Acute and Longer-Term Outcomes Using Ketamine as a Clinical Treatment at the Yale Psychiatric Hospital

Wilkinson, Samuel T.; Katz, Rachel; Toprak, Mesut; Webler, Ryan; Ostroff, Robert; Sanacora, Gerard

doi:10.4088/jcp.17m11731

Cited by 59 publications

(43 citation statements)

References 32 publications

(38 reference statements)

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“…The recent resurgence of clinical interest in the use of psychedelics for the treatment of mental disorders is evidenced by a sharp increase in studies and publications. After a decadeslong research hiatus, psychedelics have been investigated as potentially effective treatments for several mental disorders, including substance use disorders (SUDs) [1][2][3][4]; post-traumatic stress disorder (PTSD) [5][6][7][8][9][10]; anxiety, and depression secondary to a life-threatening illness [11][12][13][14]; social anxiety in autistic adults [15]; obsessive-compulsive disorder (OCD) [16]; depression [17][18][19][20][21][22]; and suicidal ideation [23]. Psychedelic drugs include a range of…”

Section: Introductionmentioning

confidence: 99%

Psychedelic Treatments for Psychiatric Disorders: A Systematic Review and Thematic Synthesis of Patient Experiences in Qualitative Studies

et al. 2020

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Introduction Interest in the use of psychedelic substances for the treatment of mental disorders is increasing. Processes that may affect therapeutic change are not yet fully understood. Qualitative research methods are increasingly used to examine patient accounts; however, currently, no systematic review exists that synthesizes these findings in relation to the use of psychedelics for the treatment of mental disorders. Objective To provide an overview of salient themes in patient experiences of psychedelic treatments for mental disorders, presenting both common and diverging elements in patients' accounts, and elucidating how these affect the treatment process. Methods We systematically searched the PubMed, MEDLINE, PsycINFO, and Embase databases for English-language qualitative literature without time limitations. Inclusion criteria were qualitative research design; peer-reviewed studies; based on verbalized patient utterances; and a level of abstraction or analysis of the results. Thematic synthesis was used to analyze and synthesize results across studies. A critical appraisal of study quality and methodological rigor was conducted using the Critical Appraisal Skills Programme (CASP). Results Fifteen research articles, comprising 178 patient experiences, were included. Studies exhibited a broad heterogeneity in terms of substance, mental disorder, treatment context, and qualitative methodology. Substances included psilocybin, lysergic acid diethylamide (LSD), ibogaine, ayahuasca, ketamine and 3,4-methylenedioxymethamphetamine (MDMA). Disorders included anxiety, depression, eating disorders, post-traumatic stress disorder, and substance use disorders. While the included compounds were heterogeneous in pharmacology and treatment contexts, patients reported largely comparable experiences across disorders, which included phenomenological analogous effects, perspectives on the intervention, therapeutic processes and treatment outcomes. Comparable therapeutic processes included insights, altered self-perception, increased connectedness, transcendental experiences, and an expanded emotional spectrum, which patients reported contributed to clinically and personally relevant responses. Conclusions This review demonstrates how qualitative research of psychedelic treatments can contribute to distinguishing specific features of specific substances, and carry otherwise undiscovered implications for the treatment of specific psychiatric disorders.

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Section: Introductionmentioning

confidence: 99%

Psychedelic Treatments for Psychiatric Disorders: A Systematic Review and Thematic Synthesis of Patient Experiences in Qualitative Studies

et al. 2020

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“…Retrospective case series have reported benefit from ongoing maintenance ketamine given at varying intervals for longer durations. 91,92 Acute dissociative effects have been reported to be more mild or noted to dissipate with repeated infusions during maintenance. 46 Anecdotal reports suggest that some patients may be able to transition to intranasal or sublingual formulations of racemic ketamine for maintenance after ketamine infusions.…”

Section: Resultsmentioning

confidence: 99%

“…98 However, single and repeated infusions of ketamine as an antidepressant have not been associated with changes in performance on neurocognitive tasks, 99,100 and there are no reports of excessive urinary symptoms in placebo-controlled trials or maintenance studies of ketamine for TRD. 47,91 Nevertheless, these remain possible long-term side effects of ketamine.…”

Section: Resultsmentioning

confidence: 99%

The Canadian Network for Mood and Anxiety Treatments (CANMAT) Task Force Recommendations for the Use of Racemic Ketamine in Adults with Major Depressive Disorder: Recommandations Du Groupe De Travail Du Réseau Canadien Pour Les Traitements De L’humeur Et De L’anxiété (Canmat) Concernant L’utilisation De La Kétamine Racémique Chez Les Adultes Souffrant De Trouble Dépressif Majeur

et al. 2020

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Objective: Patients with major depressive disorder often have limited response to first-line and second-line medications; hence, novel pharmacological treatments are needed for treatment-resistant depression (TRD). Ketamine, an N-methyl-d-aspartate (NMDA) receptor antagonist, has demonstrated rapid antidepressant effects in patients with TRD. The Canadian Network for Mood and Anxiety Treatments (CANMAT) convened a task force to review the evidence for efficacy and safety of racemic ketamine and to provide recommendations for its use in clinical practice. Methods: A systematic review was conducted with computerized search of electronic databases up to January 31, 2020 using combinations of search terms, inspection of bibliographies, and review of other ketamine guidelines and consensus statements. The level of evidence and lines of treatment were assigned according to CANMAT criteria. Recommendations were given in question–answer format. Results: Intravenous (IV) racemic ketamine given as a single infusion has Level 1 evidence for efficacy in adults with TRD. The evidence for multiple infusions, given as an acute series or as ongoing maintenance treatment, is limited to Level 3. Adverse events associated with ketamine infusions include behavioral (e.g., dissociative symptoms) and physiological (e.g., hypertension) events. There is only Level 3 or 4 evidence for non-IV formulations of racemic ketamine. Consensus recommendations are given for clinical administration of IV ketamine including patient selection, facility and personnel issues, monitoring, and maintaining response. Conclusions: Single-dose IV racemic ketamine is a third-line recommendation for adults with TRD. The need for repeated and maintenance ketamine infusions should be carefully assessed on a case-by-case basis with consideration of potential risks and benefits. Because of limited evidence for efficacy and risk for misuse and diversion, the use of oral and other formulations of racemic ketamine should be limited to specialists with ketamine-prescribing expertise and affiliations with tertiary or specialized centers.

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“…They found no serious adverse events. Wilkinson et al [ 23 ] described 14 patients who received 12‒45 ketamine infusions (0.5 mg/kg over 40 min) over 14‒126 weeks. Aside from a small number of patients ( n = 4) who had a transient increase in BP during some of their infusions, they witnessed no significant adverse events, and concluded that “Ketamine treatment was generally well tolerated in patients who received infusions on a long-term basis.” Phillips et al [ 24 ] conducted a study of 41 subjects with treatment-resistant depression, who received single blinded infusions of ketamine and midazolam, followed by six open-label ketamine infusions administered thrice weekly for two weeks, followed by another four weekly infusions.…”

Section: Resultsmentioning

confidence: 99%

Safety of Repeated Administration of Parenteral Ketamine for Depression

2020

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The objective of this study was to investigate the safety of repeated parenteral ketamine for depression. An electronic survey inquiring about the frequency of adverse events was distributed to providers of parenteral ketamine for depression. In addition, the investigators conducted a search of published studies describing six or more repeated parenteral ketamine treatments administered to individuals for depression, and extracted reported adverse events. The survey was sent to 69 providers, of which 36 responded (52% response rate); after eliminating those that were incomplete, 27 were included in the analysis. The providers in the analysis collectively reported treating 6630 patients with parenteral ketamine for depression, one-third of whom received more than 10 treatments. Only 0.7% of patients experienced an adverse effect that required discontinuation of ketamine. Psychological distress during the treatment was the most frequent cause. Other adverse events were extremely rare (such as bladder dysfunction (0.1%), cognitive decline (0.03%) and psychotic symptoms (0.03%)). Among the 20 published reports of repeated parenteral ketamine treatments, rates of significant adverse events resulting in discontinuation were low (1.2%). The rate of adverse effects reported in the survey and the published literature is low, and suggests that long-term treatment of depression with ketamine is reasonably safe.

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Acute and Longer-Term Outcomes Using Ketamine as a Clinical Treatment at the Yale Psychiatric Hospital

Cited by 59 publications

References 32 publications

Psychedelic Treatments for Psychiatric Disorders: A Systematic Review and Thematic Synthesis of Patient Experiences in Qualitative Studies

Psychedelic Treatments for Psychiatric Disorders: A Systematic Review and Thematic Synthesis of Patient Experiences in Qualitative Studies

Safety of Repeated Administration of Parenteral Ketamine for Depression

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