The safety of SSRIs in generalised anxiety disorder: any reason to be anxious?

Generalised anxiety disorder (GAD) significantly impacts upon quality of life and has a chronic and persistent nature. GAD requires pharmacological therapies that are well-tolerated, lessen the mitigating effects of common comorbidities and do not pose a high risk for dependency or abuse. Selective serotonin and serotonin-noradrenaline re-uptake inhibitors have become more viable treatments for GAD than the traditionally used benzodiazepines due to greater efficacy and a more tolerable adverse event profile. Among these newer-generation antidepressants, only paroxetine and venlafaxine are currently FDA-approved for the treatment of GAD. Paroxetine was approved after three double-blind, placebo-controlled studies demonstrated its superior efficacy compared to placebo for short-term treatment of GAD. Venlafaxine was approved for both short- and long-term treatment of GAD after demonstrating efficacy in 8-week and 6-month double-blind, placebo-controlled trials. For both paroxetine and venlafaxine, the safety and tolerability profiles during treatment of GAD are consistent with those demonstrated during the short- and long-term treatment of patients with major depressive disorder.     

Long-term treatment strategies in anxiety disorders

Anxiety disorders are prevalent and associated with increased morbidity and mortality. Some chronic anxiety disorders, including generalized anxiety disorder (GAD), may be characterized by an underlying high level of anxiety on which exacerbations of symptoms are superimposed. Effective treatment of anxiety disorders should therefore strive to attain both an acute reduction in the symptoms of anxiety (a response) and sustained resolution of the symptoms of any underlying chronic anxiety (remission). This strategy may necessitate long-term treatment of these disorders by pharmacotherapy and/or psychotherapy. Studies using the serotonin and norepinephrine reuptake inhibitor (SNRI), venlafaxine extended release (XR), suggest that these aims may be achieved using this newer class of drugs. Studies with venlafaxine XR in patients with GAD have demonstrated robust anxiolytic efficacy over placebo, particularly regarding worry, cognitive dysfunction, and muscular tension, which are specific to GAD. Administration of venlafaxine XR over both short- (8-week) and long-term (6-month) periods resulted in a significantly greater number of patients achieving response and remission than obtained with placebo. Long-term treatment with venlafaxine XR in patients with GAD showed greater efficacy than that observed in short-term studies. This was achieved without any loss of short-term efficacy and patients' social functioning was also restored. While available data indicate that venlafaxine XR is an appropriate choice of agent in the long-term treatment of GAD, more studies are needed to determine how to further increase remission rates and to maintain remission beyond 6 months.     

Generalized anxiety disorder: raising the expectations of treatment

Anxiety disorders are prevalent and associated with an increase in morbidity and mortality, particularly when present with additional psychiatric disorders. They represent a public health and economic burden, yet they are commonly underrecognized and undertreated. Benzodiazepines are effective anxiolytics, but they primarily treat the somatic symptoms of generalized anxiety disorder (GAD), and are not effective in treating the depressive symptoms that are often comorbid in chronic anxiety disorders like GAD. Some antidepressants may therefore offer the best choice of therapy. Their benefit in the treatment of GAD has been demonstrated using the tricyclic antidepressant, imipramine, and some selective serotonin reuptake inhibitors. The serotonin and norepinephrine reuptake inhibitor venlafaxine extended release (XR), has been indicated for GAD and has proven to be effective in both the short- and long-term treatment of patients with this disorder. Many patients treated with venlafaxine XR achieve and sustain remission from the symptoms of GAD, which is the goal of treatment.     

Evidence-based pharmacotherapy of Generalized Anxiety Disorder

Generalized Anxiety Disorder (GAD) is a common and often disabling disorder. This paper reviews the pharmacological treatment of GAD, based on the findings of published meta-analyses and randomized placebo-controlled studies. In doing so, it aims to address three fundamental questions: What is the first-line treatment for GAD? How long should treatment continue? What is the best intervention in patients who do not respond to first-line and second-line treatments? 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-uptake inhibitor venlafaxine is a reasonable alternative. Little is known about the optimal length of therapy after response to acute treatment but relapse-prevention studies with paroxetine suggest that continuation treatment should last for at least 6 months. The management of patients who do not respond to first-line treatment is uncertain, but some patients may benefit from certain tricyclic antidepressants, buspirone, or pregabalin.     

Paroxetine treatment of generalized anxiety disorder

Generalized anxiety disorder (GAD) is a prevalent and disabling anxiety disorder, conservatively believed to affect at least 5% of the general population. Cardinal symptoms of GAD include chronic and uncontrollable worry, anxiety, and tension, which result in difficulty fulfilling social, professional, and family roles. Treatment options include benzodiazepines, tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), and the serotonin-norepinephrine reuptake inhibitor (SNRI) venlafaxine XR. Because of the high comorbidity of GAD with other psychiatric disorders, pharmacologic therapy should possess both anxiolytic and antidepressive properties for best outcomes. The SSRIs are a good treatment option, and paroxetine is the best studied SSRI for GAD and the only SSRI to date approved by the US Food and Drug Administration for this indication. Results of randomized, controlled studies of paroxetine have demonstrated its efficacy in the short-term treatment of GAD, in achieving and sustaining full remission, and in preventing relapse. This article provides an overview of GAD and a discussion of studies of paroxetine treatment in this anxiety disorder.     

Effectiveness of venlafaxine,extended release formulation,in the short-term and long-term treatment of generalized anxiety disorder: results of a survival analysis

A survival analysis of data from two placebo-controlled, randomized, long-term (6-month) studies was used to examine the effectiveness of venlafaxine, extended release (XR) formulation, in patients with generalized anxiety disorder (GAD). Patients in a placebo-controlled, flexible-dose study received 75 to 225 mg/day venlafaxine XR, while patients in a placebo-controlled, fixed-dose study received once-daily venlafaxine XR doses of 37.5 mg, 75 mg, or 150 mg. The survival analysis was based on the clinician's decision to discontinue treatment in a placebo-controlled study and incorporated data from all patients who were randomized. In each study, placebo-treated patients discontinued treatment due to lack of efficacy more frequently and earlier than those receiving venlafaxine XR (p < 0.001, log-rank test). A dose-response relationship was apparent, with the lowest rate of withdrawal seen at the highest venlafaxine XR dose. Survival curves for discontinuations due to adverse events did not differ significantly in either study. These results were consistent with the conventional intent-to-treat efficacy assessments of changes in anxiety severity, highlighting the superiority of venlafaxine XR over placebo in the long-term treatment of GAD. Overall, these results demonstrate the clinical effectiveness of venlafaxine XR in the short-term and long-term treatment of GAD.     

A double blind comparison of venlafaxine and paroxetine in obsessive-compulsive disorder

SUMMARY: While the usefulness of clomipramine and selective serotonin reuptake inhibitors (SSRIs) in obsessive-compulsive disorder (OCD) has been established, the efficacy of serotonin-norepinephrine reuptake inhibitors remains to be determined. This report describes the first randomized double-blind comparison study of an SNRI in patients with obsessive-compulsive disorder. The current study compares the efficacy and tolerability of venlafaxine with paroxetine. One hundred and fifty patients with primary OCD according to DSM-IV criteria were randomly assigned in a 12-week double-blind trial to receive dosages titrated upward to 300 mg/d of venlafaxine (n = 75) or 60 mg/d of paroxetine (n = 75). Primary efficacy was assessed by the change from baseline on the Yale-Brown obsessive-compulsive scale (Y-BOCS). Other assessments throughout the trial included the Hamilton depression rating scale, and the Hamilton anxiety rating scale. An intent-to-treat, last-observation-carried-forward analysis demonstrated a mean decrease on the Y-BOCS of 7.2 +/- 7.5 in the venlafaxine group and of 7.8 +/- 5.4 in the paroxetine group. In both treatment groups, a responder rate (decrease > 35% on the Y-BOCS) of approximately 40% was found. There were no significant differences between venlafaxine and paroxetine with regard to response or responder rates. The incidence of adverse events for venlafaxine and paroxetine was comparable. The most common side effects for venlafaxine were somnolence, insomnia, a dry mouth, and sweating; and for paroxetine somnolence, sweating, nausea, and headache. These results show that venlafaxine was equally effective to paroxetine in treating patients with OCD. Venlafaxine may be a useful therapy for obsessive-compulsive patients, but is not superior to SSRIs.     

Treatment of panic disorder: focus on paroxetine

Panic disorder is a chronic and disabling condition associated with significant morbidity. Treatment of panic disorder has evolved significantly in the past 20 years with the availability of serotonergic antidepressants, including the selective serotonin reuptake inhibitors (SSRIs). Of these, paroxetine was the first to receive an indication for treatment of panic disorder and has been extensively studied in this area. A series of randomized, double-blind, placebo-controlled studies have demonstrated the efficacy and safety of paroxetine treatment of panic disorder, with a majority of patients achieving panic-free status during 12-week studies. Continued treatment with paroxetine results in sustained rates of remission compared with placebo. The combination of paroxetine and cognitive behavioral therapy appears to offer benefits of efficacy and sustained therapeutic response.     

Setting New Standards for the Pharmacological Treatment of Panic Disorder

Three drugs are currently licensed for the treatment of panic disorder: the benzodiazepine, alprazolam; the tricyclic antidepressant, clomipramine; and, most recently, the selective serotonin reuptake inhibitor, paroxetine. Alprazolam and clomipramine are effective in the treatment of panic disorder, but are less than ideal agents due to their tolerability profiles. An extensive clinical trial programme has been undertaken to investigate the efficacy and tolerability of paroxetine treatment in panic disorder. This article reviews the clinical evidence for the short- and long-term efficacy and tolerability of paroxetine in panic disorder, and its effect on relapse prevention and on quality of life. The results from the short-term studies indicate that paroxetine is effective in treating panic disorder (with or without agoraphobia) either alone or in combination with cognitive-behavioural therapy. The minimum effective dose is 40 mg daily. Paroxetine was equally as effective as clomipramine in reducing the frequency of panic attacks but produced an earlier improvement in symptomatology. Continued treatment with paroxetine over periods of up to 9 months provided evidence that paroxetine maintained its anti-panic effect and prevented relapse. Paroxetine was well-tolerated during both the short- and long-term studies at doses of up to 60 mg per day. © 1997 John Wiley & Sons, Ltd.     

万拉法辛缓释剂与帕罗西汀治疗广泛性焦虑障碍的对照研究

目的研究万拉法辛缓释剂与帕罗西汀治疗广泛性焦虑障碍的疗效与安全性。方法根据DSM-IV诊断标准将广泛性焦虑障碍患者随机分成2组,万拉法辛缓释剂治疗组（25例）和帕罗西汀治疗组（23例）,均治疗8周;采用HAMA、CGI-SI评定疗效;采用TESS、实验室检查及体查评价安全性。结果HAMA、CGI-SI量表分在治疗过程中显著下降,2组疗效相当,均未有严重不良事件发生。结论万拉法辛缓释剂与帕罗西汀是安全有效的治疗广泛性焦虑障碍的药物,患者对药物的耐受性及依从性好。     

Predictors of outcome following venlafaxine extended-release treatment of DSM-IV generalized anxiety disorder: a pooled analysis of short- and long-term studies

This pooled analysis evaluated potential predictive abilities of baseline demographic factors, psychiatric history, and DSM-IV diagnostic criteria for short- and long-term outcome after treatment with venlafaxine extended release (XR) or placebo in patients with generalized anxiety disorder (GAD). Pooled data from 1,839 patients in five placebo-controlled studies of venlafaxine XR for GAD were analyzed by logistic regression. Odds ratios (ORs) were used to quantify pretreatment factors' abilities to predict response (50% reduction, baseline Hamilton Rating Scale for Anxiety [HAM-A] severity) and remission (total HAM-A score 相似文献   

An evaluation of paroxetine in generalised social anxiety disorder

It is estimated that social anxiety disorder affects approximately 13.3% individuals within the community at some point in their lifetime and is associated with significant functional impairment. A variety of drug groups have demonstrated efficacy in treating social anxiety disorder, including selective serotonin reuptake inhibitors (SSRIs). Paroxetine is an SSRI approved by the FDA and Health Canada for the treatment of a variety of psychiatric conditions. Paroxetine has been the most studied agent in social anxiety disorder and has been shown to be effective in short-term, fixed- and flexible-dose placebo-controlled trials, as well as in long-term treatment. The pharmacotherapy of social phobia will be reviewed, with a special focus on investigations with paroxetine.     

Sustained response versus relapse: the pharmacotherapeutic goal for obsessive-compulsive disorder

Convincing evidence from placebo-referenced randomized controlled trials supports efficacy for clomipramine and selective serotonin reuptake inhibitors for acute treatment of obsessive-compulsive disorder. It remains less conclusively understood whether these agents maintain efficacy over the longer term. This paper systematically reviews long-term medication studies in obsessive-compulsive disorder. Studies of clomipramine, fluoxetine and sertraline investigated 'responders' from acute treatment trials and extended treatment up to 12 months versus placebo. Responses to medication were sustained. A 24-week placebo-controlled trial of escitalopram (10 mg or 20 mg/day) and paroxetine (40 mg/day) demonstrated ongoing efficacy for all three treatments. Studies that randomized treated cases to placebo demonstrated reemergence of symptoms in the placebo-treated cohort. Six relapse prevention trials were found by systematic search. Some, but not all, revealed significant advantages for remaining on medication. Paroxetine (20-60 mg/day) and escitalopram (10 or 20 mg/day) were each found to outperform placebo in preventing relapse during 24 weeks of double-blind, randomized follow-up. Meta-analysis, using Review Manager software (4.2.8), detected overall superiority of selective serotonin reuptake inhibitors to placebo in preventing relapse among adult treatment-responders. Worsening by five Yale-Brown Obsessive Compulsive Scale points emerged from the review as a suggested threshold for relapse. Viewed collectively, these results suggest that selective serotonin reuptake inhibitors are effective long-term treatments and relapse prevention represents the treatment target for obsessive-compulsive disorder.     

Sertraline and obsessive compulsive disorder: new indication. Limited assessment

(1) Sertraline, a selective serotonin reuptake inhibitor (SSRI), is now licensed in France for the treatment of obsessive-compulsive disorder in adults. (2) In this indication the clinical file is of acceptable methodological quality, but it is incomplete: sertraline has not been compared with the other two serotonin reuptake inhibitors approved in obsessive-compulsive disorder, namely fluoxetine and paroxetine. (3) Three placebo-controlled trials have demonstrated the efficacy of sertraline in obsessive-compulsive disorder. (4) In a trial versus clomipramine, sertraline was no more effective in patients able to tolerate the drug, but the rate of treatment withdrawals for adverse events was higher on clomipramine.     

Duloxetine: a review of its use in the treatment of major depressive disorder

Duloxetine (Cymbalta) is an orally administered, selective serotonin and noradrenaline reuptake inhibitor (SNRI) that has been approved for the treatment of major depressive disorder (MDD).Based on a considerable body of evidence, duloxetine at dosages ranging from 40 to 120 mg/day was effective in the short- and long-term treatment of MDD. Significant improvements versus placebo in core emotional symptoms as well as painful physical symptoms associated with depression, were seen in most, but not all, appropriately designed studies; results of meta-analyses suggested that improvements in these efficacy measures were apparent after 1-2 weeks' treatment with the highest recommended dosage of 60 mg once daily. Short-term (< or =15 weeks) administration of duloxetine at fixed or flexible dosages between 60 and 120 mg/day was noninferior to paroxetine 20 mg once daily, noninferior or inferior to escitalopram 10-20mg once daily, and had a similar global benefit-risk (GBR) profile to that of venlafaxine extended-release (XR) 150-225 mg/day in the treatment of MDD. Longer-term (6-8 months) treatment with duloxetine was similar in efficacy to paroxetine and escitalopram. Duloxetine is generally well tolerated, although it may be appropriate to avoid initiating treatment with the 60 mg/day dosage, as this has been associated with a higher discontinuation rate due to adverse events in some (but not all) comparative studies with escitalopram and venlafaxine XR.Definitive comparisons are awaited, although duloxetine seemingly provides a useful alternative to SSRIs and other SNRIs for the treatment of MDD. It also appears to be an attractive option for MDD patients presenting with painful physical symptoms.     

Escitalopram: a review of its use in the management of anxiety disorders

Escitalopram (Cipralex, Lexapro, Seroplex, Sipralexa), the therapeutically active S-enantiomer of racemic citalopram (RS-citalopram), is a potent and highly selective serotonin reuptake inhibitor. It is effective and generally well tolerated in the treatment of moderate to severe generalised anxiety disorder (GAD) or social anxiety disorder (SAD), panic disorder (with or without agoraphobia) as well as obsessive-compulsive disorder (OCD). Moreover, escitalopram is at least as effective as paroxetine for the treatment of GAD, SAD or OCD and appears to achieve a more rapid response than racemic citalopram in the management of panic disorder. Generally, it has a more favourable tolerability profile than paroxetine in terms of fewer discontinuation symptoms. In addition, a favourable pharmacokinetic profile permits once-daily administration of the drug. Additional comparative studies are required to definitively position escitalopram with respect to other SSRIs and venlafaxine. Nevertheless, available clinical data indicate that escitalopram is an effective first-line treatment option for the management of GAD, SAD, panic disorder and OCD.     

Spotlight on paroxetine in psychiatric disorders in adults

Paroxetine is a selective serotonin reuptake inhibitor (SSRI), with antidepressant and anxiolytic activity. In 6- to 24-week well designed trials, oral paroxetine 10 to 50 mg/day was significantly more effective than placebo, at least as effective as tricyclic antidepressants (TCAs) and as effective as other SSRIs and other antidepressants in the treatment of major depressive disorder. Relapse or recurrence over 1 year after the initial response was significantly lower with paroxetine 10 to 50 mg/day than with placebo and similar to that with imipramine 50 to 275 mg/day. The efficacy of paroxetine 10 to 40 mg/day was similar to that of TCAs and fluoxetine 20 to 60 mg/day in 6- to 12-week trials in patients aged > or = 60 years with major depression. Paroxetine 10 to 40 mg/day improved depressive symptoms to an extent similar to that of TCAs in patients with comorbid illness, and was more effective than placebo in the treatment of dysthymia and minor depression. Paroxetine 20 to 60 mg/day was more effective than placebo after 8 to 12 weeks' treatment of obsessive-compulsive disorder (OCD), panic disorder, social anxiety disorder (social phobia), generalised anxiety disorder (GAD) and post-traumatic stress disorder (PTSD). Improvement was maintained or relapse was prevented for 24 weeks to 1 year in patients with OCD, panic disorder, social anxiety disorder or GAD. The efficacy of paroxetine was similar to that of other SSRIs in patients with OCD and panic disorder and similar to that of imipramine but greater than that of 2'chlordesmethyldiazepam in patients with GAD. Paroxetine is generally well tolerated in adults, elderly individuals and patients with comorbid illness, with a tolerability profile similar to that of other SSRIs. The most common adverse events with paroxetine were nausea, sexual dysfunction, somnolence, asthenia, headache, constipation, dizziness, sweating, tremor and decreased appetite. In conclusion, paroxetine, in common with other SSRIs, is generally better tolerated than TCAs and is a first-line treatment option for major depressive disorder, dysthymia or minor depression. Like other SSRIs, paroxetine is also an appropriate first-line therapy for OCD, panic disorder, social anxiety disorder, GAD and PTSD. Notably, paroxetine is the only SSRI currently approved for the treatment of social anxiety disorder and GAD, which makes it the only drug of its class indicated for all five anxiety disorders in addition to major depressive disorder. Thus, given the high degree of psychiatric comorbidity of depression and anxiety, paroxetine is an important first-line option for the treatment of major depressive disorder, OCD, panic disorder, social anxiety disorder, GAD and PTSD.     

Pharmacological treatment of generalized anxiety disorder

INTRODUCTION: Generalized anxiety disorder (GAD) is a chronic, relapsing, debilitating disorder, associated with markedly impaired social and occupational functioning. Pharmacological treatment is considered standard care and several drug classes are now FDA approved for the treatment of GAD. While there are clear data for the efficacy of short-term acute treatment, long-term treatment and treatment-resistant GAD remain challenging. AREAS COVERED: This article describes current pharmacological treatment options for GAD, with focus on benzodiazepines, azapirones, antidepressants and anticonvulsant and antipsychotic drugs. Recent findings from placebo-controlled clinical trials are reviewed and evidence-based clinical implications are discussed. A PubMed search was completed using the terms: 'generalized anxiety disorder AND treatment' and 'generalized anxiety disorder AND therapy'. Additional pivotal trials were included for a historical perspective (older landmark trials that established efficacy and safety for older drug classes in the treatment of GAD). EXPERT OPINION: Efficacy for treatment of GAD has been established for several different drug classes. At present, based on clear efficacy and good tolerability, first-line treatment with either a selective serotonin reuptake inhibitor (SSRI) or a serotonin-norepinephrine reuptake inhibitor (SNRI) is indicated. If an initial, at least moderate, clinical response is achieved under antidepressant therapy, treatment should be at least continued for 12 months.     

Paroxetine: an update of its use in psychiatric disorders in adults

Paroxetine is a selective serotonin reuptake inhibitor (SSRI), with antidepressant and anxiolytic activity. In 6- to 24-week well designed trials, oral paroxetine 10 to 50 mg/day was significantly more effective than placebo, at least as effective as tricyclic antidepressants (TCAs) and as effective as other SSRIs and other antidepressants in the treatment of major depressive disorder. Relapse or recurrence over 1 year after the initial response was significantly lower with paroxetine 10 to 50 mg/day than with placebo and similar to that with imipramine 50 to 275 mg/day. The efficacy of paroxetine 10 to 40 mg/day was similar to that of TCAs and fluoxetine 20 to 60 mg/day in 6- to 12-week trials in patients aged > or =60 years with major depression. Paroxetine 10 to 40 mg/day improved depressive symptoms to an extent similar to that of TCAs in patients with comorbid illness, and was more effective than placebo in the treatment of dysthymia and minor depression. Paroxetine 20 to 60 mg/day was more effective than placebo after 8 to 12 weeks' treatment of obsessive-compulsive disorder (OCD), panic disorder, social anxiety disorder (social phobia), generalised anxiety disorder (GAD) and post-traumatic stress disorder (PTSD). Improvement was maintained or relapse was prevented for 24 weeks to 1 year in patients with OCD, panic disorder, social anxiety disorder or GAD. The efficacy of paroxetine was similar to that of other SSRIs in patients with OCD and panic disorder and similar to that of imipramine but greater than that of 2'chlordesmethyldiazepam in patients with GAD. Paroxetine is generally well tolerated in adults, elderly individuals and patients with comorbid illness, with a tolerability profile similar to that of other SSRIs. The most common adverse events with paroxetine were nausea, sexual dysfunction, somnolence, asthenia, headache, constipation, dizziness, sweating, tremor and decreased appetite. In conclusion, paroxetine, in common with other SSRIs, is generally better tolerated than TCAs and is a first-line treatment option for major depressive disorder, dysthymia or minor depression. Like other SSRIs, paroxetine is also an appropriate first-line therapy for OCD, panic disorder, social anxiety disorder, GAD and PTSD. Notably, paroxetine is the only SSRI currently approved for the treatment of social anxiety disorder and GAD, which makes it the only drug of its class indicated for all five anxiety disorders in addition to major depressive disorder. Thus, given the high degree of psychiatric comorbidity of depression and anxiety, paroxetine is an important first-line option for the treatment of major depressive disorder, OCD, panic disorder, social anxiety disorder, GAD and PTSD.     

Generalised anxiety disorder: treatment options

In recent years generalised anxiety disorder (GAD) has become a much better defined disorder, with specific criteria distinguishing it from the other anxiety disorders; however, it still lacks the same public and scientific interests as some of the other anxiety disorders such as panic and social phobia. Nevertheless, refinement in the treatment of GAD is becoming more evident through the conduct of clinical trials. Up until the mid-1980's, treatment consisted primarily of benzodiazepines. However, as a result of growing characterisation of their abuse potential, other therapeutic options were explored. Benzodiazepines became seen as an effective short-term therapy, and buspirone and some of the newer antidepressants have become the treatment of choice for patients with GAD requiring long-term treatment. Buspirone was the first available alternative to the benzodiazepines in the US; however, the initial excitement over this agent was somewhat dampened because of its mild efficacy combined with a slow onset of action. The antidepressants were seen as beneficial for the treatment of GAD because of the high comorbidity with depression, thus allowing a better outcome for these patients. The antidepressants that offer both a good adverse effect profile and efficacy are the selective serotonin reuptake inhibitors including paroxetine, and the serotonin-norepinephrine reuptake inhibitors such as venlafaxine. Clinicians should also consider the potential benefits of psychotherapy as an adjunct to medication. There are a number of potentially new pharmacotherapies being investigated, including newer serotonin 5-HT1A receptor agonists, cholecystokinin receptor antagonists, neurokinin receptor antagonists, gabapentin and its analogues, and gamma-aminobutyric acid (GABA)A receptor modulators. However, these compounds are all in the early stages of investigation, and there are no new therapies expected to be released in the near future. Nonetheless, in the search for the ideal anxiolytic, a more positive outlook is allowed by imminent future research for new treatment options in patients with GAD.