Britta Ostermeyer

Ketamine for treatment-resistant unipolar depression: current evidence.

Currently available drugs for unipolar major depressive disorder (MDD), which target monoaminergic systems, have a delayed onset of action andsignificant limitations in efficacy. Antidepressants with primary pharmacological targets outside the monoamine system may offer the potential for more rapid activity with improved therapeutic benefit. The glutamate system has been scrutinized as a target for antidepressant drug discovery. The purpose of this article is to review emerging literature on the potential rapid-onset antidepressant properties of the glutamate NMDA receptor antagonist ketamine, an established anaesthetic agent. The pharmacology of ketamine and its enantiomer S-ketamine is reviewed, followed by examples of its clinical application in chronic, refractory pain conditions, which are commonly co-morbid with depression. The first generation of studies in patients with treatment-resistant depression (TRD) reported the safety and acute efficacy of a single subanaesthetic dose (0.5 mg/kg) of intravenous ketamine. A second generation of ketamine studies is focused on testing alternate routes of drug delivery, identifying methods to prevent relapse following resolution of depressive symptoms and understanding the neural basis for the putative antidepressant actions of ketamine. In addition to traditional depression rating endpoints, ongoing research is examining the impact of ketamine on neurocognition. Although the first clinical report in MDD was published in 2000, there is a paucity of adequately controlled double-blind trials, and limited clinical experience outside of research settings. Given the potential risks of ketamine, safety considerations will ultimately determine whether this old drug is successfully repositioned as a new therapy for TRD.

Working Well – The Texas Demonstration to Maintain Independence and Employment: 18-month outcomes

Uninsured working adults with chronic mental, behavioral and physical health conditions may have greater difficulty in accessing needed health care due to health care costs and crowded public health systems. Untreated medical conditions can lead to poorer health, which is linked to loss of employment and eventual applications for and receipt of federal benefits such as Supplemental Security Income and Social Security Disability Insurance (SSI/SSDI). The Working Well study was designed to determine whether a coordinated set of health benefits and employment supports could help low-income, working adults maintain their employment and remain independent of publicly funded disability assistance. Patients from the Harris County Hospital District, a large public health system providing indigent care in the Houston metroplex, were recruited and randomized to the intervention (N = 904) and control (N = 712) groups. The Working Well case management intervention included health naviga- tion, employment/vocational supports, expedited appointments, free medications, and no co-pays for medical visits. Participant outcomes were measured through surveys, health claims data, and state agency employment data. Intervention group participants reported greater access to care, greater likelihood of outpatient medical visits and less likelihood of receiving SSI/SSDI benefits. These findings suggest that public health care systems can provide disability prevention programs, improve access to care and reduce reliance on publicly funded disability assistance.