Anxiety Disorders: Nutt D

Allgulander C, Nutt D, Detke M, Erickson J, Spann M, Walker D, Ball SG, Russell JM. · Department of Clinical Neuroscience, Section of Psychiatry, Karolinska Institutet, Stockholm, Sweden. · J Psychopharmacol. · Pubmed #18635722 No free full text.

Abstract: The present study is a non-inferiority comparison of duloxetine 60-120 mg/day and venlafaxine extended-release (XR) 75-225 mg/day for the treatment of adults with generalized anxiety disorder (GAD). The non-inferiority test was a prespecified plan to pool data from two nearly identical 10-week, multicentre, randomized, placebo-controlled, double-blind studies of duloxetine 60-120 mg/day and venlafaxine 75-225 mg/ day for the treatment of GAD. An independent expert consensus panel provided six statistical and clinical criteria for determining non-inferiority between treatments. Response was defined as > or =50% reduction in Hamilton Anxiety Rating Scale (HAMA) total score. In the pooled sample, patients were randomly assigned to duloxetine (n = 320), venlafaxine XR (n = 333) or placebo (n = 331). For the non-inferiority analysis, the per-protocol patients who were treated with duloxetine (n = 239) or venlafaxine XR (n = 262) improved significantly more (mean HAMA reductions were -15.4 and -15.2, respectively) than placebo-treated patients (n = 267; -11.6, P < or = 0.001, both comparisons). Response rates were 56%, 58% and 40%, respectively. Discontinuation rate because of AEs was significantly higher for duloxetine (13.4%, P < or = 0.001) and venlafaxine XR (11.4%, P < or = 0.01) groups compared with placebo (5.4%). Duloxetine 60-120 mg/day met all statistical and clinical criteria for non-inferiority and exhibited a similar tolerability profile compared with venlafaxine XR 75-225 mg/day for the treatment of adults with GAD.

Nutt D, Malizia A. · No affiliation provided · J Psychopharmacol. · Pubmed #17060345 No free full text.

This publication has no abstract.

Christmas D, Hood S, Nutt D. · Psychopharmacology Unit, University of Bristol, Level 5, Dorothy Hodgkin Building, Whitson Street, Bristol BS1 3NY, UK. · Curr Pharm Des. · Pubmed #19075730 No free full text.

Abstract: Anxiety disorders are common and disabling conditions. Current drug treatment methods have limitations including resistance, delayed efficacy and side effects. The advent of sophisticated imaging techniques and the production of highly selective receptor ligands have increased our knowledge of the biological mechanisms underpinning anxiety. Our aim is to review recent discoveries in important neurological systems to provide an understanding of important current anxiolytic targets. Some of these systems, such as GABA, have been implicated in anxiety disorders for decades, but a recent greater understanding is enabling more sophisticated targeting of treatments. In other systems, including the neuropeptides, we have now developed the pharmacological tools in human subjects to begin exploring their relationship to anxiety disorders. We review GABA, serotonin, glutamate, noradrenaline, dopamine and some neuropeptides herein.

Trivedi MH, Hollander E, Nutt D, Blier P. · Department of Psychiatry, University of Texas Southwestern Medical Center at Dallas, TX 75235, USA. · J Clin Psychiatry. · Pubmed #18363453 No free full text.

Abstract: OBJECTIVE: Recent data indicate that more than 65% of patients with major depressive disorder (MDD) fail to achieve remission. This article reviews research on the current understanding and management of residual symptoms, i.e., subthreshold depressive symptoms present after recovery from a major depressive episode. DATA SOURCES: MEDLINE (1966 to June 2006) was searched using combinations of the following search terms: major depressive disorder, residual symptoms, remission, response, tachyphylaxis, antidepressant, algorithm, treatment, responsiveness, serotonin, norepinephrine, and dopamine. STUDY SELECTION: All relevant articles that were published in English and reported original study data related to residual symptoms in MDD were included. DATA EXTRACTION: Studies were examined for data related to the prevalence, presentation, consequences, treatment, and neurobiological underpinnings of residual symptoms associated with MDD. DATA SYNTHESIS: Residual symptoms are common among patients treated for MDD who do not achieve full remission. Incomplete remission is associated with increased risk of relapse, suicide, functional impairment, and higher use of health care resources. Several factors, including "downstream" neurochemical mechanisms and clinical factors such as lack of adherence, contribute to the high prevalence of residual symptoms. Various clinical strategies, including switching and substitution antidepressant therapies, are used to address unresolved depressive symptoms. Individual differences in therapeutic response contribute to inadequate treatment and are linked to numerous clinical and neurobiological factors, including noncompliance, underdosing, intolerance, disturbances in neural circuitry, and genetic variability in neurotransmitters. CONCLUSIONS: Future research is needed to more precisely characterize residual symptoms and their underlying biochemical and molecular mechanisms in order to develop more effective treatment methods.

Nutt D. · Psychopharmacology Unit, University ofBristol School of Medicine Sciences, Bristol, United Kingdom. · J Clin Sleep Med. · Pubmed #17557501 No free full text.

Abstract: Modulatory agents of gamma-aminobutyric acid type A (GABAA) receptors have been widely used for more than 40 years to treat anxiety, epilepsy, and sleep disorders; these drugs are generally safe, well tolerated, and effective. Recently, there has been a substantial growth in understanding of the mechanism of action of these drugs, which act at different sites on GABAA receptors. A variety of GABAA receptor subtypes with distinct functional roles have been characterized and an evolving awareness of GABAA receptor modulation holds promise for the future development of new, more sophisticated drug interventions that can elicit more selective effects by targeting specific subtypes of GABAA receptors. Advances in genetic engineering have led to the development of transgenic mouse models that have further refined our understanding of the pharmacology and physiology for various GABAA receptor subunits.

Nutt D, Argyropoulos S, Hood S, Potokar J. · Psychopharmacology Unit, University of Bristol, Bristol, United Kingdom. · Eur Neuropsychopharmacol. · Pubmed #16737802 No free full text.

Abstract: Generalized anxiety disorder (GAD) frequently occurs comorbidly with other conditions, including depression and somatic complaints. Comorbid GAD sufferers have increased psychologic and social impairment, request additional treatment, and have an extended course and poorer outcome than those with GAD alone; therapy should alleviate both the psychic and somatic symptoms of GAD without negatively affecting the comorbid condition. The ideal treatment would provide relief from both GAD and the comorbid condition, reducing the need for polypharmacy. Physicians need suitable tools to assist them in the detection and monitoring of GAD patients-the GADI, a new, self-rating scale, may meet this requirement. Clinical data have shown that various neurobiologic irregularities (e.g., in the GABA and serotonin systems) are associated with the development of anxiety. Prescribing physicians must take into account these abnormalities when choosing a drug. Effective diagnosis and treatment should improve patients' quality of life and their prognosis for recovery.

Bell C, Abrams J, Nutt D. · Psychopharmacology Unit, School of Medical Sciences, Bristol, UK. · Br J Psychiatry. · Pubmed #11331552 links to  free full text

Abstract: BACKGROUND: Over the past 10 years the technique of tryptophan depletion has been used increasingly as a tool for studying brain serotonergic systems. AIMS: To review the technique of tryptophan depletion and its current status as a tool for investigating psychiatric disorders. METHOD: Systematic review of preclinical and clinical studies. RESULTS: Tryptophan depletion produces a marked reduction in plasma tryptophan and consequently brain serotonin (5-HT) synthesis and release. In healthy volunteers the effects of tryptophan depletion are influenced by the characteristics of the subjects and include some mood lowering, some memory impairment and an increase in aggression. In patients with depression tryptophan depletion tends to result in no worsening of depression in untreated subjects but a relapse in those who have responded to antidepressants (particularly serotonergic agents). In panic disorder the results are similar. CONCLUSIONS: The findings that tryptophan depletion produces a relapse of symptoms in patients with depression and panic disorder who have responded to treatment with antidepressants suggests that enhanced 5-HT function is important in maintaining response in these conditions.

Nutt D. · Division of Psychiatry, School of Medical Sciences, University Walk, Bristol. · Br J Psychiatry. · Pubmed #10627792 No free full text.

Abstract: BACKGROUND: Alcohol misuse, as well as being a major form of psychiatric morbidity, is also commonly associated with other psychiatric disorders. A greater understanding of the brain mechanisms underlying the adverse effects of alcohol is now possible, thanks to significant research advances made over the past decade. AIMS: To elucidate for psychiatrists the growing knowledge of the importance of specific neurotransmitter interactions in the effects of alcohol. METHOD: A survey of the literature, extracting current knowledge of interest to psychiatrists. RESULTS: There is good evidence that the acute effects of alcohol are mediated through interactions with amino acid neurotransmitters plus parallel changes in amines such as noradrenaline, dopamine and serotonin. Neuroadaptive responses at amino acid receptors probably underlie significant components of the withdrawal syndrome and probably also contribute to neuronal death found in chronic alcoholism. CONCLUSIONS: An understanding of the pharmacology of alcohol use may lead to greater ability to treat psychiatric consequences of alcoholism, and may also prevent some of the secondary psychiatric comorbidity and later brain damage.

Nutt D, Allgulander C, Lecrubier Y, Peters T, Wittchen U. · Psychopharmacology Unit, University of Bristol, Bristol, UK. · J Psychopharmacol. · Pubmed #18635721 No free full text.

Abstract: Comparing the efficacy of different treatments in psychiatry is difficult for many reasons, even when they are investigated in "head-to-head" studies. A consensus meeting was, therefore, held to produce best practice guidelines for such studies. This article presents the conclusions of this consensus and illustrates it using published data in the field of antidepressant treatment of generalized anxiety disorder.

Bell C, Nutt D. · Psychopharmacology Unit, School of Medical Sciences, University of Bristol. · Hosp Med. · Pubmed #10396411 No free full text.

Abstract: Paroxetine is one of the specific serotonin-reuptake inhibitor antidepressants which is used in a variety of psychiatric disorders. It has recently gained considerable publicity because of its use in social anxiety disorder and its subsequent labelling by the media as a 'lifestyle drug'. This review summarizes current indications for paroxetine and outlines doses and duration of treatment for each condition.

Nutt D. · No affiliation provided · J Psychopharmacol. · Pubmed #18623627 No free full text.

This publication has no abstract.

Potokar J, Lawson C, Wilson S, Nutt D. · No affiliation provided · Biol Psychiatry. · Pubmed #10624555 No free full text.

This publication has no abstract.