No abstract

Objective Ketamine, a glutamate N-methyl-d-aspartate (NMDA) receptor antagonist, has shown rapid antidepressant effects, but small study groups and inadequate control conditions in prior studies have precluded a definitive conclusion. The authors evaluated the rapid antidepressant efficacy of ketamine in a large group of patients with treatment-resistant major depression. Method This was a two-site, parallel-arm, randomized controlled trial of a single infusion of ketamine compared to an active placebo control condition, the anesthetic midazolam. Patients with treatment-resistant major depression experiencing a major depressive episode were randomly assigned under double-blind conditions to receive a single intravenous infusion of ketamine or midazolam in a 2:1 ratio (N=73). The primary outcome was change in depression severity 24 hours after drug administration, as assessed by the Montgomery-Åsberg Depression Rating Scale (MADRS). Results The ketamine group had greater improvement in the MADRS score than the midazolam group 24 hours after treatment. After adjustment for baseline scores and site, the MADRS score was lower in the ketamine group than in the midazolam group by 7.95 points (95% confidence interval [CI], 3.20 to 12.71). The likelihood of response at 24 hours was greater with ketamine than with midazolam (odds ratio, 2.18; 95% CI, 1.21 to 4.14), with response rates of 64% and 28%, respectively. Conclusions Ketamine demonstrated rapid antidepressant effects in an optimized study design, further supporting NMDA receptor modulation as a novel mechanism for accelerated improvement in severe and chronic forms of depression. More information on response durability and safety is required before implementation in clinical practice.

The number of American children living in partner-violent households was estimated from a nationally representative sample of 1,615 dual-parent households. Approximately 15.5 million American children were estimated to live in families in which partner violence had occurred at least once in the previous year, with 7 million estimated to live in families in which severe partner violence had occurred. The prevalence of partner violence was higher among couples with children than among couples without children.

Background No medication is currently approved for the treatment of cocaine dependence, but several preclinical and clinical reports suggest agonist-like medications, e.g. amphetamine analogues, may be a productive strategy for medication development. Objective This current proof-of-concept study sought to evaluate the safety, tolerability, and effectiveness of methamphetamine as a candidate treatment for cocaine dependence. Methods A randomized, double-blind, placebo-controlled study served to evaluate three treatment conditions in 82 cocaine-dependent individuals: (1) placebo (0 mg, 6×/day; n = 27), (2) immediate release (IR) methamphetamine (5 mg, 6×/day; n = 30), (3) sustained release (SR) methamphetamine (30 mg first pill, 1×/day; 0 mg 5×/day; n = 25). The study employed a sequential, two-phase design (i.e., 4 weeks of medication and counseling followed by 4 weeks of medication/counseling plus a contingency management procedure). Results Both preparation forms of methamphetamine were well tolerated, with similar retention to placebo (0 mg, 33%; 30 mg IR, 30%, 30 mg SR, 32%). Methamphetamine SR was associated with decreased sleep and increased weight loss. Medication adherence rates were high for the first dose of the day (95%), while adherence for subsequent capsules was lower. Those in the SR condition exhibited consistently lower rates of cocaine-positive urine samples (0 mg, 60%; 30 mg IR, 66%, 30 mg SR, 29%), p<0.0001, and reported the greatest reduction in craving for cocaine, p<0.05. Conclusions SR methamphetamine significantly reduced cocaine use and craving. Additional research is warranted to develop and evaluate agonist-like medications that may effectively treat cocaine dependence.

The current study investigated the reliability of a new self-report questionnaire assessing stimuli that would likely elicit intimate partner violence. The Proximal Antecedents to Violent Episodes (PAVE) scale is a 30-item, Likert-type measure designed to assess situations that would reportedly precede the use of violence. In Study 1, an exploratory factor analysis on a clinical sample revealed 3 factors: Violence to Control, Violence Out of Jealousy, and Violence Following Verbal Abuse. In Study 2, the factor structure was replicated on a community sample using confirmatory factor analysis. In both studies, different types of batterers, on the basis of A. Holtzworth-Munroe and G. L. Stuart's (1994) typology, scored differently on the 3 factors in ways consistent with theory. Therefore, the PAVE shows promise as a reliable and valid tool to help to understand the context and function of intimate partner violence.