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.     

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.     

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.     

Efficacy and tolerability of extended release quetiapine fumarate monotherapy in the acute treatment of generalized anxiety disorder: a randomized, placebo controlled and active-controlled study

The main objective of this study was to evaluate efficacy and tolerability of once-daily extended release quetiapine fumarate (quetiapine XR) monotherapy in generalized anxiety disorder (GAD). This was a 8 week randomized, 2-week follow-up, double-blind, placebo-controlled, and active-controlled study. Patients were randomized to quetiapine XR 150 (n=219) or 300 mg/day (n=207); escitalopram, 10 mg/day (n=213); or placebo (n=215). The primary endpoint was the change from randomization at week 8 in Hamilton Anxiety Rating (HAM-A) total score. Week 8 mean HAM-A total score was significantly reduced from randomization with quetiapine XR 150 mg/day (-13.9, P<0.001), 300 mg/day (-12.3, P<0.05) and escitalopram (-12.3, P<0.05) versus placebo (-10.7); significant improvements with quetiapine XR (150 and 300 mg/day) versus placebo (P<0.001) were also shown at day 4. At week 8, significant improvements versus placebo were observed in HAM-A psychic [quetiapine XR (both doses) and escitalopram] and somatic (quetiapine XR 150 mg/day and escitalopram) cluster scores and HAM-A response and remission rates (quetiapine XR 150 mg/day). Most common adverse events were dry mouth, somnolence and sedation (quetiapine XR), headache, and nausea (escitalopram). In patients with GAD, quetiapine XR (150 and 300 mg/day) demonstrated significant efficacy at week 8 with symptom improvement as early as day 4. We concluded that quetiapine XR safety and tolerability results were consistent with the known profile of quetiapine.     

Comparison of efficacy and tolerability of reboxetine and venlafaxine XR in major depression and major depression with anxiety features: an open label study

OBJECTIVE: The aim of this study was to compare the efficacy and tolerability of reboxetine in the treatment of major depressive disorder (MDD) and MDD with anxiety features to venlafaxine XR. METHOD: Patients with MDD, aging 18 between 65 years, were randomly allocated to two groups receiving either open-label venlafaxine XR capsules (n = 50) or reboxetine tablets (n = 43). Subjects were administered Hamilton Depression Rating Scale (HAM-D) and Hamilton Anxiety Scale (HAM-A) at baseline and 2, 4, 7, 10 weeks after the baseline visit. RESULTS: Response rates to antidepressant treatment were significantly higher in the venlafaxine XR group at 10th week. When patients having anxious depression were analysed separately; response rate for anxiety of reboxetine group was significantly higher at 7th week only. Mean number of side effects were significantly higher in reboxetine group. Only one subject in each group was dropped out due to side effect. CONCLUSION: We may suggest that reboxetine is as effective and tolerable as venlafaxine XR in the treatment of MDD and MDD with anxiety features, and it may be considered a treatment option to venlafaxine XR.     

Venlafaxine XR demonstrates higher rates of sustained remission compared to fluoxetine, paroxetine or placebo

The combined serotonin-norepinephrine reuptake inhibitor, venlafaxine XR, has demonstrated significant response and remission in patients diagnosed with depression when measured with the Hamilton Depression Rating Scale (HAM-D). This pooled analysis of data from five studies compared the sustained remission of depressive symptoms in patients treated with venlafaxine XR, the selective serotonin reuptake inhibitors (SSRIs) fluoxetine or paroxetine, or placebo. Data from 1391 subjects enrolled in five active and placebo-controlled studies who met the DSM-III-R or DSM-IV criteria for major depressive disorder were analysed. Three treatment groups were compared: venlafaxine XR (n = 560), fluoxetine/paroxetine (n = 298) and placebo (n = 496). Mean treatment duration was 8 weeks. Responders were defined as those patients whose HAM-D-21 score decreased by > or = 50% from baseline. Remission was defined as a HAM-D-17 score < or = 7. Sustained remission was defined as maintenance of remission through week 8 or the end of treatment (if before week 8) and for > or = 2 weeks. Between-group rate comparisons in outcome measures were carried out using Fisher's exact and log-rank tests. Venlafaxine XR produced significantly higher rates of sustained remission in depressed patients compared to fluoxetine/paroxetine or placebo over this 8-week treatment period. As early as week 2, a significantly greater proportion of patients treated with venlafaxine achieved improved depression scores (remission and response). A significantly greater rate of remission and sustained remission occurred with venlafaxine compared to placebo. Remission was achieved earlier with venlafaxine and lasted throughout the remainder of the study. These results demonstrate that venlafaxine XR is more effective than fluoxetine/paroxetine for sustaining remission of depressive symptoms.     

Duloxetine as an SNRI treatment for generalized anxiety disorder: results from a placebo and active-controlled trial

This study examined the efficacy and tolerability of duloxetine 60-120 mg/day for the treatment of patients with generalized anxiety disorder. This was a multicenter, randomized, double-blind, flexible-dose, placebo and active-controlled (venlafaxine extended-release 75-225 mg/day) trial designed to assess duloxetine 60-120 mg/day during 10 weeks of treatment in adults with Diagnostic and statistical manual of mental disorders-IV-defined generalized anxiety disorder. The primary efficacy outcome measure was mean change from baseline to endpoint in the Hamilton Anxiety Rating Scale total score assessed using analysis of covariance. A total of 487 patients were randomly assigned to duloxetine (n=162), venlafaxine XR (n=164), or placebo (n=161). Significantly greater improvement on the Hamilton Anxiety Rating Scale total score occurred in the duloxetine (P=0.007) and venlafaxine XR (P<0.001) groups compared with the placebo group. Overall discontinuation rates did not differ among the three groups, but adverse event-related discontinuation was significantly higher in the duloxetine (14.2%, P<0.001) and venlafaxine XR (11.0%, P=0.001) groups than in the placebo group (1.9%). During the 2-week drug-tapering phase, discontinuation-emergent adverse events were significantly greater in the venlafaxine XR group (26.9%, P=0.04), but not in the duloxetine group (19.4%, P=0.448) compared with placebo (15.8%). Duloxetine 60-120 mg/day and venlafaxine XR 75-225 mg/day were each efficacious treatments for patients with generalized anxiety disorder.     

Prevention of relapse in generalized anxiety disorder by escitalopram treatment

Escitalopram has demonstrated a robust and dose-dependent efficacy in the treatment of generalized anxiety disorder (GAD) for up to 3 months. In the present study, the efficacy and tolerability of escitalopram in the prevention of relapse in GAD was investigated. A total of 491 patients with a primary diagnosis of GAD and a Hamilton Anxiety (HAMA) total score>or=20 received 12 wk of open-label treatment with a fixed dose of escitalopram (20 mg/d). Of these, 375 patients responded (HAMA total scoreor=15, or lack of efficacy, as judged by the investigator. The results of the primary analysis showed a clear beneficial effect of escitalopram relative to placebo on the time to relapse of GAD (log-rank test, p<0.001). The risk of relapse was 4.04 times higher for placebo-treated patients than for escitalopram-treated patients; the proportion of patients who relapsed was statistically significantly higher in the placebo group (56%) than in the escitalopram group (19%) (p<0.001). Escitalopram was well tolerated and 7% of the escitalopram-treated patients withdrew due to adverse events, vs. 8% of the placebo patients. The incidence of discontinuation symptoms with escitalopram during tapered withdrawal was low; the symptoms primarily being dizziness (10-12%), nervousness (2-6%), and insomnia (2-6%). Escitalopram 20 mg/d significantly reduced the risk of relapse and was well tolerated in patients with GAD.     

Efficacy of Venlafaxine ER in patients with social anxiety disorder: a double-blind, placebo-controlled, parallel-group comparison with paroxetine

This study evaluated the anxiolytic efficacy, safety and tolerability of a flexible dose of venlafaxine extended release (ER) compared with placebo and paroxetine in the short-term treatment of generalized social anxiety disorder (SAD). Adult outpatients with generalized SAD (n = 434) were randomized to receive capsules of venlafaxine ER 75 mg to 225 mg/day, paroxetine 20 mg to 50 mg/day, or placebo for 12 weeks. The primary efficacy variable was the Liebowitz social anxiety scale total score. Secondary efficacy variables included the patient-rated social phobia inventory and the proportion of responders in each group (a responder was defined as having a clinical global impression-improvement score of 1 or 2). Treatment with venlafaxine ER was associated with significantly greater improvement than treatment with placebo for all primary and secondary efficacy variables (p < 0.05). No significant differences in primary or secondary efficacy variables were observed between the venlafaxine ER and paroxetine groups. The week 12 response rates were 69%, 66% and 36% for the venlafaxine ER, paroxetine and placebo groups, respectively. Both active treatments were generally well tolerated and were associated with a similar incidence of adverse events. This study shows that venlafaxine ER is an effective, safe and well-tolerated drug treatment for SAD.     

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.     

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。     

A non-inferiority comparison of duloxetine and venlafaxine in the treatment of adult patients with generalized anxiety disorder

The present study is a non-inferiority comparison of duloxetine 60-120 mg/day and venlafaxine extended-release (XR) 75-225 mg/day for the treatment of adults with generalized anxiety disorder (GAD). The non-inferiority test was a prespecified plan to pool data from two nearly identical 10-week, multicentre, randomized, placebo-controlled, double-blind studies of duloxetine 60-120 mg/day and venlafaxine 75-225 mg/ day for the treatment of GAD. An independent expert consensus panel provided six statistical and clinical criteria for determining non-inferiority between treatments. Response was defined as > or =50% reduction in Hamilton Anxiety Rating Scale (HAMA) total score. In the pooled sample, patients were randomly assigned to duloxetine (n = 320), venlafaxine XR (n = 333) or placebo (n = 331). For the non-inferiority analysis, the per-protocol patients who were treated with duloxetine (n = 239) or venlafaxine XR (n = 262) improved significantly more (mean HAMA reductions were -15.4 and -15.2, respectively) than placebo-treated patients (n = 267; -11.6, P < or = 0.001, both comparisons). Response rates were 56%, 58% and 40%, respectively. Discontinuation rate because of AEs was significantly higher for duloxetine (13.4%, P < or = 0.001) and venlafaxine XR (11.4%, P < or = 0.01) groups compared with placebo (5.4%). Duloxetine 60-120 mg/day met all statistical and clinical criteria for non-inferiority and exhibited a similar tolerability profile compared with venlafaxine XR 75-225 mg/day for the treatment of adults with GAD.     

Treatment of pain syndromes with venlafaxine

Major depressive disorder (MDD) and anxiety disorders such as generalized anxiety disorder (GAD) are often accompanied by chronic painful symptoms. Examples of such symptoms are backache, headache, gastrointestinal pain, and joint pain. In addition, pain generally not associated with major depression or an anxiety disorder, such as peripheral neuropathic pain (e.g., diabetic neuropathy and postherpetic neuralgia), cancer pain, and fibromyalgia, can be challenging for primary care providers to treat. Antidepressants that block reuptake of both serotonin and norepinephrine, such as the tricyclic antidepressants (e.g., amitriptyline), have been used to treat pain syndromes in patients with or without comorbid MDD or GAD. Venlafaxine, a serotonin and norepinephrine reuptake inhibitor, has been safe and effective in animal models, healthy human volunteers, and patients for treatment of various pain syndromes. The use of venlafaxine for treatment of pain associated with MDD or GAD, neuropathic pain, headache, fibromyalgia, and postmastectomy pain syndrome is reviewed. Currently, no antidepressants, including venlafaxine, are approved for the treatment of chronic pain syndromes. Additional randomized, controlled trials are necessary to fully elucidate the role of venlafaxine in the treatment of chronic pain.     

Bupropion: a review of its use in the management of major depressive disorder

Bupropion is presumed to be a dopamine-norepinephrine reuptake inhibitor and is an effective antidepressant. It is available as three oral formulations: (i) bupropion immediate release (IR) [Wellbutrin] administered three times daily; (ii) bupropion sustained release (SR) [Wellbutrin SR] administered twice daily; and (iii) bupropion extended/modified release (XR) [Wellbutrin XL/Wellbutrin XR] administered once daily. All three formulations are bioequivalent in terms of systemic exposure to bupropion. Oral three-times-daily bupropion IR was effective and generally well tolerated in the treatment of major depressive disorder (MDD). It was as efficacious and as well tolerated as some tricyclic antidepressants (TCAs) and the selective serotonin reuptake inhibitor (SSRI) fluoxetine. Moreover, it was associated with less somnolence and weight gain than some TCAs. Twice-daily bupropion SR was also efficacious and generally well tolerated in the treatment of MDD. It was as effective as and had a generally similar tolerability profile to some SSRIs, but had the advantage of less somnolence and sexual dysfunction. The efficacy of bupropion XR in terms of primary efficacy measures was established in two of six well designed placebo-controlled studies. Bupropion XR also demonstrated efficacy in terms of some secondary outcomes in five of these studies. Additionally, bupropion XR was similar, in terms of the primary efficacy outcomes, to the SSRI escitalopram in two placebo-controlled trials and to the serotonin-norepinephrine reuptake inhibitor (SNRI) venlafaxine extended release (XR) in two trials (one of which was placebo-controlled), but not in a third placebo-controlled trial where venlafaxine XR was better than bupropion XR. It was generally as well tolerated as escitalopram and venlafaxine XR, but was associated with less sexual dysfunction than escitalopram. Available clinical data suggest that bupropion is an effective and generally well tolerated option in the treatment of MDD, with the newer formulations having the advantage of reduced frequency of daily administration.     

Remission rates with venlafaxine extended release in Greek outpatients with generalized anxiety disorder. A double-blind, randomized, placebo controlled study

The primary endpoints in this study were the remission rates [final Hamilton Rating Scale for Anxiety (HAM-A) total score < or =7] and reduction from baseline in the HAM-A total score in patients with generalized anxiety disorder (GAD) and no associated depression. Patients with GAD (DSM-IV and HAM-A total score >18) were randomly assigned to treatment with venlafaxine XR or placebo for 8 weeks. A 1-week placebo run-in period preceded the double-blind phase. Patients with a >20% drop in their total HAM-A score during the run-in period, were excluded from the double-blind phase. All patients started therapy with 75 mg/day venlafaxine XR or matched placebo. Patients with less than 30% decrease in their HAM-A total score at the end of the second week, doubled their dose. Patients on the 150 mg/day dose underwent a 1-week taper period. Of the 24 patients in the venlafaxine XR group, 62.5% achieved remission versus 9.1% in the placebo group (P=0.0006). The mean decrease from baseline in HAM-A total score was 19.2 points for the venlafaxine XR group and 10.8 points for the placebo group (P<0.001). Eleven placebo-treated patients and seven venlafaxine XR treated patients doubled their dose at the end of the second week of double-blind treatment. No patient interrupted therapy because of side-effects. No changes in systolic or diastolic blood pressure were observed. Venlafaxine XR 75-150 mg/day was well tolerated. The remission rates achieved with venlafaxine 75-150 mg/day in non-depressed GAD patients were high with good tolerability.     

Safety of benzodiazepines in the geriatric population

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.     

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.     

Paroxetine: safety and tolerability issues

Paroxetine is a selective serotonin re-uptake inhibitor (SSRI) available in immediate release and controlled release (CR) formulations. Paroxetine is the most potent inhibitor of serotonin re-uptake among the now available SSRIs. Paroxetine has been approved for the treatment of major depressive disorder (MDD), obsessive–compulsive disorder, panic disorder (PD), generalised anxiety disorder, post traumatic stress disorder (PTSD), and social anxiety disorder (SAD) in adults, whereas paroxetine CR is approved for the treatment of MDD, SAD, PD and premenstrual dysphoric disorder in adults. The overall efficacy of paroxetine seems to be comparable to other SSRIs in the treatment of approved indications, although paroxetine treatment induces more sedation, constipation, sexual dysfunction, discontinuation syndrome and weight gain than other SSRIs. Recent data suggest that paroxetine treatment leads to increased rates of congenital malformations, although this evidence is not conclusive. Paroxetine and paroxetine CR are not indicated for use in the paediatric population and are categorised as Pregnancy Class D. In conclusion, whether the tolerability profile of paroxetine differs substantially from other new antidepressants (including other SSRIs) needs to be determined in adequately powered well-designed randomised controlled comparative clinical trials.     

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.     

Paroxetine: safety and tolerability issues

Paroxetine is a selective serotonin re-uptake inhibitor (SSRI) available in immediate release and controlled release (CR) formulations. Paroxetine is the most potent inhibitor of serotonin re-uptake among the now available SSRIs. Paroxetine has been approved for the treatment of major depressive disorder (MDD), obsessive-compulsive disorder, panic disorder (PD), generalised anxiety disorder, post traumatic stress disorder (PTSD), and social anxiety disorder (SAD) in adults, whereas paroxetine CR is approved for the treatment of MDD, SAD, PD and premenstrual dysphoric disorder in adults. The overall efficacy of paroxetine seems to be comparable to other SSRIs in the treatment of approved indications, although paroxetine treatment induces more sedation, constipation, sexual dysfunction, discontinuation syndrome and weight gain than other SSRIs. Recent data suggest that paroxetine treatment leads to increased rates of congenital malformations, although this evidence is not conclusive. Paroxetine and paroxetine CR are not indicated for use in the paediatric population and are categorised as Pregnancy Class D. In conclusion, whether the tolerability profile of paroxetine differs substantially from other new antidepressants (including other SSRIs) needs to be determined in adequately powered well-designed randomised controlled comparative clinical trials.