Review: Benzodiazepines in generalized anxiety disorder: heterogeneity of outcomes based on a systematic review and meta-analysis of clinical trials

  title={Review: Benzodiazepines in generalized anxiety disorder: heterogeneity of outcomes based on a systematic review and meta-analysis of clinical trials},
  author={Jos{\'e} Luis R. Martin and Maria Sainz-Pardo and Toshiaki Furukawa and Eva Mart{\'i}n-S{\'a}nchez and Teresa Boquete Seoane and C Redondo Gal{\'a}n},
  journal={Journal of Psychopharmacology},
  pages={774 - 782}
No systematic review or meta-analysis using a hard outcome has been conducted on the role of benzodiazepines for generalized anxiety disorder (GAD). The objective of this study was to assess the effectiveness and efficacy of benzodiazepines in the treatment of GAD based on trial drop-out rates. We used a systematic review of randomized controlled trials that compared any of the three best established benzodiazepines (diazepam, Lorazepam and aLprazolam) against placebo. Our primary outcome for… 

Influence of covariates on heterogeneity in Hamilton Anxiety Scale ratings in placebo-controlled trials of benzodiazepines in generalized anxiety disorder: Systematic review and meta-analysis

A systematic review of placebo-controlled randomized controlled trials with benzodiazepines in generalized anxiety disorder found three factors were shown to be associated statistically with change in HAM-A; baseline Hamilton Anxiety Scale (HAM-A) score, baseline anxiety level for Benzodiazepine arm and study duration, and duration of the study.

Effectiveness of benzodiazepines: do they work or not?

  • M. Lader
  • Psychology
    Expert review of neurotherapeutics
  • 2008
The conclusion is that efficacy was significantly higher for the drugs as compared with placebo; by contrast, no convincing evidence was found of any short-term effectiveness: and adverse effects were 1.5-times more frequent in the drug-treated patients.

Efficacy of drug treatments for generalised anxiety disorder: systematic review and meta-analysis

Though the frequentist analysis was inconclusive because of a high level of uncertainty in effect sizes, the probabilistic analysis, which did not rely on significant outcomes, showed that fluoxetine and sertraline seem to have some advantages over other treatments.

Current use of benzodiazepines in anxiety disorders

Clinicians should, however, bear in mind the frequent physiological dependence associated with these substances, and suggest both pharmacological and psychological treatment alternatives before opting for a long-term benzodiazepine treatment, which may remain necessary in certain clinical conditions.

Evidence-based pharmacotherapy of Generalized Anxiety Disorder.

Due to their efficacy in GAD and comorbid anxiety and depressive disorders, their tolerability and safety, certain selective serotonin re-uptake inhibitors (escitalopram, paroxetine, sertraline) should be considered the first-line treatment for most patients, although the serotonin-noradrenaline re-ptake inhibitor venlafaxine is a reasonable alternative.

Does initial use of benzodiazepines delay an adequate pharmacological treatment? A multicentre analysis in patients with psychotic and affective disorders

It is suggested that initial BZDs treatment may prolong the overall DUI, although their prescription seems to be influenced by specific sociodemographic and clinical factors.

A comparative cost-analysis of initiating pregabalin or SSRI/SNRI therapy in benzodiazepine-resistant patients with generalized anxiety disorder in Spain.

Starting treatment with pregabalin was associated with significant reduction in medical visits and total health care resource costs of GAD compared to SSRI/ SNRI in BR patients in the Spanish NHS setting.

Pharmacological treatment of generalized anxiety disorder.

Treatment guidelines for GAD will be influenced by emerging data for established and novel pharmacological approaches, and possibly through the more accurate identification of certain patient subgroups who are likely to respond preferentially to particular interventions.

Should benzodiazepines still have a role in treating patients with anxiety disorders?

Observations may be perplexing, as most guidance recommends that benzodiazepines should be prescribed for only short periods and in only a minority of patients, but evidence from pharmacoepidemiological studies and prescribing practice surveys shows that doctors are still prepared to prescribe for longer periods, even when guidance recommends against this.

Pharmacotherapy of anxiety disorders: a critical review

A considerable database of studies shows efficacy and relative tolerability of the selective serotonin reuptake inhibitors in the major anxiety disorders, and secondary analyses of such datasets have informed questions such as optimal definition of response and remission, optimal dose and duration, and comparative efficacy of different agents.



A Meta-analytic Review of the Efficacy of Drug Treatment in Generalized Anxiety Disorder

Pharmacotherapy, especially benzodiazepines and azapirones, is effective in the short-term treatment of patients with generalized anxiety disorder and there was no superiority of 1 drug class in reducing symptomatology.

Predictors of Outcome Following Venlafaxine Extended-Release Treatment of DSM-IV Generalized Anxiety Disorder: A Pooled Analysis of Short- and Long-Term Studies

In the largest pooled analysis to date, pretreatment factors were associated with treatment outcome in patients with GAD receiving venlafaxine XR or placebo, and the strongest trends emerged for history of substance abuse or dependence and symptoms of restlessness, sleep disturbance, and difficulty concentrating.

Pharmacotherapy of generalized anxiety disorder.

The most effective treatment for managing the recurrent symptoms of this chronic disorder will remain unknown until more long-term studies using both drug and nondrug therapies are conducted.

Treatments for generalized anxiety disorder

Long-term efficacy has been shown with venlafaxine in the treatment of this chronic condition, confirming that as in depression, the goal must not just be remission beyond simple symptom resolution but also on to improved functioning and quality of life.

Long‐term pharmacological treatment of generalized anxiety disorder

Only eight long‐term reports of studies conducted in well‐defined homogeneous groups of patients diagnosed with generalized anxiety disorder were found with the methodology of these studies presenting a number of limiting factors, and results are inconclusive and no reference drug could be identified.

The effects of benzodiazepines on cognition.

Findings suggest that patients should be advised of potential cognitive effects when treated long term with benzodiazepines, although they should also be informed that the impact of such effects may be insignificant in the daily functioning of most patients.

WCA Recommendations for the Long-Term Treatment of Generalized Anxiety Disorder

Of the psychological therapies, cognitive-behavioral therapy (CBT) shows the greatest benefit in treating GAD patients, and Benzodiazepines are not recommended for long-term treatment of GAD, due to associated development of tolerance, psychomotor impairment, cognitive and memory changes, physical dependence, and a withdrawal reaction on discontinuation.

Cognitive Effects of Long-Term Benzodiazepine Use

The observation that long-term benzodiazepine use leads to a generalised effect on cognition has numerous implications for the informed and responsible prescription of these drugs.

The epidemiology of generalized anxiety disorder.

New evidence on benzodiazepine use and falls: the time factor.

Results from multivariate logistic regression models showed a greater risk of falling for BZD users but the odds ratio was higher for men than for women, and a history of treatment for alcohol abuse was a very strong risk factor for falls.