Single, Fixed-Dose Intranasal Ketamine for Alleviation of Acute Suicidal Ideation. An Emergency Department, Trans-Diagnostic Approach: A Randomized, Double-Blind, Placebo-Controlled, Proof-of-Concept Trial.

BACKGROUND: Suicidal patients often present to the emergency department, where specific anti-suicidal treatment is lacking. Ketamine, a Glutamate modulator and a rapidly acting antidepressant with anti-suicidal properties, might offer relief. AIMS: Evaluation of single, fixed-dosed intranasal ketamine for acute suicidal ideation in the emergency department. METHODS: Between August 2016 and April 2018, 30 eligible suicidal subjects, scheduled for psychiatric hospitalization, independently of their psychiatric diagnosis, were randomized to intranasal ketamine 40 mg or saline placebo. Safety and efficacy evaluations were scheduled for 30, 60, 120 and 240 min post administration and on days 1, 2, 3, 4, 5, 7, 21 and 28. Primary outcome was suicidal ideation. RESULTS: Fifteen subjects were randomized for each study group. All were analyzed for primary and secondary outcomes. Four hours post administration, the mean difference in suicidal symptoms between the groups, measured by the Montgomery-Åsberg Depression Rating Scale (MADRS) item of suicidal thoughts (MADRS-SI), was 1.267 (95% confident interval 0.1-2.43, p < 0.05) favoring treatment. Remission from suicidal ideation was evident in 80% for the ketamine group compared with 33% for the controls (p < 0.05). The mean difference in depressive symptoms, measured by MADRS, at the same time was 9.75 (95% confident interval 0.72-18.79, p < 0.05) favoring ketamine. Treatment was safe and well-tolerated. CONCLUSIONS: Single, fixed-dose, intranasal ketamine alleviated suicidal ideation and improved depressive symptoms four hours post administration. We present here an innovative paradigm for emergency department management of suicidal individuals. Future larger-scale studies are warranted. ClinicalTrials.gov Identifier: NCT02183272.

Ketamine for acute suicidal ideation. An emergency department intervention: A randomized, double-blind, placebo-controlled, proof-of-concept trial.

BACKGROUND: Depressed patients presenting to emergency departments with acute suicidal ideation are a major public health concern. Ketamine, a rapidly acting antidepressant with antisuicidal properties, might offer relief. METHODS: In a randomized, double-blind, placebo-controlled, proof-of-concept trial, 18 depressed subjects with acute suicidal ideation, who required hospitalization, were randomized to either an intravenous ketamine 0.2 mg/kg group or a saline placebo group. Safety and efficacy evaluations were scheduled for 15, 30, 60, 90, 120, 180, and 240 min, and on Days 1, 2, 3, 7, and 14 after infusion. The main outcome measure was suicidal ideation with secondary measures of depression. RESULTS: Nine subjects were randomized to each group. There were no differences between groups at baseline in any demographic or assessment scales. A reduction in suicidal ideation was noted at 90-180 min (p < .05). Ninety minutes after infusion, 88% of the ketamine group had achieved remission of suicidal ideation compared with 33% in the placebo group (p < .05). No serious adverse events were noted. CONCLUSIONS: Ketamine was safe and effective for rapid reduction in suicidal ideation in depressed, highly suicidal subjects presenting to the emergency department. Our results support further study of ketamine for acute suicidal ideation.

Repeated oral ketamine for out-patient treatment of resistant depression: randomised, double-blind, placebo-controlled, proof-of-concept study.

BACKGROUND: Ketamine has been demonstrated to improve depressive symptoms.AimsEvaluation of efficacy, safety and feasibility of repeated oral ketamine for out-patients with treatment-resistant depression (TRD). METHOD: In a randomised, double-blind, placebo-controlled, proof-of-concept trial, 41 participants received either 1 mg/kg oral ketamine or placebo thrice weekly for 21 days (ClinicalTrials.gov Identifier: NCT02037503). Evaluation was performed at baseline, 40 and 240 min post administration and on days 3, 7, 14 and 21. The main outcome measure was change in Montgomery-Åsberg Depression Rating Scale (MADRS). RESULTS: Twenty-two participants were randomised to the ketamine group, and 19 to the control, with 82.5% (n = 33) completing the study. In the ketamine group, a decrease in depressive symptoms was evident at all time points, whereas in the control group a decrease was evident only 40 min post administration. The reduction in MADRS score on day 21 was 12.75 in the ketamine group versus 2.49 points with placebo (P < 0.001). Six participants in the ketamine group (27.3%) achieved remission compared with none of the controls (P < 0.05). The number needed to treat for remission was 3.7. Side-effects were mild and transient. CONCLUSIONS: Repeated oral ketamine produced rapid and persistent amelioration of depressive symptoms in out-patients with TRD, and was well tolerated. These results suggest that add-on oral ketamine may hold significant promise in the care of patients suffering from TRD in the community.Declaration of interestNone.

Clinical utility of biomarkers of the hand in the diagnosis of schizophrenia.

A number of biomarkers were assessed in photos and prints of the hands of 95 patients with a variety of mental disorders to determine whether patients with schizophrenia could be distinguished from the others. Patients were recruited as consecutive admissions from an outpatient psychiatric day hospital population. Fourteen patients were diagnosed with schizophrenia/schizoaffective disorder and 81 were diagnosed with other mental disorders. A discriminant analysis yielded an overall 80% correct classification, with a sensitivity (schizophrenia patients identified correctly) of 78.6% and a specificity (non-schizophrenia patients identified correctly) of 80.2%. Significant differences were noted in the proximal interphalangeal joint, eponychium of the middle digit and fingernails. To determine biomarker frequency distribution patients with bipolar disorder were then compared to those with schizophrenia/schizoaffective disorder and then to patients with PTSD. The former yielded an overall 78.6% correct classification, with a sensitivity of 71.4% and a specificity of 85.7% and with similar biomarker frequency distribution for bipolar disorder as for the entire non schizophrenia group. The latter comparison yielded an overall 58.6% correct classification, with no significant differences between the features. The application of these biomarkers in clinical practice could constitute an additional tool for the psychiatrist in cases lacking diagnostic clarity.

Ten Years of Abstinence in Former Opiate Addicts: Medication-Free Non-Patients Compared to Methadone Maintenance Patients.

Fifty-five former opioid addicts who have been methadone maintained patients for 10 or more years and whose urine has tested negative for drugs for 2 or more years were compared to 99 former opioid addicts who have been medication-free for 10 or more years. Groups were comparable in age and education, but the medication-free subjects were younger when having started opioids with more severe addiction scores. Methadone maintained patients presented with a higher proportion of psychiatric comorbidity and chronic pain. Their scores of perceived sleep quality and cognitive state were poorer than the medication-free individuals. Possible explanations of the differences are discussed in this article.

Impact of lifetime psychiatric diagnosis on long-term retention and survival of former opiate addicts in methadone maintenance treatment.

OBJECTIVES: To characterize lifetime psychiatric diagnosis groups among methadone maintenance treatment (MMT) patients and associations of diagnosis to long-term (up to 20 years) retention and survival either during treatment or post discontinuation. METHODS: A total of 758 patients with available psychiatric diagnosis (98% of those ever admitted between June 1993 and June 2012) were followed-up until June 2013. Lifetime psychiatric diagnosis was assessed according to DSM-IV-TR (Axis I, II, I & II, or none). Observed urine samples at 1 and 13 months were positive for drugs if at least one was positive. Survival data were based on the Israel National Population Registry. Survival and retention in MMT were compared (Kaplan Meier) between groups. RESULTS: The Axis II (personality disorders) group had the worst mean long-term retention (5.8 years, 95% Confidence Interval (CI) 5.0-6.5) compared with the Axis I, Axis I & II or no psychiatric diagnosis groups (9.6 years, 95% CI 8.8-10.4) (P < 0.0005). Mean survival since admission (16.4 years, 95% CI 15.9-16.9) was similar for all groups. Axis II patients included more males, more drug injectors, were younger at initial opiate use and more likely left treatment before 1 year. CONCLUSIONS: Personality and coping mechanisms (Axis II) could be significant obstacles to the success of MMT, warranting special interventions to overcome them.

Achievement of take-home dose privileges is associated with better-perceived sleep and with cognitive status among methadone maintenance treatment patients.

OBJECTIVES: Methadone maintenance treatment (MMT) patients may achieve up to a 2-week privilege of methadone take-home doses (THD), which is associated with considerable responsibility. MMT patients are characterized as having poor sleep quality and low cognitive states. We studied sleep indices and cognitive status with respect to THD privileges. METHODS: A sample of 123 MMT patients stratified by THD groups was studied. Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), and the cognitive Clock Drawing Test (CDT) were performed. RESULTS: Thirty-one of 123 patients never had any THD and 92 did (25 had the maximum of 2 weeks). The never THD had history of longer duration of opiate usage and a shorter period in MMT. They had the highest rates of poor sleep (80.6%, PSQI > 5), daily sleepiness ("fall asleep while talking") (41.9%), and impaired cognitive status (58.1%, CDT < 3), while those who had 2-week privileges had the lowest (56, 8, and 28%, respectively). Logistic regression characterized THD patients as no-benzodiazepine and no-cocaine, short opiate usage duration, low ADHD scores, and no cognitive impairment (CDT = 3) and its interaction with treatment duration. CONCLUSION: Privileges that reflect patients' abstinence and rehabilitation were also expanded to be associated with better cognitive states. These finding confirm the THD dispensing performance. Including CDT as part of the decision for dispensing THD may be considered.

Use of intraoperative epiaortic ultrasonography to delineate aortic atheroma.

OBJECTIVE: A cerebrovascular accident (CVA) is a devastating complication of coronary artery bypass grafting (CABG) and a major cause for morbidity and mortality. Aortic manipulation, cannulation, and clamping during CABG may lead to release of atheromatous material from the ascending aorta, which may cause a CVA. This study assessed the hypothesis that the use of intraoperative epiaortic ultrasonography (EAUS) would supplement imaging information with that derived from manual aortic palpation and influence the surgical decision-making approach accordingly. METHODS: After undergoing a mid-sternotomy for CABG, 105 patients underwent EAUS with an 8-MHz transducer ordinarily used for conventional transthoracic echocardiography. The surgical strategy was decided on at three stages: preoperatively, after manual aortic palpation, and following EAUS. RESULTS: The preoperative strategy had assigned 105 patients to the "touched aorta" group that was planned for either on-pump or off-pump CABG (OPCAB) with proximal anastomosis to the aorta. Pathologic lesions of the atheromatotic ascending aorta were evident in 40 patients (38%), with the lesions detected in 22 patients (21%) by both palpation and EAUS, and in 18 patients (17%) by EAUS alone. The planned surgical strategy was changed in 29 patients (28%): 25 patients (24%) were converted from on-pump CABG to OPCAB, and the EAUS influenced the choice of the aortic cannulation, cross-clamping, and proximal anastomosis site in 4 patients (4%). Among the changes in surgical decision making, changes in 11 patients (10%) were based on lesion detection by both manual palpation and EAUS; in 18 patients (17%), changes resulted from pathologic evidence provided by EAUS alone. CONCLUSIONS: This study showed EAUS to be more sensitive in detecting atherosclerotic lesions than manual intraoperative palpation of the ascending aorta. This investigation contributes new data on the effect of EAUS on intraoperative surgical approach in the era of OPCAB. The use of EAUS has emerged as an important tool in intraoperative decision making, and we recommend its use routinely in CABG procedures.