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Biomedical subjects

R B Lydiard

Publications and source records attributed to R B Lydiard.

At least 37 records · Page 2Linked to original sources
PubMed1999

Feasibility of using fMRI to study mothers responding to infant cries.

While parenting is a universal human behavior, its neuroanatomic basis is currently unknown. Animal data suggest that the cingulate may play an important function in mammalian parenting behavior. For example, in rodents cingulate lesions impair maternal behavior. Here, in an attempt to understand the brain basis of human maternal behavior, we had mothers listen to recorded infant cries and white noise control sounds while they underwent functional MRI (fMRI) of the brain. We hypothesized that mothers would show significantly greater cingulate activity during the cries compared to the control sounds. Of 7 subjects scanned, 4 had fMRI data suitable for analysis. When fMRI data were averaged for these 4 subjects, the anterior cingulate and right medial prefrontal cortex were the only brain regions showing statistically increased activity with the cries compared to white noise control sounds (cluster analysis with one-tailed z-map threshold of P < 0.001 and spatial extent threshold of P < 0.05). These results demonstrate the feasibility of using fMRI to study brain activity in mothers listening to infant cries and that the anterior cingulate may be involved in mothers listening to crying babies. We are currently replicating this study in a larger group of mothers. Future work in this area may help (1) unravel the functional neuroanatomy of the parent-infant bond and (2) examine whether markers of this bond, such as maternal brain response to infant crying, can predict maternal style (i.e., child neglect), offspring temperament, or offspring depression or anxiety.

Adult↗
PubMed1999

Pharmacological treatment of anxiety in the medically ill patient.

Treatment guidelines which are available are intended for treatment of medically healthy patients. There is little information in the literature regarding the treatment of patients who are medically ill. Anxiety and anxiety disorders are frequently encountered in patients with serious medical disorders. These medically ill patients may have substantial changes in pharmacokinetic factors as a result of their current illness or treatment. Also, treatment considerations related to their accompanying medical treatment(s) are sometimes required. These various factors may result in a different initial choice of agents, alterations in the dosage of a given agent, or even preclude the use of some standard agents. In this chapter, we first present a review of the current psychopharmacologic treatment of anxiety disorders. In the second section, we review the potential pharmacokinetic consequences of serious hepatic renal, pulmonary and cardiac disease relevant to the pharmacological treatment of anxiety.

Anti-Anxiety Agents↗
PubMed1999

Evaluation of the efficacy, safety and physiological effects of fluvoxamine in social phobia.

There is no US Food and Drug Administration (FDA) approved treatment for social phobia although data suggest efficacy for several drug classes, including beta-blockers, benzodiazepines, monoamine oxidase inhibitors, and selective serotonin reuptake inhibitors (SSRIs). The SSRIs are particularly attractive due to their favourable tolerance and safety profile. An open label trial of fluvoxamine was conducted to evaluate its efficacy and safety in the treatment of social phobia (DSM-III-R) and to assess physiological changes that may accompany treatment. Fifteen non-depressed patients, aged 22-44 years (mean 31.6 years), entered the study. A 5-min performance task (public speaking simulation) preceded and concluded the active treatment period. Cardiovascular monitoring was performed during this time and blood sampled for plasma cortisol and steady-state plasma fluvoxamine concentration (at week 7). Ten patients (5 men and 5 women) completed an active 6 week treatment period of flexible dosing (50-150 mg/day). Five patients failed to complete the study due to drowsiness (n = 2), nausea (n = 1), or were lost to follow-up (n = 2). Analysis of clinical ratings indicated a statistically significant decrease in all scales from baseline to week 7 at the conclusion of the active treatment period. Clinical benefits were still evident at follow-up 1 week after drug discontinuation. Neither physiological effects nor plasma drug concentration correlated with clinical change. Fluvoxamine appeared to be effective and well tolerated in completers. Randomized clinical trials are needed to further demonstrate the efficacy of fluvoxamine in the treatment of social phobia.

Adult↗
PubMed1999

Continuing treatment of panic disorder after acute response: randomised, placebo-controlled trial with fluoxetine. The Fluoxetine Panic Disorder Study Group.

BACKGROUND: Data concerning appropriate treatment in panic disorder following an initial response to acute therapy are limited. AIMS: To assess the safety and efficacy of continued fluoxetine treatment following successful acute therapy of panic disorder. METHOD: Patients who responded to acute fluoxetine treatment were randomised to 24 weeks of continued fluoxetine or placebo. RESULTS: Fluoxetine responders randomised to continue on their acute-phase fluoxetine dose experienced statistically significant improvement in panic attack frequency and phobia rating scale score over 24 weeks of therapy, while those switched to placebo experienced statistically significant worsening in Hamilton Anxiety (HAM-A), Hamilton Depression (HAM-D) and SCL-90-R rating scores. CONCLUSIONS: Fluoxetine was associated with improved clinical outcomes compared with placebo during continuation therapy.

Adult↗
PubMed1999

Once-weekly dosing of fluoxetine in the maintenance of remission in panic disorder.

BACKGROUND: Fluoxetine and its active metabolite norfluoxetine have long half-lives of 4-6 days and 4-16 days, respectively. We postulated that, owing to the long elimination half-life, patients diagnosed with panic disorder might be maintained on fluoxetine taken once a week, after being treated initially with daily doses of fluoxetine. METHOD: Ten patients with DSM-III-R panic disorder were treated openly with fluoxetine, 20-40 mg daily. Once panic free, these patients were switched to once-weekly dosing of fluoxetine, and dosage was titrated as needed. RESULTS: All 10 patients successfully switched to once-weekly dosing. One patient reported recurrence of panic attacks 18 months after the switch. After a brief treatment for 4 weeks with benzodiazepines and daily fluoxetine, the patient was once again maintained on once-weekly dosing when rechallenged. Patients have been maintained in a panic-free state for up to 26 months with a single weekly dose of fluoxetine ranging from 10 to 60 mg. The medication was well tolerated. CONCLUSION: Fluoxetine at doses ranging from 10 to 60 mg administered once weekly appears to be effective maintenance treatment for patients with panic disorder who were initially treated successfully with daily fluoxetine. A once-weekly regimen may allow for considerable cost savings and may serve as a convenient alternative method for treating panic disorder.

Adult↗
PubMed1998

Brain circuits in panic disorder.

This paper reviews the pathophysiology of panic disorder (PD), within the context of newly described "fear circuitries," which have been well characterized in preclinical models. Substantial advances in the neurosciences have made it possible for clinical neuroscientists to refine our understanding of the pathophysiology of PD and the mechanisms of currently effective treatment. These advances have in turn helped generate testable hypotheses for future neurobiological and psychopharmacologic research. Perturbation of mutual modulation ("cross talk") between key brain transmitter systems (serotonin, norepinephrine, gamma-aminobutyric acid, corticotropin-releasing factor, and others) may underlie the pathogenesis of panic-anxiety. Restoration of normal homeostasis may be an important therapeutic component of antipanic therapy and may provide information about underlying neurocircuits. Neuroimaging, an important new tool, has already begun to bridge the gap between the preclinical and clinical neurosciences through confirmation of hypothesized dysfunction of the complex human prefrontal cortex and its subcortical components. In higher species, such as humans, dysfunction of cortical inhibition or excessive cortical activation of caudal limbic structures is postulated to lead to activation of the phylogenetically conserved amygdalofugal pathways. Consistent with probable subtypes of PD, overlapping theoretical models of panic neurocircuitries are proposed, including ventilatory dysregulation, which is coupled with neurovascular instability in a critical area of the panic neurocircuitry--the amygdalohippocampus. Neuroimaging appears a critical tool in guiding further elaboration of the interaction of cortical and subcortical components of the panic neurocircuitry, whereas challenge studies appear crucial in gathering further information regarding brain stem dysfunction.

Animals↗
PubMed1998

Paroxetine treatment of generalized social phobia (social anxiety disorder): a randomized controlled trial.

CONTEXT: The generalized type of social phobia (social anxiety disorder) is a severe and often disabling form of social anxiety that affects approximately 5% of the general population. Earlier research has shown monoamine oxidase inhibitors or benzodiazepines to be effective in treating this condition, but neither has achieved widespread use. OBJECTIVE: To compare the efficacy of paroxetine, a selective serotonin reuptake inhibitor, with placebo in adults with generalized social phobia. DESIGN: Twelve-week, multicenter, randomized, double-blind trial. SETTING: Thirteen centers across the United States and 1 in Canada. PARTICIPANTS: Between April 13, 1995, and February 28, 1996, 187 persons meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for generalized social phobia were randomized (and 183 returned for at least 1 efficacy assessment) to treatment. INTERVENTION: After a 1-week, single-blind, placebo, run-in period, patients received a double-blind, 11-week course of either paroxetine or matching-image placebo. The initial daily dosage of paroxetine (or placebo) was 20 mg with increases of 10 mg/d weekly (flexible dosing to a maximum of 50 mg/d) permitted after the second week of treatment. MAIN OUTCOME MEASURES: Number of responders based on the Clinical Global Impression Global Improvement Item ("much improved" or "very much improved"); mean change from baseline on the Liebowitz Social Anxiety Scale total score. RESULTS: Fifty (55.0%) of 91 persons taking paroxetine and 22 (23.9%) of 92 persons taking placebo were much improved or very much improved at the end of treatment (odds ratio [OR], 3.88; 95% confidence interval [CI], 2.81-5.36). Mean Liebowitz Social Anxiety Scale total scores were reduced by 39.1% (the mean baseline score of 78.0 declined by a mean of 30.5 points at follow-up) in the paroxetine group compared with 17.4% (the mean baseline score of 83.5 declined 14.5 points at follow-up) in the placebo group, a difference of 21.7% (95% CI, 8.7%-34.7%) favoring paroxetine. CONCLUSIONS: Paroxetine is an effective treatment for patients with generalized social phobia. Short-term (ie, 11-week) treatment results in substantial and clinically meaningful reductions in symptoms and disability. Future research should test whether these may be further reduced by extended treatment or supplementation with specific educational-cognitive-behavioral techniques.

Adult↗
PubMed1998

Sleep Deprivation in social phobia and generalized anxiety disorder.

BACKGROUND: Sleep deprivation has been shown to improve depressive symptoms in some patients with major depressive disorder, but it has not been tested in patients with generalized anxiety disorder (GAD) or social phobia (SP). METHODS: To determine if sleep deprivation altered anxiety or depressive symptoms in patients with GAD (n = 7) or SP (n = 8), we sleep deprived patients and normal controls (n = 18) for one night. RESULTS: On one measure of anxiety, GAD patients improved compared with controls, but there were otherwise no significant change differences between controls and SP or GAD patients. CONCLUSIONS: The lack of benefit is consistent with previous findings that sleep deprivation provides no benefit to patients with other anxiety disorders. Sleep deprivation may be a biological intervention that distinguishes anxiety from affective disorders.

Adolescent↗
PubMed1998

Abnormal peripheral benzodiazepine receptor density associated with generalized social phobia.

BACKGROUND: Peripheral benzodiazepine receptors (PBRs) are involved in regulating stress responses. Abnormally low numbers of platelet PBRs have been found in patients with panic disorder, posttraumatic stress disorder, and generalized anxiety disorder, but not in patients with obsessive-compulsive disorder (OCD) or major depressive disorder (MDD). The purpose of this study was to evaluate the PBR density on platelets from patients with generalized social phobia (GSP). METHODS: The density (Bmax) and dissociation constant (Kd) of platelet PBRs was determined for 53 medication-free patients with GSP and an equal number of control subjects (NC). RESULTS: The GSP group was found to have a significantly lower PBR Bmax than the NC group (GSP = 2764 +/- 1242 vs. NC = 4327 +/- 1850 fmol/mg protein, df = 1,100, F = 22.7, p = .00001). CONCLUSIONS: GSP shares this PBR abnormality with some other anxiety disorders but not with OCD or MDD. PBRs may play a role in the pathophysiology of some anxiety disorders.

Adult↗
PubMed1998

Comorbidity of major depression and panic disorder.

Panic disorder and major depression frequently coexist in the clinical setting. Patients with overlapping symptoms of depression and panic disorder may have more severe symptoms, may require earlier treatment, earlier and more frequent hospitalization, and may have worse outcomes. In addition, such patients are at greater risk for suicide than those having either disorder alone. In light of the importance of these clinical consequences, the authors will review the available literature on the prevalence and prognosis of comorbid depression and panic disorder and will highlight the major clinical characteristics of panic disorder in depressed patients and the treatment strategies most often used.

Comorbidity↗
PubMed1998

The role of drug therapy in social phobia.

Social phobia is a potentially disabling condition requiring effective and well tolerated treatment. The monoamine oxidase inhibitors, benzodiazepines and, more recently, the selective serotonin reuptake inhibitors (SSRIs) have all shown promise as treatments for this disorder. Paroxetine, the most thoroughly studied SSRI, has been shown to be effective in treating the symptoms of generalized social phobia in a large-scale, placebo-controlled trial. Paroxetine and the other SSRIs show promise as a new and safe therapeutic choice for patients with social phobia.

Humans↗
PubMed1998

Outcome assessment and clinical improvement in panic disorder: evidence from a randomized controlled trial of fluoxetine and placebo. The Fluoxetine Panic Disorder Study Group.

OBJECTIVE: Although panic attacks account for only a portion of the morbidity of panic disorder and panic attack frequency assessments are unreliable, studies of drug efficacy in panic disorder have generally used reduction in panic attack frequency as the primary measure of improvement. The authors studied the efficacy of fluoxetine treatment in panic disorder and measured the relative contributions of changes in symptoms to overall improvement. METHOD: Patients with a diagnosis of panic disorder (N = 243) were randomly assigned to treatment with 10 or 20 mg/day of fluoxetine or placebo. Primary outcome measures were change in panic attack frequency and clinician-rated Clinical Global Impression improvement scores. Other assessments included a panic attack inventory, clinician-rated and patient-rated versions of the Panic and Phobic Disorder Change Scale, a phobia rating scale, the Hamilton Anxiety Rating Scale, the 21-item Hamilton Depression Rating Scale, and the Sheehan Disability Scale. Correlations were determined between outcomes in individual symptom domains and overall clinical outcome. RESULTS: Fluoxetine, particularly the 20-mg/day dose, was associated with more improvement than was placebo in patients with panic disorder across multiple symptom measures, including global improvement, total panic attack frequency, phobic symptoms, and functional impairment. Global improvement was most highly correlated with reductions in overall anxiety and phobic symptoms and least correlated with reduction in panic attacks. Fluoxetine treatment for panic disorder was well tolerated, with a safety profile consistent with that observed for fluoxetine in other disorders. CONCLUSIONS: These data provide support for the efficacy and safety of fluoxetine treatment in reducing panic attacks, phobic symptoms, anxiety, and depressive symptoms in patients with panic disorder. Reductions in panic attack frequency in subjects given either fluoxetine or placebo were less closely related to overall clinical improvement than reductions in phobic avoidance, anxiety, depressive symptoms, and functional impairment, suggesting that outcome measures in this disorder should be more broadly based.

Adult↗
PubMed1998

Efficacy studies of paroxetine in panic disorder.

The optimal assessment of treatment outcome for studies assessing the efficacy of treatments for panic disorder has been a controversial topic. A recent National Institute of Mental Health (NIMH)-sponsored consensus conference addressed this important topic, and a summary paper regarding assessment of essential elements of the disorder resulted. Among other conclusions, it was agreed that several different domains should be considered as essential. This article reviews three pivotal studies assessing the efficacy of paroxetine for the treatment of panic disorder, and evaluates these studies for inclusion of those variables considered essential. Additionally, some data were reanalyzed to determine the percentage of individuals in these studies who are unequivocal responders (i.e., were both panic-free and rated on global assessment as responders). A longer-term treatment and relapse study is also mentioned briefly.

Antidepressive Agents, Second-Generation↗
PubMed1998

Anxious depression.

Depression and anxiety often coexist. When they co-occur, both anxiety and depression appear to be more severe. Increased morbidity, poorer acute and long-term outcome, increased suicide risk, and increased treatment resistance are associated with comorbid anxiety and depression. The term anxious depression has taken on newer meaning with the changes in the diagnostic system that allow for concurrent diagnosis of anxiety disorders and major depression. Attention to the subtype of both anxiety and depression could have significant effects on treatment choice by the clinician. The authors review some historical aspects of anxious depression and also highlight some of the advances in differential diagnosis and treatment of coexisting depression and anxiety.

Anti-Anxiety Agents↗
PubMed1997

Moclobemide in social phobia: a controlled dose-response trial.

Although the monoamine oxidase inhibitor phenelzine has proven efficacious in social phobia, the risk of hypertensive crises has reduced its acceptability. The reversible monoamine oxidase inhibitor moclobemide has less potential for such reactions, but its efficacy in this disorder remains unproven. A double-blind, placebo-controlled study was undertaken to assess the efficacy and safety of fixed doses of moclobemide. After a 1-week placebo run-in, subjects with social phobia were randomly assigned to placebo or one of five doses (75 mg, 150 mg, 300 mg, 600 mg, or 900 mg daily) of moclobemide for 12 weeks. Although a trend toward greater efficacy of higher doses of moclobemide was observed at 8 weeks, no differences in response to various doses of the drug and placebo were observed at 12 weeks. At 12 weeks, 35% of subjects on 900 mg of moclobemide and 33% of those on placebo were at least much improved. Moclobemide was well tolerated, insomnia being the only dose-related adverse event observed with the drug. In this dose-response trial, moclobemide did not demonstrate efficacy at 12 weeks. Some other controlled studies have found moclobemide and brofaromine, another reversible monoamine oxidase inhibitor, efficacious in social phobia. Possible reasons for inconsistent findings are discussed.

Adult↗
PubMed1997

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.

1-Naphthylamine↗