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Is Ketamine the Future Clozapine for Depression? A Case Series and Literature Review on Maintenance Ketamine in Treatment-resistant Depression With Suicidal Behavior

Chan LF, Eu CL, Soh SY, Maniam T, Shahidii Kadir Z, Chong BTW, et al.

J Psychiatr Pract, 2018 07;24(4):279-291.
PMID: 30427812 DOI: 10.1097/PRA.0000000000000316

Ketamine has shown effectiveness as a rapid-acting antidepressant with antisuicidal effects in terms of reduction of suicidal ideation in the short term. However, the evidence for long-term maintenance ketamine therapy for treatment-resistant depression (TRD) and suicidal behavior is limited. This case series (N=13) highlights the role of adjunctive serial maintenance ketamine infusions in restoring functionality in treatment-resistant unipolar and bipolar (mixed) depression with significant suicide risk and multiple comorbidities, including alcohol dependence. Two cases of TRD achieved functional remission with long-term maintenance ketamine treatment. The first case illustrates the potential synergistic interaction between ketamine and lamotrigine to achieve a sustained antidepressant response in the patient for 7 months. The second case may possibly be the longest reported case of maintenance ketamine therapy, with treatment continuing for 5 years to date. Ketamine treatment showed acute effectiveness in another 7 cases, especially in terms of reduction of suicidal ideation, albeit without significant long-term antidepressant effect. Factors that may contribute to lack of effectiveness of serial ketamine include inadequate mood stabilization in TRD in bipolar spectrum diagnoses, concomitant benzodiazepine use, complex comorbidities, and adverse effects such as significant hypertension and severe dissociation. Future systematic controlled studies are warranted to establish the efficacy and safety profile of long-term ketamine as maintenance therapy for TRD with suicidal behavior.

Matched MeSH terms: Ketamine/administration & dosage*
Erectile Dysfunction among People Who Use Ketamine and Poly-Drugs

Suppiah B, Vicknasingam B, Singh D, Narayanan S

J Psychoactive Drugs, 2016 Apr-Jun;48(2):86-92.
PMID: 27014841 DOI: 10.1080/02791072.2016.1156790

Despite the rise in recreational use of ketamine in Malaysia, there have been no studies of users or of the health-related consequences they face. This study was initiated to examine ketamine use and its health consequences. A structured questionnaire was used to elicit information. A final sample of 127 males was divided into persons who used only ketamine and those who were poly-drug users. Each group was further divided into long-period and short-period users. Urine toxicology screening for ketamine and other illicit drugs commonly used in Malaysia was also done. Our findings corroborate those of earlier studies that link ketamine use to urological problems such as frequent urination, dysuria, incontinence, painful bladder, nocturia, and urinary urgency. A new finding in this study is the significant association between ketamine use and erectile dysfunction, such that higher odds of reporting erectile dysfunction were linked to long-period users. Our findings strengthen the case for early intervention, as ketamine users are drawn from young and unmarried male participants. The association of ketamine use with erectile dysfunction, if substantiated, will help physicians in their diagnosis of erectile dysfunction, particularly among youths.

Matched MeSH terms: Ketamine/administration & dosage
Fulltext Chemical immobilization of free-ranging and captive Sunda clouded leopards (Neofelis diardi) with two anesthetic protocols: medetomidine-ketamine and tiletamine-zolazepam

Nájera F, Hearn AJ, Ross J, Ramírez Saldivar DA, Evans MN, Guerrero-Sánchez S, et al.

J Vet Med Sci, 2017 Nov 17;79(11):1892-1898.
PMID: 28904261 DOI: 10.1292/jvms.17-0259

There is currently no available information regarding the veterinary management of Sunda clouded leopards (Neofelis diardi), either in captivity or in the wild. In this study, 12 Sunda clouded leopards were anesthetized between January 2008 and February 2014 for medical exams, and/or GPS-collaring. Seven wild-caught individuals were kept in captivity and 5 free-ranging animals were captured by cage traps. Two anesthesia combinations were used: medetomidine-ketamine (M-K) or tiletamine-zolazepam (T-Z). Atipamezole (0.2 mg/kg im) was used as an antagonist for medetomidine. Medetomidine (range: 0.039-0.054 mg/kg) and ketamine (range: 3-4.39 mg/kg) were administered during 5 immobilizations, resulting in median induction times of 7 min. After a median anesthesia time of 56 min, atipamezole was injected, observing effects of antagonism at a median time of 12 min. T-Z (range: 6.8-10.8 mg/kg) was administered on 7 occasions. Median induction times observed with this combination were shorter than with M-K (4 min vs 7 min; P=0.04), and anesthesia and recovery times were significantly longer (244 and 35 min vs 56 and 16 min, respectively; P=0.02). Lower heart rates were measured in the M-K group, while lower rectal temperatures were found in the T-Z group. Both combinations resulted in safe and reliable immobilizations, although given the favorable anesthesia and recovery times of M-K, we recommend this approach over T-Z for the veterinary handling of Sunda clouded leopards.

Matched MeSH terms: Ketamine/administration & dosage*
Evaluation of anaesthetic and cardiorespiratory effects after intramuscular administration of alfaxalone alone, alfaxalone-ketamine and alfaxalone-butorphanol-medetomidine in common marmosets (Callithrix jacchus)

Miyabe-Nishiwaki T, Miwa M, Konoike N, Kaneko A, Ishigami A, Natsume T, et al.

J Med Primatol, 2020 12;49(6):291-299.
PMID: 32654222 DOI: 10.1111/jmp.12482

BACKGROUND: Anaesthesia is often required in common marmosets undergoing various procedures. The aim of this study was to evaluate anaesthetic and cardiopulmonary effects of alfaxalone, alfaxalone-ketamine and alfaxalone-butorphanol-medetomidine in common marmosets.
METHODS: The following treatments were repeatedly administered to seven female common marmosets: Treatment A, alfaxalone (12 mg kg-1 ) alone; treatment AK, alfaxalone (1 mg animal-1 ) plus ketamine (2.5 mg animal-1 ); treatment AMB, alfaxalone (4 mg kg-1 ), medetomidine (50 µg kg-1 ) plus butorphanol (0.3 mg kg-1 ); and treatment AMB-Ati, AMB with atipamezole at 45 minutes.
RESULTS AND CONCLUSIONS: Marmosets became laterally recumbent and unresponsive for approximately 30 minutes in A and AK and for approximately 60 minutes in AMB. The animals showed rapid recovery following atipamezole injection in AMB-Ati. The decrease in heart rate and SpO2 was significantly greater in AMB compared to A and AK. Oxygen supplementation, anaesthetic monitors and atipamezole should be available especially when AMB is administered.

Matched MeSH terms: Ketamine/administration & dosage*
Ketamine and xylazine combinations for short-term immobilization of wild variable flying foxes (Pteropus hypomelanus)

Sohayati AR, Zaini CM, Hassan L, Epstein J, Siti Suri A, Daszak P, et al.

J. Zoo Wildl. Med., 2008 Dec;39(4):674-6.
PMID: 19110718

Collection of biological samples from pteropid bats requires chemical restraint of the bats to minimize risks to humans and stress to the bat. The effectiveness of an intravenous combination of ketamine and xylazine for short-term restraint of wild-caught variable flying foxes (Pteropus hypomelanus) in a field situation was evaluated. Eight adult male variable flying foxes were injected intravenously with 0.1 ml of ketamine and xylaxine containing 5 mg of ketamine and 1 mg of xylazine. The mean induction time was 80 +/- 20 sec, and mean immobilization time was 26 +/- 10 min. The ketamine-xylazine combination used in this study produced effective short-term immobilization of wild variable flying foxes for the collection of biological samples.

Matched MeSH terms: Ketamine/administration & dosage*
Fulltext Esketamine Nasal Spray Plus Oral Antidepressant in Patients With Treatment-Resistant Depression: Assessment of Long-Term Safety in a Phase 3, Open-Label Study (SUSTAIN-2)

Wajs E, Aluisio L, Holder R, Daly EJ, Lane R, Lim P, et al.

J Clin Psychiatry, 2020 04 28;81(3).
PMID: 32316080 DOI: 10.4088/JCP.19m12891

OBJECTIVE: To evaluate long-term safety and efficacy of esketamine nasal spray plus a new oral antidepressant (OAD) in patients with treatment-resistant depression (TRD).
METHODS: This phase 3, open-label, multicenter, long-term (up to 1 year) study was conducted between October 2015 and October 2017. Patients (≥ 18 years) with TRD (DSM-5 diagnosis of major depressive disorder and nonresponse to ≥ 2 OAD treatments) were enrolled directly or transferred from a short-term study (patients aged ≥ 65 years). Esketamine nasal spray (28-mg, 56-mg, or 84-mg) plus new OAD was administered twice a week in a 4-week induction (IND) phase and weekly or every-other-week for patients who were responders and entered a 48-week optimization/maintenance (OP/MAINT) phase.
RESULTS: Of 802 enrolled patients, 86.2% were direct-entry and 13.8% were transferred-entry; 580 (74.5%) of 779 patients who entered the IND phase completed the phase, and 150 (24.9%) of 603 who entered the OP/MAINT phase completed the phase. Common treatment-emergent adverse events (TEAEs) were dizziness (32.9%), dissociation (27.6%), nausea (25.1%), and headache (24.9%). Seventy-six patients (9.5%) discontinued esketamine due to TEAEs. Fifty-five patients (6.9%) experienced serious TEAEs. Most TEAEs occurred on dosing days, were mild or moderate in severity, and resolved on the same day. Two deaths were reported; neither was considered related to esketamine. Cognitive performance generally either improved or remained stable postbaseline. There was no case of interstitial cystitis or respiratory depression. Treatment-emergent dissociative symptoms were transient and generally resolved within 1.5 hours postdose. Montgomery-Åsberg Depression Rating Scale total score decreased during the IND phase, and this reduction persisted during the OP/MAINT phase (mean [SD] change from baseline of respective phase to endpoint: IND, -16.4 [8.76]; OP/MAINT, 0.3 [8.12]).
CONCLUSIONS: Long-term esketamine nasal spray plus new OAD therapy had a manageable safety profile, and improvements in depression appeared to be sustained in patients with TRD.
TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02497287.

Matched MeSH terms: Ketamine/administration & dosage
Dexmedetomidine and ketamine sedation for dental extraction in children with cyanotic heart disease

Hasan MS, Chan L

J Oral Maxillofac Surg, 2014 Oct;72(10):1920.e1-4.
PMID: 24985961 DOI: 10.1016/j.joms.2014.03.032

Treating children with cyanotic congenital heart disease poses many challenges to anesthesiologists because of the multiple problems associated with the condition. The anesthetic technique and drugs used perioperatively can affect a patient's physiologic status during surgery. The adherence to certain hemodynamic objectives and the avoidance of factors that could worsen the abnormal cardiopulmonary physiology cannot be overemphasized. In the present case series, we describe the use of a dexmedetomidine-ketamine combination for dental extraction in spontaneously breathing children with cyanotic congenital heart disease. The anesthetic concerns regarding airway management, the pharmacologic effects of drugs, and maintenance of adequate hemodynamic, blood gases, and acid-base status are discussed.

Matched MeSH terms: Ketamine/administration & dosage*