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Biomedical subjects

D J Nutt

Publications and source records attributed to D J Nutt.

At least 73 records · Page 4Linked to original sources
PubMed2000

The processing of automatic thoughts of drug use and craving in opiate-dependent individuals.

This study investigated the processing of sentences describing craving and withdrawal in opiate-dependent individuals. Eighteen patients who attended a methadone maintenance clinic for obtaining methadone, 18 patients who were not treated with methadone, and 18 control family members performed on a computerized contextual priming task. The task was priming sentences (craving, withdrawal, or neutral) to words (addiction, neutral, or nonwords). The methadone group was slower to process all sentences compared with family members. They were also faster to process drug-related words following withdrawal-related sentences compared with neutral words following neutral sentences. Finally, they were slower to recognize neutral words following neutral sentences compared with the nonmethadone group. Results suggest that the processing of information describing withdrawal and craving for drugs plays an important role in opiate dependence.

Adult↗
PubMed2000

Behavioural and physiological effects induced by an infusion of antisense to alpha(2D)-adrenoceptors in the rat.

1. The aim of this study was to investigate the behavioural and physiological effects of an i.c.v. infusion of antisense oligonucleotide to the alpha(2D)-adrenoceptor subtype. Behavioural and physiological parameters were monitored for 2 days before the infusion, throughout the 3-day infusion period and for 3 days following the end of the infusion. 2. The antisense infusion resulted in a significant increase in behavioural activity characterized by increased locomotion and grooming scores. Behavioural activity scores of rats treated with antisense to alpha(2D)-adrenoceptors were significantly higher than those of rats treated with vehicle (H(2)O) or the mismatch toxicity control on day 4 and day 5 and, significantly higher than vehicle controls on day 6. 3. Body weight gain was significantly reduced in the antisense-treated rats at the end of the study compared to the vehicle (34%) and mismatch groups (30%), although daily food and water intakes were not significantly different at any time point. 4. Pupil diameters of rats infused with antisense to alpha(2D)-adrenoceptors were significantly greater than those of animals treated either with vehicle or mismatch oligonucleotide on day 5 of the study. On day 6, the pupil diameters of these animals were still significantly greater than the mismatch group. 5. In conclusion, an i.c.v. infusion of antisense to the alpha(2D)-adrenoceptor induced behavioural activation in rats, increased pupil diameter and reduced total weight gain. These effects were specific to the antisense-treated group and were fully reversed post-infusion.

Animals↗
PubMed2000

Evidence-based guidelines for treating depressive disorders with antidepressants: a revision of the 1993 British Association for Psychopharmacology guidelines. British Association for Psychopharmacology.

A revision of the British Association for Psychopharmacology guidelines for treating depressive disorders with antidepressants was undertaken in order to specify the scope and target of the guidelines and to update the recommendations based explicitly on the available evidence. A consensus meeting, involving experts in depressive disorders and their treatment, reviewed key areas and considered the strength of evidence and clinical implications. The guidelines were drawn up after extensive feedback from participants and interested parties. A literature review is given which identifies the quality of evidence followed by recommendations, the strength of which are based on the level of evidence. The guidelines cover the nature and detection of depressive disorders, acute treatment with antidepressant drugs, choice of drug versus alternative treatment, practical issues in prescribing, management when initial treatment fails, continuation treatment, maintenance treatment to prevent recurrence and stopping treatment.

Antidepressive Agents↗
PubMed2000

Sleep and daytime sleepiness the next day following single night-time dose of fluvoxamine, dothiepin and placebo in normal volunteers.

To explore the effects of sedating and non-sedating antidepressants, we conducted a placebo-controlled, double-blind cross-over study in 12 normal subjects of the effects of a single night-time dose of fluvoxamine 100 mg, dothiepin 100 mg or placebo on night-time sleep recorded at home, and sleepiness and performance the following day. Night-time sleep was altered significantly by both drugs, with main effects on rapid eye movement (REM) sleep and sleep continuity. Dothiepin increased total sleep time, REM latency and stage 2 sleep and decreased arousals, wake after sleep onset and stage 1, whereas fluvoxamine decreased total sleep time and REM time and increased wake after sleep onset. Sleep latencies in daytime naps were significantly shorter for dothiepin and longer for fluvoxamine, showing that subjects were more sleepy when taking dothiepin. Electroencephalograms (EEG) performed during performance tasks failed to distinguish significantly between drugs. There were no significant differences between groups on our measures of tracking performance or reaction time; however, these tasks were designed primarily to provide a standard setting in which to monitor continuous EEG, and were unsuitable to detect sleepiness effects themselves. Saccadic eye movement velocity, acceleration and deceleration showed small non-significant changes after both drugs. Mood self ratings showed no significant differences among the groups. Subjective measures of night-time sleep reflected the objective measures of sleep continuity, and the items for difficulty and speed of wakening in the morning were significantly higher (i.e. more difficulty and slower) in the dothiepin group. The home-recorded sleep findings after fluvoxamine in this study were very similar to sleep laboratory studies with other antidepressant drugs, thus providing more validation of the home recording method.

Adult↗
PubMed2000

Substance P antagonists: novel agents in the treatment of depression.

The field of neuropeptides has been expanding very rapidly in recent years. Apart from understanding their physiology and elucidating their functional role as putative neurotransmitters, research has focused on producing drugs that may treat a variety of illnesses in a novel way. Substance P antagonists occupy a central role in this area of intensive scientific activity. Substance P (SP), an undecapeptide, is abundant both in the periphery and in the CNS, where it is usually co-localised with one of the classical neurotransmitters, most commonly serotonin (5-HT). A role for SP is proposed in the regulation of pain, asthma, psoriasis, inflammatory bowel disease and, in the CNS, emesis, migraine, schizophrenia, depression and anxiety. A recently published positive study of MK 869, in depression, a novel SP antagonist has generated excitement amongst psychopharmacologists. It is the first time that a drug, not directly related to monoamine transmitters, has showed efficacy in depression. Although MK 869 has been suspended from further development, a host of other compounds, with similar action and better pharmacological profile, are currently under development. In this review, the pharmacology of central SP and its receptors are discussed, together with the exploration of the prospects and implications for future treatments of depression.

Animals↗
PubMed2000

The psychobiology of posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) develops after exposure to events that are threatening and/or intensely distressing. Accumulating evidence suggests that intense psychological trauma can cause long-standing alterations in the neurobiological response to stress. These alterations translate into a number of symptoms commonly experienced by patients with PTSD. Current treatments for this disorder are only partially effective in managing the disease, and patients have to endure unpleasant symptoms associated with hyperarousal. As a result, they often withdraw from social interaction and increase the use of central nervous system depressants. Data suggest that biological dysregulation of the glutamatergic, amine neurotransmitter (noradrenergic and serotonergic), and neuroendocrine pathways plays a fundamental part in the pathology of PTSD and may cause brain structural as well as functional abnormalities. Knowledge of these pathologic changes in PTSD provides direction for the development of new treatments that will offer more comprehensive management of PTSD and enable patients to enjoy a much improved quality of life. This article reviews current knowledge regarding the psychobiology of PTSD and considers specific agents that are emerging as key modulators of this pathological process.

Brain↗
PubMed2000

Consensus statement on posttraumatic stress disorder from the International Consensus Group on Depression and Anxiety.

OBJECTIVE: To provide primary care clinicians with a better understanding of management issues in posttraumatic stress disorder (PTSD) and guide clinical practice with recommendations on the appropriate management strategy. PARTICIPANTS: The 4 members of the International Consensus Group on Depression and Anxiety were James C. Ballenger (chair), Jonathan R. T. Davidson, Yves Lecrubier, and David J. Nutt. Other faculty invited by the chair were Edna B. Foa, Ronald C. Kessler, Alexander C. McFarlane, and Arieh Y. Shalev. EVIDENCE: The consensus statement is based on the 6 review articles that are published in this supplement and the scientific literature relevant to the issues reviewed in these articles. CONSENSUS PROCESS: Group meetings were held over a 2-day period. On day 1, the group discussed the review articles and the chair identified key issues for further debate. On day 2, the group discussed these issues to arrive at a consensus view. After the group meetings, the consensus statement was drafted by the chair and approved by all attendees. CONCLUSION: PTSD is often a chronic and recurring condition associated with an increased risk of developing secondary comorbid disorders, such as depression. Selective serotonin reuptake inhibitors are generally the most appropriate choice of first-line medication for PTSD, and effective therapy should be continued for 12 months or longer. The most appropriate psychotherapy is exposure therapy, and it should be continued for 6 months, with follow-up therapy as needed.

Cost of Illness↗
PubMed2000

Chest pain: panic attack or heart attack?

Chest pain is a common presentation to both primary and secondary care physicians but is often non-cardiac in origin. Patients presenting with chest pain may be experiencing a panic attack. Panic disorder is a disabling psychiatric condition with serious consequences, such as impaired social functioning and increased risk of suicide. Comorbidity of panic disorder with other psychiatric conditions is common and often leads to increased severity of anxiety symptoms and a poorer prognosis. The cost of misdiagnosing non-cardiac chest pain is high. It is important for physicians to be able to recognise panic attacks and to distinguish them from cardiac disease, thus avoiding unnecessary use of healthcare resources. This review discusses the prevalence and diagnosis of panic attack and panic disorder in patients presenting with chest pain to primary care physicians and cardiologists. Treatment options for panic disorder are considered, particularly the selective serotonin reuptake inhibitors, which are emerging as the first-line choice for the treatment of panic disorder.

Antidepressive Agents, Tricyclic↗
PubMed1999

Extraction of active clonidine-displacing substance from bovine lung and comparison with clonidine-displacing substance extracted from other tissues.

Crude methanolic clonidine-displacing substance (CDS) extracted from bovine lung competed for radioligand binding from alpha2-adrenoceptors and I2-sites present in rat brain membranes, and from I1-sites present in rat brain and kidney membranes. There was no difference in the competition of [3H]clonidine binding to alpha2-adrenoceptors present in either rat or rabbit brain membranes by the crude CDS extract and therefore either tissue could be used to estimate the number of units of CDS present in extracts. Further purification by reverse phase high performance liquid chromatography (RP-HPLC), with UV detection, of extracts obtained from bovine lung, brain and rat brain exhibited similar three-peak profiles, previously reported. Corresponding fractions competed for radioligand binding to alpha2-adrenoceptors present in rat brain membranes, eluting between 19 and 23 min, which corresponded with the middle peak of the three-peaks. Therefore, we propose the CDS-like material eluting from all these tissues to be similar. Interestingly, CDS extracted from bovine adrenal glands under the same conditions showed a similar three-peak profile, but did not repeat the displacement of binding just at 19-23 min, but at every time point after 4 min. This suggests this tissue could represent a source of CDS in this species.

Adrenal Glands↗
PubMed1999

Novel selective compounds for the investigation of imidazoline receptors.

Over several years our group has sought to synthesize and identify selective ligands for imidazoline (I) receptors, in particular the I2 binding site. As a consequence, [3H]2-(2-benzofuranyl)-2-imidazoline (2BFI) has proved extremely useful for binding and autoradiographic studies. More recently we have synthesized a BU series of compounds and examined these for their affinities for both I1 and I2 binding sites. BU224 (2-(4,5-dihydroimidaz-2-yl)-quinoline) shows high affinity for I2 receptors with a Ki of 2.1 nM. BU226 (2-(4,5-dihydroimidaz-2-yl)-isoquinoline) demonstrated slightly higher affinity (Ki 1.4 nM) for I2 receptors, but overall BU224 displayed greater selectivity for I2 over I1 receptors (832-fold) than BU226 (380-fold). Both compounds showed low (microM) affinity for alpha 2-adrenoceptors. Given BU224's ability to cross the blood brain barrier, we predict that its in vivo effects are likely to be mediated via I2 receptors. Brain dialysis revealed BU224 to dose dependently (0-20 mg/kg i.p.) elevate basal noradrenaline in rat frontal cortex and basal dopamine in striatum. In a rat model of opiate withdrawal, behavioral studies showed that BU224 (10 mg/kg, s.c.) was able to reduce acute weight loss and diarrhea, but not the number of wet dog shakes associated with the withdrawal syndrome.

Animals↗
PubMed1999

The neurobiology of social phobia.

Although Social Phobia has been recognised for centuries in comparison with other anxiety disorders, relatively little work has been done to understand its neural basis. The present review attempts to redress this balance by giving an overview of the current state of knowledge in this disorder. By putting together data from the treatment responses to specific agents, the effects of chemical challenges which have been used in other anxiety disorders and by reviewing data on central and peripheral neurotransmitter and endochrine abnormalities, it is possible to begin to generate some potentially testable theories of aetiology and mechanisms. Finally, we review the potential use of neuroimaging techniques to better detail the brain circuits and possibly neurotransmitters involved in social phobia, showing some of our preliminary work using (15)O water blood flow PET activation studies to determine the brain circuits in which metabolism is changed during the experience of social anxiety.

Brain↗
PubMed1999

Mechanisms of action of selective serotonin reuptake inhibitors in the treatment of psychiatric disorders.

Selective serotonin reuptake inhibitors (SSRIs) have demonstrated efficacy in depression and anxiety disorders. This raises the question of how the single action of serotonin reuptake inhibition can improve several psychiatric conditions. In order to understand this apparent paradox it is necessary to consider where SSRIs act in the pathogenic process underlying depression or anxiety disorders. Tryptophan depletion has been used extensively in research into depression and has shown that, in patients receiving an SSRI whose depression is in remission, depleting serotonin leads to recurrence of the disorder. Similar results have been found for panic disorder. This suggests that increased levels of serotonin are necessary in the synapse for the SSRI to be effective in the treatment of depression and panic disorder. In obsessive compulsive disorder, depletion of serotonin in patients recovered on an SSRI does not cause relapse; receptor adaptation may be more important. Variations within the SSRI drug class, such as the selectivity ratios for serotonin versus noradrenaline uptake, elimination half-life, and affinity for the 5-HT2 receptor have been identified and may be important determinants of efficacy, side effects and clinical use.

Anxiety Disorders↗
PubMed1999

The use of benzodiazepines in anxiety and other disorders.

Benzodiazepines have come under scrutiny and attack over recent years because of their abuse liability, withdrawal reactions and development of tolerance. Consequently, practitioners worldwide are discouraged from prescribing them. While some of these risks may have been exaggerated, benzodiazepines remain a useful therapeutic tool, alone or in combination, in a number of psychiatric and medical conditions. Withholding such treatment may be unjustified and detrimental to the patients' health. Further, benzodiazepines have helped researchers in their attempts to elucidate the neurobiological mechanisms underlying anxiety. This, in return, leads to the development of new effective anxiolytic treatments, with fewer problems compared to the traditional benzodiazepine compounds. Such new agents are already available or at the closing stages of clinical trials.

Anti-Anxiety Agents↗