A 1 year double-blind placebo-controlled fixed dose study of sertraline in the treatment of obsessive-compulsive disorder

The objective of this study was to evaluate the safety and efficacy, over a 1 year treatment period, of three dose levels of sertraline and placebo in the treatment of non-depressed adult out-patients with obsessive-compulsive disorder (OCD). Following 1 week of single-blind placebo washout, patients (n = 325) from 11 sites following identical protocols were randomly assigned to 12 weeks of double-blind treatment with one of three fixed doses of sertraline (50, 100 or 200 mg) or placebo. At the end of 12 weeks, treatment responders (including placebo patients) were offered an additional 40 weeks of double-blind treatment at their assigned doses. Efficacy measures were the Yale-Brown Obsessive Compulsive Scale, the NIMH Global Obsessive Compulsive Scale, Clinical Global Impressions of Severity of Illness and Global Improvement and the Maudsley Obsessive Compulsive Inventory. Patients in the pooled sertraline group showed greater improvement than placebo-treated patients on all efficacy measures, based on the endpoint analyses. Moreover, pairwise comparisons at endpoint revealed a significant effect on all three investigator-rated scales in patients receiving 50 or 200 mg of sertraline; in the 100 mg group, there was a significant effect on the NIMH Global Obsessive Compulsive Scale only. Patients completing 3 months of sertraline treatment exhibited excellent toleration and sustained improvement during an additional 40 weeks of therapy. Results support the safety, efficacy and tolerability of daily doses of 50-200 mg of sertraline in the long-term treatment of patients with OCD.     

Methodological controversies in the treatment of panic disorder.

Although the National Institutes of Health Consensus Development Conference on the Treatment of Panic Disorder endorsed the effectiveness of cognitive–behavior therapy (CBT), D. E. Klein (see record 1996-02770-008) argues that fatal flaws in all but one (negative) CBT study undermine claims about the effectiveness of CBT for panic disorder. He holds that methodologically sound CBT trials must include a drug condition and a pill placebo condition and must demonstrate the superiority of drug versus placebo; otherwise researchers are debarred from making comparative statements about the effectiveness of CBT versus drug (or placebo). The purpose of the present article is to provide a critique of Klein's arguments and to provide suggestions for resolving methodological disputes in the panic disorder field. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A comparison of alprazolam and behavior therapy in treatment of panic disorder.

The results of a clinical outcome study (N?=?57) comparing behavior therapy directed at panic disorder (panic control treatment [PCT]) with alprazolam were reported. These conditions were compared with a medication placebo and a waiting-list control group. Patterns of results on measures of panic attacks, generalized anxiety, and global clinical ratings reveal that PCT was significantly more effective than placebo and waiting-list conditions on most measures. The alprazolam group differed significantly from neither PCT nor placebo. The percentage of clients completing the study who were free of panic attacks following PCT was 87%, compared with 50% for alprazolam, 36% for placebo, and 33% for the waiting-list group. Since alprazolam may work more quickly than PCT but may also interfere with the effects of behavioral treatment, these data suggest a series of studies on the feasibility of integrating these treatments and on the precise patterns and mechanisms of action of various successful treatment approaches to panic disorder. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Gauging the effectiveness of extended imipramine treatment for panic disorder with agoraphobia

BACKGROUND: Imipramine has proven efficacy for panic disorder. This study assesses the net effectiveness of systematic, open imipramine treatment in a homogenous sample of panic disorder patients with agoraphobia. METHODS: One hundred and ten consecutive patients with DSM-III-R moderate to severe panic disorder with agoraphobia were treated with a fixed regimen of imipramine 2.25 mg/kg/day for 24 weeks. No instructions or encouragement for self-directed exposure to phobic situations or other coping strategies with panic or fear were given. Assessments were conducted at the end of the 2-week placebo run-in and at weeks 8, 16, and 24 of treatment. RESULTS: Overall, 53% had a marked and stable response. Most measures revealed that substantial improvement continued beyond week 8 of treatment. Treatment success was accompanied with significant improvements in anxiety sensitivity, dysphoric mood, and functional well-being. CONCLUSIONS: These results provide a clinically relevant reference with which to compare the effectiveness of alternative treatments in providing nearly complete symptom remission in patients with primary panic disorder with agoraphobia.     

Atherosclerotic cardiovascular disease, lipemic disorders, hypertension, obesity and diabetes mellitus in the population of a metropolitan area of southeastern Brazil. III--Hypertension

Premature ejaculation is a common sexual disturbance among men. Both open-label and double-blind studies have demonstrated the effectiveness of serotonergic medications for this disorder. These studies support the hypothesis that the serotonergic system has an important role in the modulation of sexual response, especially attainment of orgasm. Serotonergic dysfunction also has been linked to the pathogenesis of panic disorder. Several studies have demonstrated the efficacy of serotonergic drugs in this disorder. The purpose of the present study was to examine the efficacy of fluoxetine, a serotonin selective reuptake inhibitor for the treatment of comorbid premature ejaculation and panic disorder, in 10 men in an open-label design. The patients were given 20 mg of fluoxetine for 8 weeks of the study. Parameters pertaining to sexual function and measures of anxiety were examined. Improvement of premature ejaculation was noted as of week 2 of the study, whereas measures of panic and sexual satisfaction became statistically significant only as of week 4. Further studies with larger samples and longer periods of follow-up are needed in order to determine the usefulness of fluoxetine for the treatment of comorbid premature ejaculation and panic disorder.     

EMDR for panic disorder with agoraphobia: Comparison with waiting list and credible attention-placebo control conditions.

In a randomized controlled trial, eye movement desensitization and reprocessing (EMDR) for panic disorder with agoraphobia (PDA) was compared with both waiting list and credible attention-placebo control groups. EMDR was significantly better than waiting list for some outcome measure, (questionnaire, diary, and interview measures of severity of anxiety, panic disorder, and agoraphobia) but not for others (panic attack frequency and anxious cognitions). However, low power and, for panic frequency, floor effects may account for these negative results. Differences between EMDR and the attention placebo control condition were not statistically significant on any measure, and, in this case, the effect sizes were generally small (η?=?.00–.06), suggesting the poor results for EMDR were not due to lack of power. Because there are established effective treatments such as cognitive–behavior therapy for PDA, these data, unless contradicted by future research, indicate EMDR should not be the first-line treatment for this disorder. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A 2-year study of sertraline in the treatment of obsessive-compulsive disorder

The present study investigated the tolerability, safety profile, and anti-obsessional efficacy of sertraline, a selective serotonin reuptake inhibitor, during long-term treatment of patients with obsessive-compulsive disorder (OCD). Fifty-nine OCD patients who had completed a 1 year double-blind, fixed dose study comparing sertraline and placebo subsequently entered a 1-year open extension. Among the 51 patients who had been treated with sertraline during the double-blind phase, the mean total duration of sertraline treatment was 690 days. Only treatment responders who completed the 52-week double-blind treatment phase were permitted to enter the open extension. The higher rate (p < 0.02) of sertraline patients (51 out of 241) than of placebo patients (eight out of 84), who responded to treatment and entered the open-label phase is therefore consistent with the greater mean improvement observed in the sertraline group during double-blind treatment. Placebo responders differed from sertraline responders in that they were less impaired at baseline of the double-blind study [Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) of 18.5 versus 23.4] and they exhibited less improvement during double-blind treatment (-6.1 versus -11.4). In the open-label phase all patients received sertraline at a starting dose of 50 mg once a day, titrated in 50 mg increments to a maximum dose of 200 mg according to clinical response. At end-point the mean Y-BOCS score for all patients decreased by a further 3.6 points. Patients previously treated with placebo showed greater improvement after being switched to sertraline than those who received continued sertraline treatment. Patients who completed the study and received 2 full years of sertraline treatment (n = 38) exhibited a mean improvement of 15.6 points using the Y-BOCS. Sertraline was well tolerated during both the double-blind phase and the open extension, and the incidence of adverse experiences was generally reduced during the second year of treatment. Three patients discontinued open treatment because of adverse experiences. Long-term sertraline treatment did not appear to be associated with the emergence, increased incidence, or increased severity of adverse experiences or clinically significant abnormalities in laboratory tests, vital signs, or the electrocardiogram. The study supports the long-term safety and tolerability of sertraline over a 2-year treatment course and the sustained efficacy of sertraline in patients with OCD.     

The use of parametric vs. nonparametric tests in the statistical evaluation of rating scales

In psychiatric studies, treatment efficacy is usually measured by rating scales. These scales have ordinal (rank) level and the statistical evaluation of the scale scores should be performed with nonparametric rather than parametric tests. In recent years, nonparametric statistical procedures for repeated measures have been developed for the evaluation of clinical trials in psychiatry. To assess the frequency of application of nonparametric tests in psychiatric trials, an analysis was performed on all treatment studies with panic disorder patients (DSM-III/III-R) that could be traced in the literature. This survey revealed that nonparametric tests were used in only 16.7% of all studies.     

Rate of improvement during cognitive-behavioral group treatment for panic disorder

This study examined the rate of symptom improvement in patients receiving cognitive-behavioral group treatment for panic disorder in an outpatient clinic setting. Treatment was a standard program of 12 sessions that emphasized information, interoceptive and situational exposure, and cognitive restructuring, but also included diaphragmatic breathing and relaxation training as elements of treatment. Subjects were 37 patients selected from sequential admissions into an outpatient treatment program; all data were derived from ongoing quality assurance measures that are a standard part of clinical monitoring. Consequently, this study provides data not on the relative efficacy of cognitive-behavioral therapy (CBT), but on rate of improvement and effectiveness of CBT for panic disorder in actual clinical practice. Patients achieved significant treatment gains on all panic disorder dimensions assessed, and the largest reduction in symptoms was during the first third of the treatment program, thereby challenging the notion that CBT delivers its gains slowly over time. Information on rats of symptom improvement is valuable for providing patients with accurate expectations about potential treatment benefits and for helping to maintain motivation during initial treatment sessions.     

"A comparison of alprazolam and behavior therapy in treatment of panic disorder": Correction.

Reports an error in the original article by J. S. Klosko et al (Journal of Clinical & Consulting Psychology, 1990[Feb], Vol 58[1], 77–84). On pages 82 and 83, there was an error in the chi-square for the number of patients experiencing zero panic attacks among the four groups evaluated. The correct statistic is given. (The following abstract of this article originally appeared in record 1990-17776-001). The results of a clinical outcome study (N?=?57) comparing behavior therapy directed at panic disorder (panic control treatment [PCT]) with alprazolam were reported. These conditions were compared with a medication placebo and a waiting-list control group. Patterns of results on measures of panic attacks, generalized anxiety, and global clinical ratings reveal that PCT was significantly more effective than placebo and waiting-list conditions on most measures. The alprazolam group differed significantly from neither PCT nor placebo. The percentage of clients completing the study who were free of panic attacks following PCT was 87%, compared with 50% for alprazolam, 36% for placebo, and 33% for the waiting-list group.… (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Beyond brand names of psychotherapy: Identifying empirically supported change processes.

There is considerable debate about which empirical research methods best advance clinical outcomes in psychotherapy. The prevailing tendency has been to test treatment packages using randomized, controlled clinical trials. Recently, focus has shifted to considering how studying the process of change in naturalistic treatments can be a useful complement to controlled trials. Clinicians self-identifying as psychodynamic treated 17 panic disorder patients in naturalistic psychotherapy for an average of 21 sessions. Patients achieved statistically significant reductions in symptoms across all domains. Rates of remission and clinically significant change as well as effect sizes were commensurate with those of empirically supported therapies for panic disorder. Treatment gains were maintained at 6-month follow-up. Intensive analysis of the process of the treatments revealed that integrative elements characterized the treatments: Adherence to cognitive-behavioral process was most characteristic, adherence to interpersonal and psychodynamic process, however, was most predictive of positive outcome. Specific process predictors of outcome were identified using the Psychotherapy Process Q-Set. These findings demonstrate how process research can be used to empirically validate change processes in naturalistic treatments as opposed to treatment packages in controlled trials. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Antidepressants as first-line agents in the current pharmacotherapy of anxiety disorders.

Over the last decade, there has been a shift in the order of medications considered as first-line treatments for anxiety disorders. This transition was largely initiated by the introduction and consolidation of the selective serotonin reuptake inhibitors (SSRIs)—fluoxetine, paroxetine, sertraline, fluvoxamine, and citalopram—in the treatment of depression, and by the subsequent extension of these agents beyond depression to various anxiety disorders, such as obsessive-compulsive disorder and panic disorder. This article reviews important clinical considerations for prescribing SSRIs for the treatment of panic disorder, obsessive-compulsive disorder, social phobia, posttraumatic stress disorder, and generalized anxiety disorder. The SSRIs and newer atypical antidepressants have established equal or superior efficacy and a more favorable side effect profile when compared to their predecessors. However, the newer agents are not without side effects, such as nausea, diarrhea, insomnia, headaches, sexual dysfunction, sedation, and weight gain. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A double-blind multicenter trial comparing sertraline and citalopram in patients with major depression treated in general practice

The purpose of this double-blind, multicenter trial was to compare the efficacy and safety of sertraline (50-150 mg/day) with those of citalopram (20-60 mg/day) in patients with major depression in general practice during 24 weeks of treatment. The patients were assessed using the Montgomery-Asberg Depression Rating Scale and the Clinical Global Impressions of severity and improvement scales. Observed and spontaneously reported adverse events were recorded and side-effects were assessed by means of the UKU Side-Effect Scale. Altogether 400 patients were randomized into the study. A total of 308 patients completed the 24-week study in accordance with the protocol. A significant reduction in the total Montgomery-Asberg Depression Rating Scale scores was observed in both treatment groups as early as 2 weeks, with no statistically significant differences between the drugs. In the intention to treat-last observation carried forward analysis 76% responded to treatment in the sertraline and 81% in the citalopram group. The final mean doses were 82 mg/day (64% higher than baseline) in the sertraline group and 34 mg/day (70% higher than baseline) in the citalopram group. The response rate in completers in accordance with protocol was 90% in the sertraline group and 93% in the citalopram group. The side-effects were those usually seen, and both sertraline and citalopram were considered to be well tolerated. It was concluded that patients with major depression in general practice respond well to 24 weeks of treatment with sertraline or citalopram. With regard to efficacy, no statistically significant differences were found between the drugs.     

Transporting an empirically supported treatment for panic disorder to a service clinic setting: A benchmarking strategy.

This work examines the transportability of cognitive–behavioral therapy (CBT) for panic disorder to a community mental health center (CMHC) setting by comparing CMHC treatment outcome data with the results obtained in two controlled efficacy trials. Participants were 110 clients with a primary diagnosis of panic disorder with or without agoraphobia; clients were not excluded on the basis of medication use or changes, severity or frequency of panic attacks, age, or the presence of agoraphobia. Clients completed a 15-session CBT protocol. Despite differences in settings, clients, and treatment providers, the treatment outcomes for clients completing treatment in the CMHC and the efficacy studies were comparable: Of the CMHC clients who completed treatment, 87% were panic-free at the end of treatment, and clients showed significant reductions in anticipatory anxiety, agoraphobic avoidance, generalized anxiety, and symptoms of depression. The present study suggests that panic control treatment can be transported to a CMHC. Challenges facing the transportability of research-based treatment to CMHC clients, settings, and treatment providers are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Emergence of adverse events following discontinuation of treatment with extended-release venlafaxine

OBJECTIVE: The rate of adverse events following discontinuation of treatment with extended-release venlafaxine was compared with the rate associated with discontinuation of placebo administration. METHOD: The subjects were 20 outpatients with major depressive disorder who had participated in a multicenter, double-blind, placebo-controlled study of the efficacy of the new extended-release formulation of venlafaxine. RESULTS: During the 3 days after discontinuation of treatment with the study drug, seven (78%) of the nine venlafaxine-treated subjects and two (22%) of the nine placebo-treated patients reported the emergence of adverse events, a statistically significant difference. CONCLUSIONS: These results suggest that clinicians discontinuing venlafaxine treatment should consider tapering the medication dose gradually.     

A controlled, prospective, 1-year trial of citalopram in the treatment of panic disorder

BACKGROUND: The objective of this study was to evaluate the efficacy and tolerability of citalopram in the long-term treatment of adult outpatients with panic disorder with or without agoraphobia. METHOD: Patients in this double-blind, parallel-group trial were assigned to 1 of 3 fixed dosage ranges of citalopram (10 or 15 mg/day, 20 or 30 mg/day, or 40 or 60 mg/day), 1 dosage range of clomipramine (60 or 90 mg/day), or placebo. After the completed 8-week acute treatment period, the eligible patients could continue the treatment for up to 1 year. Of the 475 patients who were randomly assigned for the short-term trial, 279 agreed to continue double-blind treatment at their assigned doses. The primary efficacy measure used was the Clinical Anxiety Scale panic attack item, and the response was defined as no panic attacks (score of 0 or 1). The other key measures used were the Physician's Global Improvement Scale, the Patient's Global Improvement Scale, and the Hamilton Rating Scale for Anxiety (HAM-A). RESULTS: In all drug-treated groups, except the group receiving the lowest citalopram dose, the treatment outcome was generally better than with placebo. As determined by a life table analysis of response, the probability of response during the 12 months was significantly greater with all treatment regimens than with placebo (p < .05), with citalopram 20 or 30 mg/day demonstrating the best response. Panic attacks tended to disappear in all patients remaining in the study until the end of follow-up. Analysis of the difference in the number of patients in different treatment groups remaining in the study (perhaps the best measure of long-term efficacy) also demonstrated that the patients treated with citalopram in dosage ranges of 20 or 30 mg/day and 40 or 60 mg/day had better response than placebo-treated patients (p < .0002 and p < .004, respectively). HAM-A and Global Improvement Scale scores also showed that patients treated with active drug showed greater improvement than placebo-treated patients. All treatment groups showed no new or exceptional adverse event clusters. CONCLUSION: Citalopram in the dosage range of 20 to 60 mg/day is effective, well tolerated, and safe in the long-term treatment of patients who have panic disorder.     

Mechanism of Change in Cognitive-Behavioral Treatment of Panic Disorder: Evidence for the Fear of Fear Mediational Hypothesis.

Numerous clinical trials have demonstrated the efficacy of cognitive-behavioral treatment (CBT) for panic disorder. However, studies investigating the mechanisms responsible for improvement with CBT are lacking. The authors used regression analyses outlined by R. M. Baron and D. A. Kenny (1986) to test whether a reduction in fear of fear (FOF) underlies improvement resulting from CBT. Pre- and posttreatment measures were collected from 90 CBT-treated patients and 40 wait-list control participants. Overall, treatment accounted for 31% of the variance in symptom reduction. The potency of FOF as a mediator varied as a function of symptom facet, as full mediation was observed for the change in global disability, whereas the effects of CBT on agoraphobia, anxiety, and panic frequency were partially accounted for by reductions in FOF. Clinical implications and future research directions are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The treatment of osteoarthritis of the knee with pulsed electrical stimulation

OBJECTIVE: The safety and effectiveness of pulsed electrical stimulation was evaluated for the treatment of osteoarthritis (OA) of the knee. METHODS: A multicenter, double blind, randomized, placebo controlled trial that enrolled 78 patients with OA of the knee incorporated 3 primary efficacy variables of patients' pain, patients' function, and physician global evaluation of patients' condition, and 6 secondary variables that included duration of morning stiffness, range of motion, knee tenderness, joint swelling, joint circumference, and walking time. Measurements were recorded at baseline and during the 4 week treatment period. RESULTS: Patients treated with the active devices showed significantly greater improvement than the placebo group for all primary efficacy variables in comparisons of mean change from baseline to the end of treatment (p < 0.05). Improvement of > or = 50% from baseline was demonstrated in at least one primary efficacy variable in 50% of the active device group, in 2 variables in 32%, and in all 3 variables in 24%. In the placebo group improvement of > or = 50% occurred in 36% for one, 6% for 2, and 6% for 3 variables. Mean morning stiffness decreased 20 min in the active device group and increased 2 min in the placebo group (p < 0.05). No statistically significant differences were observed for tenderness, swelling, or walking time. CONCLUSION: The improvements in clinical measures for pain and function found in this study suggest that pulsed electrical stimulation is effective for treating OA of the knee. Studies for longterm effects are warranted.     

Anesthetic considerations in the child with Gaucher disease

Alpidem, an imidazopyridine that acts at the gamma-aminobutyric acid/benzodiazepine receptor complex, has been reported to be an effective anxiolytic with a more favorable side effect profile than benzodiazepines. The effect of alpidem was investigated in an 8-week, open, clinical trial in 13 patients with panic disorder, with or without agoraphobia. Three patients were responders (much improved or very much improved), five patients were nonresponders, and five patients dropped out after less than 6 weeks of treatment. Significant improvement was seen in the sample as a whole for spontaneous panic attacks, phobic avoidance, and anticipatory anxiety. Most improvement occurred during the first 4 weeks of treatment, and responders had milder panic disorder at baseline. Adverse effects were generally mild. After 8 weeks of treatment, taper of medication over 2 weeks occurred without significant worsening of panic disorder symptoms. The efficacy of alpidem in the treatment of panic disorder remains uncertain and requires assessment in a controlled trial.     

A multidimensional meta-analysis of treatments for depression, panic, and generalized anxiety disorder: An empirical examination of the status of empirically supported therapies.

The authors report a meta-analysis of high-quality studies published from 1990-1998 on the efficacy of manualized psychotherapies for depression, panic disorder, and generalized anxiety disorder (GAD) that bear on the clinical utility and external validity of empirically supported therapies. The results suggest that a substantial proportion of patients with panic improve and remain improved; that treatments for depression and GAD produce impressive short-term effects; that most patients in treatment for depression and GAD do not improve and remain improved at clinically meaningful follow-up intervals; and that screening procedures used in many studies raise questions about generalizability, particularly in light of a systematic relation across studies between exclusion rates and outcome. The data suggest the importance of reporting, in both clinical trials and meta-analyses, a range of outcome indices that provide a more comprehensive, multidimensional portrait of treatment effects and their generalizability. These include exclusion rates, percent improved, percent recovered, percent who remained improved or recovered at follow-up, percent seeking additional treatment at follow-up, and data on both completer and intent-to-treat samples. (PsycINFO Database Record (c) 2010 APA, all rights reserved)