Psychopathology in children of parents with opiate dependence and/or major depression

OBJECTIVE: To evaluate psychiatric disorders and impairment in school-age and adolescent children of opiate-dependent patients. METHOD: One hundred fourteen children, aged 6 to 17 years, of 69 white methadone maintenance patients with (n = 30) and without (n = 39) major depression were evaluated for DSM-III-R diagnoses by the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Epidemiologic version and best estimate, and by measures of functioning (Children's Global Assessment Scale, Social Adjustment Inventory for Children and Adolescents, WISC, Peabody Picture Vocabulary Test), and compared with children of historical controls without substance abuse history. RESULTS: Sons of opiate addicts with major depression were at increased risk for conduct disorder and global, social, and intellectual impairment compared with sons of opiate addicts without major depression and/or sons of controls with neither drug dependence nor depression. Sons of opiate addicts without major depression differed little from controls. Daughters of opiate addicts did not differ from controls in rates of disorders but had poorer social adjustment and nonverbal intelligence. CONCLUSIONS: Children of opiate-dependent patients, particularly sons of addicts with depression, may be at risk for a developmental path toward antisocial personality and poor social and intellectual functioning. Treatment settings such as methadone maintenance might afford an opportunity for primary and secondary prevention, both through early detection of childhood disorders and treatment of parental drug dependence and psychopathology.     

Managing under managed care. The role of the advanced practice nurse in Surgery

To assess the status of opioid receptors in the human brain during the process of opiate addiction, the abundance of immunoreactive mu-opioid receptors was quantitated in postmortem brains of chronic opiate addicts who had died of a heroin or methadone overdose. The immunoreactive levels of the associated enzyme protein kinase C (PKC-alpha and zeta isoforms) and G proteins (G alpha(i1/2) subunits) were also assessed in the same brains. In the frontal cortex of opiate addicts, the abundance of mu-opioid receptors was not different from that obtained in matched controls. The level of Ca2+-dependent PKC-alpha was decreased (25%), whereas that of the atypical PKC-zeta remained unchanged. The density of G alpha(i1/2) proteins also was found to be increased (40%). The results indicate that opiate addiction in humans does not appear to be associated with a reduced density of brain mu-opioid receptors. The sustained down-regulation of PKC-alpha in the brain of opiate addicts would allow the up-regulation of G alpha(i1/2) proteins aimed at compensating the postulated desensitization of the mu-opioid receptor system.     

Problems with maintenance therapy in opiate dependence and the clinical importance of methadone]

The author presents a review of experience with substitution treatment in opiate dependence. Methadone treatment is most frequently used. An individual daily dose and long-term substitution are desirable for stabilization and motivation of patients included in the methadone programme. Interaction of methadone with some drugs affects the methadone metabolism and calls for a change of the methadone dose and must not be omitted. In addition to methadone there are also other types of pharmacotherapy of opiate dependence (acetylmethadol, buprenorphine). In the Czech Republic in 1997 in the General Faculty Hospital Prague the methadone programme was started. The importance of methadone substitution treatment is beyond doubt and involves improvement of the psychosocial and health status of addicts, gives an opportunity of resocialization and reintegration into society.     

The life-time rates of three major mood disorders and four major anxiety disorders in alcoholics and controls

AIMS: While psychiatric symptoms are common in the general population and even more prevalent in alcoholics, their clinical implications are not clear. The goal of this study was to establish the life-time rates of several independent and concurrent mood and anxiety disorders in alcoholics, controls and their relatives. DESIGN: Structured interviews were administered to alcoholics entering treatment, their relatives, and controls. SETTING: The study was carried out in six different centers in the United States as part of the Collaborative Study on the Genetics of Alcoholism (COGA). PARTICIPANTS: Data were gathered from 2713 alcohol dependent subjects (probands and their alcoholic relatives) and 919 controls. MEASUREMENTS: The timeline-based Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) interview was administered face to face by trained, closely supervised interviewers. The life-time rates for concurrent and independent disorders were determined for three DSM-III-R major mood and four major anxiety disorders. FINDINGS: Some form of independent mood disorder was seen during the life-time in slightly fewer alcoholics than controls (14.0% and 17.1%), but alcoholics did show higher rates of independent bipolar disorder (2.3% vs. 1.0%). The life-time rate for independent anxiety disorders was significantly higher in alcoholics than controls (9.4% vs. 3.7%), with most of the differential related to panic disorder (4.2% vs. 1.0%) and social phobia (3.2% vs. 1.4%), but no significant group differences for agoraphobia or obsessive-compulsive disorder. In general, these findings regarding mood and anxiety disorders were reflected in close relatives. CONCLUSIONS: The large majority of alcohol-dependent men and women in this sample did not have any of the independent mood or anxiety disorders evaluated here. However, there was evidence of enhanced risks among alcoholics for independent bipolar, panic and social phobic disorders. Studies which do not distinguish carefully between independent and concurrent mood and anxiety disorders in alcoholics are likely to report much higher rates of co-morbid psychiatric disorders than those that distinguish between the two types of syndromes.     

Methadone blockade in the treatment of opiate addiction: a follow-up study

This paper describes methadone blockade treatment of 50 opiate addicts. At follow-up, 36 patients were traced and interviewed. Results show that 89% of the 36 patients cooperated with the treatment programme, 88% had no new criminal convictions and 75% remained drug-free, apart from taking methadone during the follow-up period (mean, 12-5 months). Five of the 36 patients were free of all drug addictions, including methadone.     

Estimating specificity of drug and alcohol subcultural groups with slang names for drugs.

Constructed a drug slang association test by selecting words from dictionaries on drugs such as slang for drugs or alcohol that referred to the drug or the user of drugs. Evidence for a general subculture drug factor was found in the sense that 83 opiate addicts (prisoners) knew more slang words for heroin, Benzedrine, barbiturates, and marihuana than did the 23 normals (undergraduates) or 23 alcoholics (halfway house residents). Specificity emerged from the fact that alcoholics knew more alcohol-related slang than normals or opiate addicts. Opiate addicts also knew more heroin-related slang relative to other slang. (8 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The relationship between maternal use of heroin and methadone and infant birth weight

AIMS/DESIGN: Reduction in mean birth weight and increased incidence of low birth weight are both associated with exposure to illicit heroin in pregnancy. Many studies examining neonatal outcomes in pregnant heroin users treated with methadone report improvements in birth weight. As a consequence, methadone treatment has become the 'gold standard' for the management of the pregnant heroin user. However, not all studies report significant birth weight increases associated with methadone. We undertook a number of meta-analyses on reduction in mean birth weight and incidence of low birth weight to estimate more precisely the effect of illicit heroin and methadone. FINDINGS: Results showed mean reduction in birth weight associated with heroin use: 489 g (95% CI 284-693 g), compared with methadone: 279 g (229-328 g). Similarly, the pooled relative risk estimate for low birth weight for maternal heroin use was 4.61 (95% CI 2.78-7.65), compared with 1.36 (0.83-2.22) for methadone. Analysis of data on combined heroin and methadone use produced a pooled mean reduction in birth weight of 557 g (403-710 g), with a pooled relative risk estimate for low birth weight of 3.28 (2.47-4.39). Pooling 'any' methadone data, regardless of heroin use, produced an estimated reduction in birth weight of 395 g (311-478 g) and a relative risk estimate for low birth weight of 1.90 (1.29-2.81). Combining all data in an 'any' opiate use analysis also produced a mean reduction in birth weight of 483 g (386-583 g) and a relative risk estimate for low birth weight of 3.81 (2.57-5.65). CONCLUSIONS: The current findings suggest that heroin use while receiving methadone may counteract the birth weight advantage gained from methadone alone. Whether this is due to fetal exposure to heroin plus methadone, to reduced antenatal care, other behavioural and environmental factors associated with concurrent use of heroin and methadone or a combination of these is unclear. Nevertheless, these results challenge the current belief that the pregnant user is always better off receiving methadone than not, and suggests that methadone may not be the appropriate treatment for the pregnant women who continue to use illicit heroin.     

Single-nucleotide polymorphism in the human mu opioid receptor gene alters beta-endorphin binding and activity: possible implications for opiate addiction

Opioid drugs play important roles in the clinical management of pain, as well as in the development and treatment of drug abuse. The mu opioid receptor is the primary site of action for the most commonly used opioids, including morphine, heroin, fentanyl, and methadone. By sequencing DNA from 113 former heroin addicts in methadone maintenance and 39 individuals with no history of drug or alcohol abuse or dependence, we have identified five different single-nucleotide polymorphisms (SNPs) in the coding region of the mu opioid receptor gene. The most prevalent SNP is a nucleotide substitution at position 118 (A118G), predicting an amino acid change at a putative N-glycosylation site. This SNP displays an allelic frequency of approximately 10% in our study population. Significant differences in allele distribution were observed among ethnic groups studied. The variant receptor resulting from the A118G SNP did not show altered binding affinities for most opioid peptides and alkaloids tested. However, the A118G variant receptor binds beta-endorphin, an endogenous opioid that activates the mu opioid receptor, approximately three times more tightly than the most common allelic form of the receptor. Furthermore, beta-endorphin is approximately three times more potent at the A118G variant receptor than at the most common allelic form in agonist-induced activation of G protein-coupled potassium channels. These results show that SNPs in the mu opioid receptor gene can alter binding and signal transduction in the resulting receptor and may have implications for normal physiology, therapeutics, and vulnerability to develop or protection from diverse diseases including the addictive diseases.     

Affective and adjustment problems in cocaine and opioid addicts.

Compared 74 male cocaine and 43 male opioid users on global measures of subjective distress, specifically anxiety and depression, and on various self-reported psychopathology symptoms. In contrast to opioid addicts, compulsive cocaine users were characterized by significantly fewer problems with anxiety, depression, and adjustment. Results indicate less severe psychopathology among cocaine abusers than among opioid addicts. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neurobiology of withdrawal motivation: Evidence for two separate aversive effects produced in morphine-naive versus morphine-dependent rats by both naloxone and spontaneous withdrawal.

In drug-naive rats, the rewarding effects of morphine are blocked by lesions of the tegmental pedunculopontine nucleus (TPP), but not by neuroleptics. In dependent rats (chronically treated with morphine), morphine reward is blocked by neuroleptics, but not by TPP lesions. Just as this activation of opiate receptors in naive vs dependent rats produces different mechanisms of reward, this study concludes that reduced opioid activity on these opiate receptors produces different mechanisms of aversion. Neuroleptics blocked the conditioned place aversions produced by naloxone and spontaneous withdrawal in morphine dependent, but not naive, rats, without attenuating the somatic withdrawal syndrome induced by naloxone in dependent rats. The researchers suggest that the aversive effects of endogenous opioid withdrawal in naive rats are mediated by different neural substrates than the aversive effects of exogenous opioid withdrawal in dependent rats. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Predictors of outcome in LAAM, buprenorphine, and methadone treatment for opioid dependence.

This study examined (1) predictors of treatment outcome for opioid-dependent participants in a single-site controlled trial comparing methadone, buprenorphine, and LAAM treatments and (2) the extent to which various subpopulations of patients may have more successful outcomes with each medication. The relationships between patient demographics, drug use history, and psychological status and outcome measures of treatment retention, opiate use, and cocaine use were assessed. We believe this study to be the first to demonstrate that predictors of treatment success appear to be largely similar in LAAM, buprenorphine, and methadone treatment for opioid dependence. We did not find any factors that would strongly guide selection of one medication over others. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Buprenorphine versus methadone maintenance for opioid dependence

Buprenorphine at 2 mg and 6 mg daily was compared with methadone at 35 mg and 65 mg during 24 weeks of maintenance among 125 opioid-dependent patients. As hypothesized, 6 mg of buprenorphine were superior to 2 mg of buprenorphine in reducing illicit opioid use, but higher dosage did not improve treatment retention. Self-reported illicit opioid use declined substantially in all groups, but by the third month, significantly more heroin abuse was reported at 2 mg than at 6 mg of buprenorphine or of methadone. From an initial average of $1860/month, month 3 usage dropped to $41 (methadone 65 mg), $73 (methadone 35 mg), $118 (buprenorphine 6 mg), and $351/month (buprenorphine 2 mg). Days of use also dropped from 29 days to 1.7 (methadone 65 mg), 2.8 (methadone 35 mg), 4.0 (buprenorphine 6 mg), and 6.6 days/month (buprenorphine 2 mg). This relatively low efficacy for 2 mg of buprenorphine persisted through month 6 of the trial, with 7.2 days/month and $235/month of use for buprenorphine at 2 mg versus 1.9 days/month and $65/month for the other three groups. Increased opioid abuse also was associated with significantly greater and persistent opioid withdrawal symptoms. Our secondary hypothesis, that buprenorphine would be equivalent to methadone in efficacy, was not supported. Treatment retention was significantly better on methadone (20 vs. 16 weeks), and methadone patients had significantly more opioid-free urines (51% vs. 26%). Abstinence for at least 3 weeks was also more common on methadone than buprenorphine (65% vs. 27%).(ABSTRACT TRUNCATED AT 250 WORDS)     

A controlled trial comparing buprenorphine and methadone maintenance in opioid dependence

BACKGROUND: Buprenorphine is a partial agonist at the mu-opioid receptor that has been proposed as an alternative to traditional full agonist maintenance therapy for the treatment of opioid addiction. We report on a clinical trial in which the relative safety and efficacy of long-term fixed-dose buprenorphine maintenance was examined in comparison to low- and high-dose methadone maintenance. METHODS: Two hundred twenty-five treatment-seeking opioid addicts (46 women, 179 men) were randomly assigned to receive, in a double-blind manner, either 8 mg/d of buprenorphine, 30 mg/d of methadone, or 80 mg/d of methadone maintenance over a 1-year period. Objective and subjective measures of efficacy (urine toxicology, retention, craving, and withdrawal symptoms) were examined at the study midpoint and at termination, and safety data were tabulated over the entire 52-week study period. RESULTS: Patients assigned to high-dose methadone maintenance performed significantly better on measures of retention, opioid use, and opioid craving than either the low-dose methadone or the buprenorphine group at both 26-week and 52-week time points. Performance on these measures was virtually identical between the latter two groups. No serious adverse health effects attributable to buprenorphine were noted. CONCLUSIONS: Buprenorphine maintenance at 8 mg/d appears to be less than optimally efficacious under the conditions of the present study. Continued research is needed to reconcile these findings with the more positive results reported by other investigative groups. There are no apparent health risks associated with long-term buprenorphine maintenance at this dosage.     

Prevalence of minor psychiatric disorders in an adult African rural community in South Africa

BACKGROUND: This paper reports on a two-stage community-based epidemiological study of selected minor psychiatric disorders conducted on an adult African population in South Africa. METHODS: Using a modified random cluster sampling method, 354 adults were identified as the first-stage sample, with the SRQ-20 being used as a first-stage screen. Clinical interviews based on DSM-IV checklists for generalized anxiety disorder, major depression and dysthymia were administered as the second-stage criterion to 81 subjects from the sample. RESULTS: The weighted prevalence for generalised anxiety and depressive disorders was 23.9% (95% CI 15.1%-32.7%), comprising: generalized anxiety 3.7%, major depression 4.8%, dysthymia 7.3%, and major depression and dysthymia 8.2%. Statistically significant associations were found between caseness and age, marital status, employment, income and educational level. CONCLUSIONS: The results are discussed in relation to comparative local and international data as well as in the context of the current restructuring of the mental-health care system in South Africa from tertiary curative care to integrated primary mental-health care.     

Monounsaturated oils do not all have the same effect on plasma cholesterol

The relationship between pupil size and subjective symptoms of opiate withdrawal during gradual opiate agonist detoxification has not yet been studied. In the current study, the authors sought to determine the relationship between pupil size and intensity of opiate withdrawal symptoms. To accomplish this, they examined 19 subjects meeting DSM-IV criteria for opiate dependence (304.00) on agonist therapy. All subjects were undergoing opiate detoxification with either methadone or the longer-acting 1-alpha acetylmethadol (LAMM). During two separate visits, subjects' pupil sizes were assessed in the dark using a pupillometer. At each visit, subjects completed two standardized assessment tools (the Subjective Opiate Withdrawal Scale [SOWS] and the Weak Opiate Withdrawal Scale [WOWS]) for measuring subjective symptoms of opiate withdrawal. It was found that changes in pupil size significantly correlated with WOWS, but not with SOWS, scores. Larger pupil sizes were associated with less withdrawal distress. The sensitivity of the pupillometric test to detect increases in opiate craving during opiate agonist medication reduction was 92%, with a specificity of 57%. The predictive value of a positive test was 79%, whereas the predictive value of a negative test was 80%. Pupillometry may provide an objective measure of the intensity of opiate withdrawal in subjects during gradual methadone detoxification.     

Sexual abuse and alcoholism in a female population

AIMS: (1) To study the prevalence of childhood sexual abuse before the age of 18 years (CSA) and life-time sexual abuse (LSA) in a Swedish female, general population, (2) to analyse associations between CSA and life-time alcohol dependence or abuse (ADA), and (3) to identify possible confounding factors. DESIGN AND PARTICIPANTS: The study was conducted in two phases. Phase 1: an alcohol problem screening questionnaire was sent to 3130 women aged 25-65. The answers were scored. Phase 2: based on the questionnaire scores, a randomly selected stratified sample of 479 women was invited for an interview. Of these, 316 women participated in a structured face-to-face interview. SETTING: A sector of G?teborg city with 100,000 inhabitants. MEASUREMENTS: The interviews focused on substance use and on social, psychological and behavioural characteristics, including experiences of sexual abuse. Clinical psychiatric diagnoses were made according to DSM-III-R. Bivariate analyses and multivariate logistic regression analyses were performed. FINDINGS: The prevalence of CSA and LSA was 9.8% and 13.9%, respectively. CSA increased the risk for life-time ADA and anxiety, but not for depression. When potential confounding factors (e.g. early background factors, depression and anxiety) were adjusted for, CSA under 13 years of age still predicted ADA in multivariate analyses, but CSA under 18 years of age did not. CONCLUSIONS: LSA, and especially CSA under 13 years of age, are factors that should be considered in treatment of women with ADA and in psychiatric treatment of women.     

Mu opioid receptor phosphorylation, desensitization, and ligand efficacy

Mu opioid receptors are subject to phosphorylation and desensitization through actions of at least two distinct biochemical pathways: agonist-dependent mu receptor phosphorylation and desensitization induced by a biochemically distinct second pathway dependent on protein kinase C activation (1). To better understand the nature of the agonist-induced mu receptor phosphorylation events, we have investigated the effects of a variety of opiate ligands of varying potencies and intrinsic activities on mu receptor phosphorylation and desensitization. Exposure to the potent full agonists sufentanil, dihydroetorphine, etorphine, etonitazine, and [D-Ala2, MePhe4, Glyol5]enkephalin (DAMGO) led to strong receptor phosphorylation, while methadone, l-alpha-acetylmethadone (LAAM), morphine, meperidine, DADL, beta-endorphin(1-31), enkephalins, and dynorphin A(1-17) produced intermediate effects. The partial agonist buprenorphine minimally enhanced receptor phosphorylation while antagonists failed to alter phosphorylation. Buprenorphine and full antagonists each antagonized the enhanced mu receptor phosphorylation induced by morphine or DAMGO. The rank order of opiate ligand efficacies in producing mu receptor-mediated functional desensitization generally paralleled their rank order of efficacies in producing receptor phosphorylation. Interestingly, the desensitization and phosphorylation mediated by methadone and LAAM were disproportionate to their efficacies in two distinct test systems. This generally good fit between the efficacies of opiates in mu receptor activation, phosphorylation, and desensitization supports the idea that activated receptor/agonist/G-protein complexes and/or receptor conformational changes induced by agonists are required for agonist-induced mu receptor phosphorylation. Data for methadone and LAAM suggest possible contribution from their enhanced desensitizing abilities to their therapeutic efficacies.     

Dependent opioid users assessed for methadone treatment in Otago: patterns of drug use

AIMS: To provide detailed information about the types of drugs used and the patterns of drug use for injecting drug users presenting for methadone treatment. METHODS: A retrospective case note review was carried out for 126 consecutive clients who were assessed for methadone treatment in the Otago province over a 2 year period. Patterns of drug use in the three months prior to presentation were recorded. RESULTS: Over 60% of those presenting were using three or more opioid drugs, with the most common being homebake (63%), sustained release morphine sulphate tablets (62%), buprenorphine (52%), opium poppies (50%) and methadone (41%). Use of diacetylmorphine (heroin) was reported primarily by those returning from recent overseas travel. Most clients reported the regular use of multiple other of clients using benzodiazepines daily. Almost 80% of the group were regular tobacco smokers and 11% showed evidence of alcohol disorders (abuse or dependence). Low levels of use were reported for cocaine, amphetamines, and hallucinogens. CONCLUSION: These patterns of drug use have important implications for the planning of methadone treatment programmes.     

Clinical risk factors for the generation of life events in major depression.

This study examines the relationship of anxiety disorder and dysthymia comorbidity to the generation of life events prior to major depression episode onset in a cross-sectional community sample of 76 women. Those with comorbid anxiety and dysthymia experienced higher rates of events that were at least partly dependent on their own behavior but did not differ from those without these clinical risk factors on independent life events outside of their control. This relationship remained significant even after controlling for overall severity of depression and demographic covariates. The implications of these results for understanding the increased rates of major depression onset and recurrence among those with comorbid anxiety and dysthymia are discussed as avenues of future research. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Family ties of drug abusers.

Examined the family ties of heroin addicts applying for drug treatment. Information was abstracted from the intake applications of 98 consecutive admissions to methadone maintenance program to determine the extent to which applicants were connected with family members. Results indicate that approximately 67% of Ss lived with a family member, including 26% who lived with a parent; 52% of Ss were born in the local area; 75% claimed to have close relationships with their mothers. Results imply that drug treatment programs might increase their effectiveness by using a family systems approach. (PsycINFO Database Record (c) 2010 APA, all rights reserved)