Biomedical subjects

M L Stitzer

Publications and source records attributed to M L Stitzer.

At least 37 records · Page 2Linked to original sources

PubMed1999

Use of methadone take-home contingencies with persistent opiate and cocaine abusers.

This study investigated conditions under which methadone patients with urinalysis evidence of persistent multiple drug abuse would respond to take-home incentive procedures. Study subjects submitted > or = 80% opiate and/or cocaine positive urines during a 5-week baseline period (M, W, F urine testing) while maintained on 60 mg methadone. Doses were raised to 80-100 mg methadone under blind conditions and subjects were randomly assigned to receive methadone take-home doses under one of three conditions: (a) earn a 1-day take-home privilege for each opiate and cocaine-free test delivered (daily contingent condition), (b) three negative test results required for the first take-home privilege, with each subsequent negative test earning one take-home dose; a positive test reset the contingency back to three again (weekly contingent condition), or (c) a control group that did not receive take-home privileges (no take-home control). Five of 21 subjects (24%) assigned to a contingent take-home intervention (2 from condition a, 3 from condition b) showed marked reductions in drug use and delivered 4 or more consecutive weeks of drug-free urines during a 16-week intervention. No subject in the control group met these criteria. Percent positive urines decreased by 14% and 18% from baseline in daily and weekly contingency groups, respectively, compared to a decline of 2% in the no take-home control group (planned contrast of means p < .07 and .05, respectively). Thus, the study demonstrated that take-home incentives can be effective for reducing during-treatment use of opiates and cocaine in methadone patients with a poor prognosis related to their persistent multiple drug use.

Adult↗

PubMed1999

Combined behavioral and pharmacological treatments for smoking cessation.

Combined behavioral and pharmacological therapies appear to be the best approach for treating tobacco dependence. Because these therapies operate by different mechanisms, complementary and potentially additive effects may be expected. This paper focuses on nicotine replacement therapies (NRT) combined with supportive counseling because they are the most widely used and intensively researched treatment methods. Nicotine replacement medications and counseling appear to produce additive or less than additive effects when combined. Additive effects of combined therapies are generally apparent in the number of smokers who survive the first few weeks without smoking, but may disappear at longer-term follow-up. Because any smoking in the first two post-quit weeks is strongly associated with poor treatment outcome, reduced incidence of early smoking re-exposure appears to be important for improving long-term smoking cessation. Mechanisms underlying additive effects need further clarification. What are the independent and interactive roles of compliance with medication and with behavior change prescriptions, of pharmacological withdrawal suppression, of relapse prevention skills training, and of social support provided by counseling? Given the prevalence and importance of post-quit smoking relapses, can anything be done to further reduce incidence or to counteract their deleterious effects? Do any existing treatments slow relapse? If not, how can this be accomplished? Effective treatments now exist, but these cannot have an impact unless they are used; we need to know what methods can effectively enhance use.

Antidepressive Agents, Second-Generation↗

PubMed1999

Relative potency of levo-alpha-acetylmethadol and methadone in humans under acute dosing conditions.

levo-alpha-Acetylmethadol (LAAM) and methadone are full mu-opioid agonists used to treat opioid dependence. Current labeling indicates that LAAM is less potent than methadone. Clinical studies have not determined the relative potency of these drugs. This study compared the effects of acute doses of LAAM and methadone and also examined the ability of naloxone to reverse their effects. Five occasional opioid users received once weekly doses of either placebo, LAAM, or methadone (15, 30, or 60 mg/70 kg p.o.) in agonist exposure sessions and then received naloxone (1.0 mg/70 kg i.m.) 24, 72, and 144 h after agonist exposure. Subject-rated, observer-rated, and physiological measures were assessed regularly. Comparisons of physiological and subjective measures collected in agonist exposure sessions indicate that LAAM is not less potent than methadone under acute dosing conditions. For some measures, LAAM was significantly more potent. Three subjects who entered the study were withdrawn for safety reasons due to greater than anticipated and clinically relevant respiratory depression after receiving 60 mg of LAAM. Naloxone did not fully reverse the pupil constriction produced by 60 mg of LAAM. Acute agonist effects suggest that LAAM may be more potent than methadone and more potent than current labeling indicates. An accurate LAAM:methadone relative potency estimate will aid determination of adequate doses for opioid-dependent patients inducted onto LAAM and for methadone maintenance patients who choose to switch to more convenient thrice-weekly LAAM.

Adult↗

PubMed1998

Heroin snorters versus injectors: comparison on drug use and treatment outcome in age-matched samples.

Drug use histories and treatment outcomes were compared for age, race and gender-matched samples of intravenous (IV; n = 28) versus intranasal (IN; n = 28) opiate abusers entering a 3-day inpatient detoxification unit. Data were derived from the Addiction Severity Index (ASI) interview. Both groups reported daily heroin use prior to detoxification, but IV users reported more days of alcohol and multiple drug use during the past 30 days. Despite age matching, IV users also started using alcohol at an earlier age and accumulated more lifetime months of regular alcohol, cocaine and multidrug use. IV users were more likely to enter treatment following the detox, but no significant outcome differences were noted at 1 and 3 months post-detoxification. The results show that intravenous, as compared to intranasal, opiate users have both a more severe pattern and a more extensive history of the use of non-opiate drugs.

Administration, Intranasal↗

PubMed1998

Butorphanol agonist effects and acute physical dependence in opioid abusers: comparison with morphine.

This study compared the direct effects and acute physical dependence of butorphanol and morphine, opioids with differing actions at mu versus kappa receptors. Six non-dependent heroin-using volunteers were exposed to six conditions in a within-subject, Latin square design using double-blind procedures. In each session, agonist effects of single i.m. injections of butorphanol (3 and 6 mg/70 kg), morphine (15 and 30 mg/70 kg), lorazepam (4 mg/70 kg) or saline were evaluated. Butorphanol and morphine produced effects of comparable magnitude on miosis and reports of 'any drug effect'. Volunteers reported dysphoria, confusion and sedation after butorphanol, subjective effects that overlapped with those of lorazepam, whereas morphine produced euphoria and stimulation. Acute physical dependence (i.e. precipitated withdrawal responses to naloxone 10 mg/70 kg i.m. administered 6 h after each treatment) significantly increased after 30 mg/70 kg morphine but not after butorphanol treatments. These differences in naloxone sensitivity are likely due to differences in opioid receptor (mu versus kappa) activity, affinity and efficacy of these compounds. Pharmacological ramifications of these results are discussed.

Adult↗

PubMed1998

Induction with levomethadyl acetate: safety and efficacy.

BACKGROUND: Levomethadyl acetate hydrochloride (known as LAAM) is a mu-opioid agonist approved for the treatment of opioid dependence. Clinical trials comparing LAAM and methadone have reported lower patient retention rates during LAAM induction; however, this may reflect dose and schedule differences. Few studies have systematically examined LAAM dose induction. This study compared induction with 3 different LAAM dosage levels. METHODS: In a randomized, double-blind trial, male and female opioid-dependent patients (N = 180) were assigned to 1 of 3 LAAM doses. The low-dose (25 mg) induction was constant from the onset of treatment, the medium-dose (50 mg) induction lasted 7 days, and the high-dose (100 mg) induction lasted 17 days. Safety and efficacy were assessed on retention, urinalysis and self-reported drug use, symptoms, and patient ratings of medication adequacy. RESULTS: The high-dose group had significantly fewer illicit opioid-positive urine samples in weeks 3 and 4 as compared with the low-dose group. The high-dose group had significantly lower self-reported heroin craving in weeks 2 and 3. All groups demonstrated significant decreases in illicit drug use, withdrawal symptoms, and depression. There were no between-group differences in retention; however, there was a trend (P = .08) for lower retention and a greater number of agonist adverse effects were observed in the high-dose group. Overall, LAAM doses were well tolerated by most patients. CONCLUSION: Induction with low and medium LAAM doses can be safely and effectively achieved within 7 days. Induction with higher LAAM doses can be safely achieved within 17 days, but may result in greater rates of patient dropout and opioid agonist adverse effects. Therefore, higher doses should be approached more slowly.

Adult↗

PubMed1998

The Agency for Health Care Policy and Research Smoking Cessation Clinical Practice Guideline. Findings and implications for psychologists.

Smoking is the leading cause of preventable morbidity and mortality in the United States, and the health benefits of quitting smoking are substantial. Nevertheless, over 25% of American adults (48 million individuals) continue to smoke, and the vast majority of quit attempts are unsuccessful. The Agency for Health Care Policy and Research recently addressed the smoking problem by conducting a 2-year research project that was published as the Smoking Cessation Clinical Practice Guideline (Fiore et al., 1996). This article reviews methods, analyses, and results from the Guideline project, and highlights major Guideline recommendations. Guideline findings and recommendations are discussed with respect to their implications for psychology.

Adult↗

PubMed1998

Survey assessment of methadone treatment services as reinforcers.

Offering incentives contingent on behavioral change can be an effective method for improving treatment outcome in methadone maintenance. Further, there are several incentives available within the daily operation of methadone clinics that can be used in this way. This study describes patient preferences for clinic service incentives as identified by three types of survey methodologies: multiple choice procedures, visual analog scales, and rank ordering. Methadone patients (n = 111) rated preference for three service incentives (take-home medication, dose increase, counseling sessions) using each survey. Mean and individual responses were highly consistent across surveys and indicated that, in general, take-homes were the most preferred, followed by dose increases and then counseling. The rank order survey also assessed an additional 18 service items (e.g., rent, food or gas payments; employment assistance; medical care). Consistent with other measures, most patients (64%) placed take-homes within their top five rankings, indicating a high level of preference, but this survey also revealed wide individual differences in preference ranking. The surveys described can be used to identify preferred incentives for clinic-wide use in contingency management programs or can be used to select individualized incentives for each patient. This is useful information for maximizing utilization of clinic resources.

Adult↗

PubMed1998

Dose-response analysis of opioid cross-tolerance and withdrawal suppression during LAAM maintenance.

Levo-alpha-acetylmethadol (LAAM) currently is approved as an opioid maintenance treatment. This double-blind study was designed to characterize withdrawal suppression and opioid blockade produced by two different LAAM maintenance doses. Outpatient opioid-dependent volunteers were stabilized (5-7 weeks) on 25 (n = 8) or 75 mg (n = 8) LAAM administered every-other-day with placebo administered on intervening days. After stabilization, four inpatient, randomly ordered experimental sessions were conducted at 24, 48, 72 and 96 hr after LAAM dosing; the timing of these sessions corresponds to intervals that occur during typical thrice-weekly treatment and after a missed dose. During each session, after baseline assessments, ascending doses of hydromorphone (0, 6 and 12 mg i.m.) were administered 45 min apart; physiological, subjective and observer-rated effects were recorded throughout the session. Physiological and subjective indices of opioid withdrawal measured at session base lines increased with time since the last LAAM dose, but did not depend on the maintenance dose. Withdrawal symptoms were mild in both groups, even at 96 hr after LAAM dosing. Hydromorphone produced dose-related opioid agonist effects at all intervals in the 25 mg LAAM group; these effects were attenuated substantially in the 75 mg LAAM group. Time since last LAAM dose had little influence on hydromorphone effects in either group. Thus, 75 mg LAAM provides opioid blockade and withdrawal suppression for up to 96 hr, whereas 25 mg LAAM is relatively ineffective at producing significant opioid blockade.

Adult↗

PubMed1997

Attendance incentives for outpatient treatment: effects in methadone- and nonmethadone-maintained pregnant drug dependent women.

The effectiveness of behavioral incentives for improving treatment participation and retention in samples of methadone-maintained (n = 66) and nonmethadone-maintained (n = 76) pregnant drug dependent women was examined. Subjects were randomly assigned to receive $0 (standard care) and $1, $5, or $10/day for attending at least 4 h of interdisciplinary treatment programming during the first 7 consecutive days after transfer from residential to outpatient care, with payment dispensed in the form of gift certificates. Methadone-maintained women attended nearly twice as many full treatment days as those not receiving methadone (5.2 vs 2.8 days; P < 0.001) and were retained in treatment significantly longer (86.4 vs 28.9% active in treatment at 30 days). There was no main effect of incentives and no effect on attendance in methadone patients. However, nonmethadone patients offered higher magnitude incentives ($5/$10) attended 3.3 days out of 7 on average, compared to 2.3 days for those offered $0 or $1 per day (t = 1.73; P < 0.05). The study confirmed that methadone maintenance is a powerful therapeutic adjunct which is associated with significantly better treatment retention and participation in ancillary programming than is abstinence-based treatment. It was also found that modest financial incentives can facilitate treatment participation for abstinence-based patients. However, more potent interventions would be needed to match the effectiveness of methadone in this regard.

Adolescent↗

PubMed1997

Dose-related efficacy of levomethadyl acetate for treatment of opioid dependence. A randomized clinical trial.

OBJECTIVE: To compare the clinical efficacy of different doses of levomethadyl acetate hydrochloride (known as LAAM) in the treatment of opioid dependence. DESIGN: A randomized controlled, double-blind, parallel group, 17-week study. SETTING: Outpatient facilities at Johns Hopkins University Bayview Medical Center, Baltimore, Md. PATIENTS: Opioid-dependent volunteers (N=180) applying to a treatment-research clinic. INTERVENTION: Thrice-weekly (Monday/Wednesday/Friday) oral LAAM dose conditions of 25/25/35 mg, 50/50/70 mg, and 100/100/140 mg and nonmandatory counseling. MAIN OUTCOME MEASURES: Retention in treatment, self-reported heroin use, and opioid-positive urine specimens. RESULTS: Retention was independent of subjects' sex and dose. Self-reported heroin use decreased in a dose-related manner. At final assessment, patients in the high-dose condition reported using heroin 2.5 of 30 days as compared with 4.1 or 6.3 days for patients in the medium-dose and low-dose conditions, respectively (high dose vs low dose, P<.05); urinalysis results were similarly dose related. Overall, 20 (34%) of 59 patients in the high-dose condition remained opioid-abstinent for 4 consecutive weeks, as compared with 8 (14%) of 59 in the medium-dose and 7 (11%) of 62 in the low-dose conditions (P<.01). Self-report and urinalysis data are consistent with a greater than 90% reduction in illicit opioid use by the high-dose group relative to pretreatment levels. CONCLUSION: Opioid substitution treatment with LAAM substantially reduces illicit opioid use. The clinical efficacy of LAAM is positively related to dose.

Adult↗

PubMed1997

Controlled opioid withdrawal evaluation during 72 h dose omission in buprenorphine-maintained patients.

Buprenorphine's clinical utility as an opioid dependence pharmacotherapy may be enhanced with less-than-daily dosing. This study assessed opioid withdrawal after an acute 72 h dose omission in buprenorphine-maintained patients (8 mg/day s.l.). Eight outpatients required to remain free of opioids, cocaine and benzodiazepines completed four double-blind, double-dummy, Latin-square ordered conditions. Test conditions of 8 or 16 mg s.l. buprenorphine were followed by 2 days of placebo dosing. Control conditions were buprenorphine maintenance (8 mg/day), to provide a reference for evaluation of placebo test days and naloxone administration (10 mg 70 kg i.m.) during 8 mg buprenorphine maintenance to assess withdrawal measure sensitivity. Subjective measures and pupil diameter were significantly influenced only by naloxone. The lack of subjective symptoms and physiological signs of opioid withdrawal during 72 h of acute dose omission supports the feasibility of less-than-daily dosing at buprenorphine doses of 8 mg/day in patients who have demonstrated an ability to remain drug-free for an extended period.

Adult↗

PubMed1997

Cost-effectiveness of treatment for drug-abusing pregnant women.

Neonatal intensive care unit (NICU) and drug treatment costs were compared in two groups of pregnant drug abusing women: 100 admissions to a multidisciplinary treatment program and active in care at the time of delivery and 46 controls not entering drug treatment. Clinical measures included urine toxicology at delivery, infant birthweight. Apgar scores and need for and duration of NICU services. Cost measures included drug treatment and NICU costs. Treatment patients showed better clinical outcome at delivery, with less drug use and higher infant estimated gestational age, birthweight and Apgar scores. Infants of treatment patients were also less likely to require NICU services and, for those that did, had a shorter stay. When total cost was examined (including drug treatment), mean net savings for treatment subjects was $4644 per mother/infant pair. The study demonstrates the cost-effectiveness of treatment for pregnant drug abusing women, with savings in NICU costs exceeding costs of drug treatment.

Adult↗

PubMed1997

Nicotine nasal spray and vapor inhaler: abuse liability assessment.

Acute subjective and physiological effects were examined to provide information relevant to abuse liability of new nicotine delivery systems. Subjects (n = 12) were overnight-deprived smokers who received 0, 4, 8 and 16 active puffs from nicotine-containing cigarettes (0.1 mg per puff), 0, 1, 2 or 4 nasal sprays (0.5 mg nicotine per spray) and 0, 30, 60 and 120 vapor inhalations (estimated 0.013 mg nicotine per inhalation) in a within-subject single blinded design. While smokers clearly liked cigarette puffs, there was much less evidence of liking produced by either nasal spray or vapor inhaler; only modest elevations on a measure of good drug effects were observed. The novel delivery products engendered unpleasant effects of burning throat and nose, watery eyes, runny nose, coughing and sneezing that might be expected to limit abuse liability. Nicotine plasma level and heart rate increase was dose-related for cigarettes and nasal spray but not for vapor inhaler, indicating limited nicotine delivery with the latter device. Overall, results are consistent with the conclusion that the nicotine nasal spray and vapor inhaler are of substantially lower abuse liability than cigarettes in experienced cigarette smokers receiving initial exposure to these products.

Administration, Inhalation↗

PubMed1997

Psychostimulant abuse: the case for combined behavioral and pharmacological treatments.

Behavioral and pharmacological therapies have been used alone and in combination for the treatment of substance abuse; however, to date, no single treatment approach for psychostimulant abuse has demonstrated widespread efficacy. This paper describes the various functions that are served by both behavioral therapies and pharmacotherapies and their respective mechanisms of action. It is argued that combined treatments can be expected to produce additive effects because the two approaches operate through different and potentially complementary mechanisms. Illustrations of these underlying principles and experimental support for the use of combined treatments are drawn from smoking cessation research, which has broadly applied combined behavioral and pharmacological therapies for treating abuse of nicotine, a mild stimulant. In addition, the results of recent studies that have evaluated the efficacy of behavioral techniques and/or potential pharmacotherapies for treating cocaine abuse are reviewed. Finally, methodological strategies are recommended for future evaluations of combined therapy approaches to conclusively evaluate separate and combined efficacy of treatments for psychostimulant abuse.

Behavior Therapy↗

PubMed1997

Comparative effects of alcohol and marijuana on mood, memory, and performance.

This study compared subjective and behavioral effect profiles of alcohol and smoked marijuana using technology that controlled puffing and inhalation parameters. Male volunteers (n = 5) with histories of moderate alcohol and marijuana use were administered three doses of alcohol (0.25, 0.5, or 1.0 g/kg), three doses of marijuana [4.8, or 16 puffs of 3.55% delta 9-tetrahydrocannabinol (THC)], and placebo in random order under double blind conditions in seven separate sessions. Blood alcohol concentration (10-90 mg/dl) and THC levels (63-188 ng/ml) indicated that active drug was delivered to subjects dose dependently. Alcohol and marijuana produced dose-related changes in subjective measures of drug effect. Ratings of perceived impairment were identical for the high doses of alcohol and marijuana. Both drugs produced comparable impairment in digit-symbol substitution and word recall tests, but had no effect in time perception and reaction time tests. Alcohol, but not marijuana, slightly impaired performance in a number recognition test. These data are useful for understanding the relative performance impairment produced by alcohol and marijuana at the delivered doses and the relationship between their subjective and behavioral effects.

Adolescent↗

PubMed1997

Human pharmacology of the opioid neuropeptide dynorphin A(1-13).

We evaluated the human pharmacology of dynorphin A(1-13) and determined whether this peptide can modulate naloxone-precipitated withdrawal effects. Such information could help determine its receptor mechanism of action and whether dynorphin is useful for treating opioid dependence. Six opioid-experienced subjects participated in a within-subject, placebo-controlled design. There were two phases, each with four test sessions. In phase 1, volunteers who were not physically dependent were administered 0, 0.1, 0.32 and 1 mg/kg dynorphin (15-min i.v. infusion) in ascending order, and subjective, observer-rated and physiological effects were monitored. Dynorphin produced brief, dose-related increases in drug effect ratings with both good and bad drug effects reported by different subjects. There were no significant changes in pupil size, respiratory rate, skin temperature, heart rate or blood pressure, These data are consistent with preclinical findings that dynorphin has a short duration of action and does not primarily exert its direct effects through mu-opioid receptors. In four separate sessions of phase 2, acute morphine pretreatment (45 mg/70 kg i.m.) was followed 15 or 18 hr later by dynorphin (0 vs. 1 mg/kg, 15-min i.v.) and then naloxone (1 or 3 vs. 10 mg/70 kg, 5-min i.v.). Under these conditions, dynorphin weakly potentiated naloxone-precipitated withdrawal. These data contrast with those of previous preclinical studies showing dependence-attenuating effects of dynorphin and fail to support its use as an antiwithdrawal agent in humans.

Adolescent↗

PubMed1996

Mecamylamine does not precipitate withdrawal in cigarette smokers.

Mecamylamine is an antihypertensive that acts via nicotinic antagonism and has been suggested as an aid in smoking cessation. Nicotine dependent patients may not accept mecamylamine if it precipitates withdrawal, as it does in nicotine dependent rats. This study examined mecamylamine's effects using procedures designed to measure precipitated withdrawal symptoms in humans. Ten cigarette smokers (mean of 37.5 cigarettes/day) and ten non tobacco-using subjects participated in three 6-h sessions. After a 2-h baseline period in which smokers smoked one cigarette every 30 min, oral mecamylamine (0, 10, or 20 mg randomly ordered across sessions) was administered (double-blind). No smoking was allowed for the remainder of the session. Mecamylamine reduced blood pressure and increased heart rate relative to placebo in both the smokers and the non-tobacco users. No reliable direct subjective effects of mecamylamine were observed. Smokers' subjective reports of cigarette craving and tobacco withdrawal increased, and DSST performance was disrupted over the last 4 h of each session. Effects were independent of dose (placebo versus active). These results suggest that up to 20 mg mecamylamine will not precipitate nicotine withdrawal and that this medication would be acceptable for use in smoking cessation.

Adult↗