https://www.thelancet.com/pdfs/journals/lanpsy/PIIS2215-0366(17)30272-9.pdf

Side-effects associated with ketamine use in depression: a systematic review

Objective: Narrative review of the literature on the efficacy and safety of subanaesthetic doses of ketamine for the treatment of depression. Method: Medline and PubMed databases were searched up to October 2012 using appropriate keywords. Results: The studies consistently report substantial efficacy with high response and remission rates from 4 to 72 hours (averages 77% and 43%, respectively) from single doses, though not all patients respond to ketamine. Early relapse is common. While the usual procedure involves the administration of intravenous ketamine at a dose of 0.5 mg/kg over 40 minutes, some preliminary evidence suggests other dosing regimens and routes of administration may be useful or even better. Repeated doses and maintenance pharmacological treatments have been investigated in order to prolong the antidepressant effects, with only modest success. Conclusions: Current research on the antidepressant effects of ketamine has consistently shown rapid and substantial improvement in mood in the majority of patients. However, these effects have often been found to be short-lived. Future research should focus on identifying predictors of response (e.g. clinical, genetic, pharmacokinetic, environmental), examining different dosing regimens and routes of administration, and strategies to maintain the antidepressant response.

/pdf/ketamine-as-a-new-treatment-for-depression-a-review-of-its-45v3peog72.pdf

Ketamine as a new treatment for depression: A review of its efficacy and adverse effects:

Objective

To investigate the suburothelial inflammation and urothelial dysfunction that occurs with ketamine-related cystitis (KC) and interstitial cystitis/bladder pain syndrome (IC/BPS).




Patients and Methods

Bladder tissues from 16 patients with KC, 17 patients with IC/BPS and 10 control subjects were analysed.
Immunofluorescence staining of the junction protein E-cadherin was carried out, and tryptase levels and a TUNEL assay were used to assess mast-cell activation and urothelial apoptosis, respectively.
The fluorescence intensity of E-cadherin was measured using the ImageJ method. The percentages of activated mast cells and apoptotic cells were calculated as positive cells per unit area (4 μm2).




Results

The mean (sd) ages of the patients in the KC, IC/BPS and control groups were 25.0 (3.8), 41.3 (13.7) and 50.5 (9.6) years, respectively (P < 0.05).
The mean (sd) distributions of E-cadherin in KC (10.1 [11.2]) and IC/BPS (25.1 [16.3]) tissues were significantly lower than in the control tissues (42.4 [16.7]; both P < 0.05).
The mean (sd) number of activated mast cells, measured by tryptase signals in the KC (6.5 [3.7]) and IC/BPS (4.6 [3.0]) tissues, were significantly higher than in the control tissues (1.3 [1.12]; both P < 0.05).
TUNEL staining showed a significantly higher mean (sd) number of apoptotic cells in KC (4.4 [2.5]) and IC/BPS (2.4 [1.7]) tissues than in control tissues (0.1 [0.3]; both P < 0.05).
Tissues from the KC bladders had significantly lower expression of E-cadherin (P = 0.024) and significantly higher numbers of apoptotic cells (P = 0.02) compared with the IC/BPS bladder tissues.
Greater numbers of apoptotic cells and lower expression levels of E-cadherin significantly correlated with maximum bladder capacity in the overall patient samples (P < 0.05).




Conclusions

KC and IC/BPS tissues both showed defective junction protein, increased suburothelial inflammation and increased urothelial cell apoptosis.
Decreased expression of E-cadherin and increased apoptosis were more severe in KC than in IC/BPS bladder tissues and these findings were associated with the clinical symptoms of KC and IC/BPS.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/bju.12256

Increased apoptosis and suburothelial inflammation in patients with ketamine‐related cystitis: a comparison with non‐ulcerative interstitial cystitis and controls

Ketamine is a relatively new recreational drug used by youngsters in recent decades. Its toxic effects on the genitourinary system were first reported in 2007, and now attract extensive attention from urologists, pharmacologists, and toxicologists all over the world. As many front-line health professionals and medical social workers are still unaware of this new clinical entity and an increasing number of the drug users seek help for urological symptoms, this mini-review aimed to summarise the clinical features and possible mechanisms of ketamine-induced genitourinary toxicity. By raising public awareness of these toxic effects, the authors hope that the contents of this review will be widely disseminated not only to medical professionals, but also to relevant government departments and the general public.

/pdf/genitourinary-toxicity-of-ketamine-1qq4ku56z5.pdf

Genitourinary toxicity of ketamine.

Ketamine is a popular choice for young drug abusers. Ketamine abuse causes lower urinary tract symptoms, with the underlying pathophysiology poorly understood. Disruption of urothelial barrier function has been hypothesized to be a major mechanism for ketamine cystitis, yet the direct evidence of impaired urothelial barrier function is still lacking. To address this question, 8-wk-old female C57BL/6J mice were injected intraperitoneally with 30 mg·kg(-1)·day(-1) ketamine for 12 wk to induce ketamine cystitis. A spontaneous voiding spot assay showed that ketamine-treated mice had increased primary voiding spot numbers and smaller primary voiding spot sizes than control mice (P < 0.05), indicating a contracted bladder and bladder overactivity. Consistently, significantly increased voiding frequency was observed in ketamine-treated mice on cystometrograms. These functional experiments indicate that ketamine induces voiding dysfunction in mice. Surprisingly, urothelial permeability in ketamine-treated mice was not changed when measured using an Ussing chamber system with isotopic urea and water. Mouse urothelial structure was also not altered, and intact umbrella cell structure was observed by both transmission and scanning electron microscopy. Furthermore, immunostaining and confocal microscopy confirmed the presence of a well-defined distribution of zonula occuldens-1 in tight junctions and uroplakin in umbrella cells. In conclusion, these data indicate that ketamine injection induces voiding dysfunction in mice but does not necessarily disrupt mouse bladder barrier function. Disruption of urothelial barrier function may not be the major mechanism in ketamine cystitis.

https://www.physiology.org/doi/pdf/10.1152/ajprenal.00483.2015

Intact urothelial barrier function in a mouse model of ketamine induced voiding dysfunction

Ketamine can be abused as a recreational drug, and there has been a
recent surge in its usage. The effects of ketamine on the urinary
system were unknown until the recent publication of a few case reports.
Many doctors are still unaware of this new clinical entity, termed
ketamine-associated ulcerative cystitis. We report a case that we
encountered and discuss the diagnosis and disease management in
addition to a review of the literature.

/pdf/ketamine-associated-ulcerative-cystitis-a-case-report-and-30izwawgny.pdf

Zulkifli Mz

Papers

Ketamine-associated ulcerative cystitis: a case report and literature review.