Andrew J. Saxon

Implications of Chronic Methamphetamine Use: A Literature Review

Methamphetamine (MA) abuse is increasing to epidemic proportions, both nationally and globally. Chronic MA use has been linked to significant impairments in different arenas of neuropsychological function. To better understand this issue, a computerized literature search (PubMed, 1964-2004) was used to collect research studies examining the neurobiological and neuropsychiatric consequences of chronic MA use. Availability of MA has markedly increased in the United States due to recent technological improvements in both mass production and clandestine synthesis, leading to significant public health, legal, and environmental problems. MA intoxication has been associated with significant psychiatric and medical comorbidity. Research in animal models and human subjects reveals complicated mechanisms of neurotoxicity by which chronic MA use affects catecholamine neurotransmission. This pathology may underlie the characteristic cognitive deficits that plague chronic MA users, who experience impairments in memory and learning, psychomotor speed, and information processing. These impairments have the potential to compromise, in turn, the ability of MA abusers to engage in, and benefit from, psychosocially based chemical-dependency treatment. Development of pharmacological interventions to improve these cognitive impairments in this population may significantly improve the degree to which they may be able to participate in treatment. Atypical antipsychotics may have some promise in this regard.

Post-traumatic stress disorder and smoking: a systematic review.

We conducted a systematic review of what is known about the relationship between post-traumatic stress disorder (PTSD) and smoking to guide research on underlying mechanisms and to facilitate the development of evidence-based tobacco treatments for this population of smokers. We searched Medline, PsychINFO, and the Cochrane Central Register of Controlled Trials and identified 45 studies for review that presented primary data on PTSD and smoking. Smoking rates were high among clinical samples with PTSD (40%-86%) as well as nonclinical populations with PTSD (34%-61%). Most studies showed a positive relationship between PTSD and smoking and nicotine dependence, with odds ratios ranging between 2.04 and 4.52. Findings also suggest that PTSD, rather than trauma exposure itself, is more influential for increasing risk of smoking. A small but growing literature has examined psychological factors related to smoking initiation and maintenance and the overlapping neurobiology of PTSD and nicotine dependence. Observational studies indicate that smokers with PTSD have lower quit rates than do smokers without PTSD. Yet a few tobacco cessation treatment trials in smokers with PTSD have achieved quit rates comparable with controlled trials of smokers without mental disorders. In conclusion, the evidence points to a causal relationship between PTSD and smoking that may be bidirectional. Specific PTSD symptoms may contribute to smoking and disrupt cessation attempts. Intervention studies that test behavioral and pharmacological interventions designed specifically for use in patients with PTSD are needed to reduce morbidity and mortality in this population.

Integrating Tobacco Cessation Into Mental Health Care for Posttraumatic Stress Disorder: A Randomized Controlled Trial

CONTEXT Most smokers with mental illness do not receive tobacco cessation treatment. OBJECTIVE To determine whether integrating smoking cessation treatment into mental health care for veterans with posttraumatic stress disorder (PTSD) improves long-term smoking abstinence rates. DESIGN, SETTING, AND PATIENTS A randomized controlled trial of 943 smokers with military-related PTSD who were recruited from outpatient PTSD clinics at 10 Veterans Affairs medical centers and followed up for 18 to 48 months between November 2004 and July 2009. INTERVENTION Smoking cessation treatment integrated within mental health care for PTSD delivered by mental health clinicians (integrated care [IC]) vs referral to Veterans Affairs smoking cessation clinics (SCC). Patients received smoking cessation treatment within 3 months of study enrollment. MAIN OUTCOME MEASURES Smoking outcomes included 12-month bioverified prolonged abstinence (primary outcome) and 7- and 30-day point prevalence abstinence assessed at 3-month intervals. Amount of smoking cessation medications and counseling sessions delivered were tested as mediators of outcome. Posttraumatic stress disorder and depression were repeatedly assessed using the PTSD Checklist and Patient Health Questionnaire 9, respectively, to determine if IC participation or quitting smoking worsened psychiatric status. RESULTS Integrated care was better than SCC on prolonged abstinence (8.9% vs 4.5%; adjusted odds ratio, 2.26; 95% confidence interval [CI], 1.30-3.91; P = .004). Differences between IC vs SCC were largest at 6 months for 7-day point prevalence abstinence (78/472 [16.5%] vs 34/471 [7.2%], P < .001) and remained significant at 18 months (86/472 [18.2%] vs 51/471 [10.8%], P < .001). Number of counseling sessions received and days of cessation medication used explained 39.1% of the treatment effect. Between baseline and 18 months, psychiatric status did not differ between treatment conditions. Posttraumatic stress disorder symptoms for quitters and nonquitters improved. Nonquitters worsened slightly on the Patient Health Questionnaire 9 relative to quitters (differences ranged between 0.4 and 2.1, P = .03), whose scores did not change over time. CONCLUSION Among smokers with military-related PTSD, integrating smoking cessation treatment into mental health care compared with referral to specialized cessation treatment resulted in greater prolonged abstinence. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00118534.

Ineffectiveness of AIDS education and HIV antibody testing in reducing high-risk behaviors among injection drug users.

The effectiveness of education in reducing high-risk human immunodeficiency virus (HIV) transmission behaviors was examined in 313 injection drug users. Involvement in high-risk behaviors was assessed via structured interview at study entry and 4 months following the intervention. Subjects were randomly assigned to (1) AIDS education, (2) AIDS education with optional HIV antibody testing, or (3) a wait list. The sample as a whole decreased its involvement in high-risk behaviors, but there were no significant differences as a function of experimental group assignment.

A Pilot Trial of the Alpha‐1 Adrenergic Antagonist, Prazosin, for Alcohol Dependence

BACKGROUND Current medications for alcohol dependence (AD) show only modest efficacy. None target brain noradrenergic pathways. Theory and preclinical evidence suggest that noradrenergic circuits may be involved in alcohol reinforcement and relapse. We therefore tested the alpha-1 adrenergic receptor antagonist, prazosin, as a pharmacotherapy for AD. METHODS We randomized 24 participants with AD but without posttraumatic stress disorder to receive either prazosin or placebo in a 6-week, double-blind pilot study. Medication was titrated to a target dose of 4 mg QAM, 4 mg QPM, and 8 mg QHS by the end of week 2. Participants received 5 medical management treatment sessions. Participants were reminded 3 times each day via a text pager to take medications and to call a telephone monitoring system once daily to provide self-reports of alcohol consumption and craving, the primary outcome measures. Results were analyzed using mixed linear regression adjusted for drinking days per week at baseline and week number. RESULTS Twenty of the 24 (83%) subjects completed. Among the completers, the prazosin group reported fewer drinking days per week than the placebo group during the final 3 weeks of the study. Since only 1 woman was randomized to placebo and only three women completed the trial, the following results focus on the 17 male completers. The prazosin group reported fewer drinking days per week and fewer drinks per week during the final 3 weeks of the study; average total number of drinking days for the placebo group 5.7 (SEM 1.9) versus 0.9 (SEM 0.5) for the prazosin group, and average total number of drinks 20.8 (SEM 6.5) for the placebo group versus 2.6 (SEM 1.3) for the prazosin group. Rates of adverse events were equivalent across conditions. CONCLUSIONS Prazosin holds promise as a pharmacologic treatment for AD and deserves further evaluation in a larger controlled trial.

Treatment Retention among Patients Randomized to Buprenorphine/Naloxone Compared to Methadone in A Multi-site Trial

AIMS To examine patient and medication characteristics associated with retention and continued illicit opioid use in methadone (MET) versus buprenorphine/naloxone (BUP) treatment for opioid dependence. DESIGN, SETTINGS AND PARTICIPANTS This secondary analysis included 1267 opioid-dependent individuals participating in nine opioid treatment programs between 2006 and 2009 and randomized to receive open-label BUP or MET for 24 weeks. MEASUREMENTS The analyses included measures of patient characteristics at baseline (demographics; use of alcohol, cigarettes and illicit drugs; self-rated mental and physical health), medication dose and urine drug screens during treatment, and treatment completion and days in treatment during the 24-week trial. FINDINGS The treatment completion rate was 74% for MET versus 46% for BUP (P < 0.01); the rate among MET participants increased to 80% when the maximum MET dose reached or exceeded 60 mg/day. With BUP, the completion rate increased linearly with higher doses, reaching 60% with doses of 30-32 mg/day. Of those remaining in treatment, positive opioid urine results were significantly lower [odds ratio (OR) = 0.63, 95% confidence interval (CI) = 0.52-0.76, P < 0.01] among BUP relative to MET participants during the first 9 weeks of treatment. Higher medication dose was related to lower opiate use, more so among BUP patients. A Cox proportional hazards model revealed factors associated with dropout: (i) BUP [versus MET, hazard ratio (HR) = 1.61, CI = 1.20-2.15], (ii) lower medication dose (<16 mg for BUP, <60 mg for MET; HR = 3.09, CI = 2.19-4.37), (iii) the interaction of dose and treatment condition (those with higher BUP dose were 1.04 times more likely to drop out than those with lower MET dose, and (iv) being younger, Hispanic and using heroin or other substances during treatment. CONCLUSIONS Provision of methadone appears to be associated with better retention in treatment for opioid dependence than buprenorphine, as does use of provision of higher doses of both medications. Provision of buprenorphine is associated with lower continued use of illicit opioids.

Factors affecting willingness to provide buprenorphine treatment

Buprenorphine is an effective long-term opioid agonist treatment. As the only pharmacological treatment for opioid dependence readily available in office-based settings, buprenorphine may facilitate a historic shift in addiction treatment from treatment facilities to general medical practices. Although many patients have benefited from the availability of buprenorphine in the United States, almost half of current prescribers are addiction specialists suggesting that buprenorphine treatment has not yet fully penetrated general practice settings. We examined factors affecting willingness to offer buprenorphine treatment among physicians with different levels of prescribing experience. Based on their prescribing practices, physicians were classified as experienced, novice, or as a nonprescriber and asked to assess the extent to which a list of factors impacted their prescription of buprenorphine. Several factors affected willingness to prescribe buprenorphine for all physicians: staff training; access to counseling and alternate treatment; visit time; buprenorphine availability; and pain medications concerns. Compared with other physicians, experienced prescribers were less concerned about induction logistics and access to expert consultation, clinical guidelines, and mental health services. They were more concerned with reimbursement. These data provide important insight into physician concerns about buprenorphine and have implications for practice, education, and policy change that may effectively support widespread adoption of buprenorphine.

Buprenorphine tapering schedule and illicit opioid use

AIMS To compare the effects of a short or long taper schedule after buprenorphine stabilization on participant outcomes as measured by opioid-free urine tests at the end of each taper period. DESIGN This multi-site study sponsored by Clinical Trials Network (CTN, a branch of the US National Institute on Drug Abuse) was conducted from 2003 to 2005 to compare two taper conditions (7 days and 28 days). Data were collected at weekly clinic visits to the end of the taper periods, and at 1-month and 3-month post-taper follow-up visits. SETTING Eleven out-patient treatment programs in 10 US cities. INTERVENTION Non-blinded dosing with Suboxone during the 1-month stabilization phase included 3 weeks of flexible dosing as determined appropriate by the study physicians. A fixed dose was required for the final week before beginning the taper phase. MEASUREMENTS The percentage of participants in each taper group providing urine samples free of illicit opioids at the end of the taper and at follow-up. FINDINGS At the end of the taper, 44% of the 7-day taper group (n = 255) provided opioid-free urine specimens compared to 30% of the 28-day taper group (n = 261; P = 0.0007). There were no differences at the 1-month and 3-month follow-ups (7-day = 18% and 12%; 28-day = 18% and 13%, 1 month and 3 months, respectively). CONCLUSION For individuals terminating buprenorphine pharmacotherapy for opioid dependence, there appears to be no advantage in prolonging the duration of taper.

The association of persistent pain with out‐patient addiction treatment outcomes and service utilization

AIMS To estimate the prevalence of persistent pain among veterans in out-patient addiction treatment and examine associated addiction treatment outcomes and medical and psychiatric service use. DESIGN, SETTING AND PARTICIPANTS Analysis of data from a prospective randomized controlled trial comparing on-site versus referral primary care of veterans with substance dependence (n = 582), excluding opioid dependence who had at least one follow-up interview during the 12-month study period in a Veterans Affairs (VA) out-patient addiction treatment center. MEASUREMENTS Pain status was classified as persistent (pain was rated moderate to very severe at all time-points), low (pain was rated none to mild at all time-points) or intermittent (all others). Main outcome measures were addiction treatment retention, addiction severity index (ASI) alcohol and drug composite scores, VA service utilization and treatment costs. FINDINGS A total of 33.2% of veterans reported persistent pain and 47.3% reported intermittent pain. All groups benefited from addiction treatment, but veterans with persistent pain were in treatment for an estimated 35.1 fewer days [95% confidence interval (CI) = -64.1, -6.1, P = 0.018], less likely to be abstinent from alcohol or drugs at 12 months [odds ratio (OR)(adj) = 0.52; 95% CI = 0.30,0.89; P = 0.018], had worse ASI alcohol composite scores at 12 months (beta(adj) = 0.09; 95% CI = 0.02,0.15; P = 0.007), were more likely to be medically hospitalized (OR(adj) = 2.70; 95% CI = 1.02,7.13; P = 0.046) and had higher total service costs compared to those with low pain (

Brief motivational feedback improves post-incarceration treatment contact among veterans with substance use disorders

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