Multichannel tDCS with Advanced Targeting for Major Depressive Disorder: A Tele-Supervised At-Home Pilot Study.

Introduction: Proof-of-principle human studies suggest that transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (DLPFC) may improve depression severity. This open-label multicenter study tested remotely supervised multichannel tDCS delivered at home in patients (N=35) with major depressive disorder (MDD). The primary aim was to assess the feasibility and safety of our protocol. As an exploratory aim, we evaluated therapeutic efficacy: the primary efficacy measure was the median percent change from baseline to the end of the 4-week post-treatment follow-up period in the observer-rated Montgomery-Asberg Depression Mood Rating Scale (MADRS). Methods: Participants received 37 at-home stimulation sessions (30 minutes each) of specifically designed multichannel tDCS targeting the left DLPFC administered over eight weeks (4 weeks of daily treatments plus 4 weeks of taper), with a follow-up period of 4 weeks following the final stimulation session. The stimulation montage (electrode positions and currents) was optimized by employing computational models of the electric field generated by multichannel tDCS using available structural data from a similar population (group optimization). Conducted entirely remotely, the study employed the MADRS for assessment at baseline, at weeks 4 and 8 during treatment, and at 4-week follow-up visits. Results: 34 patients (85.3% women) with a mean age of 59 years, a diagnosis of MDD according to DSM-5 criteria, and a MADRS score ≥20 at the time of study enrolment completed all study visits. At baseline, the mean time since MDD diagnosis was 24.0 (SD 19.1) months. Concerning compliance, 85% of the participants (n=29) completed the complete course of 37 stimulation sessions at home, while 97% completed at least 36 sessions. No detrimental effects were observed, including suicidal ideation and/or behavior. The study observed a median MADRS score reduction of 64.5% (48.6, 72.4) 4 weeks post-treatment (Hedge's g = -3.1). We observed a response rate (≥ 50% improvement in MADRS scores) of 72.7% (n=24) from baseline to the last visit 4 weeks post-treatment. Secondary measures reflected similar improvements. Conclusions: These results suggest that remotely supervised and supported multichannel home-based tDCS is safe and feasible, and antidepressant efficacy motivates further appropriately controlled clinical studies.

Health status and treatment-seeking stigma in older adults with trauma and posttraumatic stress disorder.

This study compared health status across four trauma/posttraumatic stress disorder (PTSD) groups of older adults with depression, anxiety, and/or at-risk drinking who attended primary care appointments (N = 1,199; mean age = 73.5 yr), mostly at Department of Veterans Affairs hospitals. The trauma and PTSD categories were PTSD (n = 81), partial PTSD (n = 127), trauma only (n = 323), and no trauma (n = 668). Physical and mental health-related quality of life (HQL), indices of social and economic impairment and stigma regarding treatment-seeking were compared among groups. Group differences were found for several indicators of functional impairment; the PTSD group had fewer close friends and higher treatment-seeking stigma beliefs related to having a disorder. Linear mixed modeling examined associations between trauma/PTSD group and HQL. After accounting for covariates, the trauma/PTSD groups differed across the Medical Outcome Study Short Form-36 scales and component scores (indicated by significant group by scale interaction). Differences among groups were confined to mental health measures; those with PTSD had worse HQL. Post hoc analyses examined the number of comorbid psychiatric diagnoses by trauma/PTSD group. Overall, findings indicate that mental HQL varies among older adults with trauma and PTSD and that although treatment-related stigma does not differ among groups, it does affect HQL.

Adding an Internet-delivered treatment to an efficacious treatment package for opioid dependence.

OBJECTIVE: To examine the benefit of adding an Internet-delivered behavior therapy to a buprenorphine medication program and voucher-based motivational incentives. METHOD: A block-randomized, unblinded, parallel, 12-week treatment trial was conducted with 170 opioid-dependent adult patients (mean age = 34.3 years; 54.1% male; 95.3% White). Participants received an Internet-based community reinforcement approach intervention plus contingency management (CRA+) and buprenorphine or contingency management alone (CM-alone) plus buprenorphine. The primary outcomes, measured over the course of treatment, were longest continuous abstinence, total abstinence, and days retained in treatment. RESULTS: Compared to those receiving CM-alone, CRA+ recipients exhibited, on average, 9.7 total days more of abstinence (95% confidence interval [CI = 2.3, 17.2]) and had a reduced hazard of dropping out of treatment (hazard ratio = 0.47; 95% CI [0.26, 0.85]). Prior treatment for opioid dependence significantly moderated the additional improvement of CRA+ for longest continuous days of abstinence. CONCLUSIONS: These results provide further evidence that an Internet-based CRA+ treatment is efficacious and adds clinical benefits to a contingency management/medication based program for opioid dependence.

Clinical efficacy of sertraline alone and augmented with gabapentin in recently abstinent cocaine-dependent patients with depressive symptoms.

BACKGROUND: Cocaine dependence is a major public health problem with no available robustly effective pharmacotherapy. This study's aim was to determine if treatment with sertraline (SERT) or SERT plus gabapentin (GBP) improved treatment retention, depressive symptoms, and/or cocaine use. METHODS: Depressed cocaine-dependent patients (N = 99) were enrolled in a 12-week, double-blind, randomized, placebo (PLA)-controlled, clinical trial and placed in research beds at a residential treatment facility (Recovery Centers of Arkansas). They were randomized by depressive symptom severity and inducted onto 1 of the following while residing at the Recovery Centers of Arkansas: SERT (200 mg/d), SERT (200 mg/d) plus GBP (1200 mg/d), or PLA. Participants transferred to outpatient treatment at the start of their third week, continued receiving study medications or PLA (weeks 3-12), and participated in weekly individual cognitive behavioral therapy. Compliance was facilitated through the use of contingency management procedures. Supervised urine samples were obtained thrice weekly and self-reported mood weekly. At the end of 12 weeks, participants were tapered off the study medication over 5 days and referred to a local treatment program. RESULTS: Sertraline, but not SERT plus GBP, showed a significantly lower overall percentage of cocaine-positive urine samples compared with that of PLA. A significantly greater percentage of participants experienced relapse in the PLA group (88.9%) compared with that of the SERT group (65.2%). Hamilton depression ratings decreased significantly over time regardless of the treatment group. Retention in treatment did not differ significantly between the treatment groups. CONCLUSIONS: Sertraline plus GBP may not be superior to SERT alone in delaying relapse among abstinent cocaine-dependent individuals undergoing cognitive behavioral therapy.

Effect of vitamin E and memantine on functional decline in Alzheimer disease: the TEAM-AD VA cooperative randomized trial.

IMPORTANCE: Although vitamin E and memantine have been shown to have beneficial effects in moderately severe Alzheimer disease (AD), evidence is limited in mild to moderate AD. OBJECTIVE: To determine if vitamin E (alpha tocopherol), memantine, or both slow progression of mild to moderate AD in patients taking an acetylcholinesterase inhibitor. DESIGN, SETTING, AND PARTICIPANTS: Double-blind, placebo-controlled, parallel-group, randomized clinical trial involving 613 patients with mild to moderate AD initiated in August 2007 and concluded in September 2012 at 14 Veterans Affairs medical centers. INTERVENTIONS: Participants received either 2000 IU/d of alpha tocopherol (n = 152), 20 mg/d of memantine (n = 155), the combination (n = 154), or placebo (n = 152). MAIN OUTCOMES AND MEASURES: Alzheimer's Disease Cooperative Study/Activities of Daily Living (ADCS-ADL) Inventory score (range, 0-78). Secondary outcomes included cognitive, neuropsychiatric, functional, and caregiver measures. RESULTS: Data from 561 participants were analyzed (alpha tocopherol = 140, memantine = 142, combination = 139, placebo = 140), with 52 excluded because of a lack of any follow-up data. Over the mean (SD) follow-up of 2.27 (1.22) years, ADCS-ADL Inventory scores declined by 3.15 units (95% CI, 0.92 to 5.39; adjusted P = .03) less in the alpha tocopherol group compared with the placebo group. In the memantine group, these scores declined 1.98 units less (95% CI, -0.24 to 4.20; adjusted P = .40) than the placebo group's decline. This change in the alpha tocopherol group translates into a delay in clinical progression of 19% per year compared with placebo or a delay of approximately 6.2 months over the follow-up period. Caregiver time increased least in the alpha tocopherol group. All-cause mortality and safety analyses showed a difference only on the serious adverse event of "infections or infestations," with greater frequencies in the memantine (31 events in 23 participants) and combination groups (44 events in 31 participants) compared with placebo (13 events in 11 participants). CONCLUSIONS AND RELEVANCE: Among patients with mild to moderate AD, 2000 IU/d of alpha tocopherol compared with placebo resulted in slower functional decline. There were no significant differences in the groups receiving memantine alone or memantine plus alpha tocopherol. These findings suggest benefit of alpha tocopherol in mild to moderate AD by slowing functional decline and decreasing caregiver burden. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00235716.

PTSD is a chronic, fluctuating disorder affecting the mental quality of life in older adults.

OBJECTIVES: Examine the longitudinal course of posttraumatic stress disorder (PTSD) in older adults and its influence on mental health quality of life (MHQoL). DESIGN: Evaluation performed at baseline, and 3 and 6 months postrandomization as part of a longitudinal trial. PARTICIPANTS AND SETTINGS: A total of 1,185 participants, with a mean (±SD) age of 73.53 (±5.98) years, at seven primary care sites (including five Veterans Affairs clinics), were divided into four groups, namely, no trauma (n = 661), trauma only (n = 319), partial PTSD (n = 114), and PTSD (n = 81), based on reports of trauma and associated PTSD symptoms. MEASUREMENTS: The prevalence of comorbid depression, anxiety, and alcohol use disorders, assessed using the Diagnostic and Statistical Manual, Fourth Edition, criteria and changes in MHQoL, as assessed by the Short Form-36 mental component score. RESULTS: At baseline, the PTSD group had higher frequencies of comorbid depression and anxiety disorders and worse MHQoL than the other groups. Both chronic (participants diagnosed with PTSD at all three assessments) and fluctuating (participants moving to or from one of the other groups) trajectories of course were observed during the follow-up period, which appeared to be separate from that of the comorbid disorders. Even after accounting for those comorbid disorders, PTSD had an independent association with poorer MHQoL at multiple time points, especially in men, whereas trauma without PTSD symptoms (trauma only) had better MHQoL. CONCLUSIONS: PTSD had chronic and fluctuating courses, with negative effects on MHQoL, while partial PTSD might represent a transitional state, underscoring the need to better identify and treat PTSD at any phase in later life.

Vitamin E and memantine in Alzheimer's disease: clinical trial methods and baseline data.

BACKGROUND: Alzheimer's disease (AD) has been associated with both oxidative stress and excessive glutamate activity. A clinical trial was designed to compare the effectiveness of (i) alpha-tocopherol, a vitamin E antioxidant; (ii) memantine (Namenda), an N-methyl-D-aspartate antagonist; (iii) their combination; and (iv) placebo in delaying clinical progression in AD. METHODS: The Veterans Affairs Cooperative Studies Program initiated a multicenter, randomized, double-blind, placebo-controlled trial in August 2007, with enrollment through March 2012 and follow-up continuing through September 2012. Participants with mild-to-moderate AD who were taking an acetylcholinesterase inhibitor were assigned randomly to 2000 IU/day of alpha-tocopherol, 20 mg/day memantine, 2000 IU/day alpha-tocopherol plus 20 mg/day memantine, or placebo. The primary outcome for the study is the Alzheimer's Disease Cooperative Study/Activities of Daily Living Inventory. Secondary outcome measures include the Mini-Mental State Examination; the Alzheimer's Disease Assessment Scale, cognitive portion; the Dependence Scale; the Neuropsychiatric Inventory; and the Caregiver Activity Survey. Patient follow-up ranged from 6 months to 4 years. RESULTS: A total of 613 participants were randomized. The majority of the patients were male (97%) and white (86%), with a mean age of 79 years. The mean Alzheimer's Disease Cooperative Study/Activities of Daily Living Inventory score at entry was 57 and the mean Mini-Mental State Examination score at entry was 21. CONCLUSION: This large multicenter trial will address the unanswered question of the long-term safety and effectiveness of alpha-tocopherol, memantine, and their combination in patients with mild-to-moderate AD taking an acetylcholinesterase inhibitor. The results are expected in early 2013.

Diabetic retinopathy and atherosclerosis: is there a link?

Diabetic retinopathy (DR) is the leading cause of blindness amongst the working-age population, and diabetes accelerated cardiovascular disease (CVD) the commonest cause of death in diabetic patients. Although, there is evidence suggesting a close association between DR and CVD, particularly in patients with Type 2 diabetes, the pathophysiology underlying the link is unclear. Here we review common risk factors and pathogenic mechanisms linking DR and CVD, and aim to highlight the need for a more holistic view of the management of diabetes and its complications. The understanding of the link between the two complications could eventually lead to refined management strategies and improved patient outcomes in the expanding diabetes epidemic.

Pathophysiology of diabetic retinopathy.

Diabetes is now regarded as an epidemic, with the population of patients expected to rise to 380 million by 2025. Tragically, this will lead to approximately 4 million people around the world losing their sight from diabetic retinopathy, the leading cause of blindness in patients aged 20 to 74 years. The risk of development and progression of diabetic retinopathy is closely associated with the type and duration of diabetes, blood glucose, blood pressure, and possibly lipids. Although landmark cross-sectional studies have confirmed the strong relationship between chronic hyperglycaemia and the development and progression of diabetic retinopathy, the underlying mechanism of how hyperglycaemia causes retinal microvascular damage remains unclear. Continued research worldwide has focussed on understanding the pathogenic mechanisms with the ultimate goal to prevent DR. The aim of this paper is to introduce the multiple interconnecting biochemical pathways that have been proposed and tested as key contributors in the development of DR, namely, increased polyol pathway, activation of protein kinase C (PKC), increased expression of growth factors such as vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF-1), haemodynamic changes, accelerated formation of advanced glycation endproducts (AGEs), oxidative stress, activation of the renin-angiotensin-aldosterone system (RAAS), and subclinical inflammation and capillary occlusion. New pharmacological therapies based on some of these underlying pathogenic mechanisms are also discussed.

Emerging role of hydrogen sulfide in health and disease: critical appraisal of biomarkers and pharmacological tools.

H2S (hydrogen sulfide) is a well known and pungent gas recently discovered to be synthesized enzymatically in mammalian and human tissues. In a relatively short period of time, H2S has attracted substantial interest as an endogenous gaseous mediator and potential target for pharmacological manipulation. Studies in animals and humans have shown H2S to be involved in diverse physiological and pathophysiological processes, such as learning and memory, neurodegeneration, regulation of inflammation and blood pressure, and metabolism. However, research is limited by the lack of specific analytical and pharmacological tools which has led to considerable controversy in the literature. Commonly used inhibitors of endogenous H2S synthesis have been well known for decades to interact with other metabolic pathways or even generate NO (nitric oxide). Similarly, commonly used H2S donors release H2S far too quickly to be physiologically relevant, but may have therapeutic applications. In the present review, we discuss the enzymatic synthesis of H2S and its emerging importance as a mediator in physiology and pathology. We also critically discuss the suitability of proposed 'biomarkers' of H2S synthesis and metabolism, and highlight the complexities of the currently used pharmacological H2S 'donor' molecules and 'specific' H2S synthesis inhibitors in their application to studying the role of H2S in human disease.

Exposure to trauma and posttraumatic stress disorder symptoms in older veterans attending primary care: comorbid conditions and self-rated health status.

OBJECTIVES: Assess the prevalence of posttraumatic stress disorder (PTSD) symptomatology and its association with health characteristics in a geriatric primary care population. DESIGN: Cross-sectional screening assessments during a multisite trial for the treatment of depression, anxiety, and at-risk drinking. SETTING: Department of Veterans Affairs (VA)-based primary care clinics across the United States. PARTICIPANTS: Seventeen thousand two hundred five veterans aged 65 and older. MEASUREMENTS: Sociodemographic information, the General Health Questionnaire (GHQ-12), questions about death wishes and suicidal ideation, quantity and frequency of alcohol use, smoking, exposure to traumatic events, and PTSD symptom clusters. RESULTS: Twelve percent (2,041/17,205) of participants screened endorsed PTSD symptoms. Veterans with PTSD symptoms from some (partial PTSD) or each (PTSD all clusters) of the symptom clusters were significantly more likely to report poor general health, currently smoke, be divorced, report little or no social support, and have a higher prevalence of mental distress, death wishes, and suicidal ideation than those with no trauma history or those with trauma but no symptoms. Group differences were most pronounced for mental distress and least for at-risk drinking. Presence of PTSD all clusters was associated with poorer outcomes on all of the above-mentioned health characteristics than partial PTSD. CONCLUSION: PTSD symptoms are common in a substantial minority of older veterans in primary care, and careful inquiry about these symptoms is important for comprehensive assessment in geriatric populations.

Randomized, double blind, placebo-controlled trial of disulfiram for the treatment of cocaine dependence in methadone-stabilized patients.

UNLABELLED: This study examined the dose-related efficacy of disulfiram for treating cocaine dependence in methadone-stabilized cocaine dependent participants. DESIGN: One hundred and sixty-one cocaine- and opioid-dependent volunteers were entered into a 14-week, double blind, randomized, placebo-controlled clinical trial at two sites. METHODS: Participants were stabilized on methadone during weeks 1-2 and received disulfiram at 0, 62.5, 125 or 250 mg/day during weeks 3-14. All participants also received weekly cognitive behavioral therapy. Thrice-weekly urine samples and weekly self-reported drug use assessments were obtained. RESULTS: Baseline subject characteristics, retention and drug use did not differ across groups. Outcome analyses were performed on those who participated beyond week 2. Opioid-positive urine samples and self-reported opioid use did not differ by treatment group. The prevalence of alcohol use was low prior to and during the trial and did not differ by treatment group. Cocaine-positive urines increased over time in the 62.5 and 125 mg disulfiram groups and decreased over time in the 250 mg disulfiram and placebo groups (p < 0.0001). Self-reported cocaine use increased in the 125 mg disulfiram group relative to the other three treatment groups (p = 0.04). CONCLUSIONS: Disulfiram may be contraindicated for cocaine dependence at doses <250 mg/day. Whether disulfiram at higher doses is efficacious in reducing cocaine use in dually cocaine and opioid dependent individuals needs to be determined.

Remission in major depression: results from a geriatric primary care population.

OBJECTIVES: While a recent task force report recommended that remission from major depression be defined according to DSM criteria, most previous work has used depressive symptom rating scales. The current study sought to identify baseline factors associated with treatment outcome in major depression, diagnosed according to DSM-IV criteria. METHODS: Data from the Primary Care Research in Substance Abuse and Mental Health for the Elderly (PRISM-E) study were utilized. This analysis focused on 792 geriatric primary care patients with major depression at baseline, which was randomized to services by a mental health professional in primary care or specialty settings. Major depression was diagnosed according to DSM-IV criteria based on a structured interview at baseline and 6 months. The primary outcome was the absence of any DSM-IV depressive disorder at six-month follow-up. Association with baseline demographic characteristics, comorbid anxiety disorder, 'at risk' drinking, number of co-occurring medical conditions, and depressive symptom severity was examined using multiple logistic regression modeling. RESULTS: Remission occurred in 228 (29%) patients with completed follow-up assessments, while 564 (71%) did not remit. Factors which increased the odds of non-remission included comorbid anxiety (OR=1.60, 95% CI 1.11-2.31), female sex (OR=1.49, 95% CI 1.04-2.15), general medical comorbidity (OR=1.15, 95% CI 1.07-1.24), and increased baseline depressive symptom severity (OR=1.04, 95% CI 1.03-1.06). CONCLUSIONS: The findings underscore the importance of using DSM criteria to define remission from major depression, and suggest that concurrent measurement of depression severity, comorbid anxiety, and medical comorbidity are important in identifying patients requiring targeted interventions to optimize remission from major depression.

Psycho-social outcomes for persons with bipolar-I disorder: Eight-year follow-up of a rural cohort from south India.

BACKGROUND: Assess psycho-social outcomes in a rural cohort of patients with bipolar-I disorder (BD). METHODS: Detailed evaluations were performed using the Longitudinal Interval Follow-up Evaluation (LIFE) assessments of community-based BD patients in southern India. Several subjective and objective outcome measures were examined. RESULTS: Only half the cohort could be described as having a good overall outcome, with persistent difficulties in inter-personal relationships in a substantial proportion of patients. Separation or divorce, or co-morbid alcohol dependence impacted a higher proportion of female patients compared to males. CONCLUSIONS: In spite of the small cohort size, this longitudinal study indicates mixed outcomes for BD patients in this setting, with several patients showing enduring psycho-social and global impairments. Even though symptomatic recovery for BD patients might be better in developing countries compared to those observed in developed nations, the notion of better psycho-social outcomes for BD in developing countries needs closer re-examination in larger cohorts.

Open-label pilot study of modafinil for methamphetamine dependence.

Methamphetamine has become a major public health issue globally, particularly in the United States. Despite this, no effective pharmacotherapy for methamphetamine abuse has been developed to date. This 6-week, open-label pilot clinical trial examined the safety and tolerability of modafinil up to 400 mg/d in 8 methamphetamine-dependent individuals. Subjects were inducted onto modafinil at 400 mg/d for more than 3 days and remained on 400 mg/d for 4.5 weeks. Participants received weekly blister packs and underwent weekly individual cognitive behavioral therapy. Adjunctive contingency management procedures were used to enhance retention. Vital signs and supervised urine samples were obtained thrice weekly, and self-reported drug use and Hamilton anxiety and depression ratings were completed once weekly. Eight subjects (50% female, 100% white, aged 35-52 years) were enrolled. Four completed the 6-week study, 3 completed a portion, and 1 withdrew consent before completing intake. Results showed that systolic blood pressure (t = 1.09, P = 0.28), diastolic blood pressure, (t = 1.18, P = 0.24), and heart rate (t = 1.55, P = 0.13) did not change over time. Scores on the modafinil side effects checklist (t = -2.63, P = 0.01), Hamilton anxiety scale (t = -2.50, P = 0.018), and Hamilton depression scale (t = -3.25, P = 0.003) all decreased over time. The proportion of urine positive for amphetamines did not change over time (t = -0.52, P = 0.61), whereas self-reported methamphetamine use did (t = -2.86, P < 0.005). These results suggest that modafinil at 400 mg/d is safe and tolerable for methamphetamine-dependent individuals.

Buprenorphine medication versus voucher contingencies in promoting abstinence from opioids and cocaine.

During a 12-week intervention, opioid dependent participants (N = 120) maintained on thrice-a-week (M, W, F) buprenorphine plus therapist and computer-based counseling were randomized to receive: (a) medication contingencies (MC = thrice weekly dosing schedule vs. daily attendance and single-day 50% dose reduction imposed upon submission of an opioid and/or cocaine positive urine sample); (b) voucher contingency (VC = escalating schedule for opioid and/or cocaine negative samples with reset for drug-positive samples); or (c) standard care (SC), with no programmed consequences for urinalysis results. VC resulted in better 12-week retention (85%) compared to MC (58%; p = 0.009), but neither differed from SC (76% retained). After adjusting for baseline differences in employment, and compared to SC, the MC group achieved 1.5 more continuous weeks of combined opioid/cocaine abstinence (p = 0.030), while the VC group had 2 more total weeks of abstinence (p = 0.048). Drug use results suggest that both the interventions were efficacious, with effects primarily in opioid rather than cocaine test results. Findings should be interpreted in light of the greater attrition associated with medication-based contingencies versus the greater monetary costs of voucher-based contingencies.

Self-, collateral- and clinician assessment of depression in persons with cognitive impairment.

OBJECTIVES: This investigation examined the associations between self-reports, collateral-source reports and a clinician's diagnosis of depression in persons with cognitive impairment. METHOD: Responses on the Geriatric Depression Scale - 15 (GDS-15) from 162 participants with a diagnosis of Mild Cognitive Impairment (n = 78) or Alzheimer's Dementia and a Mini-Mental State score >or=15 (n = 84) were compared with both their collateral sources' report on either the Neuropsychiatric Inventory Questionnaire (n = 93) and/or the collateral-source GDS-15 (n = 67), or a clinician's diagnosis of Major Depression (MD). RESULTS: Significant differences were seen between self- versus collateral-source reports of depression in these participants. Participants' reports of loss of interest (anhedonia) significantly increased the odds of disagreement with their collateral sources (OR = 3.78, 95% CI: 1.3-11.2) while reports of negative cognitions significantly decreased the odds of such a disagreement (OR = 0.31, 95% CI: 0.1-0.9). The symptom of anhedonia also showed the strongest association with the clinician's diagnosis of MD. CONCLUSION: A motivational symptom like loss of interest was seen to play an important role in depression experienced by those with cognitive impairment.

Sex and opioid maintenance dose influence response to naloxone in opioid-dependent humans: a retrospective analysis.

Pooled self-report and physiological data from 32 male and 15 female methadone or levo-alpha-acetyl methadol (LAAM) maintained volunteers were retrospectively analyzed for individual differences in response to naloxone (0.15 mg/70 kg, IM) and placebo at 20 and 40 min post-injection. Males and females were each divided by the median splitmethadone maintenance dose (MMD, in mg/kg body weight) into high and low MMD groups and MMD was used as a factor in the analyses, along with sex, drug, and time post-drug. Females in the low but not high, MMD group showed naloxone-induced increases in ratings on the Antagonist and Mixed-Action sub-scales of the Adjective Rating Scale, and the Lysergic acid diethyl amine (LSD) sub-scale of the Addiction Research Center Inventory at 20 min post-injection. Males in the high MMD group showed significant naloxone-induced increases in scores of these measures at both post-injection time-points. In addition, low MMD subjects showed more short-lived naloxone-induced increases on Visual Analogue Scale (VAS) Bad and Any drug effects ratings than high MMD subjects. These results suggest that those on a lower MMD, especially women, experience a more intense, but short-lived, response to naloxone, whereas those on a higher MMD experience a more modest, but longer-lasting effect.