Biomedical subjects

John J Worthington

Publications and source records attributed to John J Worthington.

At least 19 recordsLinked to original sources

PubMed2007

A double-blind study of the efficacy of venlafaxine extended-release, paroxetine, and placebo in the treatment of panic disorder.

To date, no large-scale, controlled trial comparing a serotonin-norepinephrine reuptake inhibitor and selective serotonin reuptake inhibitor with placebo for the treatment of panic disorder has been reported. This double-blind study compares the efficacy of venlafaxine extended-release (ER) and paroxetine with placebo. A total of 664 nondepressed adult outpatients who met DSM-IV criteria for panic disorder (with or without agoraphobia) were randomly assigned to 12 weeks of treatment with placebo or fixed-dose venlafaxine ER (75 mg/day or 150 mg/day), or paroxetine 40 mg/day. The primary measure was the percentage of patients free from full-symptom panic attacks, assessed with the Panic and Anticipatory Anxiety Scale (PAAS). Secondary measures included the Panic Disorder Severity Scale, Clinical Global Impressions--Severity (CGI-S) and--Improvement (CGI-I) scales; response (CGI-I rating of very much improved or much improved), remission (CGI-S rating of not at all ill or borderline ill and no PAAS full-symptom panic attacks); and measures of depression, anxiety, phobic fear and avoidance, anticipatory anxiety, functioning, and quality of life. Intent-to-treat, last observation carried forward analysis showed that mean improvement on most measures was greater with venlafaxine ER or paroxetine than with placebo. No significant differences were observed between active treatment groups. Panic-free rates at end point with active treatment ranged from 54% to 61%, compared with 35% for placebo. Approximately 75% of patients given active treatment were responders, and nearly 45% achieved remission. The placebo response rate was slightly above 55%, with remission near 25%. Adverse events were mild or moderate and similar between active treatment groups. Venlafaxine ER and paroxetine were effective and well tolerated in the treatment of panic disorder.

Adult↗

PubMed2006

The combination of duloxetine and bupropion for treatment-resistant major depressive disorder.

Our objective was to assess the effectiveness and safety of the combination of duloxetine and bupropion for treatment-resistant major depressive disorder (TRD). A retrospective chart review was conducted to identify patients with major depressive disorder (MDD) who had not experienced full remission of symptoms following an adequate trial of either duloxetine (n = 3) or bupropion (n = 7), and who then received the combination of these two antidepressants for TRD. Ten patients [37.2 +/- 11.3 years of age, five women, baseline Clinical Global Impressions (CGI) scale score 4.4 +/- 1.1], seven of whom had not remitted following treatment with bupropion (330 +/- 67 mg, 20.5 +/- 12.2 weeks), and three of whom had not remitted following treatment with duloxetine (90 +/- 30 mg, 18 +/- 2 weeks) received at least 4 weeks of combination treatment. The CGI was administered when the combination was first prescribed, and following 8.8 +/- 4.0 (range, 4-16) weeks of treatment. There was a significant decrease in CGI-S (Severity) scores (4.4 +/- 1.1 to 2.1+/-0.9, P <.0001) following combination treatment. Three (30%) patients were remitters at follow-up, and six (60%) were responders who did not achieve full symptom remission. The mean maximum adjunctive duloxetine and bupropion doses were 60.0 +/- 17.3 mg and 175.0 +/- 114.5 mg, respectively. Side effects reported during combination treatment were nausea (n = 2), dry mouth (n = 2), jitteriness/agitation (n = 2), fatigue/drowsiness (n = 2), increased blood pressure (n = 1), increased sweating (n = 1), insomnia (n = 1), pruritus (n = 1), headache (n = 1), sexual dysfunction (n = 1), and weight gain (n = 1). Although preliminary, these results suggest a possible role for the combination of duloxetine and bupropion for TRD.

Adult↗

PubMed2006

Preliminary support for gender differences in response to fluoxetine for generalized anxiety disorder.

Women have a higher prevalence of generalized anxiety disorder (GAD) than do men, but few studies have assessed gender differences in response to pharmacotherapy. In this study we examined gender as a correlate of response to 6 weeks of open, prospective fluoxetine treatment in 23 men and 22 women with a primary diagnosis of GAD. There was no difference by gender in age or prevalence of mood and anxiety comorbidity; however, GAD onset occurred at a significantly younger age in women compared with men. Despite a lack of difference in baseline severity measures, women had a significantly poorer response to fluoxetine as measured by both the Hamilton Anxiety Rating Scale (HAM-A) and Clinician Global Impression-Severity Scale (CGI-S). In multivariate analyses, there was a significant interaction between age of onset and gender: men with younger age of onset and women with older age of onset exhibited poorer response on the HAM-A. These data, though limited in sample size and by the post hoc nature of our analyses, offer preliminary support that women with GAD, particularly those with a later age of onset, may have a poorer response to the selective serotonin reuptake inhibitor (SSRI) fluoxetine. Larger placebo-controlled trials are needed to more definitively examine gender and treatment response in anxiety disorders.

Adult↗

PubMed2006

The relationship of anxiety disorders, anxiety sensitivity and pulmonary dysfunction with dyspnea-related distress and avoidance.

Little is known about factors that mediate the relationship between anxiety and respiratory-related distress and disability. We hypothesized that elevations in anxiety sensitivity would be associated with greater severity of dyspnea, greater dyspnea-related avoidance, and poorer subjective assessment of health in patients with dyspnea referred for pulmonary function testing, regardless of objective evidence of pulmonary dysfunction. A total of 182 consecutive patients receiving pulmonary function tests to evaluate dyspnea were screened with a patient-rated Primary Care Evaluation of Mental Disorders and completed the Anxiety Sensitivity Index and questionnaires assessing symptom severity and avoidance. Anxiety Sensitivity Index score predicted more severe subjective dyspnea and greater dyspnea-related avoidance, even after adjustment for anxiety disorders and pulmonary dysfunction. Despite some limitations, these data provide preliminary support that strategies to identify, measure, and address high levels of anxiety sensitivity should be examined to reduce subjective distress and improve functioning for patients with dyspnea.

Anxiety Disorders↗

PubMed2006

An open-label trial of risperidone augmentation for refractory anxiety disorders.

BACKGROUND: There is a paucity of data to support "next-step" treatments for the many patients with anxiety disorders who remain symptomatic after initial pharmacotherapy. METHOD: Thirty patients with a primary diagnosis of an anxiety disorder-panic disorder (PD), social anxiety disorder (SAD), or generalized anxiety disorder (GAD)-refractory to initial pharmacotherapy with an adequate (or maximally tolerated) antidepressant and/or benzodiazepine trial of at least 8 weeks' duration prior to study initiation received open-label augmentation with flexibly dosed risperidone for 8 weeks. Participants were diagnosed using the Structured Clinical Interview for DSM-IV. RESULTS: Risperidone augmentation at a mean +/- SD dose of 1.12 +/- 0.68 mg/day (range, 0.25-3.00 mg/day) resulted in a significant reduction in anxiety symptoms across disorders as measured by the Clinical Global Impressions-Severity of Illness scale and Hamilton Rating Scale for Anxiety (HAM-A) scores and for each disorder-specific primary outcome measure-the Panic Disorder Severity Scale, the Liebowitz Social Anxiety Scale, and HAM-A-in the intent-to-treat sample. Seventy percent (21/30) of participants completed the 8-week trial, with premature discontinuation due primarily to sedation and weight gain. CONCLUSIONS: Although conclusions are limited by the open-label, relatively brief nature of this trial, our data suggest that augmentation with low-dose risperidone may be a useful option for patients with PD, SAD, or GAD refractory to adequate initial intervention with antidepressants and/or benzodiazepines. Longer-term, controlled safety and efficacy data are needed to understand the place of risperidone augmentation in the algorithm of treatment options for refractory anxiety disorders.

Adult↗

PubMed2005

Olanzapine augmentation of fluoxetine for refractory generalized anxiety disorder: a placebo controlled study.

BACKGROUND: There has been little systematic study of "next-step" interventions for patients with generalized anxiety disorder (GAD) who remain symptomatic despite initial pharmacotherapy. We present one of the first randomized controlled trials for refractory GAD, comprising double blind augmentation with olanzapine or placebo for patients remaining symptomatic on fluoxetine. METHODS: Patients remaining symptomatic after 6 weeks of fluoxetine (20 mg/day) were randomized to 6 weeks of olanzapine (mean dose 8.7 +/- 7.1 mg/day) or placebo augmentation. RESULTS: Twenty-four of 46 fluoxetine-treated patients were randomized. Olanzapine resulted in a greater proportion of treatment responders based on a Clinical Global Impression-Severity Scale (CGI-S) end point score of 1 or 2 (Fisher's exact test [FET] p < .05) or a 50% reduction in Hamilton Anxiety Scale (HAMA-A) score (FET p < .05). There were no other statistically significant differences for olanzapine compared with placebo augmentation in outcome measures, though rates of remission (HAM-A <or= 7) on olanzapine were higher at the level of a trend (FET, p = .1). Average weight gain for completers was greater with olanzapine than placebo augmentation (11.0 +/- 5.1 vs. -0.7 +/- 2.4 pounds: t = 6.32, p < .001). CONCLUSIONS: Olanzapine may have a salutary effect on anxiety for some GAD patients remaining symptomatic despite initial serotonin selective reuptake inhibitor (SSRI) therapy, but the emergence of significant weight gain represents an important clinical consideration.

Adult↗

PubMed2005

Aripiprazole as an augmentor of selective serotonin reuptake inhibitors in depression and anxiety disorder patients.

More than half of anxiety and depression patients treated with an adequate course of antidepressants fail to fully improve. We retrospectively examined whether treatment-resistant depression and anxiety disorder patients responded to and tolerated augmentation with the atypical antipsychotic, aripiprazole. We report on patients with depression and anxiety disorders, including panic disorder, generalized anxiety disorder, social anxiety and post-traumatic stress disorder, who had an incomplete response to a variety of selective serotonin reuptake inhibitors (SSRIs) and who received augmentation with aripiprazole. The primary outcome measure was the Clinical Global Impression of Improvement (CGI-I). In the intent-to-treat analysis, the mean+/-SD CGI-S was 3.8+/-1.3 at endpoint. Fifty-nine percent of subjects received CGI-I ratings of 1 or 2, 'much improved' or 'very much improved,' in terms of their depression and anxiety symptoms at the end of 12 weeks. Several patients showed an early (weeks 1-5), as well as sustained, response to augmentation with doses of aripiprazole between 15 and 30 mg/day. The results suggest that aripiprazole may be effective as an augmentation for patients with persistent depressive and anxiety disorders despite initial SSRI treatment. Because this is a retrospective case review, further prospective studies are required to confirm these findings.

Adult↗

PubMed2005

Aripiprazole augmentation of selective serotonin reuptake inhibitors for treatment-resistant major depressive disorder.

BACKGROUND: Due to their favorable side effect profile, atypical antipsychotic agents offer important therapeutic advantages in mood disorders. Aripiprazole, an atypical antipsychotic agent with partial dopaminergic and serotonin 1A receptor agonist activity, may be particularly useful when used in conjunction with standard antidepressants in treatment-resistant depression. The purpose of this study was to test this hypothesis in depressed outpatients who have not experienced significant clinical improvement following an adequate trial of a selective serotonin reuptake inhibitor (SSRI). METHOD: 12 patients (mean +/- SD age = 46.6 +/- 11.3 years, 66.7% female) with major depressive disorder (MDD) diagnosed by use of the Structured Clinical Interview for DSM-IV-Axis I Disorders, who had failed to experience a clinical response following an adequate trial of an SSRI, were treated with open-label aripiprazole in addition to their SSRI for 8 weeks. Clinical response was defined as a 50% or greater decrease in depressive symptoms during the course of the trial (baseline-endpoint) as measured by the 17-item Hamilton Rating Scale for Depression total score. Data were collected from August 2003 to July 2004. RESULTS: 9/12 (75.0%) patients completed the trial. Using a completer analysis, 5/9 (55.6%) patients were classified as responders. An intent-to-treat (ITT) analysis resulted in 7 responders (58.3%). The overall proportion of remitters was 3/9 (33.3%) using a completer analysis and 5/12 (41.7%) using the ITT analysis. Aripiprazole administration appeared safe, with no severe adverse events observed in any of the study participants. CONCLUSIONS: These results suggest a possible augmentation role for aripiprazole when used in conjunction with SSRIs in SSRI-resistant MDD.

Ambulatory Care↗

PubMed2004

WSX-1: a key role in induction of chronic intestinal nematode infection.

Chronic infection by the gastrointestinal nematode Trichuris muris in susceptible AKR mice, which mount a Th1 response, is associated with IL-27p28 expression in the cecum. In contrast to wild-type mice, mice that lack the WSX-1/IL-27R gene fail to harbor a chronic infection, having significantly lower Th1 responses. The lower level of Ag-specific IFN-gamma-positive cells in WSX-1 knockout (KO) mice was found to be CD4(+) T cell specific, and the KO mice also had increased levels of IL-4-positive CD4(+) T cells. Polyclonal activation of mesenteric lymph node cells from naive WSX-1 KO or wild-type mice demonstrated that there was no inherent defect in the production of IFN-gamma by CD4(+) T cells, suggesting the decrease in these cells seen in infected WSX-1 KO mice is an in vivo Ag-driven effect. IL-12 treatment of WSX-1 KO mice failed to rescue the type 1 response, resulting in unaltered type-2-driven resistance. Infection of WSX-1 KO mice was also associated with a reduction of IL-27/WSX-1 downstream signaling gene expression within the cecum. These studies demonstrate an important role for WSX-1 signaling in the promotion of type 1 responses and chronic gastrointestinal nematode infection.

Animals↗

PubMed2004

S-adenosyl-L-methionine (SAMe) as an adjunct for resistant major depressive disorder: an open trial following partial or nonresponse to selective serotonin reuptake inhibitors or venlafaxine.

BACKGROUND: The purpose of this open trial was to evaluate the safety, tolerability, and efficacy of oral S-adenosyl-L-methionine as an antidepressant adjunct among partial and nonresponders to serotonin reuptake inhibitors or venlafaxine. METHOD: Thirty antidepressant-treated adult outpatients with persisting major depressive disorder received 800 to 1600 mg of S-adenosyl-L-methionine tosylate over a 6-week trial. RESULTS: Intent-to-treat analyses based on the Hamilton Depression Rating Scale revealed a response rate of 50% and a remission rate of 43% following augmentation with S-adenosyl-L-methionine. Gastrointestinal symptoms and headaches were the most common side effects. CONCLUSION: Augmentation of selective serotonin reuptake inhibitors or venlafaxine with S-adenosyl-L-methionine warrants a placebo-controlled trial in resistant depression.

Adult↗

PubMed2004

An open-label study of levetiracetam for the treatment of social anxiety disorder.

OBJECTIVE: Social anxiety disorder is a disabling condition characterized by excessive fear and avoidance of social and performance situations. While a variety of effective pharmacotherapies exists, many patients do not fully respond to or tolerate available agents. Preclinical and early clinical experience with levetiracetam, a novel anticonvulsant agent, suggests that levetiracetam has anxiolytic properties and a favorable adverse event profile. Levetiracetam thus warrants systematic evaluation as a treatment option for anxiety disorders. METHOD: Twenty adult outpatients who were recruited through advertisement and clinical referral and who met DSM-IV criteria for social anxiety disorder, generalized type, participated in this 8-week open-label, flexible-dose study from November 2002 to December 2003. Participants were required to have scores of >/= 50 on the Liebowitz Social Anxiety Scale (LSAS) and >/= 4 on the Clinical Global Impressions-Severity of Illness scale (CGI-S) at baseline. The presence of comorbid depression and anxiety disorders were permitted as long as social anxiety disorder was the primary disorder. Levetiracetam was initiated at 250 mg/day for the first week and flexibly titrated up to a maximum of 3000 mg/day (1500 mg b.i.d.). The primary outcome measure was change in the LSAS score at endpoint. RESULTS: There was a clinically significant 20.5-point decrease in LSAS scores in the intent-to-treat, last-observation-carried-forward analysis (t = 3.1; p <.01, N = 20). There were also significant reductions in CGI-S (p <.01) and Hamilton Rating Scale for Anxiety (p <.02) scores. CONCLUSIONS: This pilot study supports the safety and potential efficacy of a novel agent, levetiracetam, for the treatment of social anxiety disorder. Larger controlled trials are warranted to confirm these results.

Adult↗

PubMed2003

Lithium augmentation of nortriptyline for subjects resistant to multiple antidepressants.

Lithium augmentation, the most studied augmentation strategy for depression, has not been evaluated in patients with a history of non-response to multiple antidepressants. The objective of this study was to assess the efficacy of lithium augmentation for patients with a history of treatment resistant depression who also failed a prospective trial of nortriptyline. We enrolled 92 subjects with treatment resistant depression. Treatment resistance was defined by at least one, but no more than five, adequate trials of antidepressants during the current episode. Subjects were treated with nortriptyline (NT) for 6 weeks. Those subjects who tolerated NT for 6 weeks and whose depression did not respond (n=35) were randomized to receive either lithium (n=18) or placebo (N=17) augmentation of nortriptyline for an additional 6 weeks. Response was defined as an equal to or greater than 50% decrease in HAM-D-17 scores. After 6 weeks of double-blind augmentation, 12.5 % of subjects responded to lithium and 20.0% to placebo. Our results revealed no significant difference between lithium and placebo augmentation. While lithium augmentation seems to be useful in depression refractory to a single medication in some studies, our data suggest limited usefulness of this option for patients refractory to multiple treatments. More definitive data await the outcome of the NIMH Sequential Treatment Alternatives to Relieve Depression (STAR*D) study.

Adolescent↗

PubMed2003

A pilot, open study of sertraline in outpatients with treatment-resistant depression (TRD) or with a history of TRD who responded but later relapsed.

While most depressed patients are prescribed a selective serotonin reuptake inhibitor (SSRI) as an initial treatment, the use of SSRIs as a second or third-line treatment for depression is not as prevalent. This trial assessed the efficacy of sertraline for patients with treatment-resistant depression (TRD) or patients with a history of TRD who responded but later relapsed. Twelve patients with TRD who had not responded to a number of antidepressant trials (n=7), or had responded but subsequently suffered a relapse (n=5), were enrolled in an 8-week, open trial of sertraline. Both a completer analysis (n=6) and an intent-to-treat (ITT) analysis (n=12) were performed to evaluate sertraline response rates. Using a completer analysis, four patients (66.6%) were classified as responders; one (16.7%) as a partial responder and one (16.7%) as a non-responder. An ITT analysis resulted in five (41.7%) patients being classified as responders; one (8.3%) as a partial responder and six (50%) as non-responders. Of the four responders in the completer analysis, three (50%) achieved remission. Of the five responders in the ITT analysis, four (33.3%) achieved remission. Overall, two of seven (28.6%) non-responders and three of five (60.0%) relapsers responded to sertraline. The present results suggest the potential utility of sertraline for patients with TRD, or those with a history of TRD who responded but later relapsed, and warrant larger, placebo-controlled studies to further explore the potential role of sertraline for such patients.

Adult↗

PubMed2003

Hopelessness and suicidal ideation in outpatients with treatment-resistant depression: prevalence and impact on treatment outcome.

Depression and hopelessness are risk factors for suicide. The purpose of this study was to examine the extent of suicidal ideation and hopelessness in outpatients with treatment-resistant depression (TRD) and to study the impact of suicidal ideation and hopelessness on treatment with nortriptyline (NT). The degree of suicidal ideation and hopelessness was assessed during the screen visit with the use of items #3 and #30 of the Hamilton Depression Rating Scale (HAM-D) in 89 patients with TRD who entered a 6-week open trial of NT. Forty of these patients also completed the Beck Hopelessness Index (BHI) during the screen visit. In separate logistic regressions, the scores from the BHI and the two HAM-D items were then tested as predictors of clinical response to the 6-week trial with NT, controlling for the severity of depression. More than half of patients reported thoughts or wishes of death to self and significant hopelessness. A greater degree of hopelessness before treatment in completers, reflected by the score on the HAM-D item #30, predicted response to NT. More than half of patients with prominent hopelessness who completed the trial responded. Patients with TRD are more likely than not to report prominent suicidal ideation and hopelessness. Furthermore, a full 6-week trial of NT, a relatively noradrenergic tricyclic antidepressant, may be particularly useful in patients who have failed to respond to several antidepressants and also report significant hopelessness.

Adolescent↗

PubMed2003

Valproic acid for the treatment of social anxiety disorder.

The aim of the study was to examine the efficacy of valproic acid in participants with social anxiety disorder. Following a 2-week single-blind, placebo run-in period, 17 participants were enrolled in a 12-week open flexible-dose trial of valproic acid (500-2500 mg). The primary outcome measures were the mean change from baseline in the Liebowitz Social Anxiety Scale (LSAS) total score and responder status [defined as a Clinical Global Impression of Improvement score (CGI-I) < or =2]. Social anxiety symptoms as measured by the LSAS and CGI-I scores significantly improved with treatment. The mean reduction in the LSAS was 21.3 points in the last visit carried forward analysis and 19.1 points for the completer analysis, with 41.1% and 46.6% participants, respectively, achieving responder status. The results from this open-label trial suggest the potential efficacy of valproic acid for the treatment of social anxiety disorder. Placebo-controlled trials are indicated to confirm these findings.

Adult↗

PubMed2003

Combined paroxetine and clonazepam treatment strategies compared to paroxetine monotherapy for panic disorder.

Despite the widespread application of combined selective serotonin reuptake inhibitors (SSRI) and benzodiazepine treatment for panic disorder, there has been relatively little systematic assessment of the safety and efficacy of this therapeutic strategy. Although the limited number of studies to date suggest a more rapid onset of benefit with combined treatment, this study is the first to address the critical question of whether continued combined treatment confers superior efficacy. This study is a randomized, double-blind, three-arm study in patients with panic disorder (n = 60), comparing the efficacy and safety of paroxetine and placebo (PP), paroxetine coadministered with clonazepam followed by a tapered benzodiazepine discontinuation phase (PC-D), and ongoing combination treatment (PC-M). All treatment groups demonstrated significant improvement by endpoint. There was a significant advantage for the combined treatment groups early in treatment but, subsequently, outcome in all three groups was similar. A trend towards greater achievement of endpoint remission status for the PC-D group was attenuated when variability in baseline severity was considered. The results of this study should be interpreted in the context of a relatively moderate sample size and higher rates of early dropout. Combined treatment with paroxetine and clonazepam resulted in more rapid response than with the SSRI alone, but there was no differential benefit beyond the initial few weeks of therapy. Initiating combined treatment followed by benzodiazepine taper after a few weeks may provide early benefit while avoiding the potential adverse consequences of long-term combination therapy.

Adolescent↗

PubMed2003

Treatment of antidepressant-induced sexual dysfunction.

This article reviews the prevalence of antidepressant-induced sexual dysfunction and the strategies available for managing sexual adverse events. A high incidence of sexual dysfunction has been observed in patients treated with antidepressants. In particular, it has been reported in more than half of the patients treated with selective serotonin reuptake inhibitors. There are various pharmacotherapeutic strategies that can lead to reversal of sexual dysfunction. This article will review clinical studies on pharmacotherapeutic agents used to treat antidepressant-induced sexual dysfunction, as well as agents used to treat depression with a favorable sexual side-effect profile. Because sexual dysfunction can lead to treatment noncompliance and depression relapse, this is an issue that should be addressed by clinicians at initiation and throughout the course of treatment.

Antidepressive Agents↗

PubMed2003

Nortriptyline for treatment-resistant depression.

BACKGROUND: Up to 30% of patients with major depression fail to respond to an antidepressant trial, with most taking a selective serotonin reuptake inhibitor (SSRI) as initial treatment. While the tricyclic antidepressants might be effective for SSRI nonresponders, they have been relegated to third- and fourth-line treatment. This study assesses the efficacy of nortriptyline for patients with treatment-resistant major depression. METHOD: 92 patients with treatment-resistant DSM-III-R major depression, with resistance defined by at least 1, but no more than 5, well-documented adequate trials of antidepressants during the current episode, were treated openly with nortriptyline for 6 weeks. Patients were titrated up to full target doses of nortriptyline within 1 week, with target blood levels of 100 ng/mL. Response was defined as a 50% or greater decrease of baseline 17-item Hamilton Rating Scale for Depression score. We performed an intent-to-treat analysis with the last observation carried forward. RESULTS: Approximately 40% of patients were responders (N = 39) and 12% were remitters (N = 11) after 6 weeks of nortriptyline. Over a third of patients were unable to complete the trial. CONCLUSION: Nortriptyline was effective for over a third of patients with treatment-resistant depression, and nortriptyline should be considered as potential treatment if patients fail to respond to other antidepressants.

Adolescent↗