Efficacy In Anxiety Disorders Research Articles

The association between fear extinction, the ability to accomplish exposure and exposure therapy outcome in specific phobia

Great interest exists in maximizing exposure therapy efficacy in anxiety disorders. At the same time, reduced frequency and shortened duration of exposure sessions are required to meet the specific regularities in routine care settings. Extinction has emerged as the key mechanism of exposure treatment in anxiety disorders. Examining exposure treatment processes from the perspective of extinction learning might provide novel insights into variability in exposure treatment duration and outcome. The present study sought to examine the functional link between fear extinction, the ability to accomplish exposure in a predetermined time and exposure therapy outcome in specific phobia. Treatment-seeking individuals (N = 53) with spider phobia underwent a context-dependent fear conditioning paradigm prior to a standardized exposure. Spider-phobic participants who were able to complete exposure within the pre-determined time (i.e., completers) showed a more pronounced short- and long-term exposure therapy benefit. In the fear conditioning task, a more pronounced decline in CS-US contingency ratings during extinction (retrieval) was found in completers relative to non-completers. The failure to further extinguish US expectancy to the CSs in non-completers might offer a potential mechanistic explanation why non-completers have difficulties to accomplish all exposure steps in a fixed time and show less pronounced treatment gains. Our findings bear specific implications for the implementation of exposure treatment to routine care settings.

No pills, more skills: The adverse effect of hormonal contraceptive use on exposure therapy benefit

Hormonal contraceptive use can aggravate existing symptoms of anxiety and depression and influence the response to pharmacologic treatment. The impact of hormonal contraceptive use on non-pharmacological treatment efficacy in anxiety disorders is less well explored. Oral contraceptives, which suppress endogenous sex hormone secretion, can alter fear extinction learning. Fear extinction is considered the laboratory proxy of exposure therapy in anxiety disorders. This study set out to examine whether oral contraceptive use is related to exposure-based treatment response in specific phobia. We recruited spider-phobic women (n = 28) using oral contraceptives (OC) and free-cycling women (n =26, No-OC). All participants were subjected to an identical in-vivo exposure. Exposure-based symptom improvement was assessed with several behavioral and subjective indices at pre-treatment, post-treatment and six-weeks follow-up. No–OC women showed higher pre-exposure fear levels on the FSQ and SPQ. OC women showed slightly less pronounced exposure benefit compared to their free-cycling counterparts (No-OC woman) as reflected by lower levels of fear reduction from pre-treatment to follow-up on the subjective level. After correction for multiple testing, OC and No-OC women showed differences in self-report measures (SPQ, FAS and SBQ) from pre- to follow-up treatment but not from pre-to post-treatment. These findings implicate that oral contraceptive use can account for differential exposure-based fear symptom improvement. Our study highlights the importance of monitoring and managing hormonal contraceptives use in the context of non-pharmacological exposure-based interventions.

Clinical effectiveness and cost minimisation model of Alpha-Stim cranial electrotherapy stimulation in treatment seeking patients with moderate to severe generalised anxiety disorder

BackgroundCranial electrotherapy stimulation (CES) is a well-tolerated neuromodulation treatment with demonstrated trial efficacy in anxiety disorders. The aim of the current study was to demonstrate its clinical and cost effectiveness during and after CES in people with generalised anxiety disorder (GAD) who had not responded to low intensity psychological treatment in a routine health service. MethodsConsecutive sample of eligible patients with GAD waiting for individual cognitive behaviour therapy (CBT) selected from two publicly funded services in England. They received 60 min per day Alpha-Stim CES for 6–12 weeks. Primary outcome was remission on the GAD-7 scale at 12 and 24 weeks. Cost effectiveness was examined using a cost minimisation model of direct health costs. ResultsOf 161 patients recruited, 72 (44.7%) and 77 (47.8%) achieved remission on the GAD-7 at 12 and 24 weeks respectively with 122 (75.8%) receiving at least 6 weeks CES. Mean (sd) GAD-7 score at baseline significantly improved from 15.77 (3.21) to 8.92 (5.42) and 8.99 (6.18) at 12 and 24 weeks respectively (p < 0.001). 80 (49.7%) participants required further individual CBT. CES provided a saving of £540.88 per patient (95% CI −£327.12, £648.69). LimitationsParticipants were not randomised and there was no control group. Only 48 (29.9%) participants completed every assessment. ConclusionIn patients with generalised anxiety disorder not responding to low intensity psychological treatment, 6–12 weeks daily Alpha Stim CES may be effective after treatment and 3 months later, thereby reducing the need for individual CBT and saving health costs.

The α2,3-selective potentiator of GABAA receptors, KRM-II-81, reduces nociceptive-associated behaviors induced by formalin and spinal nerve ligation in rats

Clinical evidence indicates that positive allosteric modulators (PAMs) of GABAA receptors have analgesic benefit in addition to efficacy in anxiety disorders. However, the utility of GABAA receptor PAMs as analgesics is compromised by the central nervous system side effects of non-selective potentiators. A selective potentiator of GABAA receptors associated with α2/3 subunits, KRM-II-81(5-(8-ethynyl-6-(pyridin-2-yl)-4H-benzo[f]imidazo[1,5-a][1,4]diazepin-3-yl)oxazole), has demonstrated anxiolytic, anticonvulsant, and antinociceptive effects in rodents with reduced motoric side effects. The present study evaluated the potential of KRM-II-81 as a novel analgesic. Oral administration of KRM-II-81 attenuated formalin-induced flinching; in contrast, diazepam was not active. KRM-II-81 attenuated nociceptive-associated behaviors engendered by chronic spinal nerve ligation (L5/L6). Diazepam decreased locomotion of rats at the dose tested in the formalin assay (10 mg/kg) whereas KRM-II-81 produced small decreases that were not dose-dependent (10–100 mg/kg). Plasma and brain levels of KRM-II-81 were used to demonstrate selectivity for α2/3- over α1-associated GABAA receptors and to define the degree of engagement of these receptors. Plasma and brain concentrations of KRM-II-81 were positively-associated with analgesic efficacy. GABA currents from isolated rat dorsal-root ganglion cultures were potentiated by KRM-II-81 with an ED50 of 32 nM. Measures of respiratory depression were reduced by alprazolam whereas KRM-II-81 was either inactive or produced effects with lower potency and efficacy. These findings add to the growing body of data supporting the idea that α2/3-selective GABAA receptor PAMs will have efficacy and tolerability as pain medications including those for neuropathic pain. Given their predicted anxiolytic effects, α2/3-selective GABAA receptor PAMs offer an additional inroad into the management of pain.

Psychological factors and treatment effectiveness in resistant anxiety disorders in highly comorbid inpatients.

BackgroundAnxiety disorders are a group of various mental syndromes that have been related with generally poor treatment response. Several psychological factors may improve or hinder treatment effectiveness. Hope has a direct impact on the effectiveness of psychotherapy. Also, dissociation is a significant factor influencing treatment efficiency in this group of disorders. Development of self-stigma could decrease treatment effectiveness, as well as several temperamental and character traits. The aim of this study was to explore a relationship between selected psychological factors and treatment efficacy in anxiety disorders.Subjects and methodsA total of 109 inpatients suffering from anxiety disorders with high frequency of comorbidity with depression and/or personality disorder were evaluated at the start of the treatment by the following scales: the Mini-International Neuropsychiatric Interview, the Internalized Stigma of Mental Illness scale, the Adult Dispositional Hope Scale, and the Temperament and Character Inventory – revised. The participants, who sought treatment for anxiety disorders, completed the following scales at the beginning and end of an inpatient-therapy program: Clinical Global Impression (objective and subjective) the Beck Depression Inventory – second edition, the Beck Anxiety Inventory, and the Dissociative Experiences Scale. The treatment consisted of 25 group sessions and five individual sessions of cognitive behavioral therapy or psychodynamic therapy in combination with pharmacotherapy. There was no randomization to the type of group-therapy program.ResultsGreater improvement in psychopathology, assessed by relative change in objective Clinical Global Impression score, was connected with low initial dissociation level, harm avoidance, and self-stigma, and higher amounts of hope and self-directedness. Also, individuals without a comorbid personality disorder improved considerably more than comorbid patients. According to backward-stepwise multiple regression, the best significant predictor of treatment effectiveness was the initial level of self-stigma.ConclusionThe initial higher levels of self-stigma predict a lower effectiveness of treatment in resistant-anxiety-disorder patients with high comorbidity with depression and/or personality disorder. The results suggest that an increased focus on self-stigma during therapy could lead to better treatment outcomes.

Cognitive bias modification for anxiety: current evidence and future directions

Cognitive bias modification (CBM) is an innovative approach to modifying cognitive biases that confer vulnerability to anxiety. CBM interventions are designed to directly modify attention and interpretation biases via repeated practice on cognitive tasks. Analogue studies have demonstrated that CBM affects cognitive biases and anxiety in a number of anxiety conditions. Multisession CBM treatments have shown preliminary efficacy for generalized social phobia and generalized anxiety disorder, with effect sizes comparable to existing treatments. However, with any newly developing field, there are a number of important limitations of the existing data that need to be addressed before making firm conclusions regarding CBM’s efficacy for anxiety disorders. This article focuses on the theoretical rationale for CBM and the current evidence from analogue and clinical samples.

Therapeutic strategies in migraine patients with mood and anxiety disorders: clinical evidence

Mood and anxiety disorders are comorbid with migraine. The coexistence of a psychiatric disorder alters the quality of life, the total disability, the course of migraine and the final prognosis; it increases the probability of central sensitization, other chronic pain conditions and the evolution to chronic migraine. All patients presenting with frequent episodic and chronic migraine should be screened for depression and anxiety. When these conditions are present, drugs for migraine prevention that may worsen the psychiatric comorbid disorder have to be avoided. When it is possible, both conditions should be treated with a single agent. Amitriptiline can be used both in mood disorders and migraine prevention. Flunarizine and beta-blockers may help if anxiety is present. Pregabalin has demonstrated efficacy in anxiety disorders and fibromyalgia. Divalproex sodium, topiramate and lamotrigine that have demonstrated efficacy in mood stabilization are also indicated in migraine without aura (divalproex sodium and topiramate) and with aura (lamotrigine). When a specific treatment for the comorbid psychiatric disorder is needed, the selective serotonin reuptake inhibitors or the serotonin norepinephrine reuptake inhibitors are the drugs of choice both in depression and anxiety, and the cognitive behavioural therapy has good evidence of efficacy in anxiety disorders. Vagal nerve stimulation may be an option in patients with refractory chronic migraine and depression.

Treatment of generalized anxiety disorder

Treatment of generalized anxiety disorder

Antagonism of metabotropic glutamate group II receptors in the potential treatment of neurological and neuropsychiatric disorders

The metabotropic glutamate Group II receptors (mGlu2 and mGlu3 receptors) regulate the synaptic availability of glutamate and thus control the broad-ranging neural transmission of glutamate as well as glutamate-modulated transmission. The present review focuses on the potential role of Group II mGlu receptor antagonism in neurological and neuropsychiatric disorders. Recent findings have determined that agonists of metabotropic glutamate type 2/3 receptors (mGlu2/3) have antianxiety efficacy. Although it could be assumed that blockade of these receptors might engender anxiogenic responses, new data have indicted that these compounds produce antidepressant-like, wake-promoting, and pro-cognitive effects in rodents. However, there are almost no data available to define the relative importance of mGlu2 versus mGlu3 receptors in these activities. Although there are some hints that antagonism of mGlu2/3 receptors could have additional therapeutic impact, the preponderance of data suggests that agonists of the mGlu2/3 receptors would be more likely to have efficacy in anxiety disorders, positive symptoms of schizophrenia, neurodegenerative disorders, and stroke, pain, and epilepsy. The pharmacology of antagonists of mGlu2/3 receptors suggests that such compounds could have a unique place in the medicinal arsenal for mood disorders as well as disorders of cognition and arousal. Given the activity surrounding the discovery of orally available antagonists for these receptors, there may be an opportunity for clinical investigation of these possibilities in the future. Drug Dev. Res. 67:757–769, 2006. © 2006 Wiley-Liss, Inc.

Issues in the Pharmacological Treatment of Anxiety Disorders

To review the most salient issues in the pharmacotherapy of anxiety disorders. These pertain to means of achieving greater efficacy, accelerating the onset of therapeutic action, improving side-effect profile and tolerability, decreasing the propensity to induce therapeutic dependence and achieving better long-term outcome. By and large, pharmacological agents with greater efficacy in anxiety disorders have yet to be developed. Several strategies have been used with some success to make medications for anxiety disorders work faster and to lessen their side-effect burden. The field of psychopharmacology has yet to find ways of lessening or eliminating the problem of therapeutic drug dependence and, even more so, of minimizing the risk of relapse following the cessation of medication.

Issues in the pharmacological treatment of anxiety disorders

To review the most salient issues in the pharmacotherapy of anxiety disorders. These pertain to means of achieving greater efficacy, accelerating the onset of therapeutic action, improving side-effect profile and tolerability, decreasing the propensity to induce therapeutic dependence and achieving better long-term outcome.By and large, pharmacological agents with greater efficacy in anxiety disorders have yet to be developed. Several strategies have been used with some success to make medications for anxiety disorders work faster and to lessen their side-effect burden. The field of psychopharmacology has yet to find ways of lessening or eliminating the problem of therapeutic drug dependence and, even more so, of minimizing the risk of relapse following the cessation of medication.

St John??s wort versus placebo in obsessive???compulsive disorder: results from a double-blind study

Although St John's wort (Hypericum perforatum) is one of the most widely used and studied herbal medicines for depression, less is known about its efficacy in anxiety disorders, in spite of the fact that patients with anxiety disorders are among the most likely to self-medicate using alternative treatments. Pharmacokinetic evidence for the serotonergic, domaminergic and GABAminergic activity of hypericum, and a recent successful open-label study, suggests that it may be effective for obsessive-compulsive disorder (OCD). Sixty subjects were randomized to 12 weeks of treatment with St John's wort (LI 160) or matching placebo. Subjects with Hamilton Depression Scale scores of 16 or above were excluded. A flexible-dose schedule was utilized (600-1800 mg/day). The mean change on the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) with St John's wort (3.43) was not significantly different than the mean change found with placebo (3.60) (P=899). No significant differences were found on any of the Y-BOCS subscales. The percentage of patients rated as 'much' or 'very much' improved at endpoint was not significantly different between St John's wort (17.9%) and placebo (16.7%) (P=0.905). Only one patient from each group discontinued due to adverse events [sinus infection (St John's wort); confusion (placebo)]. The results fail to support the efficacy of St John's wort for OCD.

Exposure therapy and cognitive behaviour therapy have established efficacy in anxiety disorders

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