It is safe and effective to use in combination with injectable nonsteroidal pain medications as well as opioids. As concerns about opioid use have grown, it has become more widely accepted.12 The dosage determines the application and resulting effects of the drug, leading to variations in the prescribing protocol. Typical treatment for TRD includes pharmacotherapy, psychotherapy, and stimulation therapies.
Purpose of review
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.
Depressive symptoms in adults with major depressive disorder (MDD) with acute suicidal ideation or behavior
All available evidence in treatment of craving or relapse prevention was of very low quality. Ketamine hydrochloride, commonly known as ketamine, is a medication approved by the United States Food and Drug Administration (FDA) for use as a general anesthetic either on its own or in combination with other medications. Ketamine withdrawal was the likely cause, according to the researchers, especially given the timing and the fact that he was on a high dose that they suddenly stopped giving him. This section collects any data citations, data availability statements, or supplementary materials included in this article. Your email address will be used in order to notify you when your comment has been reviewed by the moderator and in case the author(s) of the article or the moderator need to contact you directly.
- Ketamine has been receiving increasing attention as an interventional treatment modality in psychiatry, especially among refractory conditions, including major depressive disorder.
- Although SSRIs are one of the primary modes of pharmacotherapy for PTSD, there are many drugs that may also be used.
- The rats were restrained for 2 hours, then placed in a cylinder filled with water and forced to swim for 20 minutes; then, after a 15-minute rest period, they were given diethyl ether until they lost consciousness.10 Zhang and colleagues repeated the TDS after a 1-week recovery period.
- As noted, there exists some hesitation for its use based on the fact that it may cause transient dissociation; however, more recent studies suggest that this may not be as frequent as previously thought.
In particular, it may be interesting to examine the extent to which ketamine effects interact with those of other interventions emerging under the banner of psychedelic-assisted psychotherapy. Additionally, included studies were heterogenous in terms of ketamine administration (dose, number, route of delivery), measurement of outcomes, length of follow-up, study design and setting, which reduces comparability. This scoping review mapped the current medical literature regarding the efficacy and safety of ketamine for DRT.
Unipolar depression and MDD
Those who received ketamine often had more significant injuries and a more complicated course of recovery including longer intensive care unit stays and multiple operations and received more morphine. They concluded that ketamine does not increase the prevalence of PTSD and may even decrease it. This may be potentially useful in environments where stressful conditions can be predicted, such as those of soldiers in active combat, who are at risk of stress-related disorders such as PTSD. PTSD has been described as a state of hyperarousal plagued by intrusive thoughts, flashbacks, and nightmares. Given that these intrusive thoughts have been linked to NMDA over activity, animal studies have shown some of the potential anxiolytic properties of NMDA antagonism by using ketamine. Zhang and colleagues conducted an animal study in which mice and rats were subjected to contextual fear to simulate PTSD.10 In this study, rats were subjected to inescapable foot shocks and were subjected to a time-dependent sensitization (TDS).
Four independent reviewers screened the titles and abstracts against the inclusion and exclusion criteria. Before independent screening, the reviewers screened titles and abstracts of 100 papers each to calculate the interrater reliability. During the full-text screening stage, reviewers were trained a potential case of acute ketamine withdrawal: clinical implications for the treatment of refractory depression american journal of psychiatry in using study eligibility forms to ensure consistency. Received 2021 Jun 15; Revised 2021 Sep 30; Accepted 2021 Oct 30; Collection date 2022 Jan.
Suicidal ideation
Randomized trials with ketamine compared to saline placebo may also result in artificially large effect sizes due to functional unblinding because of psychoactive properties of the drug. Compared to samples from prior research trials, our patient sample may also represent a more ill and complicated population. Whereas some research protocols required patients to be hospitalized overnight as part of the research protocol,1, 29 the hospitalized patients from our sample were admitted for clinical reasons of suicide risk or inability to function. Nonetheless, in this sample of complicated and severely ill patients (55.1% who had failed or not tolerated ECT and 38.9% who were inpatients), we feel a 50% response rate within 2 weeks of treatment is a significant outcome. Preliminary data from a small number of completed studies in cocaine, opioid, and alcohol use disorders suggest that ketamine may be useful in treating substance use disorders (reviewed in 60). Another recent, double-blind, placebo-controlled, phase 2 study of 96 individuals with severe alcohol use found that three ketamine infusions (0.8 mg/kg) per week significantly increased the number of days abstinent at three and six months compared to placebo.
He had a history of intermittent cannabis use prior to beginning treatment though this was not disclosed. Upon discovery of his use, further ketamine treatments were contingent upon his abstinence, which he was not able to maintain. Among the full sample, the majority of patients (96.3%) were taking one or more psychotropic medications (eAppendix 3).
- Only very low-quality evidence of efficacy and tolerability was available for any pharmacological intervention in the treatment of ketamine use disorder.
- Ketamine is highly effective for brief medical procedures that do not necessitate skeletal muscle relaxation and can be utilized as a pre-anesthetic for the induction of general anesthesia when combined with other general anesthetic agents.
- In addition, a growing literature has implicated the role of inflammation in MDD, and ketamine’s anti-inflammatory properties have thus gained increased consideration as another mechanism potentially underlying its antidepressant effects 15.
- Approximately one-third of individuals with major depressive disorder are resistant to conventional antidepressants (i.e., monoamine-based therapies), and, even among respondents, a proper therapeutic effect may require weeks of treatment.
- 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.
Similar differences have been in the use of cross-over studies (within participants) or between-participant designs. The merit of the former is the ability to observe effects in the same participants, thus negating the issue of pre-existing group difference, but it can be confounded by persisting treatment and order effects. Similarly, with studies where participants all take part in both arms, this can compound blinding issues even where participants are given active placebos. Upon reviewing the literature, we would recommend the use of active placebos where possible, in between-participant designs. During the first few days after stopping ketamine, a person might start experiencing initial withdrawal symptoms like anxiety, intense drug cravings and trouble sleeping.
Acute and longer-term outcomes using ketamine as a clinical treatment at the Yale Psychiatric Hospital
Further evidence is needed to better understand ketamine’s safety profile over longer periods of time, and its use should continue to be reserved for patients who have failed to respond to multiple existing treatment options. In the 1960s, scientists synthesized a series of short-acting derivatives of PCP, including a compound known as ketamine. Compared to the problematic and prolonged effects on mental status seen with PCP, ketamine had a shorter duration of action and was less potent.3 In 1970, ketamine was approved by the FDA for use in humans. This rapid relief of symptoms makes ketamine a suitable potential candidate for various clinical situations, including preventing or shortening hospital stays, treating acute suicidal ideation, and facilitating medication crossovers. Patients were instructed to fast for approximately 8 hours (starting at midnight) prior to each infusion. Upon the patient’s arrival to the treatment suite, baseline blood pressure, heart rate, pulse oxygenation, respiratory rate, and temperature were recorded and a peripheral intravenous (IV) catheter inserted.