Cognitive processes of generalized anxiety disorder in comorbid generalized anxiety disorder and major depressive disorder

This study examines how cognitive variables, which play a central role in the development and maintenance of generalized anxiety disorder (GAD), manifest themselves when GAD and major depressive disorder (MDD) are comorbid. Thirty-two participants were divided into two groups, a group of individuals with a principal diagnosis of comorbid GAD and MDD and a group of people with a principal diagnosis of GAD without MDD. Groups were compared using four cognitive variables: intolerance of uncertainty, poor problem orientation, cognitive avoidance, and beliefs about worry. Our results show that the group of individuals with a principal diagnosis of comorbid GAD and MDD were more intolerant of uncertainty, presented poorer problem orientation, and displayed more cognitive avoidance. The cognitive implications of these results are discussed, and diagnostic criteria are presented to facilitate the differential diagnosis between both groups.     

Serum lipid concentrations in patients with comorbid generalized anxiety disorder and major depressive disorder.

OBJECTIVE: To examine the lipid levels in a sample of patients with comorbid generalized anxiety disorder (GAD) and major depressive disorder (MDD). METHODS: Serum lipid concentrations were examined in 40 patients with both GAD and MDD, in 27 patients with MDD only, in 26 patients with GAD only, and in 24 healthy control subjects. RESULTS: All mean serum cholesterol concentrations are presented in Table 1. The mean serum total cholesterol concentration in patients with both GAD and MDD was significantly higher than in MDD-only patients, GAD-only patients, and control subjects. The triglyceride concentration was also significantly higher in patients with both GAD and MDD than in MDD-only patients, GAD-only patients, and control subjects. Patients with both GAD and MDD had a lower mean high-density lipoprotein cholesterol (HDL-C) concentration than did patients with GAD only and control subjects. The serum concentration of low-density lipoprotein cholesterol (LDL-C) was higher in patients with both GAD and MDD than in patients with MDD only and GAD only and healthy control subjects. CONCLUSIONS: Our findings indicate that the patients with both GAD and MDD have increased serum cholesterol, triglyceride, and LDL-C and reduced HDL-C levels. These patients may have a greater risk of mortality from coronary artery disease (CAD) than do patients with either depression or anxiety disorder.     

Comparison of venlafaxine extended release versus paroxetine for treatment of patients with generalized anxiety disorder

This trial was to evaluate the efficacy and tolerability of venlafaxine extended release (XR) and paroxetine for treatment of patients with generalized anxiety disorder (GAD). Sixty patients who met DSM-IV criteria for GAD were randomly assigned to either venlafaxine XR or paroxetine for 8 weeks. Efficacy was assessed with the Hamilton Rating Scale for Anxiety (HAM-A) and Clinical Global Impression-Severity of Illness (CGI-S) scale at the baseline, week 1, week 4, and week 8. The side-effects were collected with reported adverse events and laboratory tests throughout the study period. Repeated measures analysis of variance (ANOVA) on the HAM-A and CGI-S scores showed a significant decrease over time in both treatment groups without significant group difference or time x group interaction effect. There were no serious adverse events in both groups. This open trial demonstrated that either venlafaxine XR or paroxetine would be effective and tolerable for the treatment of patients with GAD. Double blind, placebo-controlled head-to-head comparison studies are needed to draw a definite conclusion.     

Efficacy, safety, and tolerability of venlafaxine extended release and buspirone in outpatients with generalized anxiety disorder.

BACKGROUND: The objective of this randomized, double-blind study was to compare the efficacy and safety of venlafaxine extended release (XR) and buspirone in outpatients with generalized anxiety disorder (GAD) but without concomitant major depressive disorder. METHOD: Male and female outpatients at least 18 years old who met the DSM-IV criteria for GAD and had scores of 18 or higher on the Hamilton Rating Scale for Anxiety (HAM-A) were randomly assigned to treatment with either venlafaxine XR (75 or 150 mg/day), buspirone (30 mg/day in 3 divided doses), or placebo for 8 weeks. The primary efficacy variables were changes in anxiety as determined by final on-therapy HAM-A total and psychic anxiety scores and Clinical Global Impressions scale (CGI) scores. Other key efficacy variables were HAM-A anxious mood and tension scores and the anxiety subscale scores of the patient-rated Hospital Anxiety and Depression scale (HAD). RESULTS: The efficacy analysis included 365 patients and the safety analysis, 405. At week 8, adjusted mean HAM-A psychic anxiety, anxious mood, and tension scores were significantly lower for venlafaxine XR-treated patients than for placebo-treated patients. On the HAD anxiety subscale, venlafaxine XR, 75 or 150 mg/day, was significantly more efficacious than placebo at all time points except weeks 1 (both dosages) and 2 (150-mg/day dosage only) and significantly more efficacious than buspirone at all time points except week 1. On the CGI-Improvement scale, scores for venlafaxine XR (both dosages) and buspirone were numerically superior to those for placebo at all time points, and statistical significance was observed at weeks 3, 4, 6, and 8 for venlafaxine XR and at weeks 6 and 8 for buspirone. The adverse events were not essentially different between treatment groups. CONCLUSION: Venlafaxine XR is an effective, safe, and well-tolerated once-daily anxiolytic agent in patients with GAD without comorbid major depressive disorder. This agent was significantly superior to buspirone on the HAD anxiety subscale. Buspirone demonstrated statistical significance versus placebo on a measure of anxiolytic response.     

A randomized controlled trial of venlafaxine extended release in generalized social anxiety disorder

BACKGROUND: Generalized social anxiety disorder is a debilitating psychiatric illness characterized by maladaptive thoughts about social situations. This double-blind study evaluated the anxiolytic efficacy, safety, and tolerability of venlafaxine extended release (ER) in adult out-patients with generalized social anxiety disorder. METHOD: Patients were randomly assigned to receive 12 weeks of treatment with a flexible dose of venlafaxine ER (75 to 225 mg/day) or placebo. The Liebowitz Social Anxiety Scale (LSAS) total score was the primary efficacy variable. Secondary efficacy variables included scores on the Clinical Global Impressions-Severity of Illness (CGI-S) and -Improvement (CGI-I) scales, Social Phobia Inventory (SPIN), and LSAS subscales. Response was defined as a CGI-I score of 1 or 2. Two definitions of remission were used: LSAS total score < or = 30 and CGI-I score of 1. RESULTS: Data from 271 patients (intent-to-treat population) were analyzed for efficacy; 279 patients were analyzed for safety. Overall, 173 patients completed the study. Improvement on the LSAS was significantly greater with venlafaxine ER treatment than with placebo at weeks 6 through 12 (p < .05, weeks 6 and 8; p < .01, week 10; and p < .001, week 12) and at weeks 8 through 12 based on CGI-S and SPIN scores. Week 12 response and remission (LSAS score < or = 30) rates were significantly greater in the venlafaxine ER group than in the placebo group (response: 44% vs. 30%, respectively, p = .018; remission: 20% vs. 7%, respectively, p < .01). Patients experienced no unexpected or serious adverse events. CONCLUSION: Venlafaxine ER is safe, well tolerated, and efficacious in the short-term treatment of generalized social anxiety disorder.     

Mirtazapine in major depression with comorbid generalized anxiety disorder.

BACKGROUND: A high proportion of patients with generalized anxiety disorder (GAD) have comorbid depressive illness. The presence of anxiety in depression has significant prognostic implications. Because of mirtazapine's early anxiolytic effects, the present study was undertaken as a preliminary investigation in patients with a diagnosis of major depression with comorbid GAD. METHOD: Mirtazapine was administered to 10 patients with DSM-IV major depressive disorder and comorbid GAD in an 8-week open-label study. Mirtazapine was increased from an initial daily dose of 15 mg to a maximum daily dose of 45 mg. RESULTS: Patients were found to have significant reductions in Hamilton Rating Scale for Depression scores, Hamilton Rating Scale for Anxiety scores, and Beck Depression Inventory scores, with improvement noted after the first week of therapy and continuing improvement over the 8 weeks of study. CONCLUSION: These positive preliminary findings support the further investigation of mirtazapine's potential value as a treatment for generalized anxiety disorder in addition to its established efficacy as an antidepressant drug.     

Efficacy of extended-release venlafaxine in nondepressed outpatients with generalized anxiety disorder

OBJECTIVE: This study evaluated the efficacy and safety of fixed doses of once-daily extended-release (XR) venlafaxine in outpatients with generalized anxiety disorder without concomitant major depressive disorder. METHOD: Adult outpatients with generalized anxiety disorder but not major depressive disorder with total scores of 18 or higher on the Hamilton Rating Scale for Anxiety and scores of 2 or higher on its anxious mood and tension factors were eligible. Patients were randomly assigned to receive placebo or venlafaxine XR (75, 150, or 225 mg/day) for 8 weeks. Primary efficacy variables were final total and psychic anxiety factor scores on the Hamilton anxiety scale and final severity and global improvement item scores on the Clinical Global Impression (CGI) scale. RESULTS: Of the 377 patients entering the study, 370 were included in a safety analysis and 349 in an efficacy analysis. Adjusted mean scores at 8 weeks (last-observation-carried-forward analysis) were significantly lower for one or more of the venlafaxine XR groups in four of four primary and three of four secondary outcome measures than for the placebo group. These included a change of 1.7 (versus 1.3) from baseline on CGI severity item scores and a final score of 2.2 (versus 2.6) on the CGI global improvement item. All doses of venlafaxine XR were well tolerated. CONCLUSIONS: Venlafaxine XR is an effective and well-tolerated option for the short-term treatment of generalized anxiety disorder in outpatients without major depressive disorder.     

文拉法辛缓释片治疗抑郁症伴躯体疼痛障碍的效果和安全性

目的探讨文拉法辛缓释片治疗抑郁症伴躯体疼痛障碍的效果及安全性,为临床合理用药提供参考。方法选取2016年2月-2017年3月江油市精神病医院收治的100例抑郁症伴躯体疼痛障碍患者,均符合《中国精神障碍分类与诊断标准(第3版)》(CCMD-3)抑郁症诊断标准,且慢性疼痛等级评价量表(GCP)评分在Ⅰ级以上并有3个月以上的持续性疼痛存在。采用随机数字表法分为观察组和对照组各50例。观察组给予文拉法辛缓释片治疗,对照组给予帕罗西汀治疗,两组均治疗8周。分别于治疗前和治疗第1、2、4、8周末采用汉密尔顿抑郁量表17项版(HAMD-17)、视觉模拟量表(VAS)进行评定,于治疗第1、2、4、8周末采用副反应量表(TESS)评价安全性。结果治疗后,观察组临床治疗总有效率高于对照组,差异有统计学意义(94.00%vs.78.00%,χ~2=5.316,P0.05);治疗第1、2、4、8周末,观察组HAMD-17和VAS评分均较治疗前低(P均0.05),治疗第2、4、8周末,对照组HAMD-17和VAS评分均较治疗前低(P均0.05),治疗后各时点,观察组HAMD-17和VAS评分均低于对照组,差异均有统计学意义(P均0.05),两组TESS评分比较差异均无统计学意义(P均0.05)。结论文拉法辛缓释片较帕罗西汀治疗抑郁症伴躯体疼痛障碍的相对效果更好,二者安全性可能相当。     

A double-blind comparison of escitalopram and venlafaxine extended release in the treatment of major depressive disorder

BACKGROUND: Escitalopram is the most selective serotonin reuptake inhibitor (SRI) antidepressant available. Venlafaxine is a non-selective SRI that also inhibits noradrenergic re-uptake. This study compared escitalopram and venlafaxine extended release (XR) in depressed outpatients at the highest doses recommended in the United States. METHOD: In this randomized trial, patients (diagnosis of DSM-IV-defined major depressive disorder; baseline Hamilton Rating Scale for Depression score of >/= 20) received 1 week of single-blind placebo treatment, followed by 8 weeks of double-blind, fixed-dose treatment with either escitalopram or venlafaxine XR (rapidly titrated to 20 mg/day and 225 mg/day, respectively, in accordance with prescribing information). The primary efficacy variable was change from baseline to week 8 in Montgomery-Asberg Depression Rating Scale (MADRS) total score. Data were collected from May to December 2002. RESULTS: Mean baseline MADRS scores for the escitalopram (N = 97) and venlafaxine XR (N = 98) groups were 30.7 and 30.0, respectively. There were no significant differences in measures of efficacy between the 2 antidepressants. Mean changes from baseline to endpoint in MADRS total score for escitalopram and venlafaxine XR were -15.9 and -13.6, respectively. Remission (MADRS score of /= 50% reduction from baseline MADRS score) rates for the escitalopram and venlafaxine XR groups were 58.8% and 48.0%, respectively. Tolerability measures favored escitalopram over venlafaxine XR treatment. The venlafaxine XR group had a higher incidence than the escitalopram group of treatment-emergent adverse events (85.0% vs. 68.4%) and discontinuation due to adverse events (16.0% vs. 4.1%; p <.01). CONCLUSION: Results of this study indicate that, when titrated rapidly to their maximum recommended doses, escitalopram is at least as effective as venlafaxine XR and significantly better tolerated. These results do not support the hypothesis that nonselective SRIs have greater efficacy than selective SRIs.     

Open-label evaluation of venlafaxine sustained release in outpatients with generalized anxiety disorder with comorbid major depression or dysthymia: effectiveness,tolerability and predictors of response

In a setting of routine clinical practice, 32 outpatients with generalized anxiety disorder (GAD) and major depression (MD) (n = 21) or dysthymia (n = 11), according to DSM-IV criteria, were consecutively treated with flexible dosages of sustained-release venlafaxine (SR-VF) for at least 8 weeks. In a 16-week follow-up, SR-VF daily dose could be modified on the basis of the therapeutic response and of the side effect profile. Symptomatological modifications were explored by means of the Clinical Global Impression (CGI) scale, Hamilton Rating Scale for Depression (HAM-D), and Hamilton Anxiety Scale (HAM-A). SR-VF was well tolerated and only 2 patients interrupted the treatment before 24 weeks; the mean final dose +/- SD was 135.5 +/- 71.8 mg (range 75-225); in 26 (81.2%) patients, a statistically significant response was observed in depressive symptomatology within the first 8 weeks. The mean total score of HAM-D showed a significant reduction during the first 8 weeks of treatment, while the mean total score of HAM-A did not present a significant reduction until week 24. In patients with MD, a statistically significant response was observed after the first 8 weeks, while the reduction of the anxiety scores required more time and, in some cases, did not appear at all. Conversely, in patients with GAD and dysthymia, anxious and depressive symptomatology improved simultaneously. Stepwise multiple regression indicated that the improvement of depression is negatively related to a high score of CGI anxiety severity, and the improvement of anxiety is related to the presence of dysthymia and, to a lesser extent, to a short duration of the illness. Our data confirm the effectiveness and tolerability of SR-VF in mixed anxiety-depressive states. The differential response suggests a pathophysiologic and clinical distinction between GAD with comorbid MD or dysthymia.     

Relationships between major depressive disorder and comorbid anxiety and personality disorders

OBJECTIVE: The aim of the study was to examine whether comorbid anxiety disorders influence depressed patients' likelihood of meeting criteria for a personality disorder (PD) and whether comorbid anxiety disorders influence the stability of the PDs in patients with remitted depression. METHODS: The initial sample consisted of 373 outpatients who met criteria for major depressive disorder (MDD) (by Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition-Patient Edition) and who were enrolled in the 8-week acute treatment phase of a study of fluoxetine for MDD. Sixty-four subjects who responded to fluoxetine treatment in the acute phase met criteria for remission throughout a 26-week continuation phase during which they remained on fluoxetine with or without cognitive behavioral therapy. Stability of PDs was defined as meeting criteria for a PD at both beginning and end point of the continuation treatment phase. RESULTS: Before fluoxetine treatment, anxious depressed patients (defined as meeting criteria for MDD as well as at least one comorbid anxiety disorder) were significantly more likely to meet criteria for any comorbid PD diagnosis compared with depressed patients without comorbid anxiety disorders. In particular, there was a significant relationship between the presence of Cluster A and C PDs and the presence of anxious depression at baseline before antidepressant treatment. After successful treatment of MDD, we found a significant relationship between anxious depression diagnosed at baseline and the stability of a Cluster C PD diagnosis. CONCLUSION: Anxious depression may place patients at greater risk of having a PD diagnosis, especially one from Cluster A or C. Once the depression remits, patients who initially met criteria for anxious depression may be more likely to maintain a Cluster C PD diagnosis compared with patients initially diagnosed with MDD alone.     

Efficacy of cognitive-behavioral therapy for comorbid panic disorder with agoraphobia and generalized anxiety disorder

The goal of this study was to evaluate the efficacy of cognitive-behavioral therapy for comorbid panic disorder with agoraphobia (PDA) and generalized anxiety disorder (GAD) by combining treatment strategies for both disorders. A single-case, multiple-baseline design across participants was used. Three participants with primary PDA and secondary GAD took part in the study. The efficacy of the treatment was assessed by means of a structured interview, self-administered questionnaires, and daily self-monitoring measures. After treatment, 2 of the 3 participants achieved high end-state functioning and maintained this level of functioning at 3-, 6-, and 12-month follow-ups. The third participant also improved but only reached high end-state functioning at 6-month follow-up. It therefore appears that the combined treatment is relatively effective for PDA-GAD comorbidity. Possible avenues for improving the treatment are suggested.     

Extended-release venlafaxine in relapse prevention for patients with major depressive disorder

Many studies have demonstrated that venlafaxine is an efficacious and safe treatment for major depressive disorder (MDD). This double-blind, placebo-controlled study was performed to evaluate the efficacy of venlafaxine extended-release (XR) (75-225 mg/day) in the prevention of relapse of depression. Patients with MDD who responded to an 8-week course of venlafaxine XR treatment, i.e., had a score < or = 3 on the Clinical Global Impressions scale-Severity of Illness item (CGI-S) and a 21-item Hamilton Rating Scale for Depression (HAM-D(21)) score < or = 10, were randomly assigned to receive continuation treatment (up to 6 months) with venlafaxine XR (n=161) or placebo (n=157). The main efficacy outcome measure was the number of patients who experienced a relapse of depression. Relapse was defined by either a combination of a patient meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for MDD and a CGI-S score > or = 4, two consecutive CGI-S scores > or = 4, or a final CGI-S score > or = 4 for a patient who withdrew from the study. The cumulative probability of relapse was calculated using the Kaplan-Meier method of survival analysis. During the 6-month evaluation period, significantly more patients in the placebo group had a relapse of MDD than did patients who continued treatment with venlafaxine XR. Cumulative relapse rates at 3 and 6 months were 19 and 28%, respectively, for venlafaxine XR, and 44 and 52%, respectively, for placebo. This study demonstrates that venlafaxine XR is an effective and safe continuation therapy.     

Impact of comorbid anxiety disorders on health-related quality of life among patients with major depressive disorder

OBJECTIVE: This study examined the impact of comorbid anxiety disorders-posttraumatic stress disorder (PTSD), generalized anxiety disorder, and panic disorder-on health-related quality of life among primary care patients enrolled in a collaborative care depression intervention study for the Department of Veterans Affairs (VA). METHODS: Baseline data were used from 324 participants in the Telemedicine Enhanced Antidepressant Management (TEAM) Study, a multisite randomized effectiveness trial targeting VA primary care patients with depression. Health-related quality of life was measured by using the Quality of Well-Being Scale, self-administered version (QWB-SA) and the mental component summary (MCS-12V) and physical component summary (PCS-12V) of the 12-item Short Form Health Survey for Veterans (SF-12V). RESULTS: A majority of participants (69 percent) had at least one anxiety disorder. Generalized anxiety disorder and PTSD predicted scores on the QWB-SA. PTSD predicted scores on the PCS-12V, but none of the comorbid anxiety disorders predicted scores on the MCS-12V. In addition, social support, depression severity, and the number of chronic medical conditions significantly predicted QWB-SA scores; the number of self-reported chronic physical health conditions and the number of depression episodes significantly predicted PCS-12V scores; and social support and depression severity significantly predicted MCS-12V scores. CONCLUSIONS: According to scores on the QWB-SA, generalized anxiety disorder and PTSD comorbid with major depressive disorder impair health-related quality of life above and beyond major depressive disorder alone.     

文拉法辛缓释剂与坦度螺酮治疗广泛性焦虑障碍的临床对照观察

目的 了解文拉法辛缓释剂与坦度螺酮治疗广泛性焦虑障碍的疗效和安全性.方法 将符合入组标准的70例患者随机分为研究组37例和对照组33例,研究组口服文拉法辛缓释剂,对照组口服坦度螺酮,疗程4周.临床疗效判定依据汉密尔顿焦虑量表(HAMA)减分率,不良反应采用不良反应量表(TESS)评定.结果 研究组有效率75.67%,对照组有效率为78.78%,两组有效率无统计学差异(χ2=0.10,P＞0.05).但在第2周时研究组抗焦虑效果研究组好于对照组(t=10.21,P＜0.01),不良反应两组之间无统计学差异.结论 文拉法辛缓释剂和坦度螺酮治疗广泛性焦虑症均有较好的疗效,不良反应少.在患者经济情况容许的情况下,可首先考虑选用文拉法辛缓释剂治疗.     

Efficacy, safety, and tolerability of venlafaxine XR in generalized anxiety disorder

Generalized anxiety disorder (GAD) is a common and chronic disorder with a low rate of spontaneous remission. A complication in treatment selection is the high rates of co-morbid major depressive disorder in this population. A number of treatments exist to treat GAD. The most recent medication to gain an indication for GAD is venlafaxine XR, a serotonin/norepinephrine reuptake inhibitor that is also approved for the treatment of major depressive disorder. More than 2,000 patients with GAD have been studied in outpatient trials of venlafaxine XR with demonstrated efficacy, tolerability and safety of this compound. This article reviews these studies, both short term and longer (6 month) continuation trials. The response to venlafaxine XR in this population, combined with good tolerability, makes this agent an appropriate first-line medication for GAD. In general, treatment with antidepressants, though associated with a longer onset of action than benzodiazepines, does not produce physiological dependency, and is useful in a patient population with a high prevalence of mood disorders.