The Effect of Dehydroepiandrosterone Administration during Rehabilitation on White Matter Integrity Among Individuals With Polysubstance Use Disorder.

OBJECTIVES: Individuals with polysubstance use disorder (pSUD) exhibit vulnerability to relapse even after prolonged abstinence, with rehabilitation efforts achieving limited success. Previous studies highlighted dehydroepiandrosterone (DHEA) as a putative therapeutic agent that may aid rehabilitation, potentially by impacting white matter (WM) properties. The current study tested, for the first time, the effect of DHEA administration during rehabilitation on WM integrity among pSUD individuals, while assessing its putative association with long-term relapse rates. METHODS: Immediately after admission to rehabilitation, 30 pSUD individuals were assigned to receive either placebo or DHEA (100 mg) daily for 3 months, via a randomized double-blind counterbalanced design. Participants also provided blood samples to assess circulating DHEA levels at treatment initiation and completed a diffusion tensor imaging (DTI) scan approximately 1 month after treatment initiation. Clinical status was evaluated 16 months after treatment initiation. Thirty matched healthy controls also underwent a DTI scan without any intervention. RESULTS: DHEA administration was not associated with reduced relapse rates compared with placebo. Nevertheless, exploratory analysis revealed that DHEA was associated with successful rehabilitation among pSUD individuals with low circulating DHEA levels at treatment initiation. White matter integrity in the splenium corpus callosum (CC) was reduced in pSUD individuals compared with healthy controls, yet pSUD individuals receiving DHEA exhibited recovery of splenium CC WM integrity. CONCLUSIONS: DHEA administration during rehabilitation may restore WM integrity in the CC among pSUD individuals. Although DHEA was not associated with reduced relapse rates in here, its therapeutic efficacy may depend on circulating DHEA levels at treatment initiation.

Depression level, not pain severity, is associated with smoked medical marijuana dosage among chronic pain patients.

BACKGROUND: The use of medical marijuana (MM) for the treatment of chronic pain is rapidly growing in the United States and Europe; however there is concern regarding the specificity of its therapeutic effects and the motivation underlying its use. While research indicates that among chronic pain prescribed opioids, depression has been associated with increased opioid dosage (regardless of pain levels), the extent to which depression and pain each contribute to MM dose among chronic pain patients is yet unknown. METHODS: This cross-sectional study included 209 chronic pain patients prescribed smoked MM, in flower or other plant form, with no concurrent opioid treatment. Ordinal regression analyses were performed in order to explore the unique contribution of mean pain level (1-10 scale), depression severity (measured by the Patient Health Questionnaire (PHQ-9)) and anxiety severity (measured by the Generalized Anxiety Disorder scale (GAD-7)) to doses of MM, while taking into account additional sociodemographic and clinical factors. RESULTS: Individuals with mild depression and those with moderate to severe depression were at significantly increased odds for using higher doses of MM in grams per month(Adjusted Odds Ratio(AOR) = 2.06,95% Confidence Interval(CI) = 1.05-4.01, and AOR = 5.95,95% CI = 1.97-17.98, respectively) compared to those without depression. In addition, individuals with mild depression were at significantly increased odds for smoking more MM joints daily(AOR = 2.07, 95% CI = 1.01-4.23) compared to individuals without depression. Mean levels of pain or anxiety severity were not significantly associated with either dose measures. CONCLUSIONS: Depression and MM dose are highly correlated and should be concurrently addressed during chronic pain treatment.

[MEDICAL MARIJUANA DEPENDENCE AMONG CHRONIC PAIN PATIENTS SUFFERING FROM DEPRESSION AND ANXIETY].

INTRODUCTION: In recent years, medical marijuana (MM) is increasingly being used for the treatment of chronic pain. Depression and anxiety have been identified as risk factors for the problematic use of prescription opioids, yet their contribution to developing MM dependence hasn't been explored up to date. In this study we explored the association between depression and anxiety severity and the risk for cannabis dependence among chronic pain patients prescribed MM. METHODS: Participants were 324 chronic pain patients prescribed MM with no cuncurrent opioid treatment. All participants were screened for depression using the Patient Health Questionnaire (PHQ-9), for anxiety using the Generalized Anxiety Disorder questionnaire (GAD-7) and for problematic use of MM according to DSM-IV criteria for cannabis dependence using the AUDADI-IT questionnaire. Logistic regression analyses controlling for additional sociodemographic and clinical factors were conducted. RESULTS: Generally, prevalence of cannabis dependence was higher among participants with levels of depression and anxiety levels compared to those without depression or anxiety. However, after controlling for confounders only participants with severe depression were significantly more likely (Adjusted Odds Ratio=5.86) to screen positive for cannabis dependence compared to those without depression. CONCLUSIONS: Severe depression may be a risk factor for problematic use of MM among chronic pain patients. Increasing use of MM calls for further explotartion of potential risk factors which may predict problematic MM use among this population.

A DNA Methylation Signature of Addiction in T Cells and Its Reversal With DHEA Intervention.

Previous studies in animal models of cocaine craving have delineated broad changes in DNA methylation profiles in the nucleus accumbens. A crucial factor for progress in behavioral and mental health epigenetics is the discovery of epigenetic markers in peripheral tissues. Several studies in primates and humans have associated differences in behavioral phenotypes with changes in DNA methylation in T cells and brain. Herein, we present a pilot study (n = 27) showing that the T cell DNA methylation profile differentiates persons with a substance use disorder from controls. Intervention with dehydroepiandrosterone (DHEA), previously shown to have a long-term therapeutic effect on human addicts herein resulted in reversal of DNA methylation changes in genes related to pathways associated with the addictive state.

The association between severity of depression and prescription opioid misuse among chronic pain patients with and without anxiety: A cross-sectional study.

BACKGROUND: In light of the increased rates of Prescription Opioid (PO) misuse and associated mortality in several developed countries in recent years, efforts have been made to identify populations who may be at increased risk for misuse of POs. Though the association between depression and PO misuse among pain patients is well documented, little is known regarding the effects of severity of depression on rates of misuse. In this study we explored rates of PO misuse among chronic pain patients screening positive for depression according to level of severity. METHODS: Participants included chronic pain patients receiving POs (N = 554). All participants were screened for depression using the Patient Health Questionnaire (PHQ-9; cut-off scores of 5, 10, 15, and 20 for mild, moderate, moderate-severe and severe depression, respectively) and for opioid misuse using the Current Opioid Misuse Measure (COMM). Logistic regression analyses controlling for additional sociodemographic and clinical factors were conducted. RESULTS: Participants who screened positive for depression were at significantly increased odds to screen positive for opioid misuse (Adjusted Odds Ratio (AOR) = 3.63; 95% Confidence Interval (CI) = 1.71-7.7) compared to those without depression. Severity of depression was significantly associated with increased odds for opioid misuse for moderate (AOR = 3.71; 95% CI = 1.01-13.76), moderate-severe (AOR = 6.28; 95% CI = 1.6-24.57) and severe (AOR = 14.66; 95% CI = 3.28-65.52) depression but not among those who screened positive for mild depression (AOR = 1.49; 95% CI = 0.39-5.68). LIMITATIONS: Cross-sectional study. CONCLUSIONS: Our results highlight the need to properly asses and address level of severity of co-morbid depression among chronic pain patients receiving POs.

Misuse of prescription opioids among chronic pain patients suffering from anxiety: A cross-sectional analysis.

OBJECTIVE: In the past two decades, chronic pain has been increasingly treated with prescription opioids, particularly in developed countries. This has drawn public concern of possible risks associated with the potential misuse of prescriptions opioids. Previous research has indicated that this may be particularly true among individuals suffering from co-occurring psychiatric disorders. The present study sought to explore rates of misuse among chronic pain patients prescribed opioids, comparing individuals with and without anxiety. METHODS: Chronic pain patients receiving prescription opioids (N=554) were screened for anxiety using the Generalized Anxiety Disorder (GAD-7) scale and for opioid misuse using the Current Opioid Misuse Measure (COMM). RESULTS: Among patients who screened positive for anxiety (GAD-7≥10), 50% also screened positive for opioid misuse, compared to 10% among those without anxiety. After controlling for possible confounding sociodemographic and clinical variables, patients with anxiety were significantly more prone to screen positive for opioid misuse (Adjusted Odds Ratio (AOR)=2.18; 95% Confidence Interval (CI)=1.37-4.17) compared to those without anxiety. This was maintained when conducting separate comparisons for severe, but not mild or moderate, level of anxiety. CONCLUSIONS: These findings highlight the importance of detecting and addressing co-occurring anxiety when treating patients with chronic pain who receive prescription opioids.

Depression and anxiety among chronic pain patients receiving prescription opioids and medical marijuana.

BACKGROUND: High rates of depression and anxiety have been consistently reported among patients suffering from chronic pain. Prescription opioids are one of the most common modalities for pharmacological treatment of pain, however in recent years medical marijuana(MM) has been increasingly used for pain control in the US and in several countries worldwide. The aim of this study was to compare levels of depression and anxiety among pain patients receiving prescription opioids and MM. METHODS: Participants were patients suffering from chronic pain treated with prescription opioids (OP,N=474), MM (N=329) or both (OPMM,N=77). Depression and anxiety were assessed using the depression module of the Patient Health Questionnaire (PHQ-9) and the Generalized Anxiety Disorder scale (GAD-7). RESULTS: Prevalence of depression among patients in the OP, MM and OPMM groups was 57.1%, 22.3% and 51.4%, respectively and rates of anxiety were 48.4%, 21.5% and 38.7%, respectively. After controlling for confounders, patients in the OP group were significantly more likely to screen positive for depression (Adjusted Odds Ratio(AOR)=6.18;95%CI=4.12-9.338) and anxiety(AOR=4.12;CI=3.84-5.71)) compared to those in the MM group. Individuals in the OPMM group were more prone for depression (AOR for depression=3.34;CI=1.52-7.34)) compared to those in the MM group. LIMITATIONS: Cross-sectional study, restricting inference of causality. CONCLUSIONS: Levels of depression and anxiety are higher among chronic pain patients receiving prescription opioids compared to those receiving MM. Findings should be taken into consideration when deciding on the most appropriate treatment modality for chronic pain, particularly among those at risk for depression and anxiety.

Problematic Use of Prescription Opioids and Medicinal Cannabis Among Patients Suffering from Chronic Pain.

Objective: To assess prevalence rates and correlates of problematic use of prescription opioids and medicinal cannabis (MC) among patients receiving treatment for chronic pain. Design: Cross-sectional study. Setting: Two leading pain clinics in Israel. Subjects: Our sample included 888 individuals receiving treatment for chronic pain, of whom 99.4% received treatment with prescription opioids or MC. Methods: Problematic use of prescription opioids and MC was assessed using DSM-IV criteria, Portenoy's Criteria (PC), and the Current Opioid Misuse Measure (COMM) questionnaire. Additional sociodemographic and clinical correlates of problematic use were also assessed. Results: Among individuals treated with prescription opioids, prevalence of problematic use of opioids according to DSM-IV, PC, and COMM was 52.6%, 17.1%, and 28.7%, respectively. Among those treated with MC, prevalence of problematic use of cannabis according to DSM-IV and PC was 21.2% and 10.6%, respectively. Problematic use of opioids and cannabis was more common in individuals using medications for longer periods of time, reporting higher levels of depression and anxiety, and using alcohol or drugs. Problematic use of opioids was associated with higher self-reported levels of pain, and problematic use of cannabis was more common among individuals using larger amounts of MC. Conclusions: Problematic use of opioids is common among chronic pain patients treated with prescription opioids and is more prevalent than problematic use of cannabis among those receiving MC. Pain patients should be screened for risk factors for problematic use before initiating long-term treatment for pain-control.

Effect of dehydroepiandrosterone add-on therapy on mood, decision making and subsequent relapse of polydrug users.

A major problem in the treatment of addiction is predicting and preventing relapse following a rehabilitation program. Recently, in preclinical rodent studies dehydroepiandrosterone (DHEA) was found to markedly improve the resistance to drug reuse. In a double-blind, placebo-controlled study, we examined the effect of DHEA on relapse rates in adult polydrug users taking part in a detoxification program enriched with intensive psychosocial interventions and aftercare. During treatment, participants (79 percent males, mean age 28) consumed DHEA (100 mg/day) or placebo daily for at least 30 days. Of the 121 initial volunteers, 64 participated for at least 1 month. While in treatment, DHEA reduced negative affect on the Positive and Negative Affect Scale (F = 4.25, P = 0.04). Furthermore, in a 16-month follow-up, we found that reuse rates in the DHEA condition were about a third compared with placebo (12 versus 38 percent; χ(2) = 5.03, P = 0.02). DHEA treatment also resulted in an increase in DHEA sulfate (DHEA-S) 1 month following treatment, and the level of DHEA-S predicted relapse in the follow-up assessment.

Characteristics of immigrant and non-immigrant patients in a dual-diagnosis psychiatric ward and treatment implications.

Two studies were conducted among patients in a male dual diagnosis (severe mental illness [SMI] with substance use) ward. The research examined the following questions: (1) Do immigrant and non-immigrant dual diagnosis patients exhibit similar or different socio-demographic, clinical and criminological characteristics? (2) What are the implications for treatment of immigrant (and non-immigrant) patients? Study one analyzed computerized hospital records of 413 male patients; Study two examined patient files of a subgroup of 141 (70 immigrant) male patients. Alongside similarities, non-immigrant patients reported higher numbers of repeat and involuntary hospitalizations and more drug use while immigrants showed longer hospitalizations, more suicide attempts, more violent suicide attempts, more violent offenses and more alcohol use. Among non-immigrants significant relationships were found between severity of SMI and crime/violence while among immigrants a significant relationship was found between suicidality and crime/violence. Implications for treatment include need for awareness of suicide risk among immigrant dual-diagnosis patients and an understanding of the differential relationship with crime/violence for the two populations.

Evaluating the clinical impact of involuntary admission to a specialized dual diagnosis ward.

BACKGROUND: We aimed to identify characteristics and outcomes of involuntary and voluntary admissions of dual-diagnosis patients in a single, large mental health center in Israel. METHODS: Using a retrospective chart review methodology, 24 patient records were reviewed spanning a period of five years; clinical and demographic variables of voluntary and involuntary admissions were compared. RESULTS: No significant differences were found in sociodemographic characteristics, admission diagnosis and length of hospitalization between the two types of admission. A smaller proportion of patients discharged from involuntary admissions were in remission compared to those discharged from voluntary admission. Nevertheless, involuntary admissions were associated with longer time to next hospitalization. LIMITATIONS: The data were based on a small number of patients in a single ward, thus the generalizability of the results is uncertain. CONCLUSIONS: The finding of the current study that involuntary admission leads to longer tenure in the community suggests that there may be clinical advantages to involuntary admissions for certain dual diagnosis patients.

Co-morbid social phobia in schizophrenia.

BACKGROUND: The co-morbid occurrence of anxiety disorders and schizophrenia has recently begun to be investigated. Social anxiety may be especially important to diagnose and manage among patients with schizophrenia. AIM: To investigate the prevalence and correlates of social phobia in patients with schizophrenia. METHOD: Diagnosis of schizophrenia and schizoaffective disorders as well as co-morbid anxiety disorders was established according to DSM-IV and the Structured Clinical Interview for Diagnosis (SCID-P Hebrew version). Severity of psychotic symptoms and social anxiety symptoms was assessed with the Positive and Negative Symptom Scale (PANSS) and the Liebowitz Social Anxiety Scale (LSAS). RESULTS: The cohort studied included 117 patients with schizophrenia. Thirteen patients were diagnosed as suffering from co-morbid social phobia (11%). There was a tendency for patients with co-morbid social phobia to have higher severity PANSS total score. There was a significant correlation between the score of the LSAS ;fear' and PANSS positive subscales. Avoidance scores were higher among patients with negative signs. CONCLUSION: Co-morbidity of schizophrenia and social anxiety disorder is not rare among patients with schizophrenia. Treatment implications need be further investigated.