Comparative efficacy of SSRIs and amisulpride in burning mouth syndrome: a single-blind study. Efficacy of venlafaxine extended-release capsules in nondepressed outpatients with generalized anxiety disorder: A 6-month randomized controlled trial. Quetiapine adjunct to selective serotonin reuptake inhibitors or venlafaxine in patients with major depression, comorbid anxiety, and residual depressive symptoms: a randomized, placebo-controlled pilot study. Clinical symptomatology and computer analyzed EEG before, during and after anxiolytic therapy of alcohol withdrawal patients. Can physiologic assessment and side effects tease out differences in PTSD trials? A double-blind comparison of citalopram, sertraline, and placebo. Fluvoxamine CR in the long-term treatment of social anxiety disorder: the 12- to 24-week extension phase of a multicentre, randomized, placebo-controlled trial. Efficacy and tolerability of long-acting injectable naltrexone for alcohol dependence: a randomized controlled trial. Moclobemide is effective and well tolerated in the long-term pharmacotherapy of social anxiety disorder with or without comorbid anxiety disorder. Abecarnil for the treatment of generalized anxiety disorder: a placebo-controlled comparison of two dosage ranges of abecarnil and buspirone. Double-blind placebo-controlled trial of fluoxetine in adolescents with comorbid major depression and an alcohol use disorder. Contingency management and levodopa-carbidopa for cocaine treatment: a comparison of three behavioral targets. A 14-month randomized clinical trial of treatment strategies for attention-deficit/hyperactivity disorder. The MTA Cooperative Group. Multimodal Treatment Study of Children with ADHD. A Randomized controlled trial of venlafaxine ER versus placebo in pediatric social anxiety disorder. Probing the safety of medications in the frail elderly: evidence from a randomized clinical trial of sertraline and venlafaxine in depressed nursing home residents. Pattern of symptom improvement following treatment with venlafaxine XR in patients with generalized anxiety disorder. L-type calcium channel blockers and Parkinson disease in Denmark. Efficacy and safety of extended-release venlafaxine in the treatment of generalized anxiety disorder in children and adolescents: two placebo-controlled trials. Kava-kava extract WS 1490 versus placebo in anxiety disorders--a randomized placebo-controlled 25-week outpatient trial. Efficacy, safety, and tolerability of venlafaxine extended release and buspirone in outpatients with generalized anxiety disorder. Efficacy and safety of crataegus extract WS 1442 in comparison with placebo in patients with chronic stable New York Heart Association class-III heart failure. A pooled, double-blind comparison of the effects of buspirone, diazepam and placebo in women with chronic anxiety. Escitalopram administered in the luteal phase exerts a marked and dose-dependent effect in premenstrual dysphoric disorder.
Although a significant amount of evidence indicates the efficacy of some antidepressants in treating psychogenic pain and somatoform disorder, very few studies have investigated their possible therapeutic action in burning mouth syndrome (BMS). The purpose of this 8-week, single-blind study was to provide preliminary data on the efficacy and tolerability of amisulpride and the selective serotonin reuptake inhibitors (SSRIs) paroxetine and sertraline for patients with BMS.
                Seventy-six patients with BMS (diagnosed according to the criteria in the literature and integrating the Diagnostic Interview Schedule-Revised for a complete psychiatric assessment), with no possible local or systemic causes and without concurrent major depression, were randomly assigned to receive amisulpride (50 mg/day), paroxetine (20 mg/day), or sertraline (50 mg/day). Efficacy assessments included a visual analogue scale (VAS) for pain intensity, the Hamilton Rating Scale for Depression (HAM-D), the Hamilton Rating Scale for Anxiety (HAM-A), and the Clinical Global Impressions scale (CGI).
                All 3 treatment regimens resulted in a significant improvement from baseline in burning mouth symptoms at week 8 as demonstrated by the quantitative (mean reduction in VAS, HAM-D, and HAM-A scores) and qualitative (percentage of responders) analyses. Amisulpride showed a shorter response latency than the SSRIs. No serious adverse events were reported, and the incidence of side effects did not differ among the 3 groups. None of the patients who received amisulpride withdrew from the trial, whereas withdrawal from the trial occurred within the first week of treatment in 11.5% of patients (N = 3) treated with paroxetine and in 21.7% of patients (N = 5) treated with sertraline.
                The data suggest that amisulpride and SSRIs may be effective treatments for BMS; they are equally effective and equally well tolerated in the short-term treatment of BMS. Amisulpride is associated with better compliance within the first week of treatment and with a shorter response latency in comparison with SSRIs. This finding may indicate that amisulpride is especially useful at the beginning of drug therapy of BMS. Double-blind, placebo-controlled trials are needed to further document the efficacy of amisulpride and SSRIs in the treatment of BMS. Generalized anxiety disorder (GAD) is a chronic disorder that is associated with debilitating psychic and somatic symptoms. Venlafaxine extended-release (XR) capsules have been shown to be effective in short-term treatment of patients with GAD without major depressive disorder (MDD), but long-term data are needed to establish whether this agent confers persistent benefits.
                To compare the 6-month efficacy and safety of a flexible dosage of venlafaxine XR in outpatients with GAD without associated MDD.
                Six-month, randomized, double-blind, placebo-controlled, parallel-group trial conducted May 1996 to October 1997.
                Fourteen outpatient clinics and private psychiatric practices in the United States.
                A total of 251 outpatients aged 18 years or older who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for GAD, had sufficient symptoms to require treatment, and did not have coexisting MDD.
                Participants were randomly assigned to receive either placebo (n=127) or venlafaxine XR (75, 150, or 225 mg/d, as required to control symptoms; n=124) for 28 weeks.
                Changes from baseline in the Hamilton Rating Scale for Anxiety (HAM-A) total score, the HAM-A psychic anxiety factor score, and the Clinical Global Impressions (CGI) scale Severity of Illness and Global Improvement scores, compared by intervention group.
                During weeks 6 through 28, response rates in the venlafaxine XR group were 69% or higher compared with rates of 42% to 46% in the placebo group (P<.001). By an evaluable-patient analysis, venlafaxine XR compared with placebo significantly improved anxiety scores from week 1 or 2 through week 28 on all primary efficacy measures, including the HAM-A total (P<.001), the HAM-A psychic anxiety factor (P<.001), and the CGI scale scores (P<.001). Adjusted mean changes from baseline to week 28 using last-observation-carried-forward methods were for HAM-A, venlafaxine XR -13.4, placebo -8.7 (P<.001); for HAM-A psychic anxiety score, venlafaxine XR -7.4, placebo -4.2 (P<.001); and for CGI-Improvement, venlafaxine XR 2.2, placebo 3.0 (P<.001). The most common treatment-emergent adverse event was nausea, followed by somnolence and dry mouth.
                This study is the first placebo-controlled demonstration of the long-term efficacy of any drug class in treating outpatients with DSM-IV-diagnosed GAD. Venlafaxine XR is an effective, rapidly acting, safe, once-daily agent for both the short- and long-term treatment of anxiety and may provide an important alternative to currently available anxiolytics. JAMA. 2000. This double-blind, placebo-controlled study examined the efficacy and tolerability of quetiapine in combination with selective serotonin reuptake inhibitors (SSRIs)/venlafaxine in 58 patients with major depressive disorder, comorbid anxiety symptoms (HAM-A-14 score > or =14), and residual depressive symptoms (HAM-D-17 score > or =18, CGI-S score > or =4). Patients had received an SSRI/venlafaxine (at a predefined therapeutic dose) for > or =6 weeks. Overall, 62% (18/29) of quetiapine- and 55% (16/29) of placebo-treated patients completed the study. The mean change in HAM-D and HAM-A total scores from baseline to Week 8 (primary endpoint) was significantly greater with quetiapine (mean dose 182 mg/day) than placebo: -11.2 vs. -5.5 (P=.008) and -12.5 vs. -5.9 (P=.002), respectively. The onset of quetiapine efficacy (HAM-D/HAM-A/CGI-I) was rapid (by Week 1) and continued through to Week 8. Significant differences (P<.05) from baseline to Week 8 were observed between groups in 7/17 HAM-D (including feelings of guilt, suicide) and 6/14 HAM-A items (including tension, cardiovascular symptoms). Response (> or =50% decrease in total score) was higher for quetiapine than placebo: HAM-D, 48% vs. 28% (not significant, NS); HAM-A, 62% vs. 28% (P=.02). Remission (total score < or =7) was higher for quetiapine than placebo: HAM-D, 31% vs. 17% (NS); HAM-A, 41% vs. 17% (NS). CGI-S, CGI-I, and the Global Assessment Scale showed that quetiapine was significantly more effective than placebo. For quetiapine, adverse events (AEs) were similar to those previously observed; sedation/somnolence/lethargy was the most commonly reported. Here quetiapine was shown to be effective as augmentation of SSRI/venlafaxine therapy in patients with major depression, comorbid anxiety, and residual depressive symptoms, with no unexpected tolerability issues. Further studies are warranted.
                2006 Wiley-Liss, Inc In a double-blind study the clinical symptomatology and quantitatively analyzed EEG of 42 hospitalized chronic alcoholics (ICD 303) undergoing alcohol withdrawal were investigated before, during and after 3 weeks' treatment with 2 pharmacokinetically different benzodiazepines: the short-acting lopirazepam (a new pyridodiazepine) and the long-acting prazepam. At the end of weeks 1 and 3 the titrated optimal daily doses were 24 and 23 mg lopirazepam and 35 and 32 prazepam, respectively, thus confirming our earlier pharmaco-EEG predictions that on a mg to mg basis the former drug is slightly more CNS potent than the latter. Thereafter, the patient population was divided into 6 subgroups: 2 groups continuing on active medication, 2 groups receiving placebo, and 2 groups with no pharmacotherapy for 1 week. Clinical assessments included the CGI, the Hamilton Anxiety Score, the Zung Self-Rating Scale for Anxiety and Depression, the Zerssen Befindlichkeitsskala and the questionnaire for somatic findings and side effect and were carried out on days 0, 7, 21 and 28 as was a radioreceptor assay for benzodiazepines in plasma. Quantitative EEG investigations were carried out on days 0, 21 and 28 and included recordings before and 2 h after one single dose of 10 mg. Statistical analysis demonstrated a marked and highly significant decrease in psychopathology as well as good drug tolerance at the end of the first week of therapy and thereafter a slight continuation in improvement until the end of the 3rd week. There were, however, no statistically significant differences between the 2 active compounds, nor were there any statistically significant differences between the 6 subgroups in the 4th week. On the other hand, blood level investigations demonstrated that even after a 3-week treatment period, blood levels dropped down to a morning minimum 12 h after the last evening medication of the short-acting lopirazepam, while plasma levels of the long-acting prazepam remained high. This was also reflected in the spectral analyzed EEG, which showed, after one single dosage of both drugs, a typical anxiolytic profile which was more pronounced after lopirazepam than prazepam, while after the chronic administration (12 h after the evening medication) only prazepam showed an anxiolytic profile. The lopirazepam-treated patients exhibited on the one hand a lack of benzodiazepine-specific alterations, but showed on the other hand EEG changes possibly reflecting clinical improvement. The relevance of the findings will be discussed. Effects of double-blind treatment of chronic posttraumatic stress disorder (PTSD) with 2 SSRIs and placebo on emotional symptoms and autonomic reactivity were assessed prospectively. PTSD subjects received citalopram (n=25), sertraline (n=23), or placebo (n=10) for 10 weeks, with psychophysiologic assessments performed before and after treatment. Intent-to-treat analysis showed that all treatment groups improved significantly in total symptoms of PTSD (as measured by the Clinician Administered PTSD Scale), all 3 PTSD symptom clusters, and sleep time. However, subtle differences in improvements in PTSD symptom clusters, physiologic reactivity, and reported adverse events were identified. Citalopram treated subjects significantly lowered systolic and diastolic blood pressures, while sertraline and placebo treated patients significantly lowered only systolic blood pressure reactivity to individualized trauma scripts. The sertraline group showed significantly more improvement in avoidance/numbing symptoms than both other groups. Considering side effects, subjects on sertraline reported more gastrointestinal problems, with early terminators having more insomnia. Early terminators on citalopram reported more fatigue and appetite changes than other treatment groups, with completers reporting more sexual dysfunction. Results support a class effect of SSRIs in treating PTSD symptoms, but suggest a possible differential effect of drugs on symptom clusters, physiologic parameters, and side effects that may have clinical relevance. Implications of symptom reduction noted in the smaller placebo group are discussed relative to recent concerns about increasing placebo response in clinical trials. Fluvoxamine CR has been reported effective in the short-term (12-wk) treatment of generalized social anxiety disorder (social phobia). Social anxiety disorder (SAD) is, however, a chronic disorder thought to require maintenance treatment. We report on data from the extension phase of a short-term study, in order to explore the efficacy and safety profile of fluvoxamine CR (100-300 mg/d) in the longer-term treatment of this disorder. Adult outpatients with generalized social anxiety disorder (GSAD) at 35 centres in Europe, South Africa, and USA were included in an acute phase study (12 wk). Subjects who demonstrated at least minimal improvement by endpoint (n=112), were offered participation in an extension phase, in which medication was continued for a further 12 wk under double-blind conditions. Efficacy was assessed using the Liebowitz Social Anxiety Disorder Scale (LSAS), the Clinical Global Impression Global Improvement score (CGI-I), the Clinical Global Impressions Severity of Illness score (CGI-S), and the Sheehan Disability Scale (SDS). Safety and tolerability assessments were also performed at regular intervals. Subjects treated with fluvoxamine CR had a numerically greater decrease in LSAS total scores than subjects treated with placebo at endpoint. Analysis of data from baseline (day 1) to endpoint (last observation carried forward) demonstrated that this difference tended towards significance, while severity of illness on the CGI-S and disability on the SDS were significantly lower in the fluvoxamine CR group than in the placebo group. The same trends were observed when only data from weeks 12-24 were included in the analysis; although the magnitude of changes was smaller in the extension phase than in the acute phase, fluvoxamine CR-treated subjects continued to show improvement compared to placebo-treated subjects. Most treatment-emergent signs and symptoms (TESS) were mild to moderate in severity. No unexpected abnormalities were reported on vital signs, electrocardiagrams, or laboratory investigations. These data support the long-term efficacy, safety, and tolerability of fluvoxamine CR in the treatment of GSAD. Given the prevalence, persistence, and disability associated with GSAD, and the relative paucity of long-term treatment studies of SAD, the current dataset provides empirical support for the current clinical consensus that pharmacotherapy of this disorder should be continued beyond the acute phase. Alcohol dependence is a common disorder associated with significant morbidity and mortality. Naltrexone, an opioid antagonist, has been shown to be effective for treatment of alcohol dependence. However, adherence to daily oral pharmacotherapy can be problematic, and clinical acceptance and utility of oral naltrexone have been limited.
                To determine efficacy and tolerability of a long-acting intramuscular formulation of naltrexone for treatment of alcohol-dependent patients.
                A 6-month, randomized, double-blind, placebo-controlled trial conducted between February 2002 and September 2003 at 24 US public hospitals, private and Veterans Administration clinics, and tertiary care medical centers. Of the 899 individuals screened, 627 who were diagnosed as being actively drinking alcohol-dependent adults were randomized to receive treatment and 624 received at least 1 injection.
                An intramuscular injection of 380 mg of long-acting naltrexone (n = 205) or 190 mg of long-acting naltrexone (n = 210) or a matching volume of placebo (n = 209) each administered monthly and combined with 12 sessions of low-intensity psychosocial intervention.
                The event rate of heavy drinking days in the intent-to-treat population.
                Compared with placebo, 380 mg of long-acting naltrexone resulted in a 25% decrease in the event rate of heavy drinking days (P = .02) [corrected] and 190 mg of naltrexone resulted in a 17% decrease (P = .07). Sex and pretreatment abstinence each showed significant interaction with the medication group on treatment outcome, with men and those with lead-in abstinence both exhibiting greater treatment effects. Discontinuation due to adverse events occurred in 14.1% in the 380-mg and 6.7% in the 190-mg group and 6.7% in the placebo group. Overall, rate and time to treatment discontinuation were similar among treatment groups.
                Long-acting naltrexone was well tolerated and resulted in reductions in heavy drinking among treatment-seeking alcohol-dependent patients during 6 months of therapy. These data indicate that long-acting naltrexone can be of benefit in the treatment of alcohol dependence. Social phobia (social anxiety disorder) is a highly prevalent and chronic disorder that is associated with significant comorbidity and disability. Despite recent advances in the pharmacotherapy of the disorder, there is a paucity of randomized controlled trials on patients with comorbid disorders and on maintenance treatment. A randomized placebo-controlled, double-blind multi-site trial of moclobemide, a reversible inhibitor of monoamine oxidase A, was undertaken with 390 subjects. After an initial 12 weeks, there was the option of continuing for an additional 6 months of treatment. The primary efficacy parameter chosen was responder status as defined by the Clinical Global Impression scale change item. From week 4 onwards, there was a significantly higher response rate on moclobemide than on placebo. Superiority of medication over placebo was similar in patients with comorbid anxiety disorders (33% of subjects) and without, as well as in patients with different subtypes of social anxiety disorder; indeed, treatment with moclobemide rather than placebo was the strongest predictor of response. Adverse events were similar across treatment groups, and were typically mild and transient. In the extension phase, response rates remained higher in the moclobemide group, and ratings of tolerability were equally high in both groups. Thus, in a large sample of social anxiety disorder patients with and without comorbid anxiety disorders, moclobemide was both effective and well-tolerated in the short as well as long-term. These data confirm and extend previous findings on the value of moclobemide in the treatment of social anxiety disorder, and strengthen the range of therapeutic options for managing this important disorder. The development of effective and well-tolerated anxiolytic agents is an area of critical clinical importance. Abecarnil, a beta carboline, is a partial benzodiazepine-receptor agonist that has demonstrated promise as an anxiolytic agent. In this study, we examine the efficacy, safety, and discontinuation-related effects of abecarnil, buspirone, and placebo in the acute and long-term treatment of patients who have generalized anxiety disorder.
                This is a double-blind, placebo-controlled study of two dosages of abecarnil and buspirone. In total, 464 patients were randomized. After a placebo run-in week, patients entered a 6-week double-blind treatment period, followed by an optional 18-week maintenance period for treatment responders. After abrupt discontinuation of the acute or maintenance treatment, patients entered a 3-week placebo-substitution follow-up period. Treatment response was assessed with the Hamilton Rating Scale for Anxiety and the Clinical Global Impressions (CGI) Scale.
                Compared with placebo, abecarnil showed significant anxiolytic activity early in the treatment period, particularly in the high-dosage group, though these differences did not maintain statistical significance at the end of the trial. Buspirone was associated with a slower onset of action and better symptom relief than placebo after 6 weeks of therapy. Withdrawal symptoms emerged in patients who abruptly discontinued abecarnil (particularly at the higher dosage) only in those receiving a longer duration of treatment.
                The results of this study need to be understood in the context of a high placebo-response rate, which hampers the ability to demonstrate significant drug-placebo differences. This study suggests that abecarnil may be an effective anxiolytic agent; further attention is warranted to assess its spectrum of clinical effectiveness. This study compared the acute phase (12-week) efficacy of fluoxetine versus placebo for the treatment of the depressive symptoms and the drinking of adolescents with comorbid major depression (MDD) and an alcohol use disorder (AUD). We hypothesized that fluoxetine would demonstrate efficacy versus placebo for the treatment of both the depressive symptoms and the drinking of comorbid MDD/AUD adolescents.
                We conducted the first double-blind placebo-controlled study of fluoxetine in adolescents with comorbid MDD/AUD. All participants in both treatment groups also received intensive manual-based Cognitive Behavioral Therapy (CBT) and Motivation Enhancement Therapy (MET).
                Fluoxetine was well tolerated in this treatment population. No significant group-by-time interactions were noted for any depression-related or drinking-related outcome variable. Subjects in both the fluoxetine group and the placebo group showed significant within-group improvement in both depressive symptoms and level of alcohol consumption. End-of-study levels of depression and drinking were low in both treatment groups.
                The lack of a significant between-group difference in depressive symptoms and in drinking may reflect limited medication efficacy, or may result from limited sample size or from efficacy of the CBT/MET psychotherapy. Large multi-site studies are warranted to further clarify the efficacy of SSRI medications in this adolescent MDD/AUD population. New data support use of levodopa pharmacotherapy with behavioral contingency management (CM) as one efficacious combination in cocaine dependence disorder treatment. A potential mechanism of the combined treatment effects may be related to dopamine-induced enhancement of the saliency of contingently delivered reinforcers. Evidence to support this mechanism was sought by evaluating levodopa-enhancing effects across distinct CM conditions that varied in behavioral targets. A total of 136 treatment-seeking, cocaine dependent subjects participated in this 12-week, randomized, placebo-controlled trial of levodopa (vs. placebo) administered in combination with one of three behavioral CM conditions. In the CM-URINE condition, subjects received cash-valued vouchers contingent on cocaine-negative urine toxicology results. In the CM-ATTEND condition, the same voucher schedule was contingent on attending thrice weekly clinic visits. In the CM-MEDICATION condition, the same voucher schedule was contingent on Medication Event Monitoring Systems- and riboflavin-based evidence of pill-taking behavior. Primary outcomes associated with each CM target behavior were analyzed using generalized linear mixed models for repeated outcomes. CM responding in the CM-ATTEND and CM-MEDICATION conditions showed orderly effects, with each condition producing corresponding changes in targeted behaviors, regardless of medication condition. In contrast, CM responding in the CM-URINE condition was moderated by medication, with levodopa-treated subjects more likely to submit cocaine-negative urines. These findings specify the optimal target behavior for CM when used in combination with levodopa pharmacotherapy. Previous studies have demonstrated the short-term efficacy of pharmacotherapy and behavior therapy for attention-deficit/hyperactivity disorder (ADHD), but no longer-term (i.e., >4 months) investigations have compared these 2 treatments or their combination.
                A group of 579 children with ADHD Combined Type, aged 7 to 9.9 years, were assigned to 14 months of medication management (titration followed by monthly visits); intensive behavioral treatment (parent, school, and child components, with therapist involvement gradually reduced over time); the two combined; or standard community care (treatments by community providers). Outcomes were assessed in multiple domains before and during treatment and at treatment end point (with the combined treatment and medication management groups continuing medication at all assessment points). Data were analyzed through intent-to-treat random-effects regression procedures.
                All 4 groups showed sizable reductions in symptoms over time, with significant differences among them in degrees of change. For most ADHD symptoms, children in the combined treatment and medication management groups showed significantly greater improvement than those given intensive behavioral treatment and community care. Combined and medication management treatments did not differ significantly on any direct comparisons, but in several instances (oppositional/aggressive symptoms, internalizing symptoms, teacher-rated social skills, parent-child relations, and reading achievement) combined treatment proved superior to intensive behavioral treatment and/or community care while medication management did not. Study medication strategies were superior to community care treatments, despite the fact that two thirds of community-treated subjects received medication during the study period.
                For ADHD symptoms, our carefully crafted medication management was superior to behavioral treatment and to routine community care that included medication. Our combined treatment did not yield significantly greater benefits than medication management for core ADHD symptoms, but may have provided modest advantages for non-ADHD symptom and positive functioning outcomes. Social anxiety disorder, which occurs in 2% to 5% of children and adolescents, is associated with significant distress and functional impairment.
                The objective of the randomized, masked controlled trial conducted in 48 academic and community centers in the United States was to evaluate the efficacy of venlafaxine ER in children and adolescents with generalized social anxiety disorder. A volunteer sample of 293 outpatients, age 8 to 17, who met diagnostic criteria for social anxiety disorder and were enrolled between February 2000 and March 2003 participated. Venlafaxine ER or placebo was titrated from a starting dose of 37.5 mg to a maximum dose of 225 mg over 16 weeks. The primary dependent measures were the Social Anxiety Scale, child or adolescent version (SAS-CA) and for responder analysis, a (dichotomized) Clinical Global Impressions-Improvement (CGI-I) score.
                Compared with placebo, intent-to-treat random regression analyses indicated a statistically significant advantage for venlafaxine ER (p = .001) on the SAS-CA. On the CGI-I responder analysis, 56% (95% confidence interval [CI], 47%-64%) of venlafaxine ER treated subjects responded, which was statistically superior to placebo (37% [95% CI, 29%-45%]). Three venlafaxine ER and no placebo patients developed treatment-emergent suicidality; there were no completed suicides.
                Venlafaxine ER is an effective and reasonably well-tolerated treatment for generalized social anxiety disorder in children and adolescents. As with other antidepressants, careful clinical monitoring for adverse events, including treatment-emergent suicidality, is essential. In nursing home residents and other frail elderly patients, old age and potential drug-drug and drug-disease interactions may affect the relative safety and efficacy of medications. The purpose of this study was to examine the efficacy and tolerability of venlafaxine and sertraline for the treatment of depression among nursing home residents.
                The study was a 10-week randomized, double-blind, controlled trial of venlafaxine (doses up to 150 mg/day) versus sertraline (doses up to 100 mg/day) among 52 elderly nursing home residents with a DSM-IV depressive disorder and, at most, moderate dementia. The primary measure of outcome was the Hamilton Rating Scale for Depression (HAM-D). Adverse events were monitored and recorded systematically during the trial.
                Twelve subjects were discontinued due to serious adverse events (SAE), 5 were discontinued due to other significant side effects, and 2 withdrew consent. Tolerability estimated by the time to termination was lower for venlafaxine than sertraline for serious adverse events (log rank statistic = 5.28, p =.022), for serious adverse events or side effects (log rank statistic = 8.08, p =.005), or for serious adverse events, side effects, or withdrawal of consent (log rank statistic = 10.04, p =.002). Mean (SD) HAM-D scores at baseline were 20.2 (3.4) for sertraline and 20.3 (3.7) for venlafaxine; intent-to-treat endpoint HAM-D scores were 12.2 (5.1) and 15.7 (6.2) (F = 3.45; p =.069). There were no differences in categorical responses for the intent-to-treat sample or completers.
                In this frail elderly population, venlafaxine was less well tolerated and, possibly, less safe than sertraline without evidence for an increase in efficacy. This unexpected finding demonstrates the need for systematic research on the safety of drugs in the frail elderly. The efficacy of anxiolytic drugs in generalized anxiety disorder (GAD) is conventionally assessed by evaluating changes in the total score of psychometric scales such as the Hamilton Rating Scale for Anxiety (HAM-A). The purpose of this pooled analysis of data was to evaluate the efficacy of venlafaxine extended release (XR) on individual items of the HAM-A and the Brief Scale for Anxiety (BSA).
                Data were pooled from 5 studies of patients with GAD who were treated with either venlafaxine XR or placebo for 8 weeks (N = 2,021) and up to 6 months (N = 767). Individual items of the HAM-A and the BSA were examined. and, using the mean changes from baseline to endpoint, an effect size for each item was calculated by dividing the difference between baseline and endpoint values for each item by the standard deviation of this difference. The effect sizes determined for the venlafaxine group were compared with those for the placebo group. Items from each scale that are concordant with the DSM-IV diagnostic criteria for GAD were selected for further examination, and the specific effect sizes of each item were expressed after controlling for placebo effects.
                The effect size of the majority of the 14 items of the HAM-A scale and the 10 items of the BSA scale associated with treatment with venlafaxine XR was greater than with placebo at both 8 weeks and 6 months. Furthermore, the effect sizes at 6 months were generally greater than at 8 weeks in venlafaxine XR-treated patients. Effect sizes associated with venlafaxine XR were greatest for the HAM-A items that were most closely related to diagnostic symptoms of GAD, namely anxious mood, tension, intellectual functioning, and behavior at interview at both 8 weeks and 6 months. Similarly, GAD-related BSA items of inner tension, worrying over trifles, hostile feelings, and muscular tension were associated with the greatest improvements with venlafaxine XR at both time-points.
                The HAM-A and BSA items that most closely corresponded to DSM-IV diagnostic criteria for GAD showed the largest improvement during treatment with venlafaxine XR. This indicates that the specific symptoms of GAD can be treated effectively with venlafaxine XR, both in the short and longer term. This study was undertaken to investigate L-type calcium channel blockers of the dihydropyridine class for association with Parkinson disease (PD), because some of these drugs traverse the blood-brain barrier, are potentially neuroprotective, and have previously been evaluated for impact on PD risk.
                We identified 1,931 patients with a first-time diagnosis for PD between 2001 and 2006 as reported in the Danish national hospital/outpatient database and density matched them by birth year and sex to 9,651 controls from the population register. The index date for cases and their corresponding controls was advanced to the date of first recorded prescription for anti-Parkinson drugs, if prior to first PD diagnosis in the hospital records. Prescriptions were determined from the national pharmacy database. In our primary analyses, we excluded all calcium channel blocker prescriptions 2 years before index date/PD diagnosis.
                Employing logistic regression analysis adjusting for age, sex, diagnosis of chronic pulmonary obstructive disorder, and Charlson comorbidity score, we found that subjects prescribed dihydropyridines (excludes amlodipine) between 1995 and 2 years prior to the index date were less likely to develop PD (odds ratio, 0.73; 95% confidence interval, 0.54-0.97); this 27% risk reduction did not differ with length or intensity of use. Risk estimates were close to null for the peripherally acting drug amlodipine and for other antihypertensive medications.
                Our data suggest a potential neuroprotective role for centrally acting L-type calcium channel blockers of the dihydropyridine class in PD that should be further investigated in studies that can distinguish between types of L-type channel blockers. The authors evaluated the efficacy, safety, and tolerability of extended-release venlafaxine in the treatment of pediatric generalized anxiety disorder.
                Two randomized, double-blind, placebo-controlled trials were conducted at 59 sites in 2000 and 2001. Participants 6 to 17 years of age who met DSM-IV criteria for generalized anxiety disorder received a flexible dosage of extended-release venlafaxine (N=157) or placebo (N=163) for 8 weeks. The primary outcome measure was the composite score for nine delineated items from the generalized anxiety disorder section of a modified version of the Schedule for Affective Disorders and Schizophrenia for School-Age Children, and the primary efficacy variable was the baseline-to-endpoint change in this composite score. Secondary outcome measures were overall score on the nine delineated items, Pediatric Anxiety Rating Scale, Hamilton Anxiety Rating Scale, Screen for Child Anxiety Related Emotional Disorders, and the severity of illness and improvement scores from the Clinical Global Impression scale (CGI).
                The extended-release venlafaxine group showed statistically significant improvements in the primary and secondary outcome measures in study 1 and significant improvements in some secondary outcome measures but not the primary outcome measure in study 2. In a pooled analysis, the extended-release venlafaxine group showed a significantly greater mean decrease in the primary outcome measure compared with the placebo group (-17.4 versus -12.7). The response rate as indicated by a CGI improvement score <3 was significantly greater with extended-release venlafaxine than placebo (69% versus 48%). Common adverse events were asthenia, anorexia, pain, and somnolence. Statistically significant changes in height, weight, blood pressure, pulse, and cholesterol levels were observed in the extended-release venlafaxine group.
                Extended-release venlafaxine may be an effective, well-tolerated short-term treatment for pediatric generalized anxiety disorder. 101 outpatients suffering from anxiety of non-psychotic origin (DSM-III-R criteria: agoraphobia, specific phobia, generalized anxiety disorder, and adjustment disorder with anxiety) were included in a 25-week multicenter randomized placebo-controlled double-blind trial with WS 1490, a special extract of kava-kava. In the main outcome criterion, the Hamilton Anxiety Scale (HAMA), there was a significant superiority of the test drug starting from week 8 on. WS 1490 was also found to be superior with respect to the secondary outcome variables. HAMA subscores somatic and psychic anxiety, Clinical Global Impression, Self-Report Symptom Inventory-90 Items revised, and Adjective Mood Scale. Adverse events were rare and distributed evenly in both groups. These results support WS 1490 as a treatment alternative to tricyclic antidepressants and benzodiazepines in anxiety disorders, with proven long-term efficacy and none of the tolerance problems associated with tricyclics and benzodiazepines. 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.
                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).
                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.
                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. The purpose of this study was to investigate whether long-term therapy with crataegus extract WS 1442 is efficacious as add-on therapy to preexisting diuretic treatment in patients with heart failure with a more advanced stage of the disease (New York Heart Association [NYHA] class III), whether effects are dose dependent, and whether the treatment is safe and well tolerated.
                Exercise capacity was assessed by use of seated bicycle ergometry with incremental workloads. Scores for subjective symptoms and complaints made by the patients were analyzed. Efficacy and tolerability of the treatments were judged by both the patients and investigators. Safety was assessed by the documentation of adverse events and the safety laboratory.
                A total of 209 patients were randomized to treatment with 1800 mg of WS 1442, 900 mg of WS 1442, or with placebo. After 16 weeks of therapy with 1800 mg of WS 1442 per day, maximal tolerated workload during bicycle exercise showed a statistically significant increase in comparison with both placebo and 900 mg of WS 1442. Typical heart failure symptoms as rated by the patients were reduced to a greater extent by WS 1442 than by placebo. This difference was significant for both doses of WS 1442. Both efficacy and tolerability were rated best for the 1800 mg of WS 1442 group by patients and investigators alike. The incidence of adverse events was lowest in the 1800 mg of WS 1442 group, particularly with respect to dizziness and vertigo.
                The data from this study confirm that there is a dose-dependent effect of WS 1442 on the exercise capacity of patients with heart failure and on typical heart failure-related clinical signs and symptoms. The drug was shown to be well tolerated and safe. Pooled data were analyzed for 367 female patients enrolled in a double-blind, placebo-controlled, multi-centre trial comparing buspirone, a non-benzodiazepine anxiolytic, and diazepam in the treatment of generalized anxiety disorder. After a 4 to 7-day wash-out period, patients were allocated at random to receive one or other of the trial medications or placebo over a 4-week period. Mean daily dosages were 24.5 mg for buspirone and 20.8 mg for diazepam (range 10 mg to 60 mg for both drugs). Patients were assessed on entry and at weekly intervals using the Hamilton Anxiety Rating Scale, and at the end of treatment both patients and physicians gave an overall opinion of response to treatment. Details of adverse events were also recorded. The results showed that both buspirone and diazepam were approximately equal in efficacy and superior to placebo. Menstruation and the occurrence of premenstrual tension did not alter the anxiolytic activity of either drug. Patients taking diazepam had significantly more adverse effects, i.e. drowsiness, weakness, fatigue, inco-ordination and depression, than did those in the buspirone group. In a separate commentary, the anxiety disorder and the data from the study are reviewed to place them in the overall perspective of gynaecological care. This is the first placebo-controlled trial evaluating the efficacy of the selective serotonin reuptake inhibitor (SSRI), escitalopram, in the treatment of premenstrual dysphoric disorder (PMDD). Women with PMDD (intention-to-treat population, n = 151) were treated intermittently for 3 months, during luteal phases only, with 10 mg/d escitalopram, 20 mg/d escitalopram, or placebo. Escitalopram was found to exert a marked and a dose-dependent symptom-reducing effect, 20 mg/d being clearly superior to 10 mg/d. Although the primary outcome parameter, that is, the sum of the symptoms irritability, depressed mood, tension, and affective lability, was decreased by 90% with 20 mg/d escitalopram, the effect of active treatment on breast tenderness, food craving, and lack of energy was more modest and not significantly different from that of placebo; this outcome supports our previous assumption that the former symptoms are more inclined to respond to intermittent administration of an SSRI than are the latter. Although the placebo response was high, the difference between the placebo group and the 20-mg/d escitalopram group with respect to the percentage of subjects displaying 80% or greater reduction in the rating of the cardinal symptom of PMDD, that is, irritability, was considerable: 30% versus 80%. Adverse events were those normally reported in SSRI trials, such as nausea and reduced libido, and were not more common in patients given 20 mg/d of escitalopram than in patients given the lower dose. This study supports the usefulness of escitalopram for the treatment of PMDD and sheds further light on how different components of this syndrome are differently influenced by intermittent administration of an SSRI.
Medication treatments can be effective in paediatric anxiety disorders, acting to reduce core symptoms, and should be considered as part of the treatment of these disorders. The greatest number of trials showing efficacy to date have assessed the SSRIs in treating paediatric OCD.
There is no clear evidence to show that any particular class of medication is more effective or better tolerated than any other. As quantitative data was only available for the SSRIs and venlafaxine the routine use of benzodiazepines cannot be recommended, especially given concerns of dependency and treatment -related emergent adverse events associated with this class of drugs. 

Future RCTs could help identify potential clinical moderators of treatment efficacy. Studies of the long-term efficacy of medication treatment, optimal dosage, as well as direct comparisons of pharmacotherapy and psychotherapy are also warranted.