Faculty Bibliography

There is a belief among methadone patients that triple therapy for HIV reduces methadone potency. This cross-sectional study compared the rate of methadone metabolism (peak-trough blood levels) in two groups of methadone-maintained patients, AIDS patients receiving triple therapy (N = 17), and HIV patients without triple therapy (N = 19). These preliminary findings suggest that triple therapy may increase the rate of methadone metabolism, though further studies are warranted.

BACKGROUND:The effects of major depressive disorder (MDD) on the course of substance dependence may differ depending on the temporal relationship of depression to dependence. We investigated the effects of MDD on the outcome of substance dependence under 3 circumstances: (1) lifetime onset of MDD prior to lifetime onset of dependence onset, (2) current MDD occurring during a period of abstinence, and (3) current MDD during substance use that exceeded the expected effects of intoxication or withdrawal. METHODS:A sample of 250 inpatients with DSM-IV cocaine, heroin, and/or alcohol dependence were followed up at 6, 12, and 18 months. The Psychiatric Research Interview for Substance and Mental Disorders (PRISM) was used to make DSM-IV diagnoses. Using Cox proportional hazards models, stable remissions (those lasting at least 26 weeks) from DSM-IV cocaine, heroin, and/or alcohol dependence and from use were studied, as well as subsequent relapses of dependence and use. RESULTS:Patients with current substance-induced MDD were less likely to remit from dependence (adjusted hazards ratio, 0.11) than patients with no baseline MDD. A history of MDD prior to lifetime onset of substance dependence also reduced the likelihood of remission relative to the absence of such a history (adjusted hazard ratio, 0.49). Major depressive disorder during sustained abstinence predicted dependence relapse (adjusted hazards ratio, 3.07) and substance use after hospital discharge compared with those without abstinence MDD (adjusted hazards ratio, 1.45). CONCLUSION/CONCLUSIONS:The timing of depressive episodes relative to substance dependence served as an important factor in the remission and relapse of substance dependence and substance use.

Treatment of opiate dependence with naltrexone has been limited by poor compliance. Behavioral Naltrexone Therapy (BNT) was developed to promote adherence to naltrexone and lifestyle changes supportive of abstinence, by incorporating components from empirically validated treatments, including Network Therapy with a significant other to monitor medication compliance, the Community Reinforcement Approach, and voucher incentives. An overview is presented of the BNT treatment manual. In an uncontrolled Stage I trial (N = 47), 19% completed the 6-month course of treatment. Retention was especially poor in the subsample of patients who were using methadone at baseline (N = 18; 39% completed 1 month, none completed 6 months), and more encouraging among heroin-dependent patients (N = 29; 65% completed 1 month, 31% completed 6 months). Thus, attrition continues to be a serious problem for naltrexone maintenance, although further efforts to develop interventions such as BNT are warranted.

UNLABELLED:The effect of concurrent nonopiate drug use on outcome of treatment for opiate dependence. METHOD/METHODS:Forty-seven opiate-dependent patients received a 6-month course of outpatient treatment with naltrexone and cognitive-behavioral therapy (behavioral naltrexone therapy, BNT) at a university-based research clinic. Opiate-negative urines and naltrexone ingestion were rewarded with monetary vouchers. Abstinence from other drugs was encouraged verbally, but no contingencies were placed on nonopiate drug use. The proportions of all urines (collected twice weekly) positive for cocaine, cannabis, and benzodiazepines over the course of treatment were evaluated as predictors of outcome of opiate dependence treatment, as measured by proportion of opiate-positive urines, days retained in treatment, and proportion of naltrexone doses taken, using Pearson product moment correlations and one-way analysis of variance (ANOVA). RESULTS:The majority of patients (78%) used a nonopiate drug at least once during the trial. There were no significant correlations between concurrent drug use measures and opiate dependence treatment outcomes, indicating no simple linear relationship between these measures. However, when concurrent drug use was trichotomized into abstinent, intermittent, and heavy use groups, groups with intermittent use had superior outcome compared to both abstinent and heavy use groups in several contrasts. CONCLUSIONS:Intermittent use of nonopiate drugs is common during outpatient treatment for opiate dependence and may be a favorable prognostic indicator. This may support a "harm reduction" approach as opposed to a strict abstinence-oriented approach. Further research is needed to identify the optimal therapeutic stance toward other drug use during treatment for opiate dependence.

The aim of this study was to examine the self-medication hypothesis (SMH) of substance abuse. The SMH suggests that drug abuse is driven by an attempt to alleviate specific psychological distress. One prediction from the SMH hypothesis is that drugs of abuse, because of their different pharmacological properties, attract specific patient subgroups. Specifically, this study tested the hypothesis' that opiate abusers experience difficulty managing aggression and that cocaine abusers suffer from distress associated mostly with depression. The State-Trait Anger Expression Inventory (STAXI) and the Beck Depression Inventory II were used to examine levels of anger and depression among three groups of substance abusers (opiates, cocaine, cannabis), defined by their primary drug of abuse. Anger and depression scores were elevated, but contrary to Khantzian's hypothesis, there were few differences between groups, and if anything, opiate addicts were more depressed and the cocaine abusers were angrier on several subscales. Data are discussed in terms of diagnosis and clinical treatment implications.

There is considerable debate about the appropriate conceptualization of pathological gambling and its place in psychiatric nosology. The authors examined the existing research on different areas of pathological gambling to find evidence for a particular model of this disorder. There are 2 dominant models of pathological gambling: as a nonpharmacologic addiction and as an obsessive-compulsive spectrum disorder. The data available from different areas seem to converge in suggesting that pathological gambling has characteristics that are similar to those of substance abuse, and less close to those of obsessive-compulsive disorder, although those conceptualizations are not mutually exclusive. An alternative model of pathological gambling is that it constitutes a heterogeneous disorder with some subtypes resembling obsessive-compulsive disorder, and other subtypes being closer to substance abuse disorders. Improved understanding of the conceptualization of this disorder may help improve the quality of the treatments available.

The aim of this study was to determine treatment adherence relative to frequency of violence and posttraumatic stress disorders (PTSD) among new methadone patients. Ninety-six opiate-abusing patients were evaluated for childhood physical and sexual abuse (CPSA), adulthood exposures to violence (ADVIOL), PTSD, and treatment adherence. Overall, 43% of the subjects dropped out of treatment within 3 months of intake. Occurrence of trauma or PTSD did not predict drop-out rates. A 2 (Gender) x 2 (PTSD) analysis of covariance (ANCOVA) with severity of other drug use on admission as a covariate, however, revealed a main effect for PTSD, F(4, 71) = 7. 69, p < or =.01, such that those patients with current PTSD revealed significantly more ongoing drug use at 3 months (M = 24.3, SD = 20. 9) than those without (M = 8.9, SD = 11.8). Examination of ongoing cocaine use using a 2 (Gender) x 2 (PTSD) ANCOVA also revealed a main effect for PTSD, F(4, 17) = 8.24, p < or = .005, such that those patients with current PTSD revealed significantly more ongoing cocaine use at 3 months postadmission (M = 51.6, SD = 37.6) than those without (M = 24.3, SD = 20.9). For both genders, CPSA and ADVIOL were associated with higher rates of PTSD, which in turn predicted poorer treatment adherence as measured by ongoing co-occurring drug abuse 3 months postadmission. Results underscore the need for routine assessment and targeted treatment of trauma in methadone patients.

OBJECTIVE:There appears to be a link between depression and cocaine that is both complex and elusive. The purpose of this study was to examine the effect of venlafaxine, a broad spectrum antidepressant, in the treatment of 13 patients who were diagnosed with cocaine dependence and comorbid major depressive disorder (MDD). METHOD/METHODS:The majority of the patients in the study were part of a larger double-blind trial using desipramine. This subgroup consisted of people who had failed to respond to desipramine or could not tolerate its side effects. Thirteen patients were enrolled, 10 men and 3 women. Of the patients, 11 completed the 12-week study. All of the patients had a Hamilton Depression (HAM-D) score greater than 14 at baseline, and each had used at least $20 worth of cocaine per week in the 4 weeks prior to entering the study. In addition, all of the patients received weekly relapse prevention therapy throughout the study. The median dose of venlafaxine was 150 mg/day. RESULTS:The 11 patients who completed the study had significant reductions in mood symptoms by the end of the study. The average total HAM-D score at baseline was 18.0 +/- 3.2; at Week 2, it was 1.9 +/- 0.94; and at the end of the study, it was 1.4 +/- 1.8. The majority of patients reported reductions of cocaine use short of abstinence. All subjects reported a greater than 75% reduction in cocaine use compared to baseline. There were no serious side effects. CONCLUSIONS:The results of this small study indicate that venlafaxine may be a safe, well-tolerated, rapidly acting, and effective treatment for patients with a dual diagnosis of depression and cocaine dependence.

PURPOSE/OBJECTIVE:Substance use by pregnant women is socially stigmatized and may be legally punishable. This societal condemnation raises concerns about underascertainment of prenatal substance exposure of offspring if mothers are asked specifically about their behavior during gestation, versus their life histories without reference to gestational dates. This study assessed agreement between life history-focused and pregnancy-focused assessments of prenatal exposure, and percentages of offspring classified as exposed to a range of substances by each measure, in a sample of school-aged children of methadone-maintained, opioid-dependent parents. METHODS:Prenatal exposure was assessed in 172 offspring of 109 mothers by: (a) questionnaires administered to mothers about substance use during pregnancy; and (b) best-estimate (BE) diagnoses of substance use disorders in mothers overlapping with pregnancy dates. BE diagnoses were based on interviews with the Schedule for Affective Disorders and Schizophrenia-Lifetime Version, conducted by trained mental health professionals with mothers about their life histories of psychiatric and substance use disorders, as well as mothers' medical records. Chance-corrected agreement between the measures was examined using kappa statistics. Percentages of offspring classified as exposed by each method were compared using McNemar chi 2 tests. RESULTS:Except for cigarettes, agreement between the measures was poor. Except for alcohol, diagnosed episodes of substance use disorders in mothers with dates overlapping pregnancy classified more offspring as exposed than mothers' responses to the questionnaire focusing on behavior while pregnant, though the differences in proportions identified as exposed were not always large or statistically significant. IMPLICATIONS/CONCLUSIONS:When retrospective ascertainment of prenatal exposure is necessary, asking mothers for their own life histories, without reference to pregnancy dates, may be the preferred approach.

The authors examine methadone plasma levels in 31 depressed methadone-maintained opiate addicts enrolled in a 12-week placebo-controlled, double-blind study of sertraline. Between baseline and week 6, patients on sertraline showed a mean increase in methadone plasma level/dose (P/D) ratio of 26% (SD = 43%, range -32% to +118%), while patients on placebo showed a mean decrease of 16% (SD = 27%, range -62% to +50%). This difference was significant (p < 0.02). The sertraline and placebo groups did not differ in reported side effects or methadone dose adjustments. Between weeks 6 and 12, methadone P/D in the sertraline group decreased back towards baseline, and the treatment groups did not differ significantly at week 12. The results suggest sertraline may produce a modest increase in methadone serum levels over the first six weeks of treatment. Depression and anxiety disorders are common in methadone-maintained patients. Serotonin uptake inhibitors are attractive choices for treatment due to their low toxicity and low abuse potential, but these agents variously inhibit isoenzymes responsible for the metabolism of methadone. Clinicians treating depressed or anxious methadone patients with second-generation antidepressants should monitor for clinical signs of increased or decreased methadone levels and consider monitoring serum methadone levels.