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Biomedical subjects

J C Pecknold

Publications and source records attributed to J C Pecknold.

At least 19 recordsLinked to original sources
PubMed2001

Sertraline treatment of generalized social phobia: a 20-week, double-blind, placebo-controlled study.

OBJECTIVE: The authors evaluated the efficacy, safety, and tolerability of sertraline, a selective serotonin reuptake inhibitor, in the treatment of generalized social phobia. METHOD: Adult outpatients with generalized social phobia (N=204) from 10 Canadian centers were randomly assigned to receive sertraline or placebo in a 2:1 ratio for a 20-week double-blind study following a 1-week, single-blind, placebo run-in. The initial dose of sertraline was 50 mg/day with increases of 50 mg/day every 3 weeks permitted after the fourth week of treatment (dosing was flexible up to a maximum of 200 mg/day). Primary efficacy assessments were the percentage of patients rated much or very much improved on the Clinical Global Impression (CGI) improvement item and the mean changes from baseline to study endpoint in total score on the social phobia subscale of the Marks Fear Questionnaire and total score on the Brief Social Phobia Scale. RESULTS: In intent-to-treat endpoint analyses of 203 of the patients, significantly more of the 134 patients given sertraline (N=71 [53%]) than of the 69 patients receiving placebo (N=20 [29%]) were considered responders according to their CGI improvement scores at the end of treatment. The mean reductions in the social phobia subscale of the Marks Fear Questionnaire and in the total score on the Brief Social Phobia Scale were 32.6% and 34.3% in the sertraline group and 10.8% and 18.6% in the placebo group, respectively. Analysis of covariance showed superiority of sertraline over placebo on all primary and secondary efficacy measures. Sertraline was well tolerated: 103 (76%) of the 135 sertraline-treated patients and 54 (78%) of the 69 placebo-treated patients completed the study. CONCLUSIONS: Sertraline is an effective treatment for patients with generalized social phobia.

Adult↗
PubMed2000

Prevention of relapse in generalized social phobia: results of a 24-week study in responders to 20 weeks of sertraline treatment.

The aim of this study was to evaluate the efficacy, tolerability, and effects on quality of life of sertraline, a selective serotonin reuptake inhibitor, in the prevention of relapse of generalized social phobia. Fifty adult outpatients with generalized social phobia who were rated much or very much improved on the Clinical Global Impression Scale of Improvement (CGI-I) after 20 weeks of sertraline treatment (50-200 mg/day) were randomly assigned in a one-to-one ratio to either continue double-blind treatment with sertraline or immediately switch to placebo for another 24 weeks. The initial 20-week study was placebo-controlled, and 15 responders to placebo also continued to receive double-blind placebo treatment in the continuation study. Eighty-eight percent of patients in the sertraline-continuation group and only 40% of patients in the placebo-switch and placebo-responder groups completed the study. In intent-to-treat endpoint analyses, 1 (4%) of 25 patients in the sertraline-continuation group and 9 (36%) of 25 patients in the placebo-switch group had relapsed at study endpoint (chi2 = 8.0, Fisher exact test, p = 0.01). The relative risk (hazards ratio) for relapse associated with placebo-switch relative to sertraline-continuation treatment was 10.2 (95% confidence interval, 1.3-80.7). Mean CGI-Severity, Marks Fear Questionnaire (MFQ) Social Phobia subscale, and Duke Brief Social Phobia Scale (BSPS) total scores were reduced by 0.07, 0.34, and 1.86 in the Sertraline-Continuation group and increased by 0.88, 4.09, and 5.99 in the Placebo-Switch group (all F > 5.3, p < 0.03), respectively. CGI-Severity, MFQ Social Phobia subscale, and BSPS scores also increased in the Placebo-Responder group. Discontinuations because of lack of efficacy were 4% in the sertraline-continuation group, 28% in the placebo-switch group (chi2 = 5.36, Fisher exact test, p = 0.049), relative to sertraline, and 27% in the placebo-responder group. Sertraline was effective in preventing relapse of generalized social phobia. Future research should assess whether improvements may be maintained or further increased by longer periods of treatment or through the addition of cognitive-behavioral techniques.

Adult↗
PubMed1997

A risk-benefit assessment of buspirone in the treatment of anxiety disorders.

Anxiety disorders include generalised anxiety disorder, panic disorder, obsessive-compulsive disorder (OCD) and social phobia. Consideration of the chronicity of these disorders reveals that anxiety disorders first occur during early adolescence or young adulthood, and can wax and wane over periods of 5 to 10 years. Thus, in considering treatment, the emphasis must be placed on long term, rather than short term, management. Comorbidity studies reveal that untreated patients with anxiety disorders are at risk of social and psychological consequences, as well as disability resulting from comorbid and secondary disorders. Comparisons between buspirone and the benzodiazepines in treating patients with generalised anxiety disorder reveal that long term use of benzodiazepines is associated with adverse effects, particularly in elderly patients. Buspirone appears to have an onset of action equivalent to that of the benzodiazepines, to be well tolerated in the long term, to lack problems of habituation and withdrawal, and to be useful in patients with masked comorbid depression. In patients with panic disorder and social phobia, buspirone has not been clearly shown to be effective in comparison with the reference standards; in those patients with OCD, there are only preliminary indications of efficacy, which merit a more adjunctive role.

Anti-Anxiety Agents↗
PubMed1995

Fluoxetine in panic disorder: pharmacologic and tritiated platelet imipramine and paroxetine binding study.

Serotonergic implication in panic disorder has been demonstrated by the efficacy of serotonin reuptake blockers in treatment. Fluoxetine, a potent 5-HT reuptake blocker, has been suggested to have anti-panic efficacy. This open study examines 30 patients (eight males and 22 females) with an average age of 36.9 years, ranging from 18 to 62, who were treated for eight weeks with fluoxetine (mean dose 20 mg per day). All patients fulfilled DSM-III-R criteria of panic disorder with agoraphobia as determined in a SCID interview schedule. Out of 28 patients who started medication, 64% of the patients completed the clinical trial and 36% of the patients dropped out of treatment because of increased anxiety or a lack of efficacy. Thirty-two percent of the patients had zero panic attacks by week 3. By the end of eight weeks of treatment, 48% of the patients had zero panic attacks. There was a significant reduction in anxiety and phobic avoidance and panic attacks. Tritiated platelet imipramine and paroxetine bindings revealed significantly lower maximal binding for patients with panic disorder in comparison with controls. Paroxetine Bmax showed a trend to increase in the direction of control values by the end of the trial.

Adolescent↗
PubMed1993

Discontinuation reactions to alprazolam in panic disorder.

Panic disorder is a chronic illness with only some degree of spontaneous recovery. It is not surprising therefore that discontinuation of an effective medical treatment may be followed by relapse. Therefore the timing and methodology of discontinuing that treatment are now recognized as essential facets of optimal clinical management. In addition to relapse, rebound and the withdrawal syndrome have been reported with many psychotropic agents, particularly with the benzodiazepines. This paper discusses data from three discontinuation studies with alprazolam i.e. the Phase I Cross-National Collaborative Panic discontinuation study after short-term treatment, the Phase I discontinuation study after long-term treatment, and data from the Montreal site of the Alprazolam SR discontinuation study. Phase I of the Cross-National Collaborative Study of Panic Disorder investigated the discontinuation of alprazolam in two populations. There was an intensive, placebo-controlled, time-limited study of discontinuation after short-term treatment (8 weeks) in the first population. For the second, there was a less rigorous open follow-up of patients who had been treated for 5-12 months with alprazolam. The dose-reduction regimen of alprazolam in both studies was approximately the same--a 1 mg decrease every 3-7 days. In the short-term treatment study, 109 patients were treated for 8 weeks, tapered for 4 weeks and observed for another 2 weeks post discontinuation. Significant relapse in the alprazolam-treated group occurred during discontinuation. Rebound of panic attacks occurred in 27% of patients given alprazolam, and distinct transient withdrawal syndrome occurred in 35%. Indicative of the withdrawal syndrome were confusion, clouded sensorium, heightened sensory perception, dysosmia, paresthesias, muscle cramps, muscle twitch, blurred vision, diarrhea, decreased appetite, and weight loss. The clinical course in the alprazolam-treated patients revealed a marked exacerbation of symptoms during the end of the tapering period and the first week without medication, which was followed by improvement during the second post-taper week. In the long-term treatment study, 142 patients were treated with alprazolam for periods ranging from 5 months to 1 year (mean, 27.5 weeks). In this naturalistic study, 76% of the patients reported improvement, 6.3% reported no change, and 10.6% reported that they were worse. During discontinuation, 12.8% of the 128 patients whose dosage was tapered reported some kind of nonspecified withdrawal symptoms. Of the 142 patients, 47.2% were able to taper their medication dosage and to discontinue treatment; 19.7% tapered but restarted alprazolam shortly after discontinuation; 33.1% were unable or unwilling to taper or discontinue alprazolam.(ABSTRACT TRUNCATED AT 400 WORDS)

Agoraphobia↗
PubMed1993

Survey of the adjuvant use of benzodiazepines for treating outpatients with schizophrenia.

A retrospective survey of the use of benzodiazepines by 149 outpatients with schizophrenia found that 59% were on neuroleptics alone and 41% were receiving both neuroleptics and benzodiazepines. Of the group receiving both, 64% were taking a benzodiazepine as a hypnotic agent; 23% of those were taking alprazolam as an anxiolytic. The patients taking neuroleptics and alprazolam required significantly less neuroleptic medication than the group receiving neuroleptics alone.

Adult↗
PubMed1993

Gepirone and the treatment of panic disorder: an open study.

Gepirone, an azapirone, is a potent 5-hydroxytryptamine 1A (5-HT1A) agonist. We report an uncontrolled 6-week study in 21 patients (4 men, 17 women: mean age, 36.71 years) with a concurrent DSM-III-R diagnosis of generalized anxiety disorder and panic disorder with agoraphobia. After a 2-week medication-free period, patients were started on 2 mg of gepirone per day increasing over 3 weeks to 12 mg/day. Three patients dropped out in the first week, and one patient violated the protocol. They were therefore excluded from analysis. Two patients who dropped out at weeks 4 and 5 because they found the treatment ineffective were included. Twelve of the 17 patients (70.6%) had at least a 50% reduction in their panic attacks by week 6, and 9 of them had at least a 50% reduction by week 3. Ten patients had "0" panic attacks by week 6 (59%). On the Hamilton Anxiety Scale, 65% had a 50% or greater reduction in total score, mostly beginning in week 1. On Global Assessment, by week 6, 11 were much improved or better (65%). Adverse effects were rare and consisted of stomach upset, dizziness, or headaches. This preliminary study suggests the possible efficacy of gepirone in panic disorder.

Adult↗
PubMed1992

Use of buspirone in patients with generalized anxiety disorder and coexisting depressive symptoms. A meta-analysis of eight randomized, controlled studies.

This report presents the results of a retrospective analysis of pooled efficacy data from eight studies in which buspirone was compared to placebo in 520 patients with generalized anxiety disorder (GAD). In addition to evaluating overall efficacy in the composite patient data base, four criteria were used to identify subsets of patients with GAD who had coexisting depressive symptoms of at least moderate intensity: (1) a score of > or = 2 on the Hamilton Anxiety (HAM-A) Rating Scale item 6 (depressed mood), (2) a score of > or = 2 on the Hamilton Depression (HAM-D) Rating Scale item 1 (depressed mood), (3) a HAM-D total score of > or = 18, or (4) a HAM-D Retardation Factor value (items 1, 7, 8, and 14) greater than the median for the group. Overall, patients treated with buspirone demonstrated significant (p < or = 0.001) improvement over baseline in total HAM-A scores compared to patients who received placebo. Buspirone also produced significant (p < or = 0.001) global improvement compared to placebo as assessed by the attending physician. Of the GAD patients stratified according to the four criteria for coexisting depressive symptoms, a substantial percentage (44-64%) of the total patient sample exhibited significant depressive symptoms as part of their anxiety disorder. Patients with GAD and coexisting depressive symptoms of at least moderate intensity exhibited significantly greater improvement with buspirone compared to placebo treatment regardless of the stratification criterion used. They also responded at least as well or better to buspirone therapy as did those with GAD who had less intense depressive symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Discontinuation of alprazolam after long-term treatment of panic-related disorders.

Discontinuation of alprazolam after long-term treatment of 142 patients with panic-related disorders was examined in five study sites using a telephone interview. The majority (67%) of patients interviewed discontinued alprazolam for a period of at least 3 days after a gradual dosage reduction schedule over a 4-week period at the end of the long-term treatment study. A marked difference among the study sites in percentages of patients discontinuing therapy with alprazolam suggests that physician intervention played an important role in determining the ability of patients successfully to discontinue use of alprazolam: 90% and 95% of patients ceased therapy at two sites whereas only 21%, 38%, and 66% of patients discontinued therapy at the other three sites. The mean daily dosage for patients who continued using alprazolam decreased from 5.1 mg/day at the end of the long-term segment to 2.7 mg/day at the time of the poststudy interview. This decline indicates a lack of tolerance to the therapeutic effectiveness of alprazolam over an extended period of time.

Adult↗
PubMed1990

Sequence of improvement in agoraphobia with panic attacks.

In a multi-center comparison of alprazolam to placebo in the treatment of agoraphobia with panic attacks, the sequence of sustained remission in both treatment groups, was panic attacks before phobias. This may suggest that phobias are secondary to panic attacks in the pathogenesis of the disorder, although other explanations may account for these data and are discussed.

Adult↗
PubMed1990

Sleep studies and neurochemical correlates in panic disorder and agoraphobia.

Although panic disorder is classified by the DSM III among the anxiety disorders, there is evidence from epidemiological and neurochemical studies that links panic to the affective disorders. In addition several of the effective pharmacological treatments suggest, as in the depressive disorders, serotonergic involvement. As part of the evaluation of patients who would take part in the Cross National Collaborative Panic study, polysomnography, the dexamethasone suppression test and platelet imipramine binding and 5HT-uptake were scheduled. 44 patients who met DSM III criteria on the SCID interview schedule for Panic Disorder consented to enter the study. After being medication free for two weeks, these patients had three consecutive all night polysomnograms, followed by a dexamethasone suppression test and platelet study of imipramine binding and 5HT-uptake. In our studies we were unable to find for the panic group as a whole a correlation with reported parameters of sleep architecture in endogenous depression. Similarly the imipramine binding differentiated the panickers from the depressed group. Only the 5HT-uptake was similar in both groups. We also found a subgroup of panickers who resembled depressives in terms of the imipramine binding, 5HT-uptake platelet studies and REM latency. In the analysis of the imipramine and 5HT-uptake over the treatment period, we noted changes which suggest a role for serotonin, certainly in a subgroup of panickers and possibly for the group of panic disorder as a whole.

Adult↗
PubMed1989

Evaluation of buspirone as an antianxiety agent: buspirone and diazepam versus placebo.

Buspirone has previously been demonstrated to be efficacious in the treatment of anxiety. This four-week double-blind parallel study compared buspirone to diazepam and placebo in the treatment of 119 outpatients diagnosed as having generalized anxiety disorder. After a seven-day placebo washout period, eligible patients were randomized to one of three treatment groups. Buspirone (5 mg) and diazepam (5 mg) were administered BID and individually titrated to an optimal therapeutic dose by the end of week two. Buspirone and diazepam were equally effective in reducing Hamilton Anxiety (HAM-A) total and psychic factor scores from baseline values. Buspirone alone was significantly better than placebo in reducing the HAM-A somatic factor score. Sixty-seven percent of both active treatment groups who were classified as "ill" on the baseline global psychopathology rating scale achieved a "not ill" status by study end. There were no significant differences between treatment groups at endpoint on the 56-item Symptom Checklist self-rating scale. Buspirone was demonstrated to be as effective as diazepam in relieving anxiety in this outpatient sample.

Adult↗
PubMed1989

Trimipramine, anxiety, depression and sleep.

The presence of mixed symptoms of anxiety and depression are well known to every clinician. Panic, generalised anxiety and obsessive-compulsive disorder all have considerable overlap with major depressive illness. Factor analysis of anxiety and depression symptoms has sought to predict response to treatment as well as to establish a diagnosis. Sleep disturbances are important concomitants of both syndromes. The analysis of the architecture and phasing of sleep stages has been proposed as a biological marker to separate anxiety and depression. The modification of REM and delta sleep has been correlated with antidepressant action. The earliest studies of trimipramine noted antidepressant, anxiolytic and hypnotic effects. Further observations have shown this drug to have atypical effects on REM sleep. In addition, despite its structural similarity to other tricyclic antidepressants, its pharmacological profile in animals is very different: there is no synaptosomal reuptake of serotonin or noradrenaline, and no desensitisation of beta-adrenoceptors after long term administration. A series of studies was carried out on 99 patients. Admission criteria for the studies specified a minimum score of 20 on the Anxiety Status Inventory as well as the presence of moderate depression. An uncontrolled trial demonstrated the anxiolytic efficacy of trimipramine. Further controlled trials showed superior anxiolytic efficacy of trimipramine to amitriptyline and doxepin with comparable anxiolytic efficacy of trimipramine with maprotiline. All agents had equal antidepressant effects.

Anxiety↗
PubMed1988

Alprazolam in panic disorder and agoraphobia: results from a multicenter trial. I. Efficacy in short-term treatment.

Following promising preliminary evidence, the benzodiazepine-derivative alprazolam was studied in a large, placebo-controlled, eight-week, flexible-dose trial in patients with agoraphobia with panic attacks and panic disorder. Of 526 patients, 481 completed three weeks of treatment; however, significantly more placebo (102/234) than alprazolam (21/247) recipients subsequently dropped out of the trial, primarily citing ineffectiveness (of placebo) as the reason. Alprazolam was found to be effective and well tolerated. There were significant alprazolam-placebo differences in improvement for (1) spontaneous and situational panic attacks, (2) phobic fears, (3) avoidance behavior, (4) anxiety, and (5) secondary disability, all significant by the end of week 1. At the primary comparison point (week 4), 82% of the patients receiving alprazolam were rated moderately improved or better vs 43% of the placebo group. At that point, 50% of the alprazolam recipients vs 28% of placebo recipients were free of panic attacks.

Adolescent↗
PubMed1988

Alprazolam in panic disorder and agoraphobia: results from a multicenter trial. II. Patient acceptance, side effects, and safety.

In a multicenter placebo-controlled study, the safety, side effects, and patient acceptance of alprazolam for the treatment of panic disorder and agoraphobia were examined. A total of 525 patients meeting DSM-III criteria for agoraphobia with panic attacks or panic disorder were randomly assigned to receive alprazolam or placebo, which they took for eight weeks. The mean daily dose at the end of the study was 5.7 mg of alprazolam or 7.5 capsules of placebo daily. Potentially serious reactions to alprazolam occurred in ten of 263 subjects who received the drug. These included acute intoxication (three), hepatitis (two), mania (two), amnesia (one), aggressive behavior (one), and depression (one). Treatment-related side effects that were worse in patients taking alprazolam than in those taking placebo included sedation, fatigue, ataxia, slurred speech, and amnesia. Sedation was the most frequent but tended to subside with dose reduction or continued administration of the drug. Patient acceptance of alprazolam, as measured by the rate of completion for study participants, was high. Eighty-four percent of patients receiving active drug completed the study compared with 50% receiving placebo.

Adult↗
PubMed1988

Alprazolam in panic disorder and agoraphobia: results from a multicenter trial. III. Discontinuation effects.

Preliminary reports of discontinuation of alprazolam therapy in patients with panic disorder have revealed worsening of symptoms despite gradual withdrawal of medication. In this study, 126 patients with panic disorder and phobic avoidance received either alprazolam or placebo in doses of 2 to 10 mg daily for eight weeks. The medication was tapered over a period of four weeks, and patients were observed for another two weeks after all medication was discontinued. Sixty of the 63 alprazolam-treated patients and 49 of the 63 placebo-treated patients entered the taper and discontinuation study. After improvement in the active treatment period, the alprazolam-treated group had significant relapse between the first and last week of taper. However, during the second postdiscontinuation week, outcome scores were not significantly different from those of the placebo-treated group who did not deteriorate during taper. Twenty-seven percent of the alprazolam-treated group reported a rebound of panic attacks during taper and 13% reported a rebound of anxiety on the Hamilton Anxiety Scale. No serious or life-threatening withdrawal symptoms were reported, but distinct, transient, mild to moderate withdrawal syndrome occurred in 35% of the alprazolam-treated group and in none of the placebo-treated group. The coexistence of symptom rebound and a withdrawal syndrome occurred in 10% of the alprazolam-treated group, but both subsided by the end of the second week without alprazolam. We recommend that patients with panic disorder be treated for a longer period, at least six months, and that medication be tapered over a more prolonged period, at least eight weeks, especially where high doses are employed.

Adult↗
PubMed1988

Secondary depression in panic disorder and agoraphobia. I. Frequency, severity, and response to treatment.

Depressive symptomatology in 481 subjects with panic disorder and phobic avoidance was studied as part of an investigation of the efficacy of alprazolam in panic disorder. Subjects who had a major depressive episode (MDE) before the onset of their panic disorder were not included in the trial. With this exclusion criterion, 31% of subjects had a secondary MDE occurring after the onset of the panic disorder. The occurrence of secondary MDE was related to the length of time subjects were ill with panic disorder. Compared with the subjects without depression, those subjects with current MDE had higher scores on measures of anxiety and depression but not on the number of panic attacks per week. The presence of depression and the degree of phobic avoidance contributed independently to measures of the severity of the panic illness. Alprazolam was effective in reducing panic and depressive symptomatology in both depressed and nondepressed subjects with panic disorder. The presence of an MDE was not predictive of the outcome of treatment for the panic and phobic symptoms. Subjects with or without depression responded similarly to alprazolam.

Adult↗