Exploring Differences in Baseline Characteristics among Adults Entering Integrated Residential Treatment for Co-occurring Disorders in 2013 and 2017.

Little is known about patients' addiction severity, substance use, or mental health symptoms upon entering integrated treatment. This is the first study to compare baseline characteristics among cohorts of patients with co-occurring disorders entering a private integrated residential treatment program in 2013 and 2017; a period when severe and persistent mental illness diagnoses, mental health service use, and overdose deaths increased. Our sample includes 3400 patients entering private, integrated residential treatment during 2013 (n = 1535) and 2017 (n = 1865). Trained staff completed admission interviews of all participants that included the Addiction Severity Index (ASI), a semi-structured interview to evaluate the past 30-day functioning of the following domains: medical, employment, alcohol, drug, legal, family or social support systems, and psychiatric. We used a p-value of 0.05 to assess significance. With the exception of the drug composite score, the 2017 cohort scored higher than the 2013 cohort on all other composite scores. Compared to the 2013 cohort, the 2017 cohort reported more days using alcohol, cocaine, amphetamines, and engaging in polysubstance use. Conversely, the 2017 cohort reported fewer days using other prescription opioids and sedatives than the 2013 cohort. After controlling for age, the 2017 cohort reported more days of marijuana use than the 2013 cohort. The 2017 cohort reported higher rates of the following symptoms: depression, anxiety, hallucinations, and suicidal ideation. Findings underscore differences among integrated treatment patient cohorts for baseline addiction severity, substance use, or mental health symptoms.

A comparison of 2013 and 2017 baseline characteristics among treatment-seeking patients who used opioids with co-occurring disorders.

The opioid epidemic is a public health crisis that has captured the attention of the media and political leaders, but how much do we know about its implications for substance use disorder treatment providers? This study is the first to investigate the differing baseline characteristics among patients with co-occurring disorders who used opioids and entered residential treatment in 2013 and 2017. Our sample consisted of 1413 unique adults who reported using opioids upon admission to integrated residential treatment for co-occurring substance use and mental health disorders during 2013 (n = 718) and 2017 (n = 695). Opioid use was defined as self-reported use of heroin or illicit use of prescription opioids, including methadone, during the month prior to admission into the treatment program. All study participants completed an admission interview that included the Addiction Severity Index (ASI). The 2017 cohort demonstrated higher severity than the 2013 cohort on the employment, psychiatric, and alcohol and drug ASI composite scores. A comparison of days per month that the cohorts used various substances also reveals this trend, with the following comparisons listing the 2017 cohort data first, and the 2013 cohort data second: (1) alcohol (8.6 days vs. 7.0 days); (2) cocaine (4.1 days vs. 2.2 days); (3) amphetamines (6.2 days vs. 3.6 days); and (4) polysubstance use in one day (16.6 days vs. 11.6 days). The 2017 cohort was also intoxicated from alcohol more days per month (7.2 days vs. 5.1 days). However, the 2017 cohort reported fewer days using prescription opioids (9.9 days vs. 12.4 days). A higher proportion of the 2017 cohort reported (1) depression (74% vs. 68%); (2) anxiety (88% vs. 84%); (3) hallucinations (14% vs 8%); and (4) and suicidal ideation (22% vs. 17%).

Decrease in Healthcare Utilization and Costs for Opioid Users Following Residential Integrated Treatment for Co-Occurring Disorders.

BACKGROUND: Opioid use results in higher healthcare utilization and costs, particularly among those with co-occurring mental health disorders. Presumably, effective treatment would result in a reduction in healthcare utilization and costs. To date, research has not examined this question. As such, the purpose of this study was to estimate and compare pre- and post-treatment healthcare utilization and costs for individuals receiving residential integrated treatment for co-occurring mental health and opioid use disorders. METHODS: A single-group, repeated measures design was used to examine changes in pre- and post-treatment healthcare utilization and costs among a sample of individuals with co-occurring mental health and opioid use disorders who received residential, integrated treatment. RESULTS: Significant reductions in emergency rooms visits, inpatient admissions, and resulting costs were observed in the six months following treatment. CONCLUSIONS: Residential, integrated treatment of co-occurring mental health and opioid use disorders can significantly decrease both utilization and cost of healthcare among opioid users with co-occurring mental health disorders.

A Comparison of Opioid and Nonopioid Substance Users in Residential Treatment for Co-Occurring Substance Use and Mental Disorders.

The past decade has seen a marked increase in the illicit use of opioids, as well as a doubling of the percentage of individuals seeking treatment for opioid use disorders. However, little is known about the differences between opioid users and nonopioid users in residential treatment. Further, no studies have been published that compare opioid users and nonopioid users in treatment for co-occurring substance use and mental disorders. To address this gap, this study examined differences between opioid and nonopioid substance users in residential treatment for co-occurring disorders. Data was drawn from 1,972 individuals treated between 2009 and 2011 at one of three private residential treatment centers that provide integrated treatment for co-occurring substance use and mental disorders. Data was collected at program intake, and 1- and 6-month postdischarge using the Addiction Severity Index and the University of Rhode Island Change Assessment. To examine within-group changes in substance use, addiction severity, and mental health across time, linear mixed-model analyses were conducted with facility, year, age, gender, and race included as covariates. The authors found more similarities than differences between the two groups on baseline characteristics, treatment motivation, length of stay, and outcomes on measures of substance use, addiction severity, and mental health. The results demonstrate that though opioid users entered treatment with higher levels of substance use-related impairment, they were just as successful in treatment outcomes as their non-opioid-using peers.

Characteristics and Outcomes of Young Adult Opiate Users Receiving Residential Substance Abuse Treatment.

Opiate use patterns, user characteristics, and treatment response among young adults are of interest due to current high use prevalence and historical low levels of treatment engagement relative to older populations. Prior research in this population suggests that overall, young adults present at treatment with different issues. In this study the authors investigated potential differences between young adult (18-25 years of age) and older adult (26 and older) opiate users and the impact of differences relative to treatment motivation, length and outcomes. Data for this study was drawn from 760 individuals who entered voluntary, private, residential treatment. Study measures included the Addiction Severity Index (ASI), the Treatment Service Review (TSR), and University of Rhode Island Change Assessment (URICA). Interviews were conducted at program intake and 6-month post-discharge. Results indicate that older adults with a history of opiate use present at treatment with higher levels of severity for alcohol, medical, and psychological problems and young adults present at treatment with greater drug use and more legal issues. Significant improvement for both groups was noted at 6 months post treatment; there were also fewer differences between the two age groups of opiate users. Results suggest different strategies within treatment programs may provide benefit in targeting the disparate needs of younger opiate users. Overall, however, results suggest that individualized treatment within a standard, abstinence-based, residential treatment model can be effective across opiate users at different ages and with different issues, levels of severity, and impairment at intake.

Gender differences in treatment retention among individuals with co-occurring substance abuse and mental health disorders.

BACKGROUND: A significant number of individuals with co-occurring substance abuse and mental health disorders do not engage, stay, and/or complete residential treatment. Although prior research indicates that women and men differ in their substance abuse treatment experiences, our knowledge of individuals with co-occurring substance abuse and mental health disorders as well as those attending private residential treatment is limited. OBJECTIVES: The purpose of this study is to examine gender differences on treatment retention for individuals with co-occurring substance abuse and mental health disorders who participate in private residential treatment. METHODS: The participants were 1,317 individuals (539 women and 778 men) with co-occurring substance abuse and mental health disorders receiving treatment at three private residential treatment centers. Bivariate analyses, life tables, and Cox regression (survival analyses) were utilized to examine gender effects on treatment retention, and identify factors that predict treatment retention for men and women. RESULTS: This study found that women with co-occurring disorders were more likely to stay longer in treatment when compared to men. The findings indicate the factors influencing length of stay differ for each gender, and include: type of substance used prior to admission; Addiction Severity Index Composite scores; and Readiness to Change/URICA scores. Age at admission was a factor for men only. CONCLUSIONS/IMPORTANCE: These findings can be incorporated to develop and initiate program interventions to minimize early attrition and increase overall retention in private residential treatment for individuals with co-occurring substance use and mental health disorders.

Differences between older and younger adults in residential treatment for co-occurring disorders.

OBJECTIVE: The purpose of this study was to examine differences between older and younger adults who received integrated treatment for co-occurring substance use and mental disorders, including differences on demographic and baseline characteristics (e.g., substance use, readiness for change, mental health symptoms, and severity of problems associated with substance use), as well as predictors of retention in treatment. METHODS: This study included 1400 adults who received integrated substance abuse and mental health treatment services at one of two private residential facilities offering residential and outpatient services. Initial analyses consisted of basic descriptive and bivariate analyses to examine differences between older (≥ 50 years old) and younger (< 50 years old) adults on baseline variables. Next, three ordinary least squares regression models were employed to examine the influence of baseline characteristics on length of stay. RESULTS: Three main findings emerged. First, older adults differed from younger adults on pre-treatment characteristics. Older adults used more alcohol and experienced greater problem severity in the medical and alcohol domains, while younger adults used more illicit drugs (e.g., heroin, marijuana, and cocaine) and experienced problems in the drug, legal, and family/social domains. Second, while readiness to change did not differ between groups at baseline, older adults remained enrolled in treatment for a shorter period of time (nearly four days on average) than younger adults. Third, the pattern of variables that influenced length of stay in treatment for older adults differed from that of younger adults. Treatment retention for older adults was most influenced by internal factors, like psychological symptoms and problems, while younger adults seemed influenced primarily by external factors, like drug use, employment difficulties, and readiness for change. CONCLUSIONS: The results of this study add to the limited knowledge base regarding older adults receiving integrated treatment for co-occurring substance use and mental health disorders by documenting that age-based differences exist in general and in the factors that are associated with the length of stay in residential treatment.

The impact of a sleep hygiene intervention on residents of a private residential facility for individuals with co-occurring mental health and substance use disorders: results of a pilot study.

An increasing number of Americans are experiencing sleep problems. There is evidence of a complex, bidirectional relationship between sleep disorders, substance abuse, and mental health symptoms. Institutional settings have been shown to elicit sleep problems as well. This pilot study was conducted with 28 patients in private, residential, dual-diagnosis treatment for addiction and mental health disorders. Upon admission, consenting patients were administered the Addiction Severity Index to assess pretreatment substance use and mental health symptoms. Patients followed a normal course of treatment as well as participated in a nightly sleep hygiene group that included relaxation suggestions. Evaluations with the Addiction Severity Index were completed again 30 days after discharge from treatment. Significant improvements in some substance use patterns as well as mental health symptoms were noted. Although results cannot be directly attributed to the use of a sleep hygiene group, this pilot study lays the foundation for future investigations of interventions supporting sleep in the dual-diagnosis population.

Neuropsychopharmacology and neurogenetic aspects of executive functioning: should reward gene polymorphisms constitute a diagnostic tool to identify individuals at risk for impaired judgment?

Executive functions are processes that act in harmony to control behaviors necessary for maintaining focus and achieving outcomes. Executive dysfunction in neuropsychiatric disorders is attributed to structural or functional pathology of brain networks involving prefrontal cortex (PFC) and its connections with other brain regions. The PFC receives innervations from different neurons associated with a number of neurotransmitters, especially dopamine (DA). Here we review findings on the contribution of PFC DA to higher-order cognitive and emotional behaviors. We suggest that examination of multifactorial interactions of an individual's genetic history, along with environmental risk factors, can assist in the characterization of executive functioning for that individual. Based upon the results of genetic studies, we also propose genetic mapping as a probable diagnostic tool serving as a therapeutic adjunct for augmenting executive functioning capabilities. We conclude that preservation of the neurological underpinnings of executive functions requires the integrity of complex neural systems including the influence of specific genes and associated polymorphisms to provide adequate neurotransmission.

Early intervention of intravenous KB220IV--neuroadaptagen amino-acid therapy (NAAT) improves behavioral outcomes in a residential addiction treatment program: a pilot study.

Substance use disorders (SUD) are inheritable and the culprit is hypodopaminergic function regulated by reward genes. We evaluated a natural dopaminergic agonist; KB220 intravenous (IV) and oral variants, to improve dopaminergic function in SUD. Our pilot experiment found a significant reduction of chronic symptoms, measured by the Chronic Abstinence Symptom Severity (CASS) Scale. The combined group (IV and oral) did significantly better than the oral-only group over the first week and 30-day follow-up period. Next, the combination was given to 129 subjects and three factors; Emotion, Somatic, and Impaired Cognition, with eigenvalues greater than one were extracted for baseline CASS-Revised (CASS-R) variables. Paired sample t-tests for pre and post-treatment scales showed significant declines (p = .00001) from pre- to post-treatment: t = 19.1 for Emotion, t = 16.1 for Somatic, and t = 14.9 for Impaired Cognition. In a two-year follow-up of 23 subjects who underwent KB220IV therapy (at least five IV treatments over seven days) plus orals for 30+ days: 21 (91%) were sober at six months, 19 (82%) having no relapse; 19 (82%) were sober at one year, 18 (78%) having no relapse; and 21 (91%) were sober two-years post-treatment, 16(70%) having no relapse. We await additional research and advise caution in interpreting these encouraging results.

Neurogenetics and Nutrigenomics of Neuro-Nutrient Therapy for Reward Deficiency Syndrome (RDS): Clinical Ramifications as a Function of Molecular Neurobiological Mechanisms.

In accord with the new definition of addiction published by American Society of Addiction Medicine (ASAM) it is well-known that individuals who present to a treatment center involved in chemical dependency or other documented reward dependence behaviors have impaired brain reward circuitry. They have hypodopaminergic function due to genetic and/or environmental negative pressures upon the reward neuro-circuitry. This impairment leads to aberrant craving behavior and other behaviors such as Substance Use Disorder (SUD). Neurogenetic research in both animal and humans revealed that there is a well-defined cascade in the reward site of the brain that leads to normal dopamine release. This cascade has been termed the "Brain Reward Cascade" (BRC). Any impairment due to either genetics or environmental influences on this cascade will result in a reduced amount of dopamine release in the brain reward site. Manipulation of the BRC has been successfully achieved with neuro-nutrient therapy utilizing nutrigenomic principles. After over four decades of development, neuro-nutrient therapy has provided important clinical benefits when appropriately utilized. This is a review, with some illustrative case histories from a number of addiction professionals, of certain molecular neurobiological mechanisms which if ignored may lead to clinical complications.

Can the chronic administration of the combination of buprenorphine and naloxone block dopaminergic activity causing anti-reward and relapse potential?

Opiate addiction is associated with many adverse health and social harms, fatal overdose, infectious disease transmission, elevated health care costs, public disorder, and crime. Although community-based addiction treatment programs continue to reduce the harms of opiate addiction with narcotic substitution therapy such as methadone maintenance, there remains a need to find a substance that not only blocks opiate-type receptors (mu, delta, etc.) but also provides agonistic activity; hence, the impetus arose for the development of a combination of narcotic antagonism and mu receptor agonist therapy. After three decades of extensive research, the federal Drug Abuse Treatment Act 2000 (DATA) opened a window of opportunity for patients with addiction disorders by providing increased access to options for treatment. DATA allows physicians who complete a brief specialty-training course to become certified to prescribe buprenorphine and buprenorphine/naloxone (Subutex, Suboxone) for treatment of patients with opioid dependence. Clinical studies indicate that buprenorphine maintenance is as effective as methadone maintenance in retaining patients in substance abuse treatment and in reducing illicit opioid use. With that stated, we must consider the long-term benefits or potential toxicity attributed to Subutex or Suboxone. We describe a mechanism whereby chronic blockade of opiate receptors, in spite of only partial opiate agonist action, may ultimately block dopaminergic activity causing anti-reward and relapse potential. While the direct comparison is not as yet available, toxicity to buprenorphine can be found in the scientific literature. In considering our cautionary note in this commentary, we are cognizant that, to date, this is what we have available, and until such a time when the real magic bullet is discovered, we will have to endure. However, more than anything else this commentary should at least encourage the development of thoughtful new strategies to target the specific brain regions responsible for relapse prevention.

Generational association studies of dopaminergic genes in reward deficiency syndrome (RDS) subjects: selecting appropriate phenotypes for reward dependence behaviors.

UNLABELLED: Abnormal behaviors involving dopaminergic gene polymorphisms often reflect an insufficiency of usual feelings of satisfaction, or Reward Deficiency Syndrome (RDS). RDS results from a dysfunction in the "brain reward cascade," a complex interaction among neurotransmitters (primarily dopaminergic and opioidergic). Individuals with a family history of alcoholism or other addictions may be born with a deficiency in the ability to produce or use these neurotransmitters. Exposure to prolonged periods of stress and alcohol or other substances also can lead to a corruption of the brain reward cascade function. We evaluated the potential association of four variants of dopaminergic candidate genes in RDS (dopamine D1 receptor gene [DRD1]; dopamine D2 receptor gene [DRD2]; dopamine transporter gene [DAT1]; dopamine beta-hydroxylase gene [DBH]). METHODOLOGY: We genotyped an experimental group of 55 subjects derived from up to five generations of two independent multiple-affected families compared to rigorously screened control subjects (e.g., N = 30 super controls for DRD2 gene polymorphisms). Data related to RDS behaviors were collected on these subjects plus 13 deceased family members. RESULTS: Among the genotyped family members, the DRD2 Taq1 and the DAT1 10/10 alleles were significantly (at least p < 0.015) more often found in the RDS families vs. controls. The TaqA1 allele occurred in 100% of Family A individuals (N = 32) and 47.8% of Family B subjects (11 of 23). No significant differences were found between the experimental and control positive rates for the other variants. CONCLUSIONS: Although our sample size was limited, and linkage analysis is necessary, the results support the putative role of dopaminergic polymorphisms in RDS behaviors. This study shows the importance of a nonspecific RDS phenotype and informs an understanding of how evaluating single subset behaviors of RDS may lead to spurious results. Utilization of a nonspecific "reward" phenotype may be a paradigm shift in future association and linkage studies involving dopaminergic polymorphisms and other neurotransmitter gene candidates.

Overcoming qEEG abnormalities and reward gene deficits during protracted abstinence in male psychostimulant and polydrug abusers utilizing putative dopamine D2 agonist therapy: part 2.

BACKGROUND: It is well established that in both food- and drug-addicted individuals there is "dopamine resistance" associated with the DRD2 gene A1 allele. Based on earlier studies, evidence is emerging wherein the potential of utilizing a natural, nonaddicting, safe, putative D2 agonist may play a significant role in the recovery of individuals with reward deficiency syndrome, including those addicted to psychoactive chemicals. FINDINGS: Positive outcomes demonstrated by quantitative electroencephalographic (qEEG) imaging in a randomized, triple-blind, placebo-controlled, crossover study involving oral Synaptose Complex KB220Z™ showed an increase of alpha waves and low beta wave activity in the parietal brain region. Using t statistics, significant differences observed between placebo and Synaptose Complex KB220Z™ consistently occurred in the frontal regions after week 1 and then again after week 2 of analyses (P = 0.03). This is the first report to demonstrate involvement of the prefrontal cortex in the qEEG response to a natural putative D2 agonist (Synaptose Complex KB220Z™), especially evident in dopamine D2 A1 allele subjects. Independently, we have further supported this finding with an additional study of 3 serious polydrug abusers undergoing protracted abstinence who carried the DRD2 A1 allele. Significant qEEG differences were found between those who received 1 dose of placebo compared with those who were administered Synaptose Complex KB220Z™. Synaptose Complex KB220Z™ induced positive regulation of the dysregulated electrical activity of the brain in these addicts. The results are indicative of a phase change from low amplitude or low power in the brain to a more regulated state by increasing an average of 6.169 mV(2) across the prefrontal cortical region. In the first experiment we found that while 50% of the subjects carried the DRD2 A1 allele, 100% carried ≥ 1 risk allele. Specifically, based on the proposed addiction risk score for these 14 subjects, 72% had moderate-to-severe addiction risk. Similar findings were obtained by repeating the experiment in 3 additional currently abstinent polydrug abusers carrying the DRD2 A1 allele. CONCLUSION: This seminal work will provide important information that may ultimately lead to significant improvement in the recovery of individuals with psychostimulant and polydrug abuse problems, specifically those with genetically induced dopamine deficiency. Based on this small sample size, we are proposing that with necessary large populations supporting these initial results, and possibly even additional candidate genes and single nucleotide polymorphisms, we may eventually have the clinical ability to classify severity according to genotype and possession of risk alleles, along with offering a safe, nonaddicting, natural dopaminergic receptor agonist that potentially upregulates instead of downregulates dopaminergic receptors, preferably the D2 subtype.

Neurogenetics of dopaminergic receptor supersensitivity in activation of brain reward circuitry and relapse: proposing "deprivation-amplification relapse therapy" (DART).

BACKGROUND AND HYPOTHESIS: It is well known that after prolonged abstinence, individuals who use their drug of choice experience a powerful euphoria that often precipitates relapse. While a biological explanation for this conundrum has remained elusive, we hypothesize that this clinically observed "supersensitivity" might be tied to genetic dopaminergic polymorphisms. Another therapeutic conundrum relates to the paradoxical finding that the dopaminergic agonist bromocriptine induces stronger activation of brain reward circuitry in individuals who carry the DRD2 A1 allele compared with DRD2 A2 allele carriers. Because carriers of the A1 allele relative to the A2 allele of the DRD2 gene have significantly lower D2 receptor density, a reduced sensitivity to dopamine agonist activity would be expected in the former. Thus, it is perplexing that with low D2 density there is an increase in reward sensitivity with the dopamine D2 agonist bromocriptine. Moreover, under chronic or long-term therapy with D2 agonists, such as bromocriptine, it has been shown in vitro that there is a proliferation of D2 receptors. One explanation for this relates to the demonstration that the A1 allele of the DRD2 gene is associated with increased striatal activity of L-amino acid decarboxylase, the final step in the biosynthesis of dopamine. This appears to be a protective mechanism against low receptor density and would favor the utilization of an amino acid neurotransmitter precursor like L-tyrosine for preferential synthesis of dopamine. This seems to lead to receptor proliferation to normal levels and results in significantly better treatment compliance only in A1 carriers. PROPOSAL AND CONCLUSION: We propose that low D2 receptor density and polymorphisms of the D2 gene are associated with risk for relapse of substance abuse, including alcohol dependence, heroin craving, cocaine dependence, methamphetamine abuse, nicotine sensitization, and glucose craving. With this in mind, we suggest a putative physiological mechanism that may help to explain the enhanced sensitivity following intense acute dopaminergic D2 receptor activation: "denervation supersensitivity." Rats with unilateral depletions of neostriatal dopamine display increased sensitivity to dopamine agonists estimated to be 30 to 100 x in the 6-hydroxydopamine (6-OHDA) rotational model. Given that mild striatal dopamine D2 receptor proliferation occurs (20%-40%), it is difficult to explain the extent of behavioral supersensitivity by a simple increase in receptor density. Thus, the administration of dopamine D2 agonists would target D2 sensitization and attenuate relapse, especially in D2 receptor A1 allele carriers. This hypothesized mechanism is supported by clinical trials utilizing amino acid neurotransmitter precursors, enkephalinase, and catechol-O-methyltransferase (COMT) enzyme inhibition, which have resulted in attenuated relapse rates in reward deficiency syndrome (RDS) probands. If future translational research reveals that dopamine agonist therapy reduces relapse in RDS, it would support the proposed concept, which we term "deprivation-amplification relapse therapy" (DART). This term couples the mechanism for relapse, which is "deprivation-amplification," especially in DRD2 A1 allele carriers with natural D2 agonist therapy utilizing amino acid precursors and COMT and enkepalinase inhibition therapy.