Biomedical subjects

David S Baldwin

Publications and source records attributed to David S Baldwin.

At least 19 recordsLinked to original sources

PubMed2006

Cost-effectiveness analysis of escitalopram compared with paroxetine in treatment of generalized anxiety disorder in the United Kingdom.

BACKGROUND: Generalized anxiety disorder (GAD) is associated with substantial economic burden. OBJECTIVE: To assess, from a societal perspective, the cost-effectiveness of escitalopram and paroxetine in the treatment of GAD in the UK. METHOD: A decision analytic model with a 9 month time horizon was adapted to the UK setting. Model inputs included drug- and nondrug-specific probabilities from head-to-head trial data, published literature, and expert opinion. Main outcome measures were success (response after 12 wk of treatment and no relapse during the following 24 wk) and costs. Resource use was based on National Institute for Health and Clinical Excellence guidance for GAD patient management, and estimated unit costs came from standard national sources. Human capital approach was used to estimate costs of absence from work. The analysis was performed from the societal perspective. RESULTS: Escitalopram-treated patients were associated with 14.4% higher first-line treatment success and significantly lower discontinuation rates due to adverse events than were those treated with paroxetine. Treatment with escitalopram yielded lower expected costs with greater effectiveness compared with paroxetine. These clinical advantages led to less sick leave and resource use as a result of lower switch rates and use of secondary care. Total expected 9 month costs were 1408 pounds sterling (2560 US dollars) lower for escitalopram-treated patients than for paroxetine-treated patients. Sensitivity analyses on key parameters demonstrated robustness of the model. CONCLUSIONS: Escitalopram appears to be cost-effective compared with paroxetine in the treatment of GAD in the UK.

Anxiety Disorders↗

PubMed2006

Evidence-based guidelines for anxiety disorders: can they improve clinical outcomes?

Evidence-based medicine (EBM) enables clinicians to justify decision making, enhances the quality of medical practice, identifies unanswered research questions, and ensures the efficient practice of medicine. Implementation of evidence-based mental health programs requires education, time, and improved effort by administration, regulatory, and clinical professionals. Essential to these efforts are consistent incentives for change, effective training materials, and clear clinical guidelines. Guidelines exist within the framework of EBM. Good guidelines are simple, specific, and user friendly, focus on key clinical decisions, are based on research evidence, and present evidence and recommendations in a concise and accessible format. Potential limitations of guidelines to improve clinical outcomes in anxiety disorders are the widespread distribution of anxiety symptoms in primary care, health inequalities across patient groups, persistent misconceptions regarding psychotropic drugs, and low confidence in using simple psychological treatments. Clinical guidelines generally specify therapeutic areas covered and not covered, but often there is no mention of cost or cost effectiveness of treatment. Guidelines can inform clinical decision making, but administrators of drug formularies may regard themselves as being primarily responsible for limiting costs and access to certain medications, even if these decisions are at odds with guideline recommendations.

Anti-Anxiety Agents↗

PubMed2006

A double-blind, randomized, parallel-group, flexible-dose study to evaluate the tolerability, efficacy and effects of treatment discontinuation with escitalopram and paroxetine in patients with major depressive disorder.

This multinational, randomized, double-blind, flexible-dose study evaluated the short- and long-term antidepressant tolerability and efficacy of escitalopram and paroxetine. Tolerability was assessed by monitoring adverse events throughout the study, and discontinuation events during brief treatment interruption and tapered withdrawal. Discontinuation-emergent effects were evaluated in two separate double-blind periods. First, to mimic the consequences of non-compliance, patients were randomized to one of two treatment interruption periods (placebo-substitution for 3-5 days). Second, patients were randomized to a 1-2-week tapered withdrawal period randomly scheduled between weeks 28 and 31. The pre-specified primary efficacy endpoint was the mean change from baseline in total Montgomery-Asberg Depression Rating Scale (MADRS) score at week 8, using the principle of last observation carried forward. A total of 323 patients entered 8 weeks of double-blind treatment and received at least one flexible dose of escitalopram (10-20 mg/day) or paroxetine (20-40 mg/day). Patients who demonstrated evidence of a significant clinical improvement (Clinical Global Impression-Improvement of 1 or 2) at week 8 entered a 19-week, double-blind maintenance period during which they were treated with the same dose they received at week 8, followed by a 1-2-week tapered withdrawal period. A total of 89 patients (28%) withdrew during the study; significantly (P<0.01) more patients withdrew from the paroxetine group (34%) than from the escitalopram group (21%), and significantly (P<0.05) more paroxetine patients withdrew due to lack of efficacy. The mean MADRS total score improved for both treatment groups from baseline to week 8, with no statistical difference between groups. In severely depressed patients (baseline MADRS total score >or=30), escitalopram was superior (P<0.05) to paroxetine at week 27 (end of maintenance treatment). There was a high prevalence of sexual dysfunction at baseline: the mean Arizona Sexual Experience Scale (ASEX) score was approximately 20 points in both treatment groups. Mean total ASEX scores increased slightly above baseline values during the acute period and declined slightly below baseline values towards the end of the maintenance period. During taper and cessation of treatment, patients in the paroxetine group demonstrated significantly more discontinuation symptoms relative to escitalopram based on the Discontinuation Emergent Signs and Symptoms scores.

Citalopram↗

PubMed2006

Escitalopram and paroxetine in the treatment of generalised anxiety disorder: randomised, placebo-controlled, double-blind study.

BACKGROUND: It is uncertain whether higher doses of selective serotonin reuptake inhibitors have greater efficacy in generalised anxiety disorder. AIMS: To assess the efficacy of different doses of escitalopram in generalised anxiety disorder. METHOD: Randomised, double-blind, placebo-controlled, fixed-dose, parallel-group, 12-week study, with 681 patients: placebo (n=139); escitalopram, 5 mg/day, (n=134); 10 mg/day (n=136); 20 mg/day (n=133); paroxetine, 20 mg/day (n=139). RESULTS: Mean change in the primary efficacy measure was greater with escitalopram 10 and 20 mg than with placebo; 10 mg was more efficacious than paroxetine. Paroxetine was superior to placebo on some secondary measures, at some time points. Compared with placebo, more patients withdrew because of adverse events with escitalopram 20 mg and paroxetine. CONCLUSIONS: Escitalopram was efficacious in generalised anxiety disorder, 20 was not significantly superior to 10 mg/day. Escitalopram 10 mg was more efficacious than paroxetine.

Adult↗

PubMed2006

Estimating the prevalence and impact of antidepressant-induced sexual dysfunction in 2 European countries: a cross-sectional patient survey.

OBJECTIVE: Sexual dysfunction is a common side effect of antidepressant treatment, but recognition of the problem is variable. The aim of this study was to estimate the prevalence and impact of sexual dysfunction during antidepressant treatment in 2 European countries. METHOD: A cross-sectional survey of 502 adults in France and the United Kingdom. All participants were diagnosed with depression and taking a selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI), starting within the previous 3 months. Information was gathered about other medications and conditions known to impair sexual functioning, recent changes in sexual functioning, and the impact of any changes. The Medical Outcomes Study 12-Item Short-Form Health Survey and the Arizona Sexual Experience Scale were administered to measure health status and sexual functioning. Data were collected from June to July of 2002. RESULTS: Applying a prevalence estimate algorithm, 26.6% of the French sample and 39.2% of the U.K. sample were classified as having antidepressant-induced sexual dysfunction; 34.2% of men and 32.5% of women were classified with antidepressant-induced sexual dysfunction. There was no clear pattern of antidepressant-induced sexual dysfunction related to specific antidepressants. Patients with antidepressant-induced sexual dysfunction reported that changes in sexual functioning negatively affected their self-esteem, mood, and relationships with sexual partners. 23.8% of the French sample and 25.2% of the U.K. sample reported that they perceived that their partner was dissatisfied with their sex life. CONCLUSION: The prevalence of antidepressant-induced sexual dysfunction in this study is similar to previous estimates reported in the literature. The impact of antidepressant-induced sexual dysfunction is substantial and negatively affects quality of life, self-esteem, mood, and relationships with sexual partners.

Adrenergic Uptake Inhibitors↗

PubMed2006

What is the threshold for symptomatic response and remission for major depressive disorder, panic disorder, social anxiety disorder, and generalized anxiety disorder?

OBJECTIVE: Symptom-free remission is a goal for treatment in depression and anxiety disorders, but there is no consensus regarding the threshold for determining remission in individual disorders. We sought to determine these thresholds by comparing, in a post hoc analysis, scores on the Clinical Global Impressions scale (CGI) and disorder-specific symptom severity rating scales from all available studies of the treatment of major depressive disorder, panic disorder, generalized anxiety disorder, and social anxiety disorder with the same medication (escitalopram). We also sought to compare the standardized effect sizes of escitalopram for these 4 psychiatric disorders. DATA SOURCES AND STUDY SELECTION: Raw data from all randomized, double-blind, placebo-controlled, acute treatment studies sponsored by H. Lundbeck A/S (Copenhagen, Denmark) or Forest Laboratories, Inc. (New York, N.Y.), published through March 1, 2004, with patients treated with escitalopram for DSM-IV major depressive disorder (5 studies), panic disorder (1 study), generalized anxiety disorder (4 studies), or social anxiety disorder (2 studies) were compared with regard to the standardized effect sizes of change in CGI score and scores on rating scales that represent the "gold standard" for assessment of these disorders (the Montgomery-Asberg Depression Rating Scale, the Panic and Agoraphobia Scale, the Hamilton Rating Scale for Anxiety, and the Liebowitz Social Anxiety Scale, respectively). DATA SYNTHESIS: In all indications, treatment with escitalopram showed differences from placebo in treatment effect from 0.32 to 0.59 on the CGI-S and CGI-I and standardized effect sizes from 0.32 to 0.50 on the standard rating scales. There were no significant differences among the different disorders. Moderate to high correlations were found between scores on the CGI and the standard scales. The corresponding standard scale scores for CGI-defined "response" and "remission" were determined. CONCLUSION: Comparison of scores on the standard scales and scores on the CGI suggest that the traditional definition of response (i.e., a 50% reduction in a standard scale) may be too conservative.

Anxiety Disorders↗

PubMed2006

Which factors predict placebo response in anxiety disorders and major depression? An analysis of placebo-controlled studies of escitalopram.

BACKGROUND: The placebo response rate has increased in several psychiatric disorders and is a major issue in the design and interpretation of clinical trials. The current investigation attempted to identify potential predictors of placebo response through examination of the placebo-controlled clinical trial database for escitalopram in 3 anxiety disorders and in major depressive disorder (MDD). METHOD: Raw data from placebo-controlled studies (conducted from 2002 through the end of 2004) of escitalopram in patients meeting DSM-IV criteria for MDD and anxiety disorders (generalized anxiety disorder [GAD], social anxiety disorder [SAD], panic disorder) were used. Potential predictors examined were type of disorder, location of study, dosing regimen, number of treatment arms, gender of patients, and duration and severity of disorder. RESULTS: Placebo response (defined as the percent decrease from baseline in the reference scale) was higher in GAD and MDD studies conducted in Europe (p < .0001 and p = .0006, respectively) and was not associated with gender or duration of episode. In GAD, the placebo response rate was higher in a European fixed-dose study, which also had more treatment arms. In SAD and in U.S. specialist-treated MDD, a higher placebo response rate was predicted by decreased baseline disorder severity. CONCLUSION: Additional work is needed before definitive recommendations can be made about whether standard exclusion criteria in clinical trials of antidepressants, such as mild severity of illness, maximize medication-to-placebo differences. This analysis in a range of anxiety disorders and MDD suggests that there may be instances in which the predictors of placebo response rate themselves vary across different conditions.

Adult↗

PubMed2006

Symptoms of fatigue and sleepiness in major depressive disorder.

Fatigue and sleepiness (hypersomnia) are symptoms that are highly prevalent in patients with major depressive disorder (MDD). Individuals who complain of fatigue but do not have diagnosable depression are at a higher risk for developing MDD later in life than individuals who do not complain of fatigue. Fatigue and sleepiness also appear to be particularly difficult to treat, as they are often encountered as residual symptoms among MDD patients who have remitted following treatment with standard antidepressants. There are 3 main approaches for addressing fatigue and sleepiness in depression: first, prescribing antidepressant medications that are less likely to exacerbate these particular symptoms; second, prescribing antidepressant medications that are more likely to resolve these symptoms; third, the use of adjunctive treatments to specifically target residual fatigue and sleepiness in depression.

Antidepressive Agents↗

PubMed2006

Consensus statement and research needs: the role of dopamine and norepinephrine in depression and antidepressant treatment.

During a special session, the faculty identified several specific areas related to the role of dopamine and norepinephrine in depression and antidepressant treatment that either warrant the clinician's attention or are in need of more research. Areas of interest include fatigue and lethargy in depression, treatment strategies for treatment-resistant depression, the somatic presentation of depression, neurobiology of fatigue and its role in determining treatment, symptom rating scales, and sexual side effects. In addition, the faculty discussed the importance of patient psychoeducation and self-management as well as the ways in which disease models of depression affect treatment.

Antidepressive Agents↗

PubMed2005

Discontinuation symptoms in depression and anxiety disorders.

The present overview investigates whether different antidepressants have differing discontinuation symptoms upon treatment cessation, if these symptoms vary between depression and anxiety disorders, and with length of treatment. Data came from two comparative studies of escitalopram in major depressive disorder (MDD) (one vs. venlafaxine XR and one vs. paroxetine), two studies in social anxiety disorder (SAD) (one of which used paroxetine as the active reference), and one study in generalized anxiety disorder (GAD), using paroxetine as an active reference [total number of patients: escitalopram (n=1051); paroxetine (n=336); venlafaxine XR (n=124); placebo (n=239)]. All studies included a defined discontinuation period and used the Discontinuation Emergent Signs and Symptoms (DESS) checklist to record the number of discontinuation symptoms. All three antidepressants showed more discontinuation symptoms compared with placebo (p<0.001). Patients reported significantly fewer discontinuation symptoms with escitalopram than with paroxetine and venlafaxine XR in MDD (p<0.05). Escitalopram showed significantly fewer discontinuation symptoms than paroxetine in SAD (p<0.05) and GAD (p<0.001). For each antidepressant, no differences in discontinuation symptoms were observed between the three indications and there was no evidence for increased symptom incidence with increased length of treatment. Thus, discontinuation profiles differ between antidepressants of the same class and are broadly similar in different disorders. No evidence was seen for a higher discontinuation burden with longer treatment.

Adult↗

PubMed2005

Antidepressants and their effect on sleep.

Given the relationship between sleep and depression, there is inevitably going to be an effect of antidepressants on sleep. Current evidence suggests that this effect depends on the class of antidepressant used and the dosage. The extent of variation between the effects of antidepressants and sleep may relate to their mechanism of action. This systematic review examines randomised-controlled trials (RCTs) that have reported the effect that antidepressants appear to have on sleep. RCTs are not restricted to depressed populations, since several studies provide useful information about the effects on sleep in other groups. Nevertheless, the distinction is made between those studies because the participant's health may influence the baseline sleep profiles and the effect of the antidepressant. Insomnia is often seen with monoamine oxidase inhibitors (MAOIs), with all tricyclic antidepressants (TCAs) except amitriptyline, and all selective serotonin reuptake inhibitors (SSRIs) with venlafaxine and moclobemide as well. Sedation has been reported with all TCAs except desipramine, with mirtazapine and nefazodone, the TCA-related maprotiline, trazodone and mianserin, and with all MAOIs. REM sleep suppression has been observed with all TCAs except trimipramine, but especially clomipramine, with all MAOIs and SSRIs and with venlafaxine, trazodone and bupropion. However, the effect on sleep varies between compounds within antidepressant classes, differences relating to the amount of sedative or alerting (insomnia) effects, changes to baseline sleep parameters, differences relating to REM sleep, and the degree of sleep-related side effects.

Antidepressive Agents↗

PubMed2005

Suicide in depressive disorders: a retrospective case-control study of 127 suicides.

BACKGROUND: Depressive disorders are associated with a significant risk of suicide. Inpatient status and recent discharge from hospital have been identified as times of high risk of suicide within the course of illness. METHOD: A matched retrospective case control study of 127 patients with depression requiring inpatient care who died by suicide as inpatients or in the 12 months following discharge from hospital. Single and multivariable conditional logistic regression identified independent risk and protective factors for suicide. RESULTS: A history of deliberate self harm is a significant risk factor for suicide in patients with depression (OR 6.96; 95% CI 3.41-14.19), as is living alone (OR 2.11; 95% CI 1.15-3.87) and paid employment (OR 2.80; 95% CI 1.48-5.32). Admission to hospital during social crisis is associated with a reduction in suicide risk (OR 0.43; 95% CI 0.24-0.75). LIMITATIONS: This is a retrospective case-control study, using clinical data not originally collected for research purposes. CONCLUSIONS: General population risk factors for suicide are less predictive of suicide in patients with depression requiring inpatient treatment. Clinicians need to be aware of factors which increase or reduce the risk of suicide in this group.

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

Escitalopram in the treatment of generalized anxiety disorder.

The selective serotonin reuptake inhibitor escitalopram is the active enantiomer of citalopram and has proven efficacy in the treatment of major depression, panic disorder and social phobia. Accumulating data indicate that it is also efficacious in the treatment of patients with generalized anxiety disorder. This drug profile summarizes the current evidence-base for the treatment of generalized anxiety disorder, describes the findings of a series of randomized placebo-controlled and comparator-controlled trials of escitalopram, examines the strengths and weaknesses of current treatment approaches and considers potential new therapies for the treatment of this common, chronic and impairing anxiety disorder. In summary, escitalopram is effective and well tolerated in both the short- and long-term treatment of generalized anxiety disorder, and has advantages over benzodiazepines and the selective serotonin reuptake inhibitor paroxetine.

Anxiety Disorders↗

PubMed2004

Evidence-based pharmacotherapy of Generalized Anxiety Disorder.

Generalized Anxiety Disorder (GAD) is a common and often disabling disorder. This paper reviews the pharmacological treatment of GAD, based on the findings of published meta-analyses and randomized placebo-controlled studies. In doing so, it aims to address three fundamental questions: What is the first-line treatment for GAD? How long should treatment continue? What is the best intervention in patients who do not respond to first-line and second-line treatments? Due to their efficacy in GAD and comorbid anxiety and depressive disorders, their tolerability and safety, certain selective serotonin re-uptake inhibitors (escitalopram, paroxetine, sertraline) should be considered the first-line treatment for most patients, although the serotonin-noradrenaline re-uptake inhibitor venlafaxine is a reasonable alternative. Little is known about the optimal length of therapy after response to acute treatment but relapse-prevention studies with paroxetine suggest that continuation treatment should last for at least 6 months. The management of patients who do not respond to first-line treatment is uncertain, but some patients may benefit from certain tricyclic antidepressants, buspirone, or pregabalin.

Anti-Anxiety Agents↗

PubMed2004

Effect of short-term SSRI treatment on cognitive bias in generalised anxiety disorder.

RATIONALE: There is considerable evidence showing that individuals with generalised anxiety disorder (GAD) selectively process threat-related information, e.g. they have a bias to interpret ambiguous information in a threat-related manner. Cognitive theories of anxiety, which provide the basis of cognitive-behaviour therapy, propose that such processing biases play an important role in causing and maintaining anxiety. OBJECTIVES: Given that treatment with selective serotonin re-uptake inhibitors (SSRIs) appears to be effective for GAD, we examined whether it is successful in removing cognitive bias. METHODS: The clinical group included 19 patients with a diagnosis of GAD, and the control group consisted of a non-clinical sample of volunteers, matched for age, gender and years in education. The patients were assessed on measures of interpretative bias (homophone task), anxiety and depression before being prescribed an SSRI (paroxetine or citalopram). After 4 weeks, the cognitive task and mood measures were repeated in the patient group. RESULTS: Prior to treatment, the GAD group showed a significantly greater level of threat-related interpretive bias than controls. Following SSRI treatment, there were significant reductions in both interpretive bias and in anxiety levels in the GAD group. Furthermore, individuals who showed greater clinical improvement (e.g. reflected by reduced anxiety scores) showed a correspondingly greater reduction in their cognitive bias. CONCLUSION: The results suggest that SSRIs are effective in modifying both subjective anxiety levels and threat-related interpretive bias.

Adult↗

PubMed2004

Suicide in schizophrenia: a retrospective case-control study of 51 suicides.

The aim of this study was to identify factors associated with suicide in patients with schizophrenia who required inpatient admission and to compare these factors with the risk profile of patients with other diagnoses also requiring inpatient care. A retrospective, matched case-control study of 51 patients with schizophrenia requiring psychiatric inpatient care was undertaken. A priori specified risk factors were investigated within the schizophrenia group and compared with those of patients with other psychiatric diagnoses. The results show that previous suicide attempts are associated with an increased risk of suicide across all diagnoses. The presence of depressive symptoms and involvement of police with the index admission become more significant factors in patients with schizophrenia, compared to those with other diagnoses. Supportive mental health accommodation is associated with a reduced risk of suicide. Suicide of individuals is difficult to predict in patients with schizophrenia. Young men appear particularly vulnerable at times of inpatient care. Depressive symptoms and previous suicide attempts are significant risk factors.

Adult↗

PubMed2004

Sexual dysfunction associated with antidepressant drugs.

The term 'sexual dysfunction' describes a disturbance in sexual desire and the psychophysiological changes that characterise the normal sexual response cycle, and cause marked personal distress and interpersonal difficulty. Epidemiological studies indicate that sexual dysfunction is common in the general population, but more common in depressed individuals in community settings and clinical samples. Most antidepressant drugs have adverse effects on sexual function, but accurate identification of the incidence of treatment-emergent dysfunction has proved troublesome. Futhermore, investigations of sexual dysfunction associated with antidepressants have one or more methodological flaws. There may be some advantages for bupropion, moclobemide, nefazodone and reboxetine over other antidepressants. Many approaches have been adopted for management of patients with sexual dysfunction associated with antidepressant treatment, including waiting for the problem to resolve, behavioural strategies to modify sexual technique, individual and couple psychotherapy, delaying the intake of antidepressants until after sexual activity, reduction in daily dosage, 'drug holidays', use of adjuvant treatments, and switching to a different antidepressant.

Adolescent↗