmentation showed significant reductions in anxiety (HADS-A -3.17) and depressive (HADS-D -2.11) symptoms and in overall illness severity (CGI-S -1.11), and improvements in mental well-being (WEMWBS 7.5) and positive changes in emotional responsiveness (OQUESA-RP -3.56; OQUESA-AC -4.22): these were not seen with 'treatment as usual'. There were no significant changes in blood levels of inflammatory cytokines in either group. Celecoxib augmentation appeared associated with beneficial effects on anxiety and depressive symptoms and mental well-being. The findings from this pilot study merit further exploration within a double-blind, randomised placebo-controlled study.

Hair cortisol concentration in anxiety disorders: exploration of relationships with symptom severity and inflammatory markers.

BACKGROUND: Hair cortisol concentration (HCC) can be used to periodically assess hypothalamic-pituitary-adrenal (HPA) axis function, and appears correlated with prolonged exposure to stress. METHODS: Serial assessment (at Baseline, Week 6 and Week 12) of participants (n = 35) with anxiety disorders by psychopathological rating scales, with assays of HCC and levels of peripheral anti- and pro-inflammatory cytokines. Patients underwent antidepressant treatment for an initial 6 weeks, followed by cyclo-oxygenase inhibitor-2 (COX-2) inhibitor (celecoxib) augmentation or 'treatment as usual' for a further 6 weeks. RESULTS: At Baseline (n = 35), HCC was elevated in patients with single-episode but not recurrent-episode anxiety disorders, mean IL-12p70 levels were low, and mean TNF-α levels were elevated. Following 6 weeks of antidepressant treatment (n = 33), mean HCC was within the normal range but mean IL-2 level was low. Celecoxib augmentation (n = 18) was associated with a reduction in anxiety symptoms and normalisation of mean IL-2 levels. LIMITATIONS: Small sample size. Not all participants were assessed at all time points. CONCLUSION: Serial assessment of HCC is practicable in patients with anxiety disorders. These preliminary findings warrant further investigation in larger samples.

Structured review of the use of the Arizona sexual experiences scale in clinical settings.

BACKGROUND: Approximately 40% of women and 30% of men describe sexual dysfunction, although recognition in medical settings is suboptimal, due to problems in reporting and eliciting concerns relating to sexual function and satisfaction. Screening questionnaires may help to support this aspect of clinical practice. The Arizona sexual experiences scale (ASEX) includes items that quantify sex drive, arousal, vaginal lubrication or penile erection, ability to reach orgasm, and satisfaction from orgasm. METHOD: We investigated the validity and other psychometric properties of the ASEX, and the findings from the populations in which it has been employed, by searching MEDLINE, EMBASE, and Google Scholar using the terms, Arizona sexual experiences scale, Arizona Sexual Experience Questionnaire, and ASEX. We eliminated duplications, letters, and papers not available in English, and grouped the remaining papers into the categories of psychometric, epidemiological, and outcome-based studies. RESULTS: After elimination of letters and duplicates, papers not in English, and preclinical and irrelevant studies, 104 papers were analyzed. The ASEX has excellent internal consistency, scale reliability and strong test-retest reliability. Analyses of variance reveal significant differences in total ASEX scores between patients and controls and between females and males. ASEX appears to be useful in a range of clinical situations including patients with primary sexual dysfunction, specific psychiatric disorders, specific physical illnesses, and treatment emergent sexual dysfunction. DISCUSSION: The ASEX appears to be a reliable instrument for identifying and quantifying sexual dysfunction across a range of populations in various clinical settings. Little is known about its utility in patients with anxiety disorders or relationships between ASEX scores and biological parameters.

Lithium and sexual dysfunction: an under-researched area.

OBJECTIVE: Lithium treatment remains an important part of the management of many patients with bipolar disorder, but the incidence of treatment-emergent sexual dysfunction with lithium is uncertain, and little is known about how it might be managed. METHOD: Systematic computerised literature search of preclinical and clinical studies. RESULTS: Thirteen relevant papers were identified. Preclinical studies suggest lithium can reduce testosterone levels and impair nitric oxide mediated relaxation of cavernosal tissue. Clinical reports suggest lithium may reduce sexual thoughts and desire, worsen erectile function and reduce sexual satisfaction. Concomitant benzodiazepine prescription with lithium is associated with an increased risk of sexual dysfunction. Sexual dysfunction during lithium treatment appears significantly associated with a lower level of overall functioning and may reduce compliance. CONCLUSION: The findings of this systematic review reveal the paucity of information about the incidence, associated factors and management of sexual dysfunction with lithium treatment and highlight the need for well-designed studies in this area.

Lessons from an evaluation of major change in adult mental health services: effects on quality.

BACKGROUND: The move from inpatient to community services in mental health has sparked debate internationally but the evidence base for successful service models is sparse. AIM: To evaluate the impact of bed reduction on quality of services when accompanied by redesign of community services. METHODS: Qualitative and quantitative data were collected 6 months before and 6 months after the redesign was implemented. RESULTS: Bed numbers reduced by 35%. Number of admissions and occupied bed days (OBD) reduced; bed occupancy and proportion of detained patients increased. Access to community services improved but quality of assessments did not. Transitions across pathways were rated as difficult by clinicians. There was an overall reduction in staff numbers; staff sickness levels and dissatisfaction with working conditions increased. Service users were generally positive about the redesign but GPs and staff were not. CONCLUSIONS: Multi-faceted evaluation of change in cost-pressured services is feasible and should guide developments to minimise negative effects on quality of care.

Treatment with citalopram, but not with agomelatine, adversely affects sperm parameters: a case report and translational review.

BACKGROUND: Adverse effects of antidepressant drug treatmenton sexual function are well documented but the effects of antidepressants on sperm production have not been researched extensively. METHODS: A narrative of an interventional case report of sperm parameters in a 30-year-old Caucasian man with a diagnosis of mixed depressive and anxiety disorder, who underwent citalopram treatment, followed by agomelatine treatment. Clinical observations prompted a review of the pre-clinical and clinical literature on the effects of antidepressant administration or treatment on sperm production and parameters. Findings from the review are discussed to suggest potential underlying mechanisms. RESULTS: Abnormal sperm parameters were associated with treatment with the SSRI citalopram. There was an improvement in sperm concentration, motility, progressive motility and sperm morphology following its withdrawal. There was no similar association during subsequent treatment with agomelatine. The clinical observations reflect findings from animal studies, which indicate that antidepressants can have untoward effects on spermatogenesis. CONCLUSIONS: SSRI treatment can be associated with impaired semen quality. Potential underlying mechanisms include changes in sperm DNA integrity, activation of IDO and shifting tryptophan metabolism. Further studies of the effects of antidepressants on spermatogenesis might benefit from including investigation of changes in IDO activity during antidepressant administration.

Investigation of cortisol levels in patients with anxiety disorders: a structured review.

Anxiety disorders are common and distressing medical conditions, which typically arise in adolescence or early adult life. They can persist for many years, reducing quality of life, limiting academic and occupational achievement, and being responsible for considerable economic pressures. Although a range of psychological and pharmacological treatments are available, their success is often limited, and many patients remain troubled by significant symptom-related disability for long periods. The detailed pathophysiology of each anxiety disorder is not established, and novel treatments that are based solely on current understanding of conventional neurotransmitter function are unlikely to be substantially more effective or better tolerated than current treatments. Investigations of hypothalamo-pituitary axis function across panic disorder, generalized anxiety disorder, specific phobias and social anxiety disorder have produced intriguing findings but not revealed a consistent pattern of endocrine disturbance, perhaps reflecting differences in methodology and the nature and size of the clinical samples. There is a persistent need for large, prospective studies using standardized methods for investigation and data analysis (164 words).