PubMed Health⌕ Search

Biomedical subjects

J Bearn

Publications and source records attributed to J Bearn.

At least 19 recordsLinked to original sources

Effects of methadone on cognition, mood and craving in detoxifying opiate addicts: a dose-response study.

RATIONALE: Methadone is the most widespread pharmacological treatment for opiate dependency but relatively little is known of its effects on cognitive and psychomotor functioning, drug craving and mood. OBJECTIVE: The present study aimed to assess the acute effects of methadone in patients admitted to an opiate detoxification programme. METHODS: Patients were randomly allocated to one of two groups who received either 50% or 100% of their daily stabilisation dose, and a placebo, in a double-blind, cross-over design. Twenty patients completed the study, all were assessed pre- and post-drug on 2 separate testing days. RESULTS: Performance on a task tapping episodic memory (delayed recall of a prose passage) was significantly impaired following the 100% daily dose of methadone. Methadone treatment had no effect on craving or mood. Patients were unable to distinguish between methadone and placebo treatments. CONCLUSIONS: A single dose of methadone can induce episodic memory impairment in patients who have a history of heroin use averaging more than 10 years. Such impairment can be avoided by giving methadone in divided doses.

Adult↗

Are the Twelve Steps more acceptable to drug users than to drinkers? A comparison of experiences of and attitudes to Alcoholics Anonymous (AA) and Narcotics Anonymous (NA) among 200 substance misusers attending inpatient detoxification.

The present study is a cross-sectional interview-based investigation comparing experiences of and attitudes towards Alcoholics Anonymous (AA) and Narcotics Anonymous (NA) in a sample of 200 patients attending inpatient substance misuse detoxification services. Two hundred consecutive admissions were recruited; 100 each from one drug and one alcohol in-patient treatment service in which attendance at AA/NA was a voluntary adjunct to a generic treatment programme. Although there were no differences in the history of AA/NA attendance, the drug users (who were on average younger) reported significantly more positive attitudes towards AA/NA, more willingness to attend during their in-patient treatment and greater intention to attend following completion of their detoxification. In particular, despite no differences in spiritual/religious orientation, the drug users reported more positive views of the Twelve Steps. As AA/NA remain popular and accessible forms of substance misuse support, it is critical that we develop a clearer understanding of their impact and of the scope for their integration with generic forms of substance misuse treatment.

Adult↗

Neural responses associated with cue evoked emotional states and heroin in opiate addicts.

Ten male opiate addicts, who were current heroin injectors, underwent positron emission tomographic (PET) scanning during exposure to a sequence of six alternating drug related and neutral video cues, on two occasions. After the second scan, each subject received heroin or placebo using a randomised single-blind procedure. This design allowed the investigation of patterns of brain activity during a range of self-reported cue evoked emotional states, both in the presence and absence of heroin. Self-reports of 'urge to use' correlated strongly with increased regional blood flow (rCBF) in the inferior frontal and orbitofrontal cortex target regions of the mesolimbic dopaminergic system, implicated in conditioning and reward. 'Urge to use' was also associated with highly significant increased rCBF in the right pre-cuneus, an area associated with episodic memory retrieval, and in the left insula, implicated in the processing of the emotional components of stimuli. Self-reports of feeling 'high' correlated with rCBF activation in the hippocampus, an area relevant to the acquisition of stimulus-associated reinforcement.

Adult↗

Naltrexone and lofexidine combination treatment compared with conventional lofexidine treatment for in-patient opiate detoxification.

This study compares a naltrexone/lofexidine combination treatment with a 7-day course of lofexidine alone in the treatment of opiate withdrawal in 22 opiate-dependent patients. Withdrawal symptoms were significantly less severe on days 4-7, and 9-13, in the naltrexone/lofexidine combination group. There were no significant differences in the percentage of patients completing detoxification or in the mean length of stay for the two groups. Both treatments had similar, minimal effects on blood pressure. The naltrexone/lofexidine combination was associated with a more rapid resolution of the opiate withdrawal syndrome than a 7-day lofexidine-only treatment schedule, without substantial increases in withdrawal symptoms or hypotensive side-effects.

Adult↗

Activation of reward circuitry in human opiate addicts.

The neurobiological mechanisms of opiate addictive behaviour in humans are unknown. A proposed model of addiction implicates ascending brainstem neuromodulatory systems, particularly dopamine. Using functional neuroimaging, we assessed the neural response to heroin and heroin-related cues in established opiate addicts. We show that the effect of both heroin and heroin-related visual cues are maximally expressed in the sites of origin of ascending midbrain neuromodulatory systems. These context-specific midbrain activations predict responses to salient visual cues in cortical and subcortical regions implicated in reward-related behaviour. These findings implicate common neurobiological processes underlying drug and drug-cue-related effects.

Adult↗

Lofexidine for opiate detoxification: review of recent randomised and open controlled trials.

The objective of this article was to review the data from recently published trials of lofexidine in the treatment of opiate withdrawal, with particular attention to evidence on efficacy, side-effects (particularly hypotension), and the acceptability of this new treatment to the patient population. The authors reviewed data contained within peer-reviewed published reports of clinical trials of lofexidine compared with detoxification using reducing doses of the opiate agonist methadone or the alpha-adrenergic agonist clonidine. Five published reports of clinical trials of lofexidine have been identified from peer-reviewed journals in the eight years between 1990 and 1998--all published within the last three years. Three of the reports compare lofexidine with clonidine, while the remaining two compare it with methadone detoxification. The three comparisons with clonidine find lofexidine to be similar in its moderating effect on the withdrawal syndrome, but without the same extent of problems with hypotension. Comparisons with methadone show a more rapid resolution of withdrawal symptoms with lofexidine--particularly with the accelerated 5-day lofexidine protocol. Such problems of hypotension as were encountered with lofexidine were adequately managed with dose reduction. Acceptability of the treatment to the patient (as measured by retention in treatment) appears to be greater with lofexidine than clonidine, although possibly less than with methadone. Lofexidine is an alpha-2 adrenergic agonist that is increasingly used in the management of opiate withdrawal--notably in the UK. The available data indicate that it is a useful new addition to the armamentarium of the clinician. Future studies should explore its application with improved protocols and in new treatment settings. This article reviews the recent advances in the study of lofexidine as a new treatment for opiate detoxification. It examines the background of the development and introduction of lofexidine into the U.K., with data on the extent to which it is now used in the U.K. in the treatment of opiate addiction. A review is then provided of the published evidence on the use of lofexidine in the management of opiate detoxification, mainly concentrating on the data from recent double-blind randomised trials. Finally, the possible future role of lofexidine in this field is considered.

Clonidine↗

Accelerated lofexidine treatment regimen compared with conventional lofexidine and methadone treatment for in-patient opiate detoxification.

This open study compares an accelerated 5-day lofexidine regimen with orthodox 10-day lofexidine and methadone regimens in the treatment of opiate withdrawal in 61 polysubstance abusing opiate addicts. Significant differences in levels of withdrawal symptoms were found on days 11, 13-15 and 17-20, symptoms resolving most rapidly in the 5-day lofexidine treatment group, whilst withdrawal responses in the 10-day lofexidine treatment group were intermediate between the 5-day lofexidine and standard methadone treatment conditions. When the two lofexidine regimens were separately compared with methadone the 5-day lofexidine treatment was significantly more effective on day 10, 11 and 13-20, whilst the 10-day lofexidine treatment was not significantly different from methadone. There were no significant differences in rates of completion of detoxification between the three treatments. Both the lofexidine treatment regimens had a similar effect on blood pressure. Five patients experienced side effects which resolved with dose reduction, all remaining in the study. An accelerated 5-day lofexidine regimen may attenuate opiate withdrawal symptoms more rapidly than conventional 10-day lofexidine or methadone treatment schedules without exacerbating hypotensive side effects.

Adult↗

Randomised double-blind comparison of lofexidine and methadone in the in-patient treatment of opiate withdrawal.

This study compares the clinical responses to methadone and lofexidine in the treatment of opiate withdrawal in 86 polydrug-abusing opiate addicts, using a randomised double-blind study design. The lofexidine treatment more severe symptoms from day 3 to 7 and again on day 10 (the last day of treatment), but thereafter both groups showed a similar progressive symptom decline. There was no significant difference in rates of treatment completion. Both treatments had similar effects on blood pressure. Lofexidine is broadly clinically equivalent to methadone, and appears to be a non-opiate treatment of opiate withdrawal without serious limiting hypotensive side effects.

Adolescent↗

Contrasting neuroendocrine responses in depression and chronic fatigue syndrome.

Hypothalamic-pituitary-adrenal (HPA) axis and central 5-HT function were compared in chronic fatigue syndrome (CFS), depression and healthy states. 10 patients with CFS and 15 patients with major depression were matched for age, weight, sex and menstrual cycle with 25 healthy controls. Baseline-circulating cortisol levels were highest in the depressed, lowest in the CFS and intermediate between the two in the control group (P = 0.01). Prolactin responses to the selective 5-HT-releasing agent d-fenfluramine were lowest in the depressed, highest in the CFS and intermediate between both in the healthy group (P = 0.01). Matched pair analysis confirmed higher prolactin responses in CFS patients than controls (P = 0.05) and lower responses in depressed patients than controls (P = 0.003). There were strong inverse correlations between prolactin and cortisol responses and baseline cortisol values. These data confirm that depression is associated with hypercotisolaemia and reduced central 5-HT neurotransmission and suggest that CFS may be associated with hypocortisolaemia and increased 5-HT function. The opposing responses in CFS and depression may be related to reversed patterns of behavioural dysfunction seen in these conditions. These findings attest to biological distinctions between these disorders.

Adult↗

Neuroendocrine responses to d-fenfluramine and insulin-induced hypoglycemia in chronic fatigue syndrome.

Chronic fatigue syndrome (CFS) is a disorder characterized by severe physical and mental fatigue and fatiguability of central rather than peripheral origin. We hypothesized that CFS is mediated by changes in hypothalamopituitary function and so measured the adrenocorticotrophic hormone (ACTH), cortisol, growth hormone, and prolactin responses to insulin-induced hypoglycemia, and the ACTH, cortisol, and prolactin responses to serotoninergic stimulation with dexfenfluramine in nondepressed CFS patients and normal controls. We have shown attenuated prolactin responses to hypoglycemia in CFS. There was also a greater ACTH response and higher peak ACTH concentrations (36.44 +/- 4.45 versus 25.60 +/- 2.78 pg ml), whereas cortisol responses did not differ, findings that are compatible with impaired adrenal cortical function. This study provided evidence for both pituitary and adrenal cortical impairment in CFS and further studies are merited to both confirm and determine more precisely their neurobiological basis so that rational treatments can be evolved.

Adrenocorticotropic Hormone↗

Clozapine.

Explore the source record for details and available documents.

Ambulatory Care↗

A study of the effects of desipramine treatment alone and in combination with L-triiodothyronine on 6-sulphatoxymelatonin excretion in depressed patients.

Urinary 6-sulphatoxymelatonin (alpha MT6s) excretion was measured after one day and one, two and three weeks of desipramine treatment in eight depressed patients. There was significant increase in the urinary excretion of alpha MT6s after one week of treatment, and at no time was there any decrease in alpha MT6s excretion. These findings are opposed to the hypothesis that desipramine reduces noradrenergic neurotransmission in the human pineal. In a further five patients whose depression was resistant to desipramine alone, urinary alpha MT6s excretion was measured during treatment with adjunctive L-triiodothyronine (T3). There was no change in alpha MT6s excretion, and thus the previously reported potentiation of the efficacy of tricyclic antidepressants in combination with T3 does not appear to be mediated through an alteration in noradrenergic neurotransmission.

Adult↗