Age affects temporal response, but not durability, to serial ketamine infusions for treatment refractory depression.

RATIONALE: Ketamine is a novel, rapid-acting antidepressant for treatment refractory depression (TRD); however, clinical durability is poor and treatment response trajectories vary. Little is known about which patient characteristics predict faster or more durable ketamine responses. Ketamine's antidepressant mechanism may involve modulation of glutamatergic signaling and long-term potentiation (LTP); these neuroplasticity pathways are also attenuated with older age. OBJECTIVE: A retrospective analysis examining the impact of patient age on the speed and durability of ketamine's antidepressant effects in 49 veterans receiving serial intravenous ketamine infusions for TRD. METHOD: The relationship between age and percent change in Beck Depression Inventory (BDI-II) scores was compared across six serial ketamine infusions (twice-weekly for 3 weeks) using a linear-mixed model. RESULTS: A significant Age-X-Infusion number interaction (F = 3.01, p = .0274) indicated that the relationship between age and treatment response depended on infusion number. Follow-up tests showed that younger age significantly predicted greater clinical improvement at infusion #4 (t = 3.02, p = .004); this relationship was attenuated at infusion #5 (t = 1.95, p = .057) and was absent at infusion #6. Age was not a significant predictor of treatment durability, defined as percent change in BDI-II 3 weeks following infusion #6. CONCLUSIONS: These data preliminarily suggest that younger age is associated with a faster response over six serial ketamine infusions; by infusion #6 and subsequent weeks of clinical follow-up, age no longer predicts ketamine's antidepressant activity. Age may mediate the speed but not the durability or total efficacy of ketamine treatment, suggesting that dissociable mechanisms may underlie differing aspects of ketamine's antidepressant activity.

Attention-Deficit/Hyperactivity Disorder Symptoms Are Associated with Greater Delay Discounting of Condom-Protected Sex and Money.

Attention-deficit/hyperactivity disorder (ADHD) is associated with increased risk of detrimental life outcomes. Recent research also indicates that ADHD is associated with sexual risk behavior, such as unprotected sex. Some risky sexual behaviors may be driven, in part, by preference for immediate rewards, referred to as delay discounting, which is prominent in etiological models of ADHD. Therefore, the present study examined the effect of delay on preference for both monetary and sexual outcomes in adults with many ADHD symptoms (both on and off medication) and with fewer ADHD symptoms. Online participants (N = 275; n = 161 males, n = 114 females) completed a monetary delay discounting task, assessing preference for smaller sooner versus larger delayed hypothetical money, and the Sexual Delay Discounting Task, assessing preference for condom use in hypothetical casual sex scenarios based on delay until condom availability. Those with greater ADHD symptoms discounted delayed monetary outcomes as well as delayed condom-protected sex (i.e., preferred sooner money rewards and immediate unprotected sex) significantly more than those with fewer symptoms; however, no effect of current medication use was found across monetary or sexual delay discounting among those with greater ADHD symptoms. This study is the first to demonstrate the relation between ADHD symptoms and reduced condom-use likelihood. Increased discounting of delayed condom-protected sex might constitute one mechanism of risky sexual behavior among individuals with ADHD symptoms. Interventions geared toward increasing condom use in situations in which condoms may otherwise be unavailable, may mitigate risky sexual behaviors and their associated harms in this population.

Who is 'Molly'? MDMA adulterants by product name and the impact of harm-reduction services at raves.

Methylenedioxymethamphetamine (MDMA), often sold as 'Ecstasy' or 'Molly', is commonly used at music festivals and reported to be responsible for an increase in deaths over the last decade. Ecstasy is often adulterated and contains compounds that increase morbidity and mortality. While users and clinicians commonly assume that products sold as Molly are less-adulterated MDMA products, this has not been tested. Additionally, while pill-testing services are sometimes available at raves, the assumption that these services decrease risky drug use has not been studied. This study analyzed data collected by the pill-testing organization, DanceSafe, from events across the United States from 2010 to 2015. Colorimetric reagent assays identified MDMA in only 60% of the 529 samples collected. No significant difference in the percentage of samples testing positive for MDMA was determined between Ecstasy and Molly. Individuals were significantly less likely to report intent to use a product if testing did not identify MDMA (relative risk (RR) = 0.56, p = 0.01). Results suggest that Molly is not a less-adulterated substance, and that pill-testing services are a legitimate harm-reduction service that decreases intent to consume potentially dangerous substances and may warrant consideration by legislators for legal protection. Future research should further examine the direct effects of pill-testing services and include more extensive pill-testing methods.

Symptomatology and predictors of antidepressant efficacy in extended responders to a single ketamine infusion.

BACKGROUND: Antidepressant response to a single subanesthetic dose infusion of the glutamatergic modulator ketamine is transient in most depressed patients; however, a minority continue to experience an extended response. This study examined depressive symptoms and potential clinical predictors of extended response to ketamine in subjects with mood disorders. METHODS: Subjects were diagnosed with either major depressive disorder (MDD) or bipolar depression. All subjects were treatment-resistant and experiencing a major depressive episode of at least moderate severity. MDD subjects were unmedicated and those with bipolar depression were receiving therapeutic-dose lithium or valproate. All subjects received a single 0.5mg/kg ketamine infusion. Data were collected pre-infusion (baseline) and at days one, 14, and 28 post-infusion. RESULTS: Twelve of 93 (12.9%) participants continued to meet response criteria (50% reduction in Montgomery-Asberg Depression Rating Scale (MADRS) score) at two weeks. All depressive symptoms assessed by the MADRS were improved at two weeks in ketamine responders except for sleep duration/depth. A positive family history of alcohol use disorder in a first-degree relative (FHP) and greater dissociation during the infusion were associated with better antidepressant response at two weeks. Improved measures of apparent sadness, reported sadness, inability to feel, and difficulty concentrating at day 1 correlated most strongly with antidepressant effects at two weeks. LIMITATIONS: Post-hoc design, small sample size, diagnostic heterogeneity. CONCLUSIONS: Static (FHP) and dynamic (improved depressive symptoms) factors may be clinically useful in predicting whether a patient will have an extended response to ketamine.

Risks, Benefits, and Recommendations for Pastoral Care on Inpatient Psychiatric Units: A Systematic Review.

OBJECTIVE: A systematic review was conducted of the biomedical literature regarding pastoral care (PaC) providers on inpatient psychiatric units with the aim of answering 3 questions: (1) What are the risks and benefits of PaC providers' presence on inpatient psychiatric units? (2) What are current recommendations for integration of PaC providers into a psychiatric team? and (3) What gaps exist in the literature? METHODS: PubMed, PsycInfo, Embase, CINAHL, and Scopus were searched from the start of each database to July 9, 2014 using terms related to PaC providers and inpatient psychiatry. Two independent reviewers performed full-text reviews of each article identified by independent review of all titles/abstracts from the electronic search and by a hand search of articles included in reference lists. Inclusion criteria were: English-language article, published in a peer-reviewed journal, and focus on a PaC provider working in a psychiatric hospital setting. One author performed data extraction. RESULTS: Forty-nine articles were identified by electronic (84%) and hand search (16%), 18 of which were evaluative studies: 5 qualitative and 13 quantitative. Most of the literature viewed integration of PaC providers in inpatient treatment teams as beneficial. Potential harms were noted and mitigation strategies suggested, including providing training to PaC providers concerning psychiatric illness, clearly defining roles, and enhancing team integration. None of the articles reported outcomes data. CONCLUSIONS: Psychiatric inpatients often have unmet spiritual needs. Although the literature suggests potential benefits of PaC providers for psychiatric inpatients, more rigorous studies are needed to establish these benefits as efficacious. The authors of this review recommend the cautious integration of PaC providers into the psychiatric inpatient care team.