Biomedical subjects

Jonathan R T Davidson

Publications and source records attributed to Jonathan R T Davidson.

At least 37 records · Page 2Linked to original sources

PubMed2005

Antidepressant therapy in patients with ischemic heart disease.

Depressive disorders are common in patients with ischemic heart disease and have serious consequences in terms of the risk of further cardiac events and cardiac mortality. Among survivors of acute myocardial infarction, up to one fifth meet diagnostic criteria for major depression, and the presence of major depression carries a >5-fold increased risk for cardiac mortality within 6 months. This article reviews clinical trial data on the cardiac safety profiles of antidepressant agents with the aim of discussing clinical considerations in selecting the most appropriate treatment of comorbid depression in patients with ischemic heart disease. Tricyclic antidepressants are effective against depression but are associated with cardiovascular side effects including orthostatic hypotension, slowed cardiac conduction, antiarrhythmic activity, and increased heart rate. Selective serotonin reuptake inhibitors, by contrast, have benign cardiovascular profiles and are well tolerated in patients with cardiac disease. The safety of dual-acting serotonin and noradrenaline reuptake inhibitors has not been well studied. Intervention with a selective serotonin reuptake inhibitors has the potential to provide the depressed patient with ischemic heart disease relief from their depressive symptoms and may offer a potential improvement in their cardiovascular risk profile.

Antidepressive Agents↗

PubMed2005

Trauma, resilience and saliostasis: effects of treatment in post-traumatic stress disorder.

There has been growing interest in the concept of resilience and the question as to whether psychotropic medications or psychosocial treatments might have resilience-enhancing effects. This pilot study investigates resilience in a sample of patients with post-traumatic stress disorder (PTSD) before and after treatment. Effects of treatment with tiagabine, fluoxetine, sertraline alone, and sertraline with cognitive behavioural therapy on resilience were assessed using the Connor-Davidson Resilience Scale (CD-RISC). Changes in resilience after treatment were measured and response to treatment was predicted from demographic, resilience and baseline disability measures. Changes in resilience following treatment were statistically significant. Items that showed the greatest change related to confidence, control, coping, knowing where to turn for help and adaptability. Items showing the least change related to religious and existential aspects of resiliency, effort, acting on a hunch, decision-making and goals. In linear and logistic regression models, gender, baseline CD-RISC score, baseline Sheehan Disability Scale score and an individual item from the CD-RISC scale, 'Sense of Humor', were significant predictors of response to treatment. Treatment of PTSD significantly improved resilience and reduced symptoms in this sample. Further controlled studies are indicated.

Adaptation, Psychological↗

PubMed2005

Maintenance therapy with fluoxetine in posttraumatic stress disorder: a placebo-controlled discontinuation study.

The effect of fluoxetine (FLU) in posttraumatic stress disorder was studied in a one-year trial. Subjects received open-label treatment for 6 months, followed by double-blind randomized treatment with FLU or placebo (PBO) for 6 months. Rates of relapse were compared using the Clinical Global Impressions of Improvement. One hundred twenty-three subjects entered open-label treatment, of whom 114 returned at least once. Sixty-two subjects were randomized to receive FLU or PBO, of whom 57 returned at least once and were analyzed. The dose of FLU ranged from 10 to 60 mg/d; at randomization, mean doses were 48.6 and 42.1 mg for FLU and PBO groups. Rates of relapse were 22% for FLU versus 50% for PBO (P = 0.02), and time to relapse on FLU was longer than for PBO (P = 0.02, log-rank statistic). The odds ratio for relapse on PBO relative to FLU was 3.50. No significant differences were found on other measures. Fluoxetine was well tolerated during double-blind treatment.

Adult↗

PubMed2005

Hyperforin plasma level as a marker of treatment adherence in the National Institutes of Health Hypericum Depression Trial.

BACKGROUND: A previously reported clinical trial of Hypericum perforatum (St John's wort) in depression did not demonstrate efficacy. We assessed treatment adherence by measuring plasma hyperforin and evaluated the possible impact of adherence on study results. METHODS: Outpatients with major depression (N = 340) were randomized to an 8-week trial of H. perforatum (900-1500 mg/d), sertraline (50-100 mg/d) as active comparator, or placebo. Plasma was available from 292 patients (86% of randomized). Samples from the placebo and H. perforatum groups were assayed for hyperforin, and samples from the sertraline group for sertraline/N-desmethyl-sertraline. RESULTS: Of the 104 patients randomized to placebo, 18 (17%) had detectable plasma hyperforin. Of the 97 patients randomized to H. perforatum, 17 (17%) had no detectable plasma hyperforin. All the assayed sertraline patients (N = 91) had plasma sertraline/N-desmethyl-sertraline. The clinical trial conclusions remained unchanged when only patients with plasma assay consistent with random assignment were included in the analyses. CONCLUSIONS: One of every 6 patients assigned to placebo had plasma hyperforin, and 1 of every 6 patients assigned to H. perforatum had no detectable plasma hyperforin. The finding underscores the difficulty of enforcing treatment adherence in clinical trials of preparations that are readily available in the community.

Adult↗

PubMed2005

Predictors of posttraumatic outcomes following the 1999 Taiwan earthquake.

This cross-sectional study examined 10-month outcomes in survivors after the 1999 earthquake in Taiwan. Two hundred fifty-two randomly selected subjects were interviewed to assess the following: categorical assignment to full or partial posttraumatic stress disorder (PTSD/PTSS), symptoms of PTSD, and general psychiatric morbidity. Using regression models, the following potential independent predictor variables were evaluated: age, gender, earthquake exposure, previous trauma, current depression, and general well-being. Variables predictive of PTSD/PTSS included female gender and current depression. Current depression and impaired well-being were predicted by greater PTSD severity. Greater psychiatric morbidity was predicted by female gender, current depression, number of traumatic experiences, and impaired well-being. These variables, particularly female gender, current depression, and impaired well-being, should be considered in assessing earthquake survivors who are at increased risk for developing posttraumatic sequelae.

Comorbidity↗

PubMed2005

Neuroactive steroids and suicidality in posttraumatic stress disorder.

OBJECTIVE: Recent studies suggest that neuroactive steroids may be altered in posttraumatic stress disorder (PTSD). Since high rates of suicidality accompany PTSD, the authors investigated neuroactive steroid levels and correlations to suicide attempts in veterans with this disorder. METHOD: Male veterans with PTSD enrolled in a larger study during inpatient hospitalization (N=130) were assessed for suicidal ideation or suicide attempt in the last 6 months. Serum levels of dehydroepiandrosterone (DHEA), androstenedione, testosterone, and estradiol were determined. The authors investigated associations between neuroactive steroids and suicidality. RESULTS: High rates of suicidality were observed. Close to 70% of these patients had suicidal thoughts, and 25% had attempted suicide in the last 6 months. Patients who had attempted suicide demonstrated significantly higher median DHEA levels than those who had not attempted suicide (15.6 versus 8.3 ng/ml), an association that persisted after adjustment for age. CONCLUSIONS: These findings suggest that higher DHEA levels may be linked to suicidality in veterans with PTSD and may be associated with the risk of self-harm.

Androstenedione↗

PubMed2005

Levetiracetam in social phobia: a placebo controlled pilot study.

While serotonergic antidepressants are now established as first-line pharamcotherapy for generalized social anxiety disorder (SAD), other agents with different mechanisms have shown promise in treating SAD. The aim of this pilot study is to examine the efficacy and safety of levetiracetam (LEV), an anticonvulsant with calcium channel modulating properties, in treating SAD. Adult outpatients meeting DSM-IV criteria for SAD were randomly assigned (2:1) to double-blind treatment with either LEV (500-3000 mg/day) or placebo (PBO) for 7 weeks. The primary outcome measures were the change from baseline in the Brief Social Phobia Scale (BSPS) and response using the Clinical Global Impression of Improvement scale (CGI-I). The mean (SD) BSPS scores at baseline and endpoint were 45.4 (9.7) and 31.2 (19.7) for LEV (n=9), compared to 43.5 (8.4) and 37.8 (19.9) for PBO (n =7) (ITT; ns). Rates of response were 22% for LEV and 14% for PBO using the CGI-I. Using a BSPS response criterion (>30% reduction), response rates were 44% for LEV and 14% for PBO. The effect sizes of LEV relative to PBO were 0.33 for the BSPS and 0.50 for the LSAS. In summary, the results of this study, while negative on the pre-defined measures, suggest promise for LEV as a new treatment of SAD. Further work should be carried out with larger sample sizes and optimal dosing strategies of the drug.

Adult↗

PubMed2005

Evidence-based guidelines for the pharmacological treatment of anxiety disorders: recommendations from the British Association for Psychopharmacology.

These British Association for Psychopharmacology guidelines cover the range and aims of treatment for anxiety disorders. They are based explicitly on the available evidence and are presented as recommendations to aid clinical decision making in primary and secondary medical care. They may also serve as a source of information for patients and their carers. The recommendations are presented together with a more detailed review of the available evidence. A consensus meeting involving experts in anxiety disorders reviewed the main subject areas and considered the strength of evidence and its clinical implications. The guidelines were constructed after extensive feedback from participants and interested parties. The strength of supporting evidence for recommendations was rated. The guidelines cover the diagnosis of anxiety disorders and key steps in clinical management, including acute treatment, relapse prevention and approaches for patients who do not respond to first-line treatments.

Adolescent↗

PubMed2005

The use of aripiprazole in obsessive-compulsive disorder: preliminary observations in 8 patients.

OBJECTIVE: To assess the effectiveness of aripiprazole, an atypical antipsychotic with dopamine- and serotonin-stabilizing properties, as monotherapy in treating obsessive-compulsive disorder (OCD). METHOD: Adult subjects meeting DSM-IV criteria for OCD who were not currently receiving pharmacotherapy for the disorder were entered into an 8-week open-label trial of treatment with aripiprazole (10-30 mg/day). Efficacy assessments included the Yale-Brown Obsessive Compulsive Scale (YBOCS) and the Clinical Global Impressions-Improvement scale. Safety assessments included evaluation of vital signs, weight, and treatment-emergent side effects. Data were collected from June 2003 to August 2004. RESULTS: Eight subjects were enrolled, 7 of whom took at least 1 dose of study medication. Using the last observation carried forward, the mean total YBOCS score decreased from 23.9 at baseline to 17.6 at the final visit (p = .06). More pronounced improvement was observed in compulsive symptoms (p < .05) compared with obsessive symptoms (p = .09). Three subjects (43%) responded to treatment, showing a 30% or greater reduction in YBOCS total score. Two subjects discontinued treatment within 1 week due to side effects (akathisia, nausea). While no changes were noted in vital signs, a mean weight gain of 1.8 kg was observed. CONCLUSION: Although from a small, open-label study, these results suggest that aripiprazole holds promise for treating OCD. Larger, controlled studies of aripiprazole as monotherapy and as augmentation in partial responders to selective serotonin reuptake inhibitors are needed.

Adult↗

PubMed2005

Safety and efficacy of escitalopram in the long-term treatment of generalized anxiety disorder.

INTRODUCTION: Generalized anxiety disorder (GAD) is a chronic disorder that requires long-term treatment. Escitalopram has previously been shown to be effective and well tolerated in the acute treatment of GAD. METHOD: Three 8-week, double-blind, placebo-controlled trials of nearly identical design were conducted of escitalopram in moderate-to-severe GAD (DSM-IV criteria). Patients completing these trials were given the option of entering a 24-week, open-label, flexible-dose trial of escitalopram (10-20 mg/day). Data were collected from September 20, 2000, to August 15, 2002. RESULTS: Two hundred ninety-nine (56.8%) of 526 patients completed 24 weeks of open-label treatment. The mean Hamilton Rating Scale for Anxiety (HAM-A) score at baseline of open-label treatment was 13.1. Long-term escitalopram treatment led to continuing improvement on all anxiety and quality-of-life (QOL) scores. Of those completing 24 weeks of treatment, 92.0% were responders (Clinical Global Impressions-Improvement scale score < or = 2), and the mean HAM-A score in the completed analysis was 6.9; using the last observation carried forward (LOCF), 75.9% were responders, and the mean HAM-A score in the LOCF analysis was 9.2 at endpoint. Insufficient therapeutic response and adverse events led to withdrawal of 4.2% and 9.9% of patients, respectively. Mean increase in weight from baseline was 3.0 lb. No clinically notable changes in mean laboratory, vital sign, or electrocardiographic values were observed. CONCLUSION: These results support the long-term tolerability and effectiveness of escitalopram in the treatment of GAD.

Adult↗

PubMed2004

Fluoxetine, comprehensive cognitive behavioral therapy, and placebo in generalized social phobia.

BACKGROUND: Generalized social phobia is common, persistent, and disabling and is often treated with selective serotonin reuptake inhibitor drugs or cognitive behavioral therapy. OBJECTIVE: We compared fluoxetine (FLU), comprehensive cognitive behavioral group therapy (CCBT), placebo (PBO), and the combinations of CCBT/FLU and CCBT/PBO. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Two academic outpatient psychiatric centers. PATIENTS: Subjects meeting a primary diagnosis of generalized social phobia were recruited via advertisement. Seven hundred twenty-two were screened, and 295 were randomized and available for inclusion in an intention-to-treat efficacy analysis; 156 (52.9%) were male, 226 (76.3%) were white, and mean age was 37.1 years. INTERVENTIONS: Treatment lasted for 14 weeks. Fluoxetine and PBO were administered at doses from 10 mg/d to 60 mg/d (or equivalent). Group comprehensive cognitive behavioral therapy was administered weekly for 14 sessions. MAIN OUTCOME MEASURES: An independent blinded evaluator assessed response with the Brief Social Phobia Scale and Clinical Global Impressions scales as primary outcomes. A videotaped behavioral assessment served as a secondary outcome, using the Subjective Units of Distress Scale. Adverse effects were measured by self-rating. Each treatment was compared by means of chi2 tests and piecewise linear mixed-effects models. RESULTS: Clinical Global Impressions scales response rates in the intention-to-treat sample were 29 (50.9%) (FLU), 31 (51.7%) (CCBT), 32 (54.2%) (CCBT/FLU), 30 (50.8%) (CCBT/PBO), and 19 (31.7%) (PBO), with all treatments being significantly better than PBO. On the Brief Social Phobia Scale, all active treatments were superior to PBO. In the linear mixed-effects models analysis, FLU was more effective than CCBT/FLU, CCBT/PBO, and PBO at week 4; CCBT was also more effective than CCBT/FLU and CCBT/PBO. By the final visit, all active treatments were superior to PBO but did not differ from each other. Site effects were found for the Subjective Units of Distress Scale assessment, with FLU and CCBT/FLU superior to PBO at Duke University Medical Center, Durham, NC. Treatments were well tolerated. CONCLUSIONS: All active treatments were superior to PBO on primary outcomes. Combined treatment did not yield any further advantage. Notwithstanding the benefits of treatment, many patients remained symptomatic after 14 weeks.

Adult↗

PubMed2004

Posttraumatic stress disorder in callers to the Anxiety Disorders Association of America.

We surveyed callers to the Anxiety Disorders Association of America (ADAA) with posttraumatic stress disorder (PTSD) and subthreshold PTSD (SPTSD). Most subjects heard about ADAA through media referrals and were satisfied with the service given by the association. The most frequent requests were for written information, learning how to cope with anxiety, and access to a local support group. Among callers, rates of PTSD (n=80) and SPTSD (n=111) were 8.0% and 11.1%, respectively. PTSD or SPTSD subjects were more likely to be younger, female, and with lower income than their no-Axis I psychiatric disorder controls (NAC) who had been exposed to trauma. In addition, they presented with more history of trauma, especially violent trauma, psychiatric comorbidity, recent psychotropic use, and side effects. More medical comorbidity, increased health service use, and reduced work productivity were also found among the PTSD and SPTSD subjects. SPTSD subjects were comparable to PTSD subjects on most of the measures with a few exceptions (more likely to be married, to have less psychiatric comorbidity, less medication use for mood and social fear, and fewer sedation and sexual side effects, and to have less health service use and work impairment). In conclusion, callers to ADAA with PTSD were particularly impaired and used the health care system extensively. Although the SPTSD subjects were not as impaired as those with PTSD, they were disadvantaged in many ways.

Adult↗

PubMed2004

Escitalopram in the treatment of generalized anxiety disorder: double-blind, placebo controlled, flexible-dose study.

Escitalopram has been shown in clinical trials to improve anxiety symptoms associated with depression, panic disorder, and social anxiety disorder. This study was designed to evaluate the efficacy and tolerability of escitalopram in the treatment of generalized anxiety disorder (GAD). Outpatients (18 years or older) who met DSM-IV criteria for GAD, with baseline Hamilton Rating Scale for Anxiety (HAMA) scores > or = 18, were randomly assigned to double blind treatment with escitalopram (10 mg/day for the first 4 weeks and then flexibly dosed from 10-20 mg/day) or placebo for 8 weeks, following a 1-week, single-blind, placebo lead-in period. The primary efficacy variable was the mean change from baseline in total HAMA score at Week 8. The escitalopram group (N = 158) showed a statistically significant, and clinically relevant, greater improvement at endpoint compared with placebo (N = 157) in all prospectively defined efficacy parameters. Significant improvement in HAMA total score and HAMA psychic anxiety subscale score for the escitalopram-treated group vs. the placebo-treated group was observed beginning at Week 1 and at each study visit thereafter. Mean changes from baseline to Week 8 on the HAMA total score using a last-observation-carried-forward (LOCF) approach were -11.3 for escitalopram and -7.4 for placebo (P<.001). Response rates at Week 8 were 68% for escitalopram and 41% for placebo (P<.01) for completers, and 58% for escitalopram and 38% for placebo LOCF values (P<.01). Treatment with escitalopram was well tolerated, with low rates of reported adverse events and an incidence of discontinuation due to adverse events not statistically different from placebo (8.9% vs. 5.1%; P=.27). Escitalopram 10-20 mg/day is effective, safe, and well tolerated in the treatment of patients with GAD.

Adolescent↗

PubMed2004

Social anxiety disorder in callers to the Anxiety Disorders Association of America.

Social anxiety disorder (SAD) is among the most common anxiety disorders with a lifetime prevalence of up to 16%. Among callers to the Anxiety Disorders Association of America (ADAA), we surveyed 1,000 participants using a 97-item questionnaire to understand the characteristics of participants with SAD and subthreshold SAD (SSAD). Current prevalence rates of SAD (n=295) and SSAD (n=41) were 29.5% and 4.1%, respectively. SAD and SSAD participants were more likely to be younger, single, with less education and lower income than their no axis-I-psychiatric-disorder controls (NAC). In addition, they presented with more psychiatric comorbidity, lifetime numbers of trauma, recent psychotropic use and side effects. Increased medical comorbidity, health service utilization, as well as reduced work productivity were also found, particularly among SAD participants. SSAD participants were comparable to SAD participants for most of the measures with a few exceptions, mainly less psychiatric comorbidity, less medication use for panic attack and social fear, and fewer visits to the health professionals. In conclusion, SAD was highly prevalent among callers to the ADAA. SAD participants were particularly impaired and tended to use the health care system extensively. Although SSAD participants were less impaired than those with SAD, they were disadvantaged in many ways. Early diagnosis and better treatment are urged for reducing costs and improving life. An organization such as ADAA can play a vital role in bringing this about.

Adult↗

PubMed2004

Assessing patient beliefs in a clinical trial of Hypericum perforatum in major depression.

Little is known about the beliefs of patients suffering from major depression as to the causes of their illness and effective treatments. This study introduces a new instrument for capturing these beliefs, the Explanatory Model for Depression (EMD) Questionnaire, and explores the beliefs of patients participating in a clinical trial of an alternative medicine, Hypericum perforatum. Although the EMD was originally conceptualized as having five factors pertaining to models of the illness and treatment approaches, the data suggest that patient beliefs are aligned on two factors pertaining to internal and external locus of control. Strong beliefs on either of the EMD locus of control subscales are associated with more severe depression. More importantly, strong beliefs on the external locus of control subscale are associated with less improvement over the 8-week period of observation. These results support the role of patients' beliefs in their recovery from depression and suggest that patients who believe the causes of their depression are outside of their control are less likely to improve over time. It is important to note that beliefs did not mediate the effect of treatment on depression in this study, perhaps because patients were blinded to their treatment condition. Future studies should explore whether patient beliefs have an even greater impact when patients are aware of the treatment they are receiving and can determine whether that treatment is consistent with their beliefs.

Adult↗

PubMed2004

Explanatory attributions of anxiety and recovery in a study of kava.

OBJECTIVE: A need exists to understand illness attribution and treatment beliefs among those seeking botanical treatment for anxiety. The objectives of this study are to evaluate explanatory beliefs about reasons for generalized anxiety disorder (GAD), and to evaluate the extent to which subjects thought different approaches might be most helpful, in a study of botanical treatment. DESIGN: Post hoc analysis of data from two similarly randomized controlled clinical trails. SETTING: Psychiatric research clinic in an academic medical center. SUBJECTS: Fifty-one (51) outpatients participating in two randomized, double-blinded, placebo-controlled trials of kava in GAD. INTERVENTIONS: Kava and placebo. MAIN OUTCOME MEASURES: Hamilton Anxiety Scale and Global Improvement Scale. RESULTS: Subjects thought their conditions were largely related to personality factors, stressful life experiences, or cognitive patterns. These beliefs correlated positively with treatment response, whereas endorsement of belief in an energy imbalance or biologic abnormality correlated negatively with improvement. CONCLUSION: Subjects felt more strongly that cognitive patterns, personality and stress were causative of their GAD and of greatest relevance to recovery. Biologic/genetic factors were somewhat relevant, whereas the importance of energy imbalance and spiritual/religious factors were minimal. When treating patients, it is important to consider the patient's belief systems regarding the disorder, as well as credibility of treatment.

Adult↗

PubMed2004

Remission in post-traumatic stress disorder (PTSD): effects of sertraline as assessed by the Davidson Trauma Scale, Clinical Global Impressions and the Clinician-Administered PTSD scale.

Rates of remission were examined in two controlled 12-week studies of sertraline and placebo for post-traumatic stress disorder (PTSD). The performance of three scales was evaluated: the self-rated Davidson Trauma Scale (DTS), and two interviewer scales: the Clinician Administered PTSD Scale (CAPS) and Clinical Global Impressions (CGI). Sertraline proved significantly superior to placebo with respect to remission on all three ratings. Rates of remission were very similar for all scales, ranging from 23.1-26.3% for sertraline and 13.9-14.9% for placebo. Traditional thresholds for the CAPS and DTS were tested relative to the CGI and to each other. The CAPS and DTS thresholds of < 20 and < 18 were found to be valid.

Adult↗

PubMed2004

Efficacy of the novel anxiolytic pregabalin in social anxiety disorder: a placebo-controlled, multicenter study.

Pregabalin is a novel compound in development for the treatment of anxiety disorders. The safety and efficacy of pregabalin for the treatment of social anxiety disorder was evaluated in a double-blind, multicenter clinical trial in which 135 patients were randomized to 10 weeks of double-blind treatment with either pregabalin 150 mg/d. pregabalin 600 mg/d, or placebo. The primary efficacy parameter was change from baseline to end point in the Liebowitz Social Anxiety Scale (LSAS) total score. Safety was assessed through clinical and laboratory monitoring, and recording spontaneously reported adverse events. Ninety-four patients (70%) completed the 11-week double-blind treatment phase. LSAS total score was significantly decreased by pregabalin 600 mg/d treatment compared with placebo (P = 0.024, analysis of covariance). Significant differences (P < or = 0.05) between pregabalin 600 mg/d and placebo were seen on several secondary measures including the LSAS subscales of total fear, total avoidance, social fear, and social avoidance, and the Brief Social Phobia Scale fear subscale. Pregabalin 150 mg/d was not significantly better than placebo on any measures. Somnolence and dizziness were the most frequently occurring adverse events among patients receiving pregabalin 600 mg/d. In conclusion, pregabalin 600 mg/d was an effective and well-tolerated treatment of social anxiety disorder.

Adolescent↗