There is a paucity of research into pharmacological management of ketamine use disorder. The limited very low-quality evidence suggests benzodiazepine regimens may be most salient for future exploration in management of ketamine intoxication and withdrawal, whereas case reports suggest naltrexone, lamotrigine, and paliperidone palmitate plus bupropion may potentially merit further investigation with regard to craving/relapse prevention. Ketamine has different routes of administration and the most studied for TRD is the intravenous route, the oral, subcutaneous, sublingual and intranasal routes have also been evaluated (28). The oral route has low bioavailability (only 8%) (29), improving up to 24% – 30% with liquid sublingual formulations (30).
Medical uses
A list of studies that appeared to meet the inclusion criteria but were excluded, and reasons for exclusions, are provided in Supplementary Table 1. In light of these findings surrounding ketamine’s psychotherapeutic potential, we systematically review the extant evidence on ketamine’s effects in treating mental health disorders. In the past two decades, subanaesthetic doses of ketamine have been demonstrated to have rapid and sustained antidepressant effects, and accumulating research has demonstrated ketamine’s therapeutic effects for a range of psychiatric conditions. Another study by McGhee and colleagues utilized the PCL-M to determine the diagnosis of PTSD in patients and aimed to determine the prevalence of PTSD in 603 burn patients during their procedure compared to those who did not.11 Two hundred completed the PCL-M and 147 underwent at least one procedure. The reported prevalence was 27% for those receiving ketamine as compared to 46% for those who did not.
Some users also say they feel restless or irritable as their body adjusts to functioning without ketamine. However, recreational ketamine use has significant risks, and the drug can lead to psychological dependence. As a user increases their doses to get the same desired effects, they might develop a dangerous pattern of use that’s hard to break. Ketamine is an anesthetic that’s often used in medical settings to manage pain and, more recently, to treat conditions like depression.
Ketamine was dosed at 0.5mg/kg (based on standard research protocols4, 16), mixed in 500cc of 0.9% normal saline and infused over 40 minutes. For patients with a body-mass index ≥ 30, we initially adjusted the dose based on ideal body weight (see eAppendix 1). During the infusion, blood pressure was monitored at least every 10 minutes, and heart rate and pulse oxygenation were monitored continuously.
Eating disorders
Optimal dosing, modes of administration and the most effective forms of adjunctive psychotherapeutic support should be examined further. The Food and Drug Administration (FDA) recently approved the use of intranasal esketamine for the treatment of TRD (40,41). However, it is important to bear in mind that sedative and dissociative adverse effects are more marked than those described by the use of ketamine (40,41). Although esketamine could currently be considered as a therapeutic option over ketamine in patients with TRD, there is insufficient evidence regarding the optimal dose, duration, and frequency for the expected therapeutic effects. Adverse effects are generally mild and self-limited, although more complex adverse effects require monitoring by experienced personnel. Experimental studies are needed to compare the efficacy and safety of ketamine versus electroconvulsive therapy as the first-line treatment for this entity.
Following the 2nd, 3rd, and 4th infusions, CADSS scores at 40 minutes were 5.86 (SD 6.25), 4.52 (SD 5.03), and 4.53 (SD 7.16), respectively. Following the 2nd, 3rd, and 4th infusions, mean CADSS scores at 70–80 minutes were 0.07 (SD 0.26), 0.04 (SD 0.19), and 0.00 (SD 0.00), respectively. That paper noted that all of these studies were even shorter than the usual trials required by regulators—meaning that there is no evidence for a long-term benefit for the drug. They noted that at the time, he was clear-headed, “cooperative,” and able to converse with them without problems.
Data Availability Statement
Similar to our ECT guidelines, outpatients were not permitted to drive on days of infusion and were discharged to the care of a responsible adult. Criteria for discharge readiness were 1) a return to pre-dose hemodynamic parameters, 2) a CADSS score of 0 (or equal to or below pre-treatment score), and 3) at least 30 minutes of observation following the completion of the infusion. Institutional Review Board granted a waiver of full review for a medical record review. The Veteran’s Administration/Department of Defense currently includes the use of selective serotonin reuptake inhibitors (SSRIs) for use as pharmacotherapy for PTSD.2 The SSRIs included in this recommendation are sertraline and paroxetine. Although SSRIs are one of the primary modes of pharmacotherapy for PTSD, there are many drugs that may also be used.
Data availability
- Some 41.6% (5/12) of the clinical trials will use doses of 0.5 mg / kg intravenously and six studies did not specify the doses used in their intervention.
- Responders had an average of 4.1 ± 0.8 infusions and a significant decrease in their compulsion scores.
- GRADE scoring was appropriate for only a single outcome, and evidence for all reported outcomes deemed very low quality.
- A wealth of evidence indicates the value of ketamine in treating severe pain, including conditions such as trauma, fractures, abdominal and flank pain, low back pain, and extremity pain.
Detoxification, commonly known as detox, refers to the physiological process of eliminating harmful substances from the body. It is the initial step in overcoming addiction and paving the way for a healthier, substance-free life. During detoxification, the body works to metabolize and eliminate the toxins accumulated from prolonged substance abuse. While cravings can become less intense during this time, they may still happen, so ongoing treatment and emotional support are important.
- There is a paucity of research into pharmacological management of ketamine use disorder.
- Since then, human studies have confirmed ketamine’s rapid antidepressant effects in humans (see Sect. 3.1).
- Results of individual studies included in the synthesis were presented in a separate table for each psychiatric diagnosis.
- After psychiatric consultation, signed informed consent (See Supplemental Information) and medical clearance (including basic lab work, urine toxicology, electrocardiogram, and history and physical examination), patients began intravenous infusions.
Likewise, the anesthetic and antidepressant effects were highlighted in subjects who received complementary ECT (23). Self-limited adverse effects were most reported, although more complex reactions such as hallucinations, restlessness, alterations in body perception, time and colors or sounds were also observed (26,27). Despite the growing clinical evidence reviewed below, ketamine is FDA-approved for anesthetic purposes but not for the treatment of psychiatric conditions. Nevertheless, the paradigm shifting nature of ketamine’s effects—with antidepressant response manifesting within hours rather than weeks—furthered the discovery and research of novel compounds with mechanisms of action similar to those of ketamine. Given ketamine’s potential adverse effects—including dissociation, nausea, hypertension, and tachycardia—researchers examined ketamine’s enantiomers in an effort to reproduce its antidepressant effects while reducing adverse effects.
Efficacy and safety of ketamine in the management of anxiety and anxiety spectrum disorders: a review of the literature
This may indicate that S-ketamine and the S-enantiomers are responsible for the negative psychoactive properties of ketamine. Despite clinical evidence supporting ketamine as an effective augmentation strategy, economic considerations present an additional barrier to increased utilisation. While ketamine itself is a generic medication and carries a low unit cost, the interventional nature of administration results in additional expenses that add to the cost of treatment. Off-label use of generic ketamine often costs patients thousands of dollars because of overhead clinic expenses and treatments are rarely covered by insurance. Patients may be eligible for insurance coverage of intranasal esketamine treatment after two failed antidepressant trials, making it the most financially accessible ketamine option for the general population. However, administration of esketamine a potential case of acute ketamine withdrawal: clinical implications for the treatment of refractory depression american journal of psychiatry requires the clinic to enrol in a risk evaluation and mitigation strategy (REMS) programme, requiring adherence to regulations that require increased resources and financially limit administration to settings with high patient throughput.
And, according to the researchers, clinicians don’t yet understand how to treat ketamine withdrawal. There is a relative paucity of literature regarding the use of ketamine to treat PTSD compared to that emerging for use in refractory MDD management. Ketamine’s primary use is by anesthesiologists, certified registered nurse anesthetists, dentists, emergency physicians, pain specialists, psychiatrists, and paramedics; these disciplines need to function as an interprofessional team to optimize the drug’s effectiveness while minimizing the potential for adverse events. All clinicians who administer ketamine should understand the indications and contraindications. Records of clinical trials and publications with empirical data in English and Spanish were included. Initially, patients were treated with a single- or double-infusion protocol (0.5mg/kg over 40 minutes intravenously).
The researchers found that the antidepressant effects of repeated infusions were cumulative, with the severity of depressive symptoms decreasing after each infusion. The 23 participants with a 50% decrease in MADRS score (classified as responders) received four additional weekly infusions; notably, these weekly maintenance infusions were sufficient to maintain the antidepressant effects obtained with repeated infusions. Another double-blind, randomized, placebo-controlled study of twice weekly versus thrice weekly IV ketamine administered over four weeks similarly demonstrated the effectiveness of repeated infusions in maintaining antidepressant effect; no significant difference was seen between the different dosing frequencies 39. In the first double-blind, placebo-controlled human study of ketamine for the treatment of MDD, seven patients received a single intravenous (IV) infusion of ketamine (0.5 mg/kg). Compared to saline infusion, ketamine significantly improved depressive symptoms within 72 h 22. A subsequent, adequately powered, randomized, double-blind, placebo-controlled trial of single-dose IV ketamine infusion (0.5 mg/kg) in 18 individuals with TRD found that, within two hours of infusion, ketamine significantly improved depressive symptoms compared to placebo saline infusion.
