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Biomedical subjects

Malcolm Lader

Publications and source records attributed to Malcolm Lader.

12 recordsLinked to original sources
PubMed2006

Mortality in schizophrenia.

PURPOSE: The purpose of this article is to describe the current status of knowledge on excess mortality in schizophrenia and its causative factors, and to expand upon previous work evaluating approaches that may reduce mortality rates. METHODS: Literature available since 1995 was identified in a computerized search of the bibliographical databases Medline and Embase, using the topics 'mortality' and 'schizophrenia', and in a cross-reference search for articles that were particularly relevant. RESULTS: Schizophrenia is associated with mortality rates that are two to three times higher than those expected or observed in the general population. This excess of mortality is accounted for by a combination of an increased risk of suicide, in particular in young male patients soon after diagnosis, and more importantly, a higher number of natural deaths. In order to diminish the level of suicide among people with schizophrenia, the majority of research has focused on the identification of risk factors that predispose patients to attempt or commit suicide, while unhealthy styles, polypharmacy and inadequate healthcare have been shown to contribute to the high natural mortality. The link between the use of antipychotics and mortality has not been yet clarified. CONCLUSION: Dramatically increased mortality of schizophrenia patients is well established. It is time to move beyond this topic, and work towards interventions that aim at reducing the mortality risk in such patients.

Antipsychotic 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

Escitalopram versus paroxetine for social anxiety disorder: an analysis of efficacy for different symptom dimensions.

BACKGROUND: A previous factor analysis of pooled data demonstrated that the Liebowitz Social Anxiety Scale (LSAS) can be divided into six subscales. This paper examines data from a fixed-dose trial of escitalopram versus paroxetine, in order to determine the differential effects of these agents on symptom dimensions in social anxiety disorder (SAD). METHODS: Data from a 24-week randomised, placebo-controlled, comparative study of fixed doses of escitalopram (5 mg, 10 mg, 20 mg) versus paroxetine (20 mg) in SAD were examined. The six factors identified in a previous factor analysis of baseline data from escitalopram studies on the primary efficacy scale, the LSAS, were used to compute subscale scores. These were analysed using analysis of covariance (ANCOVA), and standardised effect sizes were calculated. RESULTS: The combined escitalopram data and the paroxetine data both demonstrated significant superiority to placebo on each of the 6 LSAS factors at week 24 (OC analysis). Escitalopram doses of 5 mg, 10 mg, and 20 mg were generally more effective than placebo for each of the factors. Escitalopram 20 mg was significantly more effective than paroxetine 20 mg on 5 of the 6 symptom dimensions. CONCLUSION: Factor analysis of the LSAS allows for useful secondary analyses that support and extend the primary efficacy analysis of this instrument. The analysis here indicates that different escitalopram doses are effective across the various symptom dimensions of SAD.

Analysis of Variance↗
PubMed2005

Management of panic disorder.

Selective serotonin reuptake inhibitors are the first-line treatment for panic disorder. They are effective and well tolerated. Although tricyclic antidepressants are equally effective, they are less well tolerated than the selective serotonin reuptake inhibitors. Monoamine oxidase inhibitors can be efficacious but have a range of unwanted effects that preclude their use as first-line treatments. Benzodiazepines should be reserved for short-term use and for treatment-resistant patients who do not have a history of dependence and tolerance. Also, they can be combined with selective serotonin reuptake inhibitors in the first weeks of treatment to tide the patient over before the onset of the response. Cognitive behavioral therapy is the psychologic treatment of first choice. The methods of combining drug and nondrug treatments need careful and thorough exploration.

Antidepressive Agents↗
PubMed2005

Atypical antipsychotics: from potassium channels to torsade de pointes and sudden death.

Syncope and sudden death are features of schizophrenia that can be attributed to ischaemic heart disease, the use of antipsychotics (because of proarrhythmia or other reasons such as pharyngeal dyskinesia) or the psychiatric disease itself. Cases have been described with most antipsychotics and have led to the withdrawal, temporary suspension from the market or restricted use of antipsychotics, such as sultopride, droperidol, sertindole or thioridazine. Reviewing the available data shows that all antipsychotics tested affect the cardiac potassium channel, with the concentration that produces 50% inhibition (IC50) ranging from 1 nmol/L (haloperidol) to 6 micromol/L (olanzapine). Experimental in vitro or in vivo electrophysiological studies have shown a dose-dependent increase in the duration of the action potential with various degrees of indicators of serious arrhythmogenicity. However, this does not always translate clinically into an increased duration of the QT interval or increased risk of torsade de pointes or sudden death in clinical trials or pharmacoepidemiological studies. In turn, QT prolongation in clinical trials does not always translate to an increased risk of torsade de pointes or sudden death. The reasons for these apparent discrepancies are unclear and could be related to insufficiently powered field studies, low plasma and tissue drug concentrations with reference to in vitro data or drug effects on other receptors or ion channels that have a protective effect. Alternatively, risks that were not apparent from preclinical or clinical data could be related to the use of the drug in high-risk patients, metabolic interactions or other factors that would only be encountered in large postmarketing populations. The assessment of cardiovascular safety, both preclinical and during premarketing clinical trials, needs to be supported by appropriately powered pharmacoepidemiology studies.

Animals↗
PubMed2004

Pooled analysis of venlafaxine XR efficacy on somatic and psychic symptoms of anxiety in patients with generalized anxiety disorder.

We evaluated the relative efficacy of venlafaxine XR on the psychic versus somatic symptoms of anxiety in patients with generalized anxiety disorder as determined by the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition. Data were pooled and analyzed from 1,841 patients with generalized anxiety disorder who participated in five short-term (8-week) double-blind, multicenter, placebo-controlled studies, two of which had long-term (6-month) extensions. Somatic and psychic anxieties were studied using the Hamilton rating scale for anxiety (HAM-A) factor scores. We examined response rates (> or =50% improvement over baseline severity score) in the overall population and in patients with mainly somatic symptomatology at baseline (somatizers). Venlafaxine XR significantly reduced factor scores for both psychic and somatic HAM-A factors compared with placebo, from the first and second weeks of treatment, respectively. Patients treated with venlafaxine XR had significantly higher rates of response than patients receiving placebo on the psychic (58% vs. 38%, P<.001 at week 8; 66% vs. 35% at week 24, P<.001) and somatic (56% vs. 43%, P<.001 at week 8; 67% vs. 47% at week 24, P<.001) factors of the HAM-A. There was a TreatmentxFactor interaction (P<.027) in response rates: Patients treated with venlafaxine showed similar somatic and psychic anxiety response rates, whereas placebo-treated patients showed higher somatic compared with psychic response rates. Somatizers showed similar rates of response to the total population for the somatic factor of the HAM-A in either treatment group. Patients with generalized anxiety disorder treated with venlafaxine XR showed similar absolute rates of response on somatic and psychic symptoms, but relative to patients treated with placebo, more improvement in psychic than somatic symptoms.

Adult↗
PubMed2004

Efficacy and tolerability of escitalopram in 12- and 24-week treatment of social anxiety disorder: randomised, double-blind, placebo-controlled, fixed-dose study.

Selective serotonin reuptake inhibitors are the pharmacological treatment of choice for the treatment of social anxiety disorder (SAD). The efficacy and tolerability of fixed doses of escitalopram were compared to those of placebo in the long-term treatment of generalised SAD, using paroxetine as an active reference. Patients with a DSM-IV diagnosis of SAD between 18-65 years of age were randomised to 24 weeks of double-blind treatment with placebo (n = 166), 5 mg escitalopram (n = 167), 10 mg escitalopram (n = 167), 20 mg escitalopram (n = 170), or 20 mg paroxetine (n = 169). Based on the primary efficacy parameter, Liebowitz Social Anxiety Scale (LSAS) total score at Week 12 (LOCF), a significantly superior therapeutic effect compared to placebo was seen for 5 and 20 mg escitalopram and for all doses for the OC analyses. Further improvement in LSAS scores was seen at Week 24 (OC and LOCF), with significant superiority over placebo for all doses of escitalopram, and 20 mg escitalopram was significantly superior to 20 mg paroxetine. Response to treatment (assessed by a Clinical Global Impression-Improvement score < or = 2) was significantly higher for all active treatments than for placebo at Week 12. Clinical relevance was supported by a significant decrease in all the Sheehan disability scores, and the good tolerability of escitalopram treatment. It is concluded that doses of 5-20 mg escitalopram are effective and well tolerated in the short- and long-term treatment of generalised SAD.

Adolescent↗
PubMed2004

Escitalopram in the treatment of social anxiety disorder: analysis of efficacy for different clinical subgroups and symptom dimensions.

Escitalopram has demonstrated efficacy for the acute treatment of social anxiety disorder (SAD) in two placebo-controlled trials and for long-term treatment in a relapse-prevention study. Social anxiety disorder is a heterogeneous disorder. This study questions whether this new selective serotonin reuptake inhibitor is effective across different subgroups of patients. Data from two randomised, placebo-controlled, 12-week escitalopram SAD trials were pooled. General linear models were used to determine the efficacy of escitalopram in different patient subgroups. Furthermore, a factor analysis of the primary efficacy scale, the Liebowitz Social Anxiety Scale (LSAS), was undertaken, and a determination made of whether treatment effects were similar for the different symptom dimensions. Escitalopram was effective in both younger and older patients, in male and female patients, and in patients with more and less severe social anxiety symptoms. The LSAS factor analysis showed six factors, which were differentially associated with different areas of disability. Escitalopram was significantly superior to placebo for all six symptom dimensions. The treatment effects of escitalopram were independent of gender, symptom severity and chronicity, and comorbid depressive symptoms. A six-factor model of social anxiety symptoms is supported by the distinctive association between these symptom dimensions and different areas of disability, but did not predict differential response to escitalopram.

Adolescent↗
PubMed2003

Causes and management of hyponatremia.

OBJECTIVE: To review clinical information on the incidence and causes of hyponatremia (defined as a serum sodium level <130 mEq/L), the most common electrolyte abnormality seen in general hospital patients, and to discuss the diagnosis and treatment of hyponatremia in relation to these factors. DATA SOURCES: Primary sources and review articles were identified via MEDLINE (1981-July 2003) for entries on hyponatremia. We limited the search to specific topics including incidence, risk factors, diagnosis, treatment, and clinical disorders and medications associated with hypotonic hyponatremia. STUDY SELECTION AND DATA EXTRACTION: All of the articles identified were evaluated, and relevant and representative information was included in this review. DATA SYNTHESIS: Hyponatremia can result from several disease states, injury, surgery, physical exercise, or the administration of certain drugs (e.g., antidepressants, antiepileptics) and is associated with advanced age. Drug-induced hyponatremia is often asymptomatic and usually resolves following water restriction and monitoring of medication. Symptoms of hyponatremia are primarily neurologic; the principal danger of hyponatremia relates to effects on central nervous system function due to changes in brain size. CONCLUSIONS: Although hyponatremia can be a serious condition, appropriate measures for the management of at-risk and affected patients will lead to full recovery in most cases.

Drug-Related Side Effects and Adverse Reactions↗
PubMed2001

Tianeptine and paroxetine in major depressive disorder, with a special focus on the anxious component in depression: an international, 6-week double-blind study dagger.

Tianeptine (37.5 mg/day) and paroxetine (20 mg/day) were compared in a population of depressive patients without past or current history of co-morbid anxiety and/or important anxiolytic treatment. In a 6-week, double blind trial, the special focus was on anxious symptoms.Both drugs showed good efficacy on depressive symptomatology, assessed with MADRS and HDRS, but no difference was detected between tianeptine and paroxetine, for any assessment criterion. Despite the choice of selected depressive patients, without any co-morbid anxious disorder, anxiety scale scores at inclusion (HAMA and BAS) were appreciable but correlated poorly with depressive scores. Both tianeptine and paroxetine improved the apparent anxious component in depression. Tolerability of both drugs was good, although significantly better with tianeptine.Thus tianeptine and paroxetine are effective and safe treatments for major depression and may also act directly on the anxious component of the psychopathology. Copyright 2001 John Wiley & Sons, Ltd.

Journal Article↗