The N-methyl-D-aspartate receptor antagonist ketamine has rapid onset activity in treatment-resistant depression, post-traumatic stress disorder and obsessive compulsive disorder. Due to similarities in brain network activity in depression and anxiety disorders, we hypothesized that ketamine might also be active in other refractory anxiety disorders. We evaluated the efficacy and safety of ketamine in 12 patients with refractory generalized anxiety disorder and/or social anxiety disorder who were not currently depressed, using an ascending single dose study design (0.25, 0.5, 1 mg/kg administered subcutaneously) at weekly intervals. Within 1 h of dosing, patients reported reduced anxiety, which persisted for up to seven days. A dose-response profile was noted for anxiolytic effects, dissociative side effects, and changes in blood pressure and heart rate, with minor changes at 0.25 mg/kg, and progressively greater and more durable changes at the higher doses. Ten of 12 patients were treatment responders at 0.5–1 mg/kg. Ketamine was safe and well tolerated in this population. Ketamine may be a potential therapeutic alternative for patients with refractory generalized anxiety disorder/social anxiety disorder. Along with its demonstrated effectiveness in patients with treatment-resistant depression, obsessive compulsive disorder and post-traumatic stress disorder, these data raise the intriguing possibility that ketamine may have broad efficacy in disorders characterized by negative emotional states, and that these disorders may share a common precipitating neurobiology.
(2011). The importance of interfaces in protein drug delivery – why is protein adsorption of interest in pharmaceutical formulations? Expert Opinion on Drug Delivery: Vol. 8, No. 7, pp. 949-964. doi: 10.1517/17425247.2011.577062
1 June 2007 in International Journal of Pharmaceutics
Objective: In this maintenance treatment study, we sought to evaluate the effect on anxiety ratings, safety and tolerability of 3 months of weekly ketamine in 20 patients with treatment-refractory DSM IV generalised anxiety disorder (GAD) and/or social anxiety disorder (SAD), and subsequent assessment of remission post-treatment. Methods: This was an uncontrolled open-label study in 20 patients who had been responders in an ascending dose ketamine study. The study was undertaken in a university clinic. Patients received one or two weekly ketamine doses of 1 mg/kg injected subcutaneously for 3 months. Data were collected from December 2015–June 2017. Results: There were 10 women (50%) and 10 men (50%); 15 patients (75%) met criteria for GAD and 18 (90%) for SAD. One hour after dosing, Fear Questionnaire ratings decreased by ~50%, as did Hamilton Anxiety ratings. Clinician Administered Dissociative States Scale mean scores declined over time, from 20 points at week 1 to 8.8 points at week 14. Compared with pre-dose values, mean systolic and diastolic blood pressure increased by ~10 mm Hg at 30 min. The most common adverse events were nausea, dizziness and blurred vision. Of the 20 patients, 18 reported improved social functioning and/or work functioning during maintenance treatment. Conclusions: Weekly ketamine dosing was safe and well tolerated, and post-dose dissociative symptoms tended to reduce after repeated dosing. Patients reported marked improvements in functionality and in their personal lives. Maintenance ketamine may be a therapeutic alternative for patients with treatment refractory GAD/SAD. Trial Registration: http://www.anzctr.org.au/ACTRN12615000617561
Chronic wounds display aberrant wound healing or wound healing that deviates from normal. The term ‘chronic wounds’, implies that these wounds do not heal in a timely fashion. They are often predisposed to infection, and not uncommonly result in amputation. Growth factors and cytokines play a pivotal role in cutaneous wound healing. It has been noted that some growth factors are deficient in chronic wounds, therefore it has been suggested that local or topical application of these factors may compensate for any deficiency and allow normal wound healing to progress. This paper reviews current work on the application of topical growth factors to wounds. Some potential problems are identified and suggestions are made for future areas where research may improve the effectiveness of this form of therapy.