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Biomedical subjects

D Nutt

Publications and source records attributed to D Nutt.

At least 37 records · Page 2Linked to original sources
PubMed1997

Management of patients with depression associated with anxiety symptoms.

Current diagnostic classifications separate depression from anxiety, yet these conditions commonly coexist in clinical practice, forming a spectrum of disorders between these extremes. Treatment options for depression with anxiety include tricyclic antidepressants (TCAs) and serotonin selective reuptake inhibitors (SSRIs). As SSRIs are nonsedating, this proves that sedation as produced by TCAs is not required for anxiolytic actions. SSRIs are effective in anxiety disorders and against anxiety symptoms in depressed patients. The adverse event profile of SSRIs compares favorably with that of TCAs, and SSRIs are much safer in overdose. When the diagnosis of depression with anxiety is established, it is important to institute prompt, effective treatment in view of the potential risk of suicide. The SSRIs appear to be the treatment of choice for such patients.

Antidepressive Agents, Tricyclic↗
PubMed1996

The biological, social and clinical bases of drug addiction: commentary and debate.

This article summarizes the main discussions at a meeting on the biological, social and clinical bases of drug addiction focused on contemporary topics in drug dependence. Four main domains are surveyed, reflecting the structure of the meeting: psychological and pharmacological factors; neurobiological substrates; risk factors (including a consideration of vulnerability from an environmental and genetic perspective); and clinical treatment. Among the topics discussed were tolerance, sensitization, withdrawal, craving and relapse; mechanisms of reinforcing actions of drugs at the behavioural, cognitive and neural levels; the role of subjective factors in drug dependence; approaches to the behavioural and molecular genetics of drug dependence; the use of functional neuroimaging; pharmaceutical and psychosocial strategies for treatment; epidemiological and sociological aspects of drug dependence. The survey takes into account the considerable disagreements and controversies arising from the discussions, but also reaches a degree of consensus in certain areas.

Brain↗
PubMed1996

Moclobemide in the treatment of social phobia.

Social phobia is a common disorder which is associated with considerable suffering and impairment. Effective treatments have now been developed and they represent an important advance in the management of the disorder. Moclobemide is a reversible inhibitor of monoamine oxidase A (RIMA) which has an established place in the treatment of depression. The efficacy of moclobemide in social phobia has been demonstrated in short-term treatment for up to 12 weeks in three placebo-controlled studies. It has also proved to be effective in long-term treatment in a placebo-controlled study and in open treatment studies. This paper reviews the efficacy of moclobemide in social phobia.

Benzamides↗
PubMed1995

The effects of clonidine on cardiovascular responses to standing in healthy volunteers.

This study assessed the effects of clonidine on blood pressure (BP) and heart rate responses to active standing, recorded continuously using a Finapres monitor. Ten subjects were given a placebo infusion over 1 h, followed by clonidine hydrochloride 1.5 micrograms/kg over 2 h. During placebo and at 1, 3 and 19 h following the clonidine infusion, heart rate and blood pressure were recorded during the second half of supine rest for 10 min, active standing and quiet standing for 7 min. Clonidine did not alter the size of immediate drop in BP on standing, although the nadir was lower. BP recovery was impaired, with a loss of the usual BP overshoot in most subjects and with delays in reaching supine levels of diastolic BP (6.1 versus 9.6 s; p < 0.01) and systolic BP (8.1 versus 12.3 s; p < 0.05). The compensatory initial heart rate rise was significantly increased from 47 to 53 beats/min (p < 0.05), although the peak rate reached was reduced from 114 to 104 beats/min (p < 0.05). These results demonstrate that impairment of central sympathetic vasomotor drive leads to a delay in BP recovery and loss of initial BP overshoot immediately after standing, together with impaired maintenance of early steady-state BP.

Adult↗
PubMed1995

Inhibition of amine oxidase activity by derivatives that recognize imidazoline I2 sites.

Nonadrenergic imidazoline binding sites (imidazoline I2 sites) have been described to be colocated with monoamine oxidase (MAO) in the mitochondrial fraction of various cell types. In the present work, the authors considered whether this colocation could be associated with a functional interplay. In rat liver membranes, [3H]-idazoxan binding to I2 receptors was competed for by naphazoline and idazoxan, which also shared a high affinity for alpha-2 adrenoceptors (alpha-2 ARs). The chemicals 2-n-heptylimidazoline (S 15430), 1-methyl-5-n-heptylimidazole (S 15674), 2-benzofuran-2-yl-imidazoline (RX 801077) and 2-(1,3-benzodioxanyl)-2-imidazoline (RX 821029) exhibited higher affinity for I2 receptors than for alpha-2 ARs. The most selective agent was S 15430 with a 150-fold higher affinity for liver I2 receptors than for adipocyte alpha-2 ARs. Moreover, [3H]-idazoxan binding was also competed for by several MAO inhibitors (MAOI) that are not imidazoline or guanidinium derivatives such as tranylcypromine, harmaline, clorgiline and pargyline. Rat liver MAO activity was not only inhibited by MAOIs but also by some imidazoline derivatives: cirazoline, naphazoline, S 15674, RX 801077 and RX 821029. Idazoxan had no effect on MAO activity; it neither inhibited MAO nor prevented the inhibition induced by other imidazolines or MAOIs. This suggested that the ligand recognition site of I2 receptors was distinct from the MAOI target site. Furthermore, some imidazolines inhibited the activity of bovine plasma amine oxidase, an enzyme that does not possess the same cofactor as MAO and is insensitive to harmaline or pargyline.(ABSTRACT TRUNCATED AT 250 WORDS)

Amine Oxidase (Copper-Containing)↗
PubMed1994

Regionally specific changes in extracellular noradrenaline following chronic idazoxan as revealed by in vivo microdialysis.

The selective alpha 2-adrenoceptor antagonist idazoxan was administered chronically (0.8 mg/kg per h) to rats for a period of 10 days via osmotic minipumps. On day 11, 24 h after removal of the pumps, the rats were anaesthetised and microdialysis probes were implanted into either the frontal cortex or hippocampus. Basal noradrenaline release in the frontal cortex was significantly elevated compared with the saline control group. Each animal was then challenged with idazoxan (10 mg/kg s.c.). Inhibition of presynaptic alpha 2-adrenoceptors resulted in a significant increase in noradrenaline release in the saline control group. However, animals treated chronically with idazoxan, showed a markedly attenuated response to the single dose idazoxan challenge in the frontal cortex. No significant change in either basal release or in response to idazoxan challenge was observed in the hippocampus in the chronic idazoxan-treated animals as compared with the chronic saline control group. Chronic idazoxan administration results in selective enhancement of noradrenaline release in the frontal cortex but not in the hippocampus. This would be consistent with a down-regulation of presynaptic alpha 2-adrenoceptors with the subsequent loss of presynaptic noradrenergic negative feedback inhibition.

Adrenergic alpha-Antagonists↗
PubMed1994

Selective serotonin reuptake inhibitors: meta-analysis of discontinuation rates.

A meta-analysis was carried out of 42 published randomized controlled studies comparing the selective serotonin reuptake inhibitors (SSRIs) with the tricyclic antidepressants (TCAs) that measured discontinuation rates for side effects and lack of efficacy by treatment group in order to compare the discontinuation rates for side effects and lack of efficacy. These discontinuation rates were pooled to produce the main outcome measure. Seven studies were placebo controlled and the discontinuation rates in these studies were also pooled in a separate analysis. Significantly fewer patients receiving SSRIs discontinued treatment because of side effects (14.9%) compared with those receiving TCAs (19%) (p < 0.01). There was also a significant difference in discontinuation rates due to side effects in the placebo- and TCA-controlled studies analysed separately, SSRIs (19%) compared with TCAs (27%) (p < 0.01). In both analyses a similar proportion of patients discontinued for lack of efficacy on SSRIs and TCAs. There is a significant and clinically important advantage for the SSRIs compared with the TCAs in the acceptability of treatment measured by the number of discontinuations due to side effects reported in published studies. The risk-benefit calculation favours the SSRIs since there were similar levels of efficacy but more discontinuations with the TCAs. The selection of an antidepressant for first-line treatment requires critical evaluation of the full risk-benefit equation.

Antidepressive Agents, Tricyclic↗
PubMed1993

Flumazenil in alcohol withdrawal.

This is a preliminary study to explore the theory that there may be abnormalities of the benzodiazepine receptor, or a possible endogenous inverse agonist ligand in alcohol withdrawal. The benzodiazepine antagonist flumazenil was administered to 8 alcoholics in early withdrawal in a double blind placebo controlled design. Self ratings of mood and physical symptoms, and observer ratings of withdrawal symptoms revealed differences in the effects of flumazenil and placebo. Flumazenil had an immediate slight anxiogenic action which was short-lived. It then appeared to ameliorate withdrawal symptoms, quite markedly in 2 patients.

Adult↗
PubMed1992

Panic attacks. A neurochemical overview of models and mechanisms.

The delineation of panic disorder as a distinct diagnostic entity has provided renewed impetus for research into panic. This review describes and examines the range of neurobiological theories of panic attacks. It illustrates the diversity of mechanisms that have been invoked to explain the production of panic attacks, and which have influenced much of the current thinking about the neurochemistry of anxiety.

Bicarbonates↗
PubMed1992

The effects of electroconvulsive therapy on plasma insulin and glucose in depression.

The effects of ECT on plasma insulin and glucose were assessed in 20 depressed patients, during the first, third and fifth session of ECT. After each administration of ECT there was a significant rise in blood glucose and plasma insulin levels, both of which peaked at 15 minutes. Insulin responses tended to attenuate over the course of ECT, whereas the glucose responses were similar for all three treatments. ECT was effective in all patients, although two months after the last treatment nine patients had partially relapsed (Hamilton score greater than 15). Those who relapsed had a more attenuated insulin response at the fifth treatment than those who had remained well, which suggests that insulin response to ECT may be predictive of clinical outcome.

Aged↗
PubMed1990

Cerebrospinal fluid monoamine metabolites in alcoholic patients who attempt suicide.

Reduced cerebrospinal fluid (CSF) levels of the serotonin metabolite 5-hydroxyindoleacetic acid have been reported to be commonly associated with suicidal behaviour. Alcoholics are known to often manifest suicidal behaviour. Therefore, we compared cerebrospinal fluid levels of monoamine metabolites in alcoholics who had (n = 20) and had not (n = 108) attempted suicide and healthy volunteers (n = 30). There were no significant differences among the 3 groups for CSF levels of either 5-hydroxyindoleacetic acid, the dopamine metabolite homovanillic acid, norepinephrine, or the norepinephrine metabolite 3-methoxy-4-hydroxyphenylglycol.

Adult↗
PubMed1990

Overexcitement and disinhibition. Dynamic neurotransmitter interactions in alcohol withdrawal.

In alcohol withdrawal, abnormalities occur in a number of neurotransmitter systems: there is reduced inhibitory function, and increased activity of excitatory systems. The former, indicated by reduced GABA and alpha-2-adrenoceptor activity, acts in conjunction with, and is exacerbated by, the latter, which itself may be due to the potentiation of NMDA activity by depletion of magnesium, and overactivity of catecholaminergic and CRF neurones. These dysfunctions produce immediate effects and may also contribute to the long-term changes in brain excitability by a kindling-like process. It is possible that early and active treatment may oppose this process. Present strategies for treatment of alcohol withdrawal enhance GABA and alpha-2 inhibitory, or reduce excitatory, mechanisms. Future possibilities include the use of CRF and/or NMDA antagonists.

Alcohol Withdrawal Delirium↗