Biomedical subjects
Publications and source records attributed to L San.
Sociodemographic, toxicologic, and psychopathologic characteristics of 22 buprenorphine addicts and 45 heroin addicts admitted for inpatient detoxification were compared. Although the buprenorphine addicts were older, clinically significant differences were not apparent. The availability of buprenorphine may be the main reason for its abuse.
The spontaneous physical dependence of buprenorphine was assessed in opioid addicts who switched from heroin to sublingual or intravenous buprenorphine. Twenty-two patients were randomly assigned to double-blind administration of methadone (n = 11) or placebo (n = 11) for 13 days after abrupt withdrawal of buprenorphine. Methadone was administered according to four pre-established dosing schedules depending on the previous amount of daily consumed buprenorphine. No methadone-treated patient required modification of the therapeutic regimen, whereas eight of eleven placebo-treated patients needed treatment with methadone. Buprenorphine withdrawal syndrome was of opioid type, began somewhat more slowly, and showed a peak until day 5. The occurrence, time-course and characteristics of buprenorphine withdrawal syndrome make it necessary to reconsider the abuse potential of this analgesic.
Long-term opioid consumption can induce hypoadrenalism through impairment of the hypothalamic-pituitary-adrenal axis. Results of the present study showed that, in heroin addicts, saliva cortisol concentrations varied according to the amount of recently consumed heroin and the time elapsed since the last self-administration. Hypercortisolism was observed either after abrupt withdrawal of heroin or the last dose of methadone. Post-detoxification hypercortisolism was still present on day 16 after the last opioid consumption, whereas it was not observed in abstinent addicts for a mean period of 4 months. During detoxification treatment, mean AUC8-24 cortisol in saliva of clonidine or guanfacine-treated patients was significantly higher than that in methadone-treated patients. It may be hypothesized that elevated cortisol levels may account for untoward effects of adrenergic agonist therapy which, in turn, may represent an added risk factor for relapse during detoxification. Further studies are necessary to correlate the severity of withdrawal symptoms to cortisol levels in opioid addicts detoxified with alpha 2-adrenergic agonist substitution.
Abuse of cocaine is becoming a major problem among heroin addicts in Spain. Between 1987 and 1988, 75% of patients admitted as inpatients for detoxification from opiate dependence had consumed cocaine during the 6 months prior to admission and 25% had abused cocaine daily or several times/week. These cocaine abusers showed more toxicologic and psychopathologic problems than opiate addicts who did not abuse cocaine. The opiate addicts who also abused cocaine had begun using illicit drugs earlier and showed a higher frequency of anti-HIV antibodies. They also had more antisocial personality disorders and persistence of depressive symptoms during opiate detoxification than heroin addicts who did not abuse cocaine. Based on these findings, we insist on the need to develop different treatments for detoxifying patients with this dual addiction.
Naltrexone and placebo as adjuvant treatment of opioid dependence were compared in a double-blind, controlled clinical trial in 50 heroin addicts. The overall efficacy was assessed by the degree of treatment acceptance, percentage of relapse in heroin consumption, presence of side effects, and overall retention on naltrexone. A total of 50 patients of both sexes, aged from 18 to 30 years, who fulfilled DSM-III-R criteria for opioid dependence were included in the study. All patients completed detoxification with clonidine on an inpatient basis for 2 weeks and subsequently, on an out-patient basis, received oral naltrexone (350 mg per week) for a month. At the beginning of the second month patients were randomly allocated to treatment with naltrexone (28 patients) or placebo (22 patients) until a 6-month treatment period in a double-blind fashion had been completed. During the study period (1 year) all patients followed the same therapeutic schedule. Patients in both groups were comparable in terms of socio-demographic data and toxicological history. The efficacy of naltrexone was not superior to that of placebo as there were no significant differences in acceptance of treatment, retention rates, opioid and other drug consumption, drug compliance or side effects.
The efficacy of clonidine, methadone, and guanfacine in rapid detoxification of heroin inpatients was assessed in a randomized controlled clinical trial. Signs and symptoms of abstinence and of side effects were analysed in 90 heroin addicts successfully completing a 12-day inpatient trial. All patients fit DSM-III criteria for opioid dependence, the age range being 18 to 36 years. All three drugs were effective in controlling abstinence; however, the course of abstinence was different in the methadone group as compared to the adrenergic agonists, the latter showing limitations in their ability to suppress withdrawal manifestations. While mean number of withdrawal signs and symptoms was significantly lower during days 2 to 5 in the methadone group (p less than 0.01), adrenergic agonists were slightly more effective at the end of the trial. Incidence of side effects was closely related to the dose administered. Hypotensive action of adrenergic agonists was more marked in orthostatic position. The present results suggest that methadone is superior to adrenergic agonists. Between these drugs clonidine appears to be less effective than guanfacine in controlling some withdrawal manifestations, and causes more side effects, mainly of cardiovascular nature.
The peripheral blood samples obtained from 32 ballet students with a mean age of 17.5 years and 32 age-matched non- dancers who comprised a control group were analysed using the microdeterminations of lymphocyte blast transformation and mixture rosette forming cells. The percentage of lymphocyte blast transformation of ballet students was normal, but their percentage of E-rosette forming cells was lower than that of controls at rest. A significant increase in the percentage of zymosan-complement rosette forming cells was seen during dancing. The study suggests that a saving effect on expenditure of cellular immunofunction is exhibited in ballet students at rest and that intensive ballet-exercise induces an immediate humoral immune response change. However, the effect needs to be dynamically observed and the clinical implication of the response change remains to be proved.
After buprenorphine was introduced as an analgesic, several clinical observations have stimulated the investigation of its potential abuse by heroin addicts. To evaluate the prevalence of buprenorphine use by a group of heroin abusers being treated on an outpatient basis, a cross-sectional study was carried out where the information given by the 188 subjects was verified by urine drug analyses. The patients had three different therapeutic modalities: methadone maintenance program (MMP), antagonist maintenance program (AMP), and drug-free program (DFP). The urine samples were analyzed with an enzyme immunoassay technique for the detection of heroin, methadone, dextropropoxyphene, cannabis and benzodiazepines. Buprenorphine was investigated with a radioimmunoassay technique. Overall 66% of the patients admitted having used buprenorphine throughout their toxicologic history (period prevalence) and 6.7% had positive urine controls for this drug (5% in the MMP group, 0% in the AMP group and 12% in the DFP group) (point prevalence). In 72% of the cases the drug was administered intravenously. In addition, a clinically statistically significant association was found between positivity for heroin and buprenorphine. The possible tolerance to the latter is suggested by the fact that the mean current dose was higher than the mean initial dose. In the study population, the use of cannabis and benzodiazepines was also very high. The results suggest that most patients had a previous history of buprenorphine use. This drug could have a higher potential for abuse than that found in previous experimental studies.
A multicentre prospective study was performed in eight centres in Spain in order to assess the usefulness of naltrexone in the treatment of opiate dependents and abusers (113 dependents and 37 abusers) non-selected in terms of social class or professional skill. The fundamental criterion for evaluation of clinical outcome was the retention rate. At 6 months this parameter was 40%, i.e. higher than any previously reported for non-selected patients. The adverse effects were mild and did not lead to therapeutic failures. Non-pharmacological factors may have contributed to the good clinical results obtained.
Predictors of either detoxification success or failure were evaluated during an inpatient trial that compared the efficacy of methadone, clonidine and guanfacine for rapid heroin detoxification. The analysis of such predictors was stimulated by the fact that in order to achieve 90 patients who completed the study (30 in each group), a total of 170 patients had to be included. Of 80 detoxification failures, 10 occurred in the methadone group, 32 in the guanfacine group, and 38 in the clonidine group. Voluntary request for discontinuation of the detoxification schedule was the first cause of failure. There were not statistically significant differences with regard to sociodemographic characteristics and pattern of drug consumption among patients in the three groups who completed detoxification with success or failure. The treatment drug, the type of schedule and the score obtained from the Symptom Checklist-90/Revised (SCL-90/R) were the only predictors of either detoxification success or failure. Inpatient opioid detoxification would be a useful strategy for patients with more severe psychological symptoms.
The efficacy of a rapid detoxification schedule (8 to 10 days) with clonidine or methadone was evaluated in 30 patients addicted to heroin. The dose of study drug was preestablished according to the subject's weight and the amount of opioid consumption, and the total daily dose was reduced by approximately 15% during the study. All subjects completed the detoxification program and stayed in the hospital for at least 12 days. Clonidine and methadone therapies proved to be highly effective. There was a marked reduction in anxiety during opioid detoxification, although subjects' experiences differed according to the drug used. On the day of discharge, subjects who had received methadone still had attenuated withdrawal symptoms, whereas there were no such symptoms in the clonidine group. Muscular aching, flatulence, and daily drowsiness were more common among subjects in the methadone group, while subjects in the clonidine group had more sleep disturbances and weeping. Syncopal episodes and bradycardia occurred more frequently in the clonidine group.
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In a randomized double-blind study, the clinical efficacy of methadone vs. methadone and guanfacine was assessed in terms of evolution of opioid withdrawal symptoms during inpatient detoxification. A total of 144 patients were included and randomly allocated to three different treatment groups: methadone alone, and two combined treatment schedules (methadone plus 3 or 4 mg of guanfacine). No differences were observed among the three groups with regard to retention rate throughout the study period. Both therapies, methadone and methadone plus guanfacine, determined a slight increase in withdrawal scores when methadone was discontinued. However, guanfacine was unable to effectively control methadone-associated withdrawal symptoms. These results indicate that guanfacine does not effectively reduce the opioid withdrawal symptoms.
Drug-addicted patients (N = 435) admitted for treatment in different clinical settings were studied. Patients were classified according to their self-report of consumed drugs and to the results of urine screening tests. Of the patients, 77.8% were active consumers, 9.6% were included in a methadone maintenance program, and 12.6% were abstinent. In the active consumer patients, positive urine screening results surpassed by far the information provided in the self-reports. Most patients tested positive to several drugs, while only 8.7% tested negative to all screened drugs. These results indicate that the information provided by drug-dependent patients lacks reliability when an analytical screening method is used simultaneously.
The serotonin (5-hydroxytryptamine, 5-HT) uptake sites assessed with both [3H]imipramine and [3H]paroxetine, and the 5-HT2A receptors were simultaneously measured in platelets from 24 male subjects meeting the American Psychiatric Association's DSM-IV criteria for alcohol dependence and admitted for inpatient detoxification. Blood samples from alcoholic patients were collected during acute alcohol intoxication (day 0), during withdrawal (day 1), and after 2 weeks of abstinence (day 14). All patients met the criteria for type II alcoholism. Alcohol misuse was found to be associated with an increased number and a lower affinity of [3H]paroxetine binding in comparison to the control values. Abstinence from alcohol for 2 weeks (day 14) resulted in a decrease in the number of 5-HT uptake sites labelled with [3H]paroxetine compared to normal values, together with a significant decrease in the number of 5-HT2A binding sites. The present data indicate that altered serotonergic function existing in alcoholic patients is a reversible phenomenon that normalizes after detoxification and withdrawal.
Evidence from several studies supports the involvement of several neurotransmitter systems in the mechanism of action and the clinical efficacy of the electroconvulsive therapy (ECT). However, more recent studies have reported serotonin, through the activation of several receptors, to be the neurotransmitter most frequently altered in ECT. With regard to the serotonergic system, several levels of alteration can be targeted, that concerning serotonin and its metabolite concentrations, that concerning changes in the density of presynaptic and postsynaptic receptors located both in brain tissue or in platelets, and finally, alterations at the intracellular signalling system or second messenger level.
So far, there is increasing evidence of the active role of molecular biology in the psychiatric nosology as well as in the identification of psychiatric fenotypes. In this respect, the neurotransmitter serotonin (5-HT) has been involved in the etiopathogeny of multiple psychiatry conditions, such as affective disorder, schizophrenia, panic disorder, obsessive-compulsive disorder, alcoholism, eating disorder and personality disorder. The 5-HT2 receptor family includes the subtype 5-HT2A, a G protein coupled receptor whose activation leads to the stimulation of the enzyme phospholipase C and to the subsequent hydrolysis of the membrane located phosphoinositides, with the synthesis of the second messengers inositol triphosphate and diacylglicerol. This paper includes a review of the main findings concerning the polymorphism of the 5-HT2A in psychiatric disorders.