Switching from long-term benzodiazepine therapy to pregabalin in patients with generalized anxiety disorder: a double-blind, placebo-controlled trial

2011 ◽  
Vol 26 (4) ◽  
pp. 461-470 ◽  
Author(s):  
Sallie J Hadley ◽  
Francine S Mandel ◽  
Edward Schweizer

To evaluate the efficacy of pregabalin in facilitating taper off chronic benzodiazepines, outpatients ( N = 106) with a lifetime diagnosis of generalized anxiety disorder (current diagnosis could be subthreshold) who had been treated with a benzodiazepine for 8–52 weeks were stabilized for 2–4 weeks on alprazolam in the range of 1–4 mg/day. Patients were then randomized to 12 weeks of double-blind treatment with either pregabalin 300–600 mg/day or placebo while undergoing a gradual benzodiazepine taper at a rate of 25% per week, followed by a 6-week benzodiazepine-free phase during which they continued double-blind study treatment. Outcome measures included ability to remain benzodiazepine-free (primary) as well as changes in Hamilton Anxiety Rating Scale (HAM)-A and Physician Withdrawal Checklist (PWC). At endpoint, a non-significant higher proportion of patients remained benzodiazepine-free receiving pregabalin compared with placebo (51.4% vs 37.0%). Treatment with pregabalin was associated with significantly greater endpoint reduction in the HAM-A total score versus placebo (−2.5 vs +1.3; p < 0.001), and lower endpoint mean PWC scores (6.5 vs 10.3; p = 0.012). Thirty patients (53%) in the pregabalin group and 19 patients (37%) in the placebo group completed the study, reducing the power to detect a significant difference on the primary outcome. The results on the anxiety and withdrawal severity measures suggest that switching to pregabalin may be a safe and effective method for discontinuing long-term benzodiazepine therapy.

2021 ◽  
Author(s):  
Zhongxia Shen ◽  
Lijun Cui ◽  
Lie Ren ◽  
Mincai Qian ◽  
Yonggui Yuan ◽  
...  

Abstract Introduction: S100B is a neurotrophic factor regulates neuronal growth and plasticity via activating astrocytes and microglia through production of neuro-inflammatory molecules like interleukin (IL)-1β involved in many mental disorders, few studies have combined S100B and cytokines to explore their roles as neuro-inflammatory biomarkers in Generalized Anxiety Disorder (GAD). Methods: Serum S100B and cytokines (IL-1β , IL-2, IL-4 and IL-10) of 108 untreated GAD cases and 123 healthy controls were determined by enzyme linked-immuno-sorbent assay (ELISA) and then compared, while Hamilton Anxiety Rating Scale (HAMA) scores were measured to evaluate anxiety severity. Results: The serum S100B and IL-1β, IL-2 levels of GAD cases were lower than HC significantly (P<0.001), the IL-4 level of GAD were higher than HC (P<0.001), while IL-10 had no significant difference between two groups (P=0.215). The ROC area of S100B, IL-1β, IL-2 and IL-4 in diagnosis of GAD was (0.740 ± 0.032) , (0.900 ± 0.021) , (0.920 ± 0.018) and (0.696 ± 0.037) , all of them suggested a good predicting value (P < 0.001) , while the ROC area of IL-10 was (0.544 ± 0.038) (P = 0.251). The sensitivity of S-100B, IL-1β, IL-2 in diagnosis of GAD was 73.1%, 80.6%, 85.2%, while the specificity was 61.0%, 86.2%, 80.5%. The combination ROC area of S100B, IL-1β , IL-2 and IL-4 was (0.985 ± 0.006)(P < 0.001). Serum S100B was positively correlated with IL-2 and IL-4 (P <0.05)., while was negatively with HAMA scores (P <0.001). Conclusion: The serum S-100B, IL-1β, IL-2 levels of GAD were down-regulated while IL-4 was up-regulated, both IL-2 and IL-4 had a good diagnosis value in GAD separately while the combination of S100B and cytokines had a better diagnosis value which means the neuro-inflammation in GAD is a network regulated by many factors.


2021 ◽  
Author(s):  
Zhongxia Shen ◽  
Lijun Cui ◽  
Lie Ren ◽  
Yonggui Yuan ◽  
Xinhua Shen

Abstract Introduction: S100B is a neurotrophic factor regulates neuronal growth and plasticity via activating astrocytes and microglia through production of neuro-inflammatory molecules like interleukin (IL)-1β involved in many mental disorders, few studies have combined S100B and cytokines to explore their roles as neuro-inflammatory biomarkers in Generalized Anxiety Disorder (GAD). Methods: Serum S100B and cytokines (IL-1β , IL-2, IL-4 and IL-10) of 108 untreated GAD cases and 123 healthy controls were determined by enzyme linked-immuno-sorbent assay (ELISA) and then compared, while Hamilton Anxiety Rating Scale (HAMA) scores were measured to evaluate anxiety severity. Results: The serum S100B and IL-1β, IL-2 levels of GAD cases were lower than HC significantly (P<0.001), the IL-4 level of GAD were higher than HC (P<0.001), while IL-10 had no significant difference between two groups (P=0.215). The ROC area of S100B, IL-1β, IL-2 and IL-4 in diagnosis of GAD was (0.740 ± 0.032) , (0.900 ± 0.021) , (0.920 ± 0.018) and (0.696 ± 0.037) , all of them suggested a good predicting value (P < 0.001) , while the ROC area of IL-10 was (0.544 ± 0.038) (P = 0.251). The sensitivity of S-100B, IL-1β, IL-2 in diagnosis of GAD was 73.1%, 80.6%, 85.2%, while the specificity was 61.0%, 86.2%, 80.5%. The combination ROC area of S100B, IL-1β , IL-2 and IL-4 was (0.985 ± 0.006)(P < 0.001). Serum S100B was positively correlated with IL-2 and IL-4 (P <0.05)., while was negatively with HAMA scores (P <0.001). Conclusion: The serum S-100B, IL-1β, IL-2 levels of GAD were down-regulated while IL-4 was up-regulated, both IL-2 and IL-4 had a good diagnosis value in GAD separately while the combination of S100B and cytokines had a better diagnosis value which means the neuro-inflammation in GAD is a network regulated by many factors.


2020 ◽  
Vol 15 ◽  
Author(s):  
Sara Fuladi ◽  
Seyed Ahmad Emami ◽  
Amir Hooshang Mohammadpour ◽  
Asieh Karimani ◽  
Ali Akhondpour Manteghi ◽  
...  

Background: Anxiety disorders are the most universal psychiatric problems in the general population. Due to their chronic nature, these diseases are managed with a multi-drug regimen lasting for a long period of time. Medication discontinuation leads to 25% and 80% recurrence in the first month and the first year, respectively. Despite several treatment approaches, there is no specific and optimal method for patient management. Therefore, it is necessary to find some new theraputic approaches with fewer side effects. Withania somnifera is a plant with GABAergic property responsible for its anxiolytic effect. The aim of this study was to investigate the effect of W. somnifera root extract as an alternative therapy to reduce standard generalized anxiety disorder (GAD) symptoms. Methods: Forty patients who met the inclusion criteria (with a confirmed diagnosis of GAD as stated in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) took part in this randomized double-blind placebo-controlled trial and were randomly selected for participation in the treatment group (W. somnifera extract, 1g/day; n = 22) or the placebo group (n = 18). All patients were under treatment with Selective Serotonin Reuptake Inhibitors (SSRIs) and were prescribed one capsule of the extract or placebo per day for six weeks. The Hamilton anxiety rating scale (HAM-A) was used to assess the severity of GAD symptoms at baseline as well as the second and sixth weeks of the trial. Results: Comparison of the HAM-A scores during the course of the trial revealed a significant amelioration ofHAM-A score in the treatment group versus placebo (14 and 8 units reduction, respectively (P < 0.05)). Moreover, there was a significant difference in the reduction of GAD score between the second (P =0.04) and sixth week (P =0.02) in the treatment group. The extract was safe and no adverse effect was observed during the trial. Conclusion: W. somnifera extract offers some potential advantages as a safe and effective adjunctive therapy to SSRIs in GAD.


2019 ◽  
Vol 110 ◽  
pp. 31-37 ◽  
Author(s):  
Jerome Sarris ◽  
Gerard J. Byrne ◽  
Lachlan Cribb ◽  
Georgina Oliver ◽  
Jenifer Murphy ◽  
...  

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