Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Simultaneous and independent use of cocaine and alcohol by heroin addicts was shown to variably modulate the ability of their T cells to form E-rosettes with sheep erythrocytes (E). As reported previously, the percentages of E-rosette-forming T cells of both active and total types were depressed in association with heroin addiction. We show here that the kinetic curve of the rate of E-rosette formation is also depressed by heroin use and that the use of cocaine but not alcohol by heroin addicts reverses depression of E-rosette formation by heroin. The percentages of E-rosette-forming T cells from the bloods of heroin addicts who used both alcohol and cocaine, as well as the kinetic rate curves of E-rosette formation, were intermediate between the essentially normal levels found for heroin addicts who used cocaine and the severely depressed levels evident for users of heroin alone or heroin plus alcohol. Modulation of the levels of E-rosette formation by alcohol used in conjunction with cocaine and/or heroin was variably dose dependent. Polydrug effects evident by analyses of E-rosette formation were not seen when the percentages of lymphocytes reactive with LYT-3 (anti-E-receptor, 9.6 epitope) and OKT-3 (anti-total T cell) monoclonal antibodies were assessed cytofluorometrically, although the data suggested that subnormal percentages of LYT-3+ T cells were present when heroin addicts also used cocaine. These findings are relevant to basic understanding of T-cell physiology from a neuroimmunological perspective and also suggest ways that addictive drugs may modulate the immunocompetence of drug addicts.
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PMID:Coordinate and independent effects of heroin, cocaine, and alcohol abuse on T-cell E-rosette formation and antigenic marker expression. 309 6

The function of the central serotonergic system was examined indirectly through the measurement of prolactin (PRL) and cortisol responses to fenfluramine challenges in 27 heroin addicts 2 months after detoxification and in nine healthy volunteers. Heroin abusers included nine addicts with comorbid depressive disorders (Group A), nine with aggressive behavior and antisocial personality (Group B), and nine with heroin addiction uncomplicated by other Axis I and II psychiatric disorders (Group C). PRL and cortisol responses of patients in Group A were blunted, while those of patients in Groups B and C did not differ from those of the healthy volunteers. Cortisol responses in Group A differed significantly from those in the other patient groups and in the normal comparison group for AUC analyses, but the diagnosis x time interaction showed a significant difference only between Group A and the normal group. Our data suggest that the function of the serotonergic system is impaired in heroin addicts with comorbid depression but not in heroin addicts who are not clinically depressed. Thus, the serotonergic system does not appear to be impaired by prolonged opioid exposure, per se.
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PMID:Serotonin function in detoxified heroin abusers: prolactin and cortisol responses to fenfluramine challenge. 857 Jul 67

The serotonergic (5-HT) function of 36 mothers of heroin addicts, of whom 16 subjects were without psychopathological features (group A) and 20 subjects had major depressive disorders (group B), as well as 10 age- and sex-matched healthy controls, was examined by L-D-fenfluramine stimulation of secretion of prolactin (PRL) and cortisol. The subjects' addict relatives were also tested for personality features and hormonal responses to L-D-fenfluramine. The PRL and cortisol responses to the stimulus were normal in mothers of group A, and blunted in mothers of group B. A high frequency (70%) of heroin addicts with comorbid depression was found among the sons of group B mothers. The sons of depressed mothers showed reduced PRL and cortisol responses to fenfluramine. A significant direct correlation has been demonstrated between the PRL areas under curves (AUC) of mothers and sons in response to the 5-HT agonist. Our data suggest that genetic 5-HT impairment is not involved in the pathogenesis of heroin addiction or codependence per se, and is probably linked to the presence of familial depression in comorbidity with the addictive disorder.
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PMID:Serotonergic function in mothers of opioid addicts: correlation with comorbid depression. 925 22

High dose buprenorphine is used as substitution treatment in human heroin addiction. Deaths have been reported in addicts using buprenorphine, frequently in association with benzodiazepines. In the current study, we observed the effects of buprenorphine and midazolam alone and in combination on arterial blood gases. Four groups of 10 male Sprague-Dawley rats received a parenteral injection of aqueous solvent, buprenorphine (30 mg/kg, iv), midazolam (160 mg/kg, ip), or buprenorphine (30 mg/kg, iv) plus midazolam (160 mg/kg, ip). Serial blood gases were obtained over 3 hours. There was a mild but significant effect of buprenorphine alone in comparison with the aqueous solvent on PaCO2 at 60 min (6.24 vs. 5.65 kPa, p< 0.01). There was also a mild but significant effect of midazolam alone in comparison with aqueous solvent on arterial pH at 90 min (7.33 vs. 7.41,p< 0.001) and PaCO2 at 60 min (6.52 vs. 5.65 kPa,p< 0.01). The combination of midazolam and buprenorphine produces a rapid, profound, and prolonged respiratory depression, as demonstrated by an increase in PaCO2 at 7.65 +/- 0.12 kPa at 20 min and a decrease in arterial pH at 7.25 +/- 0.02 at 20 min, with appearance of delayed hypoxia with a decrease in PaO2 at 8.74 +/- 0.20 kPa at 120 min. These data show that high doses of midazolam and buprenorphine alone have limited effects on arterial blood gases in rats while midazolam and buprenorphine appear to act in an additive or synergistic fashion to depress ventilation in rats.
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PMID:Buprenorphine and midazolam act in combination to depress respiration in rats. 1175 90

Many patients receiving sustained-action narcotics during therapy for heroin addiction have symptoms of fatigue, depression, diminished libido, and impaired sexual function. They are rarely, however, evaluated for narcotic-induced hypogonadism, or treated with sex-hormone replacement. Studies are reviewed examining the influence of narcotic administration on sex-hormone levels. These document frequent, sometimes profound, deficiencies in many men and women treated with narcotics. We have documented improved quality of life during sex-hormone replacement therapy in patients with narcotic-induced hypogonadism, most of whom were receiving their narcotics for control of chronic pain. These studies suggest that similar hormone replacement therapy may assist patients receiving narcotics for treatment of heroin addiction.
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PMID:Narcotic-induced hypogonadism during therapy for heroin addiction. 1229 1

The present study compared in a clinical non-experimental setting the efficacy of buprenorphine (BUP) and methadone (METH) in the treatment of opioid dependence: all the subjects included in the study showed severe long-lasting heroin addiction. Participants (154) were applicants to a 12 weeks treatment program, who were assigned to either METH (78) (mean doses 81.5 +/- 36.4 mg) or BUP (76) (mean doses 9.2 +/- 3.4 mg) treatment. Aim of the study was to evaluate patient/treatment variables possibly influencing retention rate, abstinence from illicit drugs and mood changes. METH patients showed a higher retention rate at week 4 (78.2 versus 65.8) (P < 0.05), but BUP and METH were equally effective in sustaining retention in treatment and compliance with medication at week 12 (61.5 versus 59.2). Retention rate was influenced by dose, psychosocial functioning and not by psychiatric comorbidity in METH patients. In contrast, BUP maintained patients who completed the observational period showed a significantly higher rate of depression than those who dropped out (P < 0.01) and the intention to treat sample (P < 0.05). No relationship between retention and dose, or retention and psychosocial functioning was evidenced for BUP patients. The risk of positive urine testing was similar between METH and BUP, as expression of illicit drug use in general. At week 12, the patients treated with METH showed more risk of illicit opioid use than those treated with BUP (32.1% versus 25.6%) (P < 0.05). Negative urines were associated with higher doses in both METH and BUP patients. As evidenced for retention, substance abuse history and psychosocial functioning appear unable to influence urinalyses results in BUP patients. Buprenorphine maintained patients who showed negative urines presented a significantly higher rate of depression than those with positive urines (P < 0.05). Alternatively, psychiatric comorbidity was found unrelated to urinalyses results in METH patients. Our data need to be interpreted with caution because of the observational clinical methodology and non-random procedure. The present findings provide further support for the utility of BUP in the treatment of opioid dependency and demonstrate efficacy equivalent to that of METH during a clinical procedure. BUP seems to be more effective than METH in patients affected by depressive traits and dysphoria, probably due to antagonist action on kappa-opioid receptors. Psychosocial functioning and addiction severity cannot be used as valuable predictors of BUP treatment outcome. High doses appear to predict a better outcome, in term of negative urines, for both METH and BUP, but not in term of retention for BUP patients.
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PMID:Buprenorphine versus methadone for opioid dependence: predictor variables for treatment outcome. 1522 87

High dose buprenorphine is used as substitution treatment in heroin addiction. However, deaths have been reported in addicts using buprenorphine. The role of norbuprenorphine, an N-dealkyl metabolite of buprenorphine, was hypothesized to explain these fatal cases. We determined the median intravenous lethal dose (LD(50)) of norbuprenorphine in male Sprague-Dawley rats. The effects of a single intravenous dose of 3 or 9 mg/kg norbuprenorphine alone on arterial blood gases were studied. Finally, the effect of pre- and post-administrations of buprenorphine on norbuprenorphine-induced changes on arterial blood gases were analyzed. Norbuprenorphine's LD(50) was 10 mg kg(-1). Norbuprenorphine 3 mg kg(-1) produces the rapid onset of sustained respiratory depression, as demonstrated at 20 min by a maximal significant increase in PaCO(2) (8.4+/-0.9 versus 5.7+/-0.1 kPa), decrease in arterial pH (7.25+/-0.06 versus 7.44+/-0.01), and hypoxia (8.3+/-0.6 versus 11.1+/-0.2 kPa). Buprenorphine not only protected against the effects of 3 mg kg(-1) norbuprenorphine in a dose-dependent manner but also reversed the effects when given afterward. Binding experiments suggest a role for micro- and to a lesser extent for delta-opioid receptors in buprenorphine protective effect against norbuprenorphine-induced respiratory depression. In conclusion, our data clearly show that norbuprenorphine alone causes important deleterious effects on ventilation in rats. However, buprenorphine protective effect calls into question the role for norbuprenorphine in respiratory toxicity associated with buprenorphine use.
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PMID:Buprenorphine is protective against the depressive effects of norbuprenorphine on ventilation. 1616 27

The present study compared retrospectively in a clinical non-experimental setting the efficacy of buprenorphine (BUP) in different subgroups of dually diagnosed and non-dually diagnosed opioid-dependent patients: all the subjects included in the study showed severe long-lasting heroin addiction and 68.4% were affected by psychiatric comorbidity. Participants (206) (mean age 32.2+/-8.9, 177 males-29 females) were applicants to a long-term buprenorphine treatment program (mean doses 7.9+/-0.42 mg). Aim of the study was to evaluate dual diagnosis variables possibly influencing retention rate and abstinence from illicit drugs. The patients were divided into 5 subgroups on the basis of dual diagnosis: group 1: major depression (MD) 29.61%; group 2: generalized anxiety (GAD) (11.2%); group 3: personality disorders (PD), antisocial-borderline (21.84%); group 4: schizophrenia (SC)(6.3%); group 5: substance use disorder without overt psychiatric comorbidity (SUD) (31.1%). Group 1 patients affected by MD showed the highest retention rate at 12 months (72.1%) in comparison with the other groups of patients: group 2 GAD (39.1%), group 3 PD (17.8%), group 4 SC (7.7%) and group 5 SUD, without comorbidity (45.3%) (p=0.006, p<0.001, p<0.001, p=0.002). Similarly, at 12 months, the patients affected by MD showed less risk of illicit opioid use (16.4%) than those affected by GAD (34.8%), PD (42.2%), SC (53.8%) and SUD without comorbidity (34.4%) (p=0.06, p=0.003, p=0.008, p=0.017). When evaluated on the whole sample, retention rate was not influenced by dose. In contrast, the higher BUP doses were associated with less risk of illicit opioid use, than lower doses (p<0.001). Multivariate analysis and factor analysis showed a greater association of outcome measures (retention rate and negative urines rate) with comorbid diagnosis (depression) (respectively 0.64) than with buprenorphine doses (respectively 0.54). Our data need to be interpreted with caution because of the retrospective methodology applied to a clinical non-experimental setting. BUP seems to be more effective in opioid-dependent patients affected by depression, probably due to the kappa opioid-receptors antagonist action, counteracting dysphoria, negativism and anxiety. High doses of BUP appear to predict a better outcome, in terms of negative urines, but not in terms of retention.
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PMID:Buprenorphine treatment outcome in dually diagnosed heroin dependent patients: A retrospective study. 1630 10

Buprenorphine is an opioid agonist-antagonist with a 'ceiling effect' for respiratory depression. Compared with methadone, its unique pharmacology offers practical advantages and enhanced safety when prescribed as recommended and supervised by a physician. Buprenorphine has been approved in several countries as an efficient and safe maintenance therapy for heroin addiction. Its use resulted in a salutary effect with a reduction in heroin overdose-related deaths in countries that implemented office-based buprenorphine maintenance. In France, however, where high-dose buprenorphine has been marketed since 1996, several cases of asphyxic deaths were reported among addicts treated with buprenorphine. Death resulted from buprenorphine intravenous misuse or concomitant sedative drug ingestion, such as benzodiazepines. In these situations of abuse, misuse, or in association with elevated doses of psychotropic drugs, buprenorphine may cause severe respiratory depression. Unlike other opiates, the respiratory effects from buprenorphine are not responsive to naloxone. However, the exact mechanism of buprenorphine-induced effects on ventilation is still unknown. The role of norbuprenorphine, the main N-dealkylated buprenorphine metabolite with potent respiratory depressor activity, also remains unclear. Experimental studies investigating the respiratory effects of combinations of high doses of buprenorphine and benzodiazepines suggested that this drug-drug interaction may result from a pharmacodynamic interaction. A pharmacokinetic interaction between buprenorphine and flunitrazepam is also considered. As there are many questions regarding the possible dangers of death or respiratory depression associated with buprenorphine use, we aimed to present a comprehensive critical review of the published clinical and experimental studies on buprenorphine respiratory effects.
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PMID:Does high-dose buprenorphine cause respiratory depression?: possible mechanisms and therapeutic consequences. 1695 55

In humans, asphyxic deaths and severe poisonings have been attributed to high-dosage buprenorphine, a maintenance therapy for heroin addiction. However, in rats, intravenous buprenorphine at doses up to 90 mg kg(-1) was not associated with significant effects on arterial blood gases. In contrast, norbuprenorphine, the buprenorphine major cytochrome P450 (CYP) 3A-derived metabolite, is a potent respiratory depressant. Thus, our aim was to study the consequences of CYP3A induction on buprenorphine-associated effects on resting ventilation in rats. We investigated the effects on ventilation of 30 mg kg(-1) buprenorphine alone or following cytochrome P450 (CYP) 3A induction with dexamethasone, using whole body plethysmography (N=24) and arterial blood gases (N=12). Randomized animals in 4 groups received sequential intraperitoneal dosing with: (dexamethasone [days 1-3]+buprenorphine [day 4]), (dexamethasone solvent [days 1-3]+buprenorphine [day 4]), (dexamethasone [days 1-3]+buprenorphine solvent [day 4]), or (dexamethasone solvent [days 1-3]+buprenorphine solvent [day 4]). Buprenorphine alone caused a significant rapid and sustained increase in the inspiratory time (P<0.001), without significant effects on the respiratory frequency, the tidal volume, the minute volume, or arterial blood gases. In dexamethasone-pretreated rats, there was no significant alteration in the respiratory parameters, despite CYP3A induction and significant increase of the ratio of plasma norbuprenorphine-to-buprenorphine concentrations. In conclusion, dexamethasone did not modify the effects of 30 mg kg(-1) buprenorphine on rat ventilation. Our results suggest a limited role of drug-mediated CYP3A induction in the occurrence of buprenorphine-attributed respiratory depression in addicts.
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PMID:Dexamethasone hepatic induction in rats subsequently treated with high dose buprenorphine does not lead to respiratory depression. 1708 76


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