The high rise in the population suffering from depression depicts the need for improved and highly effective treatment options for this condition. Efforts to develop existing drugs into user-friendly dosage forms with a number of advantages in major depressive states, including but not limited to: sustained drug release, reduced drug dosing frequency, improved tolerance and adherence, suitability for use in diverse populations and different treatment scenarios, as well as less central nervous system side effects are required. One such non-invasive drug delivery route that could provide the aforementioned benefits in the treatment of depression is the transdermal route. A number of conventional and emerging transdermal delivery strategies have been investigated for some potent antidepressants and results depict the potential of this route as a viable means for systemic delivery of therapeutically relevant doses of the tested agents, with Emsam®, the commercially available patch of selegiline, being an evidence for the same. The investigated approaches include the formulation of transdermal patches, use of vesicular drug carriers, pro-drug approach, microemulsification, chemical as well as physical enhancement technologies. This review provides a comprehensive account of the rationale, developments made till date, scope and future prospects of delivering antidepressants via the transdermal1 route of administration.

Although extensive evidence suggests antidepressants are a non-effective treatment for the majority of depressive cases where they are prescribed and despite other developed countries taking steps to provide alternative treatments, Canada's prescription rates continue rising and no state action is being taken. The primary purpose of this study is to explore whether the media in English-speaking Canada, represented by its "newspaper of record," The Globe and Mail, has been performing its essential role in informing Canadians about the controversy surrounding antidepressants and the pharmaceutical system that that has made them central to treating depression. Data was collected in the form of newspaper articles from between 2000 and 2015 in order to analyze media coverage to ensure the essential facts were reported and to qualify to what degree a patient advocacy role challenging the norms of contemporary treatment has been adopted. / February 2017

Major depressive disorder (MDD) is a prevalent and enervating mental illness affecting millions globally. Unfortunately, a significant proportion of patients do not receive clinical benefit from existing antidepressant medications. The limited effectiveness of currently available antidepressant drugs emphasizes the need to identify more effective medications for individuals who are treatment-resistant. We have previously reported abnormally elevated poly (ADP-ribose) polymerase-1 (PARP1) gene expression levels in the postmortem brain from MDD brain donors. PARP1 is a DNA damage repair enzyme that is also linked to neuroinflammation through multiple biochemical pathways. PARP1 upregulation in MDD could indicate a role for this enzyme in the etiopathology of MDD, particularly as it relates to neuroinflammation. In fact, we have shown that drugs that inhibit PARP1 produce antidepressant-like properties in two different rodent behavioral models that mimic depressed mood in humans. In the present study, we utilized a unique rodent behavioral model that produces depressive-like behavior by combining psychological stress with stimulation of inflammation. Depressive behavior produced by this experimental paradigm is not reversed by the prototypical antidepressant fluoxetine. This treatment-resistant depression was elicited by treating rats with injections of lipopolysaccharide (LPS; 0.1 ug/kg/day) and daily exposure to chronic unpredictable stress (CUS) for 28 days. Depressive behaviors were measured with sucrose preference and forced swim tests in 5 treatment groups (n=6-8 rats per group) including unstressed rats, CUS rats, CUS+LPS rats, and CUS+LPS rats treated with either the PARP1 inhibitor 3-aminobenzamide (3AB) or the antidepressant fluoxetine. We evaluated the role of neuroinflammation in this model by measuring the amount of microglial activation in several brain regions in rats from all treatment groups. Microglia activation was measured by quantifying the relative amount of expression of the microglia marker protein, IBA1, using an anti-IBA1 antibody. 3AB demonstrated robust and unique antidepressant activity superior to fluoxetine in the treatment-resistant rat model. IBA1-immunoreactivity levels were elevated in brains from CUS and CUS+LPS rats, although there was no evidence that LPS increased IBA1-immunoreactivity above levels found in CUS rats that did not receive LPS. Levels of IBA1-immunoreactivity in the brains from rats treated with either fluoxetine or 3AB trended lower as compared to the CUS and CUS+LPS groups, although this effect did not reach statistical significance. The lack of significant differences is likely related to small sample sizes; experiments are underway to increase the sample sizes of each group. The findings provide further support for the potential of PARP1 inhibitors in treating MDD and suggest that these drugs may be more effective, or more broadly effective than standard antidepressants.

Rationale Many studies demonstrate down-regulation of the norepinephrine transporter (NET) by desipramine (DMI) in vitro and in stress-naive rats. Little is known regarding regulation of the NET in stressed animals. Objective The present study was designed to investigate effects of DMI on the expression of NET and protein kinases in the stress rat. Methods Adult Fischer 344 rats were subjected to chronic social defeat (CSD) for 4 weeks. DMI (10 mg/kg, intraperitoneal (i.p.)) was administered concurrently with CSD or 1 or 2 weeks after cessation of CSD. Sucrose consumption, NET expression, and protein kinases were measured. Results CSD significantly increased messenger RNA (mRNA) and protein levels of NET in the locus coeruleus, as well as NET protein levels in the hippocampus, frontal cortex, and amygdala. These effects were nearly abolished when DMI was administered concurrently with CSD. CSD-induced upregulation of NET expression in the locus coeruleus, hippocampus, and amygdala lasted at least 2 weeks after cessation of CSD, an effect that was significantly attenuated by 1 or 2 weeks of DMI treatment starting from cessation of the CSD. Concurrent administration of DMI with CSD did not markedly interfere with CSD-induced decreases in protein levels of protein kinases A and C in these brain regions, but it did reverse the CSD-induced reduction in phosphorylated cAMP response element-binding (pCREB) protein levels in most brain regions. Conclusion These findings suggest that NET regulation by DMI occurs in both stressed and behaviorally naive rats, and DMI-induced changes in pCREB may be involved.