Ketamine and Treatment-Resistant Depression.

Major depressive disorder affects tens of millions of people each year. One-third of those affected have depression that is resistant to conventional pharmacologic, psychologic, or somatic treatments. Patients with treatment-resistant depression have few remedies other than electroconvulsive therapy or transcranial magnetic stimulation. Recent research has highlighted the promising antidepressant effects of subanesthetic ketamine infusions. This journal course examines the efficacy of ketamine for treatment-resistant depression. Evidence from 10 systematic reviews and randomized controlled trials suggest that most of the researchers concluded ketamine significantly decreased depression severity ratings at short-term assessment intervals, whereas evidence examining the long-term effects is lacking. Ketamine infusion therapy was generally well tolerated, with minimal untoward effects. Large, randomized controlled trials are needed to discern the longer-term efficacy, tolerance, and dependence profiles of ketamine infusions. Optimal dosing schedules to best prolong the antidepressant effects of ketamine have yet to be determined.

Ketamine for the treatment of depression.

Ketamine (Ketalar®) is an anesthetic agent derived from the hallucinogenic drug phencyclidine (PCP). It is a high-affinity antagonist at N-methyl-D-aspartate receptors and also binds to opioid mu and sigma receptors. Ketamine is being intensively investigated as an antidepressant therapy. To date, five short-term controlled studies and other open-label studies in patients with unipolar or bipolar depression have demonstrated that intravenous ketamine is safe and has a rapid and profound short-term effect on depressive symptoms, including suicidal thoughts, even among patients considered treatment-resistant to standard medications or electroconvulsive therapy. Before ketamine can be incorporated into clinical practice, however, its long-term safety and effectiveness need to be evaluated. Although the effectiveness of alternative routes of ketamine administration (i.e., oral, intranasal, or intramuscular) needs to be determined, intravenous ketamine could be conceptualized as a clinic-based procedural therapy for treatment resistant forms of depression.

The concept of "the will to thrive" in mental health.

Mental health nursing is focused on patients moving along the continuum between failing and thriving in terms of emotional functioning. This differs dramatically from a medical model of disease/cure. A variety of nursing theorists have both directly and indirectly identified the importance of patient's "will to thrive" although this term has never been used. Peplau spoke of self-efficacy and self-esteem. Barrett's model focuses on the patient's participation in their own recovery as a key component. This article explores the concept, akin to failure to thrive in infants, of the will to thrive in the chronically ill and its role in assessment and nursing intervention. A particular emphasis on the importance of patient responsibility is identified as vital to the process of true change.

Psychological and physiological effects of caring for patients with treatment-resistant depression.

BACKGROUND: Carers of patients with psychiatric disorders show high levels of anxiety and depression, possibly mediated through disruption of the hypothalamo-pituitary-adrenal (HPA) axis. Among carers of patients with treatment-resistant depression (TRD), we set out to determine the psychological and physiological (HPA axis) consequences of caring, and the association of these consequences with long-term outcome in patients. METHOD: Thirty-five informal carers of patients with severe TRD requiring in-patient treatment were recruited and compared with 23 controls. HPA-axis activity was assessed by measuring post-awaking salivary cortisol. The Involvement Evaluation Questionnaire (IEQ) and the General Health Questionnaire-12 (GHQ-12) were administered to measure carer burden and psychiatric caseness respectively. Independent t tests were used to compare differences between carers and controls and a linear regression model was used to determine the association of post-awakening cortisol with carer status while controlling for confounding variables. Data on long-term patient outcome (12 to 83 months), measured using the Hamilton Depression Rating Scale (HAMD), were also obtained and linear regression was used to determine the association between cortisol output in carers and remission status in patients. RESULTS: Carers experienced high carer burden and high psychiatric caseness. Carers showed reduced cortisol output after awakening, calculated as the area under the curve with respect to ground (AUCg), which remained significant after controlling for potential confounders. In a linear regression model, non-remission in patients was associated with reduced cortisol output in carers. CONCLUSIONS: Caring for patients with TRD is associated with adverse psychological and physiological changes suggesting hypocortisolism post-awakening. These changes are associated with poor patient outcome.