How Do People Who Undergo Ketamine Treatment for a Psychiatric Problem Subjectively Experience This Intervention? A Meta‐Synthesis of Qualitative Studies

ABSTRACT

Ketamine treatment has shown promising effects for different mental disorders. Yet, little is known on how people who receive ketamine for a psychiatric problem subjectively experience undergoing this intervention. We conducted a systematic literature search to identify relevant qualitative research on the first‐person experience of undergoing ketamine treatment in a psychiatric context. 24 eligible studies were identified and analysed using a thematic meta‐synthesis approach. Three main themes were identified. First, ‘The Ketamine treatment experience can be understood as a three‐stage journey with unique clinical features at each stage’. Second, ‘The subjective experience of acute ketamine treatment is multifaceted and complex’. Third, ‘Ketamine treatment can have different positive effects—but what happens if it does not work?’. In summary, the subjective experience of receiving ketamine treatment for a psychiatric problem can be understood as a journey whereby patients move towards, then undergo, and eventually depart from ketamine. Before treatment, the experiential focus lies on expectations, hopes, and feelings towards the drug. During treatment, the drug's multifaceted psychotropic effects and how they are emotionally appraised become central to experience. Once treatment is finished, the focus is on the presence or absence of clinically relevant effects. The conceptual framework we propose can guide further qualitative research on this topic and aid mental health professionals to better understand the experience of patients who undergo ketamine treatment for a psychiatric problem.

1. Introduction

In the last 2 decades, ketamine's therapeutic potential for different psychiatric disorders has attracted considerable clinical and research attention. There is now a solid corpus of literature demonstrating rapid antidepressant (Alnefeesi et al. 2022; Johnston et al. 2023; Martinotti et al. 2022; Nikolin et al. 2023) and antisuicidal effects (Bartoli et al. 2017; Phillips et al. 2020; Wilkinson et al. 2018; Witt et al. 2020) for ketamine. Furthermore, in the United States and Europe, esketamine has been approved by regulatory bodies for treatment‐resistant depression and acute suicidality related to depression (Johnston et al. 2023). Preliminary evidence suggests that ketamine could also be clinically useful in other mental health problems, including substance use disorders, posttraumatic stress disorder, obsessive–compulsive disorder, anxiety disorders and eating disorders (Bandeira et al. 2022; Feder et al. 2014; Glue et al. 2017; Ivan Ezquerra‐Romano et al. 2018; Keeler et al. 2021). In addition, innovative clinical approaches combining ketamine treatment with psychological interventions have been described, some with promising early results (Drozdz et al. 2022; Joneborg et al. 2022; Kew et al. 2023; Philipp‐Muller et al. 2023). Potential mechanisms of action, through which ketamine could exert its clinical effects, have been described on various levels of neuroscientific description, including effects on the glutamatergic as well as other neurotransmitter systems (Hess et al. 2022; Johnston et al. 2023), on synaptogenesis and neuroplasticity (Kopelman et al. 2023; Xu et al. 2021), and on the way in which new information is used to change beliefs about the world and oneself (Bottemanne et al. 2022).

While a considerable number of studies now exists on the clinical and physiological effects of ketamine in the context of psychiatric disorders, comparatively little research has been dedicated to understanding the subjective experience of the people who receive this treatment. Studying the first‐person perspective on ketamine treatment, however, is important, not only for developing a nuanced and comprehensive understanding of what it means for a person to undergo this intervention (e.g., in terms of expectations, subjective clinical effects and side effects), but also for getting a better grasp of aspects that might be improved about current treatment protocols (e.g., patient preparation, treatment administration, treatment setting, clinical support and unmet patient needs). Qualitative research approaches focusing on the subjective experience of individuals undergoing ketamine treatment can be helpful in charting this area of enquiry.

We conducted a systematic literature search and a thematic meta‐synthesis to identify and analyse currently available qualitative studies on the first‐person perspective of people undergoing ketamine treatment for a psychiatric problem. We deliberately focused on clinically relevant information that can potentially be used to further develop and improve the therapeutic use of ketamine in psychiatry.

2. Methods

2.1. Study Design

We conducted a systematic literature search and qualitative meta‐synthesis to answer the research question ‘How do individuals who receive ketamine (or its enantiomer esketamine) for a psychiatric problem subjectively experience undergoing this treatment?’. Relevant published qualitative studies were identified based on predefined inclusion and exclusion criteria. All selected studies were analysed utilising a thematic meta‐synthesis approach, enabling us to identify patterns of information that were recurrent and/or inherently relevant to our research question. Note that ‘ketamine treatment’ here is used as an umbrella term for treatment with either racemic ketamine or esketamine.

2.2. Literature Search and Data Analysis

A primary comprehensive literature search was conducted using the PubMed search engine and a combination of different search terms (see Table S1 for a list of all search terms used). Search results included all PubMed records available up to November 2023. In addition, we ran complementary searches in PsycInfo (via Ovid) and Embase, using the same search terms and time limits as for PubMed. A total of 3374 records were identified following database searching and were imported into the literature management program Zotero. After deduplication, 2676 items remained. Their titles and abstracts were independently screened by two researchers (M.T. and A.R.) for eligibility, following predefined inclusion and exclusion criteria (see Table S2 for a detailed list of these criteria). In case of disagreement, a third researcher (A.K.) was consulted to reach a decision. Briefly, we included original qualitative studies, published in English or German, that investigated the subjective experience of ketamine treatment (via any route of administration), for a clinically confirmed or self‐reported psychiatric disorder, in people aged 18 or older. Case reports/series were also included if they contained qualitative data on the first‐person experience of ketamine treatment. Qualitative studies dealing with ketamine treatment primarily for non‐psychiatric indications, entirely outside a medical context, or in healthy people were excluded. Studies were also excluded if they reported no primary qualitative data, if subjective experiences of ketamine treatment were not reported in an extractable manner, and if solely clinical outcomes and observations were reported. Following screening and eligibility assessment, 18 suitable publications were identified. To complement database searches, we also screened bibliographies of all included papers and browsed Google Scholar to identify additional suitable publications. In total, this yielded six further relevant and eligible studies. Thus, 24 studies were included in our qualitative meta‐synthesis. For details on the systematic literature search process, please refer to the flow diagram in Figure S1.

All included studies were independently assessed by two researchers (M.T. and A.R.) based on the Critical Appraisal Skills Programme checklist (Critical Appraisal Skills Programme 2023), repeatedly discussed within the research group, and were deemed to be of adequate methodological quality for inclusion in our qualitative meta‐synthesis. For details on included studies, please refer to Table 1.

TABLE 1.

Overview and characteristics of all included studies (n = 24).

Study	Number of partici‐ pants	Psychiatric problem	Country	Gender ratio [f:m]	Age [years]	Aim of the primary study	Study approach	Details of ketamine treatment	Data collection and analysis	Themes/relevant qualitative results
Kolp et al. (2006)	2	Alcoholism (additional diagnoses: 1 nicotine and caffeine dependence, 1 binge eating disorder and recurrent depressive episodes)	US, Russia	1:1	47/39	To illustrate how ketamine‐enhanced psychotherapy (KEP) can help achieve abstinence in alcoholism	Clinical case series	Residential ketamine‐enhanced psychotherapy programme (dose and mode of ketamine administration unknown)	Clinical case descriptions including patients' subjective perspective	Description of ketamine‐induced transpersonal experiences
Kolp et al. (2014)	4	1 binge alcoholism 1 compulsive eating 1 chronic depression, recurrent headaches, and combined opioid and barbiturate dependence 1 chronic depression, chronic anxiety, chronic pain, avoidant personality disorder	US, Russia	3:1	52/47/34/59	To illustrate different theoretically and practically relevant aspects of ketamine psychedelic psychotherapy	Clinical case series	Intramuscular ketamine injection (doses ranged from 50 to 250 mg) as part of ketamine psychedelic psychotherapy	Clinical case descriptions including patients' subjective perspective	Description of ketamine‐induced psychedelic experiences and observed clinical effects
Gowda et al. (2016)	1	Complicated grief reaction with catatonic symptoms, poor oral intake, severe guilt and self‐harm ideations following the death of spouse	India	0:1	28	To report on a case of rapid resolution of complicated grief following intravenous ketamine treatment	Clinical case report	Intravenous ketamine infusion (0.5 mg/kg/h over 40 min) accompanied by a therapist	Clinical case description including patient's subjective perspective	Description of phenomenological experience (trance‐like state) resolving patient's grief reaction
Correia‐Melo et al. (2017)	2	Treatment‐resistant depression	Brazil	0:2	43/66	To report on two cases of severe psychotomimetic side effects after rapid esketamine infusion	Clinical case series	Intravenous esketamine infusion (0.25 mg/kg over 10 min)	Clinical case descriptions including patients' subjective perspectives	Description of psychotomimetic and traumatic experiences associated with rapid esketamine infusion
van Schalkwyk et al. (2018)	10	Mood disorders (9/10 major depressive disorder, 1/10 bipolar disorder)	US	7:3	Mean (SD): 52.6 (13.6)	To determine whether Clinician Administered Dissociative State Scale (CADSS) captures acute psychoactive effects of ketamine and to identify key features of the acute ketamine experience, including aspects that may not be captured by current scales	Mixed‐methods study; quantitative data (CADSS scores) obtained from 110 individuals with mood disorders who underwent ketamine treatment; qualitative data obtained from subsample of 10 participants (recruited via convenience sampling) who underwent in‐depth interviews about acute ketamine experience	Intravenous ketamine infusion (0.5 mg/kg over 40 min)	Semistructured, in‐depth interview; inductive thematic analysis	(1) Altered time and sensory perception, (2) Unusual bodily sensations, (3) A sense of peace, (4) Disinhibition
Lascelles et al. (2019)	14	Treatment‐resistant depression with suicidal ideation (including 2 participants with bipolar I disorder and 2 participants with emotionally unstable personality disorder)	UK	8:6	Range: 24–64 Median: 41	To investigate patients' reports of the impact of ketamine treatment on suicidal ideation, including duration of effects and possible mechanisms	Qualitative study; interviewees recruited from a UK ketamine clinic	3 intravenous ketamine infusions (0.5 mg/kg) followed by oral ketamine or combination of oral and intravenous treatment (variable length of treatment)	Semistructured interview; thematic analysis with inductive and semantic approach	(1) Impact of ketamine on suicidal ideation, (2) Dissociative and euphoric effects, (3) Other side effects, (4) Perceived mechanisms contributing to reduced suicidal ideation [(a) Clarity of thought, (b) Focus and concentration, (c) Ability to function], (5) Self‐harm
Chaves, Wilffert, and Sanchez (2020)	708 posts	Depression, posttraumatic stress disorder	Netherlands, Brazil	Unknown	Unknown	To identify and analyse what has been posted about ketamine use (including medical use) for dealing with self‐reported depression or posttraumatic stress disorder on one of the biggest international drug fora on the internet	Qualitative study; unobtrusive observation of threaded discussions on Bluelight webpage	Unknown	In‐depth online search; content analysis	(1) Reasons for using ketamine, (2) Positive effects, (3) Negative effects, (4) Ketamine regimen, (5) Safety, (6) Interaction with other substances, (7) Addiction, (8) Suicidal ideation
Starr et al. (2020)	23	Treatment‐resistant depression	US	14:9	Range: 28–64 Mean: 46	To investigate prestudy experiences and treatment satisfaction and to characterise health changes related to emotional health, daily functioning, and social functioning in responders to esketamine plus oral antidepressant treatment	Qualitative study; analysis of reports of patients participating in an open‐label, long‐term extension safety study of esketamine plus oral antidepressant	Minimum 4‐week induction phase with esketamine nasal spray plus oral antidepressant	Standardised, semistructured interview; constant comparative analysis	(1) Specific effect of depression on health prior to study participation, (2) Changes desired by patients from treatment‐resistant depression treatment prior to study participation, (3) Early esketamine nasal spray experiences, (4) Patient satisfaction with esketamine treatment, (5) Improving patient experience, (6) Safety
Lascelles et al. (2020)	12	Treatment‐resistant depression (additional diagnoses: 1 participant bipolar I disorder, 1 participant obsessive–compulsive disorder)	UK	6:6	Range: 21–70 Median: 57	To explore the perspectives of patients with treatment‐resistant depression who received ketamine treatment, including expectations of treatment, short‐ and longer‐term effects on mood and suicidal ideation, experienced side effects, and overall views	Qualitative study; interviewees recruited from a UK ketamine clinic	3 intravenous ketamine infusions (0.5 mg/kg), each 1 week apart, followed by a break of 3 to 4 weeks, then clinical review; if ketamine treatment was continued, could be oral ketamine, a combination of regular oral and intermittent intravenous ketamine, or intermittent intravenous ketamine only	3 semistructured interviews (before treatment, a few weeks into treatment, and ≥ 2 months later); thematic analysis with inductive and semantic approach	(1) Pretreatment: finding out about ketamine treatment and expectations of it, (2) Impact of treatment on mood and suicidal ideation, (3) Side effects of ketamine treatment, (4) Overall perspectives on treatment
Griffiths et al. (2021)	13	Treatment‐resistant depression (other diagnoses: 2 participants bipolar affective disorder, 1 participant mixed anxiety depressive disorder, 1 participant schizoaffective disorder)	UK	7:6	Mean (SD): 46.1 (10.7)	To examine participants' pathways to trying ketamine treatment for depression, including their lived experiences and responses related to the treatment	Qualitative study; interviews with people receiving ketamine infusion treatment within an NHS trust	3 to 112 intravenous ketamine infusions; (doses ranged from 25 mg/40 mL to 75 mg/40 mL over 40 min)	Semistructured, in‐depth interview; interpretative phenomenological analysis	(1) Treatment decision influencers, (2) Responses experienced taking ketamine, (3) Treatment enhancers, (4) Barriers to treatment efficacy and success, (5) Advocate for treatment
Halstead et al. (2021)	1	Treatment‐resistant posttraumatic stress disorder related to racial discrimination, persistent depressive disorder, suicidality	US, Canada	1:0	58	To report on the clinical experience of ketamine‐assisted intensive outpatient psychotherapeutic treatment	Clinical case report	4 sublingual ketamine sessions (dose 150 mg) over 13 days combined with psychotherapy	Clinical case description including patient's subjective perspective	Description of receiving ketamine‐assisted psychotherapy and its clinical and personal effects
Sumner et al. (2021)	32 (included overall) 31 (assessed with interviews)	Major depressive disorder	New Zealand, UK	15:17	Mean (SD): 30.4 (8.9)	To explore psychedelic experiences and sustained impact of ketamine in major depressive disorder	Mixed‐methods study; quantitative assessment of acute psychoactive (11‐dimension altered states of consciousness questionnaire) and antidepressant effects (Montgomery‐Åsberg Depression Rating Scale); qualitative assessment of acute psychedelic experience and longer‐term effects of ketamine treatment	Single‐session intravenous ketamine (0.25 mg/kg bolus plus 0.25 mg/kg/h infusion for 45 min) administered in a magnetic resonance imaging environment	Interviews (initially with broad schedule, later in the study this was more structured) conducted at two time‐points: acute interview within an hour of the infusion and final interview between 3 and 8 weeks after treatment; reflexive thematic analysis	Acute qualitative interview: (1) Change in perception, (2) Emotional or mood changes, (3) Loss of control, (4) Questioning of existence or self, (5) Physiological Final qualitative interview: (1) Change in perspective, (2) Change in mood, (3) Change in emotion, (4) Time, (5) Expectations, (6) Future treatments
Mollaahmetoglu et al. (2021)	12	Severe alcohol use disorder, currently abstinent	UK	3:9	Mean (SD): 46.5 (11.1)	To explore participants' acute psychological experiences under ketamine infusions and perceived long‐term effects of ketamine treatment and the overall trial	Qualitative follow‐up study from a Phase II double blind, randomised controlled multisite trial of ketamine versus saline combined with psychological therapy or alcohol education	3 intravenous ketamine infusions once weekly within 3 weeks (0.8 mg/kg), ketamine administered combined with psychological therapy or alcohol education	Semistructured interview; reflexive thematic analysis	(1) Multifaceted motivations for seeking ketamine in a clinical trial, (2) Set and setting as influential in determining acute ketamine experiences, (3) The inherent contradictions of the acute ketamine experience, (4) Rapidly fluctuating and changing ketamine experiences, (5) Meaningful, spiritual and mystical experiences, (6) The ketamine infusions and the trial as potentially transformative
Dames, Kryskow, and Watler (2021)	94	Treatment‐resistant depression, chronic anxiety, obsessive–compulsive disorder, posttraumatic stress disorder, suicidality, substance use disorder and previous treatment failure	Canada	Unknown	Unknown	Quality improvement evaluation of a ketamine‐assisted psychotherapy programme delivered in a community of practice group model	Mixed‐methods cohort‐based case series, including quantitative mental health assessments and qualitative narrative participant feedback about experience in a multimodal treatment programme that went over 12 weeks and included 3 ketamine‐assisted group psychotherapy sessions	Oral ketamine for the first session (dose unknown), then intramuscular injections in 2 sessions (1 to 1.5 mg/kg)	Collection of narrative feedback from participants of the programme	Description of participants' feedback to treatment programme without systematic qualitative analysis
Robison et al. (2022)	5 (included overall) 3 (provided feedback)	Eating disorder with comorbid major depressive disorder (4 participants anorexia nervosa, 1 participant bulimia nervosa; additional diagnoses: 3 participants generalised anxiety disorder, 2 participants posttraumatic stress disorder)	US, Canada	5:0	Range: 22–43	To report on 5 cases of group‐based ketamine‐assisted psychotherapy in patients with eating disorders and comorbid depression	Clinical case series of group‐based ketamine‐assisted psychotherapy at a residential eating disorder treatment centre	4 intramuscular ketamine injections once weekly over 4 weeks (doses started at 25 mg and were increased on an individual basis, depending on tolerability, to a maximum of 100 mg), ketamine application was combined with group‐based ketamine‐assisted psychotherapy	Clinical case descriptions including patients' subjective perspective collected via an online survey	Description of patients' experiences with ketamine‐assisted group psychotherapy without systematic qualitative analysis
Breeksema et al. (2022)	17	Unipolar and bipolar treatment‐resistant depression (additional diagnoses: 1 participant personality disorder, not otherwise specified; 1 participant avoidant personality disorder and posttraumatic stress disorder symptoms; 1 participant autism spectrum disorder and posttraumatic stress disorder; 1 participant posttraumatic stress disorder; 2 participants autism spectrum disorder; 1 participant attention deficit hyperactivity disorder)	Netherlands	11:6	Range: 30–65	To explore the perspectives of treatment‐resistant depression patients participating in off‐label oral esketamine treatment	Qualitative study; interviewees recruited from an off‐label esketamine treatment programme for treatment‐resistant depression	6 weeks of oral esketamine treatment twice weekly (doses started at 0.5 or 1 mg/kg, then increased to a maximum of 3 mg/kg depending on clinical effect and tolerability), followed by 6 months of at‐home use	Semistructured, in‐depth interview; interpretative phenomenological analysis	(1) Overwhelming experiences, (2) Inadequate preparation, (3) Letting go of control (4) Mood states influence sessions, (5) Presence and emotional support, (6) Supportive settings
Willms et al. (2022)	1	Treatment‐resistant depression, generalised anxiety disorder, posttraumatic stress disorder, and 5 years of daily suicidal ideation	US	0:1	30	To report on a case of efficacious ketamine‐assisted psychotherapy where the patient independently typed, first‐person, real‐time narratives of ketamine‐induced nonordinary states of consciousness	Clinical case report of a medical student who recorded his experiences of acute ketamine treatment via typing a journal whilst receiving ketamine infusions	12 intravenous ketamine infusions (in the typed sessions doses ranged from 1.8 to 2.1 mg/kg over 60 min) combined with 2 ketamine‐assisted psychotherapy sessions (single intramuscular ketamine shot) and 2 psychotherapy sessions within an 8‐month regimen	Clinical case description including the patients' subjective perspective and typed transcripts of first‐person experience during acute ketamine treatment	Detailed description of patient's subjective perspective including journal transcripts typed whilst receiving ketamine treatment
Lapidos et al. (2023)	21	Treatment‐resistant, nonpsychotic unipolar or bipolar depression	US	15:6	Range: 27–66 Mean: 44	To characterise patients' subjective experiences with (1) receiving ketamine infusions, (2) recovering or not recovering from treatment‐resistant depression after ketamine infusions, (3) beliefs about why ketamine worked or did not prove effective for their depression	Qualitative substudy of a multisite clinical trial to discover biomarkers of ketamine response in treatment‐resistant depression	3 intravenous ketamine infusions delivered in an 8 to 11‐day period (dose of 0.5 mg/kg to a maximum of 50 mg per infusion, either 100 or 40 min, or mixed)	Semistructured interview; deductive and inductive approach; themes derived and compared across a broader construct of recovery status	(1) Experience during ketamine infusions, (2) Ketamine's place in a treatment trajectory, (3) Beliefs about ketamine's mechanisms of action, (4) Qualitative versus quantitative assessment of remission status
Mansoor, Khan, and Faridi (2023)	14	Treatment‐resistant depression	Pakistan	9:5	Range: 28–71	To explore the perspectives of patients regarding the acceptability of intravenous ketamine treatment and evaluate its clinical effects	Mixed‐methods study; quantitative data on clinical effects of ketamine treatment (Hamilton Rating Scale for Depression); qualitative data on patients' perspective	6 intravenous ketamine infusions (0.5 mg/kg over 40 min) over 2 weeks	Semistructured interviews at the start and after completion of ketamine treatment; thematic analysis	(1) Starting treatment: fear vs. hope, (2) Initial feeling of detachment, (3) Activation of social behaviours, (4) Side effects, (5) Advocates for ketamine therapy
Robison et al. (2023)	10 (included overall) 9 (provided feedback)	Burnout and symptoms of posttraumatic stress disorder	US	5:5	Mean (SD): 37 (8.5)	To report on 10 cases of group ketamine‐assisted psychotherapy in frontline healthcare workers employed during the COVID‐19 pandemic who experienced burnout and symptoms of posttraumatic stress disorder	Clinical case series of group ketamine‐assisted psychotherapy in a private outpatient clinic that went over 6 weeks and included 3 group ketamine‐assisted psychotherapy sessions	2 sublingual ketamine sessions (first session 125–200 mg, second session 250–275 mg), 1 intramuscular session (70–100 mg), ketamine administration combined with group‐based ketamine‐assisted psychotherapy	Clinical case descriptions including participants' subjective perspective collected as part of a satisfaction survey completed 1 month after the final treatment session	Description of participants' feedback on group ketamine‐assisted psychotherapy
Wolfson et al. (2023)	4 (included overall) 1 (met the inclusion criteria of the meta‐synthesis study)	Major depression (later revised to bipolar I disorder), moderate to severe anxiety, eating disorder, suicidal ideation of fluctuating severity, obsessive–compulsive disorder, attention‐deficit hyperactivity disorder, history of impulsivity and substance use	US	1:0	19	To report on a case of ketamine‐assisted psychotherapy in an adolescent with undiagnosed bipolar disorder and a complex history with multiple psychiatric diagnoses as well as medication compliance struggles	Clinical case report	Sublingual ketamine for at‐home sessions, intramuscular ketamine for in‐office sessions, combined with ketamine‐assisted psychotherapy	Clinical case description including patient's subjective perspective	Description of patient's subjective perspective
Veraart et al. (2023)	5 (included overall) 3 (provided feedback)	Treatment‐resistant depression and comorbid posttraumatic stress disorder (additional diagnoses: 1 personality disorder, obsessive–compulsive disorder and binge eating)	Netherlands	5:0	Range: 34–66	To report on 5 cases of oral esketamine treatment within a psychotherapeutic framework in patients with treatment‐resistant symptoms of depression and posttraumatic stress disorder	Clinical case series	Oral esketamine plus psychological treatment for a minimum of 6 weeks, administered once or twice a week (doses started at 0.5 or 1.0 mg/kg and were increased to a maximum of 3 mg/kg depending on clinical effects and tolerability)	Clinical case descriptions including patients' subjective perspective; patients were asked to write down a few lines about their experiences with the treatment	Description of patients' narratives without systematic qualitative analysis
Breeksema et al. (2023)	17	Unipolar and bipolar treatment‐resistant depression (additional diagnoses: 1 participant personality disorder, not otherwise specified; 1 participant avoidant personality disorder and posttraumatic stress disorder symptoms; 1 participant autism spectrum disorder and posttraumatic stress disorder; 1 participant posttraumatic stress disorder; 2 participants autism spectrum disorder; 1 participant attention deficit hyperactivity disorder)	Netherlands	11:6	Range: 30–65	To describe the phenomenology of patients' experiences during oral esketamine treatment for treatment‐resistant depression and to explore the potential therapeutic relevance of these experiences	Qualitative study; interviewees recruited from an off‐label esketamine treatment programme for treatment‐resistant depression	6 weeks of oral esketamine treatment twice per week (doses started at 0.5 or 1 mg/kg, then increased to a maximum of 3 mg/kg depending on clinical effect and tolerability)	Semistructured, in‐depth interview; interpretative phenomenological analysis	Acute (during esketamine administration): (1) Perceptual effects, (2) Detachment, (3) Tranquillity and openness, (4) Mystical‐type effects, (5) Fear and anxiety Postsession: (6) Fatigue and hangover, (7) Lifting the blanket
Garel et al. (2023)	26 (thereof 10 with further details)	Treatment‐resistant depression, (additional diagnoses: 5 anxiety disorder, 2 bipolar II disorder, 3 posttraumatic stress disorder, 2 attention deficit hyperactivity disorder, 7 personality disorder, 1 eating disorder, 1 obsessive–compulsive disorder)	Canada UK	8:2	Mean (SD): 45.1 (14.5)	To investigate how previous environmental stimuli shape the experiences of patients receiving ketamine for treatment‐resistant depression	Descriptive report of retrospective review of audio recordings of ketamine treatment sessions and semistructured phenomenological interviews conducted after ketamine treatment; ketamine treatment conducted in a clinical trial investigating the effects of music during intravenous ketamine infusions for treatment‐resistant depression	Series of intravenous ketamine‐assisted psychotherapy treatments (0.5 mg/kg over 40 min)	Description of thematically relevant excerpts of recordings of acute ketamine treatment sessions, semistructured phenomenological interviews conducted 2 weeks after treatment, and brief interviews by phone conducted 8 to 12 months after the trial	Description of ketamine experiences influenced by exposure to digital media prior to treatment

A qualitative meta‐synthesis rooted in a reflexive thematic approach was used to examine and analyse the results of all included studies (Braun and Clarke 2013; Terry and Hayfield 2021; Timulak and Creaner 2023). This approach has previously been used successfully to study the subjective experience of psilocybin treatment, another psychoactive substance that shows promising effects in mental health conditions (Crowe et al. 2023). In the analysis, we included both study participants' direct quotes (first‐order constructs) as well as study authors' descriptions of their analysis results (second‐order constructs). Following familiarisation with all included material and open coding by two independently working researchers (M.T. and A.R.), a tentative coding framework was agreed on among all research team members and all included papers were coded with this tentative scheme. Where necessary, the coding framework was further adjusted, and papers were recoded accordingly. Following repeated team discussions and reviewing of data and codes, tentative subthemes and main themes were developed. These again were repeatedly reviewed, discussed, refined and finally defined and named. For reflexive statements of all study team members, please see Data S1.

3. Results

Overall, we identified three main themes (i.e., overarching patterns of information relevant to our research question) across included papers. Each main theme consists of several subthemes that provide analytic depth and nuance. Direct quotes from relevant publications illustrating and supporting individual subthemes can be found in Table 2.

TABLE 2.

Overview of representative quotes from papers included in the meta‐synthesis, illustrating and supporting each subtheme. Punctuation as used by authors of original publications, ‘{}’ are used to indicate changes/annotations introduced by the authors of the meta‐synthesis.

Main theme 1	Subtheme	Exemplary quotes
The ketamine treatment experience can be understood as a three‐stage journey with unique clinical features at each stage.	The pre‐treatment phase (Stage 1)	‘A number of patients, having exhausted all other conventional treatments (including electroconvulsive therapy or ECT), saw esketamine as their last treatment resort’. (Breeksema et al. 2022) ‘Ten out of 27 participants said that they had no expectations going into the study, and several who had set expectations expressed trying not to. In both cases this was often to try and avoid disappointment if it didn't work for them’. (Sumner et al. 2021) ‘{…} many patients described a mixture of moderate expectations and cautious hope that esketamine therapy would enable some positive change, “some light at the end of the tunnel.”’ (Breeksema et al. 2022) ‘{…} I just thought, right “How extreme is this experience going to be? Is it going to be a ride from hell or something like that?”’ (Mollaahmetoglu et al. 2021) ‘{…} I'd try it again… am I nervous? …Yes I am, totally, absolutely…. Would I have it done? Yes, because I, I know that the rewards outweigh the risk… I've had a turn; I'm prepared to take that risk, or calculated risk, to have it done again’. (Griffiths et al. 2021) ‘I'm only able to participate in the study because I have a very flexible schedule right now… where I dose at, they each have like 9:00 to 5:00‐ish hours on a Monday through Friday. It would be really hard if I had a demanding job right now that wouldn't let me take time off during those periods. I'm just hopeful … that there's opportunity for a flexible schedule to still receive the dosing. I mean, that's something that I'm personally looking into … I'm almost building my life around trying to continue to be available to dose’. (Starr et al. 2020)
	The acute treatment phase (Stage 2)	‘{…} they reported feeling safe and being comforted by the professionalism of the trial staff as well as the clinical setting in which the trial took place {…}’ (Mollaahmetoglu et al. 2021) ‘Feeling left alone and unsupported was not only related to the physical absence of nurses. Many patients also mentioned the need for emotional support by someone empathetic, whom they trust, and/or had previously established rapport with’. (Breeksema et al. 2022) ‘Participants reported that if they experienced negative external factors, this could affect treatment experience and act as a barrier to treatment success {…}’ (Griffiths et al. 2021) ‘Participants' prior mindset and spiritual beliefs were also reported to affect their acute ketamine experience {…}’ (Mollaahmetoglu et al. 2021) ‘{…} others reported being able to make better use of existing psychological therapy (n = 2) or openness to engaging in therapy (n = 2)’. (Lascelles et al. 2020) ‘Unpleasant experiences during (early) esketamine sessions often stayed with patients, and negatively impacted subsequent sessions’. (Breeksema et al. 2022) ‘For the rest of the participants (n = 13), however, side effects were not considered major and six explicitly stated that the side effects they experienced from ketamine were much less severe than those they had experienced with conventional antidepressants’. (Lascelles et al. 2019)
	The post‐treatment phase (Stage 3)	‘It really works; I would recommend it…without a shadow of a doubt… to anyone with long term, severe depression who's tried lots of other options’. (Griffiths et al. 2021) ‘Due to the positive effects of ketamine infusions, feelings of loss and sadness were described in relation to the cessation of the ketamine infusion and the trial’. (Mollaahmetoglu et al. 2021) ‘Low dose ketamine worked for me. But it is always tempting to take more to go down the rabbit hole’. (Chaves, Wilffert, and Sanchez 2020) ‘For some, this resulted in a sense of hopelessness, whereas others maintained hope that the ketamine treatment might work again {…}’ (Lascelles et al. 2020)

Main theme 2	Subtheme	Exemplary quotes
The subjective experience of acute ketamine treatment is multifaceted and complex	The variety of ketamine‐induced mental phenomena	‘Of the participants, 15/31 described the experience as being dreamlike, as if they were asleep, or experiencing déjà vu’. (Sumner et al. 2021) ‘Similarly, some participants described an enhancement in their perception, with one participant saying how they “got very observant of things,” and another describing a capacity to hear “multiple depths” when listening to music’. (van Schalkwyk et al. 2018) ‘You don't know where you are. Are you just a little cell, or are you a particle, or…? Something, but not something with two hands, two legs and a head and a torso. (…) My self is just gone. These were really experiences outside myself’. (Breeksema et al. 2023) ‘I was picked up by a flying chariot which travelled at a rocket speed and landed on what seemed to be like heaven’. (Gowda et al. 2016) ‘First, my mind was pulled out of my body and was thrown into a void. Then, my mind started dissolving into the void and soon nothing was left except my soul. I continued alone, existing in an infinite but empty black space. I realised I had died {…}’ (Kolp et al. 2006)
	Study participants' emotional appraisal of acute ketamine experiences	‘{…} That place was um, serene and peaceful, and um, just such a burden was lifted from me. And it was refreshing to feel something that was such a change from what I normally feel’. (van Schalkwyk et al. 2018) ‘The story of [me] as a patient lying here (…) completely disappeared. (…) Just a total openness (…) a kind of primal feeling which I cannot quite describe, a clear feeling of ‘this is it!’ This unity, where for a moment [my story] diminishes. Not as a thought, more as a kind of realisation. And in a pleasant way’. (Breeksema et al. 2023) ‘I found it a really unpleasant experience to be no longer present in my body and to give up control. That's something I don't like in any case, but it happened very violently there’. (Breeksema et al. 2022) ‘{…} There was a devil and he removed my heart with his own hands; it was terrible’. (Correia‐Melo et al. 2017) ‘Some physiological responses were not pleasant experiences. These varied in type and severity, including nausea, headaches, and adverse physiological reactions {…}’ (Griffiths et al. 2021)

Main theme 3	Subtheme	Exemplary quotes
Ketamine treatment can have different positive effects—but what happens if it does not work?	Impact of ketamine treatment on clinical symptoms of psychiatric disorders	‘This lifted mood was something that was experienced during and after the infusion, and for some was sustained over a few days or longer. Participants described themselves as ‘elated’ (P2), that their ‘mood is lifted’ (P8), they “felt bright” (P7), and had “fire in their belly” (P6)’. (Griffiths et al. 2021) ‘The effect I enjoy the most is complete freedom from the anxiety that constantly eats at me’. (Chaves, Wilffert, and Sanchez 2020) ‘I think it's separate [from mood]. Because there's still days where I feel very low and normally the suicide thing would be at the back of my head or be there, but it, without any thought process, it's gone, and I can't reason that one’. (Lascelles et al. 2019) ‘{…} all participants who completed the treatment recounted that the trial had transformed their relationship with alcohol in a number of ways’. (Mollaahmetoglu et al. 2021)
	Impact of ketamine treatment on the individual person and their day‐to‐day psychosocial functioning	‘{…} Almost as if it rewired the brain very quickly and it kind of just matched things up the way they should be, rather than what they felt they were’. (Griffiths et al. 2021) ‘I have the idea that I now function more like a normal person than without the ketamine’. (Breeksema et al. 2023) ‘{…} participants who identified a change in mood directly followed this with a statement on how the change in mood improved their motivation or ability to get started on things such as work, routine chores, or socializing’. (Sumner et al. 2021) ‘Participants who experienced a change in how they felt about people, reported increased feelings of closeness, connectedness, and ability to relate’. (Sumner et al. 2021) ‘I started looking at all the good things that I was over‐looking’. (Chaves, Wilffert, and Sanchez 2020) ‘Yet another participant described the utility of mentally returning to the experience of the infusion in the days and weeks following it as a way to regain peace and serenity’. (van Schalkwyk et al. 2018)
	Nothing improved or improvements did not stay—now what?	‘They told me at the time that it would open up new pathways in my brain. And so that's kind of what I was expecting to happen … I felt so disappointed that it didn't do anything for me so that made it really kind of a very negative experience. Just like the ECT and the magnet therapy, I was extremely disappointed afterwards when it didn't work’ (Lapidos et al. 2023) ‘{…} So generally I think I feel worse…. I feel more hopeless…… Maybe I built up too much hope for it because I tried lots of other things beforehand and it seemed like this was going to be, kind of a salvation. I guess that as its not, that's probably contributed to my mood. I feel pretty kind of, oh shite, what do I do now, you know?’ (Lascelles et al. 2020)

3.1. Main Theme 1: The Ketamine Treatment Experience can Be Understood as a Three‐Stage Journey With Unique Clinical Features at Each Stage

When people undergo ketamine treatment for a psychiatric problem, three distinct stages can be delineated in their subjective experience, each associated with unique clinically relevant features and challenges. People arrive at the idea of undergoing ketamine treatment through different pathways and enter the treatment with various expectations, hopes, feelings and experiences with previous therapeutic trials. Ketamine can acutely induce a range of neuropsychological and physical effects, both pleasant and unpleasant, which can be influenced by the context in which the drug is received. Once treatment is over, the question of whether a therapeutic effect is noticeable, and how to proceed from there on, becomes an important aspect of first‐person experience.

3.1.1. Subtheme 1.1: The Pre‐Treatment Phase (Stage 1)

The experience of Stage 1, the phase leading up to ketamine treatment, encompasses several clinically relevant aspects. First, there are different pathways that can bring a person to consider ketamine treatment for their mental disorder, including self‐conducted web searches about therapeutic options, news coverage of ketamine treatment, recommendations by healthcare professionals or experiences of subjective mental health improvements following either recreational or anaesthetic use of ketamine. People approach ketamine treatment for a psychiatric problem with different motives, expectations, concerns and risk–benefit ideas, all of which can potentially influence both the acute treatment experience as well as longer‐term clinical effects. Commonly, individuals describe frustration with the inefficacy of prior treatments and feelings of hopelessness and despair regarding their mental ill health. Sometimes, they deliberately keep their expectations concerning ketamine effects low, so not to be disappointed (once again). However, ketamine treatment is also frequently associated with hope and viewed as a (sometimes last) chance for clinical improvement—especially after other treatment attempts have failed, or when more invasive interventions, such as electroconvulsive therapy, have been recommended. Prior to receiving ketamine, some people are nervous about what to expect from the treatment, especially if they have no familiarity with the drug, for example, through prior recreational or medical use or through reports from others who have personal experience with the drug. Depending on the treatment programme, people also sometimes report a need for making arrangements to properly fit ketamine treatment into their day‐to‐day life.

3.1.2. Subtheme 1.2: The Acute Treatment Phase (Stage 2)

During Stage 2, the time of actual treatment, the context in which ketamine is administered and its acute psychological and physical effects become central to experience.

In different studies, participants emphasise the influence of the environment, in which ketamine is administered, on their treatment experience. This includes interaction with staff, the looks and soundscape of the treatment facilities, the route of ketamine administration, and the overall atmosphere around treatment. Media consumption prior to ketamine administration (e.g., watching television, playing video games) as well as during the intervention (e.g., listening to music) can also differentially impact on the acute ketamine experience. When the environment is perceived as safe, trustworthy and pleasant, it can positively support the acute experience, while unpleasant environments (e.g., a noisy room or repeated interruptions during treatment) can be quite disruptive. In a similar vein, psychological therapy accompanying ketamine treatment is repeatedly reported to act synergistically with ketamine, with an increased ability to engage in psychotherapy following administration of the drug.

Acute ketamine treatment is reported to exert a range of psychological and physical effects with a complex phenomenology, described in greater detail in Main Theme 2 below. The quality and intensity of these acute effects, as well as the clinical benefits derived from ketamine, can vary considerably in the course of treatment and seem to be influenced by different factors, including pre‐treatment preparation and acute treatment context. Furthermore, initial impressions of ketamine effects in early treatment sessions can colour people's experience of later treatment sessions.

Study participants tend to be aware of and report experiencing unwanted side effects of ketamine treatment (also see Main Theme 2 below) but are frequently willing to take the risk of encountering these, especially when considering the burden of their mental health problems and the side effects of conventional psychopharmacotherapy.

The ending of an acute ketamine session is repeatedly described as a gradual comedown from the drug's effects, at times associated with exhaustion and a need for rest after a treatment session.

3.1.3. Subtheme 1.3: The Post‐Treatment Phase (Stage 3)

Stage 3, the post‐treatment phase, encompasses the experience of ending ketamine treatment and carrying on with one's life. Central to this phase is the question of whether ketamine treatment had any effect on psychiatric symptoms and on day‐to‐day psychosocial functioning.

In the included studies, participants frequently report a positive effect of ketamine treatment, often emphasising the speed and extent of experienced improvements. This is captured by descriptions of the treatment as, for example, ‘wonder drug’ (Griffiths et al. 2021), ‘lifesaver’ (Chaves, Wilffert, and Sanchez 2020), and ‘one of the best experiences of my life’ (Mollaahmetoglu et al. 2021). Repeatedly, participants of included studies express a wish to share these experiences with others and offer recommendations to further improve treatment. Especially with brief intervention protocols, when study participants experienced positive effects, they report frustration and a sense of loss related to the fact that they cannot continue ketamine treatment. In general, reported time frames for positive effects vary considerably—from hours to months—both within and between included studies. When ketamine‐induced clinical improvements are transitory, study participants also report pondering how to extend treatment by themselves or how to enhance/prolong beneficial effects, which at times opens considerations of unprescribed or illicit use.

When people do not experience a positive effect of ketamine, it can give rise to strong feelings of hopelessness and disappointment. This can also be the case when clinical improvements are experienced but remain short‐lived. However, for some people even temporary improvements spark hope that their condition is not untreatable and that it can in principle get better. Main Theme 3 summarises in greater detail what the experience of positive effects, or lack therefore, respectively, means to people.

3.2. Main Theme 2: The Subjective Experience of Acute Ketamine Treatment Is Multifaceted and Complex

Acute ketamine treatment is associated with a range of subjectively experienced mental and physical phenomena that differ along multiple dimensions such as, for example, intensity, body‐centredness, content, and complexity. The specific manifestation of these phenomena and how they are individually appraised can vary not only between individual participants but also across treatment sessions of the same person.

3.2.1. Subtheme 2.1: The Variety of Ketamine‐Induced Mental Phenomena

Ketamine treatment can acutely induce a multitude of mental phenomena that vary in intensity, body‐centeredness, content and complexity. While some study participants report relatively mild acute ketamine effects, for example, a vague feeling that something has changed, or a feeling of being ‘high’ (Griffiths et al. 2021; Starr et al. 2020; Sumner et al. 2021), ‘loop’ (Starr et al. 2020), ‘woozy’ (van Schalkwyk et al. 2018; Willms et al. 2022), ‘giddy’ (Griffiths et al. 2021), ‘spacey’ (van Schalkwyk et al. 2018) or ‘drunk’ (Lascelles et al. 2019, 2020; Starr et al. 2020), others describe more intense perceptual changes such as perceiving colours or sounds more intensely, loosing track of time, feeling floaty or recognising a detachment from or interruption of (often incessant negative) thoughts and feelings. Further down on the intensity spectrum are dream‐like sequences, severe distortions of space and time, (pseudo‐)hallucinatory experiences, full‐blown trip experiences and the experience of complete ego dissolution or non‐existence. The extent to which the body features in the experience of acute ketamine treatment also varies across reports, ranging from feeling heavy, paralysed or somehow bodily changed, to distorted perceptions of body parts, up to a feeling of complete bodily detachment or dissolution.

Content‐wise, there is great variability in the subjective experience of acute ketamine effects as well. Themes that are reported include experiences of (near‐)death or dying, experiences of meeting deceased people and religious entities, experiences coloured by content from popular media or fictional literature (e.g., Disney films, Alice in Wonderland) and experiences of travelling to other worlds/realities/realms/dimensions, heaven or through the universe or outer space.

3.2.2. Subtheme 2.2: Study Participants' Emotional Appraisal of Acute Ketamine Experiences

The emotional appraisal of acute ketamine experiences varies not only between study participants but also within individual people across treatment sessions.

On the emotionally positive side, acute ketamine treatment is associated with feelings of having a burden lifted, lightness, calmness, relaxation, euphoria, amusement, contentment, peacefulness or perfection. In some individuals, specific experiences, such as ego dissolution, are described as deeply meaningful, related to important existential insights, and associated with a sense of unity, spirituality, growth or finality. Related to these experiences, study participants sometimes describe a feeling of smallness compared to the rest of universe, putting into perspective the gravity of their individual problems. In a similar vein, some study participants report that ketamine's acute effects also aided in integrating and coming to peace with previous traumatic or emotionally difficult experiences.

On the emotionally negative side of acute ketamine experiences are drug‐induced feelings of panic, anxiety, paranoia, discomfort or distress. Here too, specific experiences are seen as particularly negative by some people. For example, threatening hallucinations, the impression of having no control over one's body or over the ketamine‐induced experience as a whole, the elicitation of intrusive traumatic memories, sudden realisations of one's own dysfunctional behavioural patterns, and certain forms of ego dissolution are described at times as extremely frightening and potentially traumatic. Interestingly, in some participants, an emotionally negative acute ketamine experience does not seem to preclude deriving a clinical benefit. In addition to the above‐mentioned experiences, ketamine also has well‐known unpleasant physiological side effects, for example, nausea, vomiting, perioral numbness/tingling, elevated blood pressure, headache, sedation or dizziness that are repeatedly described and which sometimes can be treatment‐limiting.

Of note, some people describe their experiences of acute ketamine treatment as neither positive nor negative but as simply strange, confusing or hard to put into words.

3.3. Main Theme 3: Ketamine Treatment Can Have Different Positive Effects—But What Happens if It Does Not Work?

Ketamine treatment can positively impact on clinical symptoms of mental disorders, shifting for example mood and emotionality towards positivity and reducing suicidality. In addition, it can also positively influence a person's day‐to‐day psychosocial functioning and their overall outlook on life. However, not all people who receive ketamine treatment experience such positive effects and in those who do, the effects may last only briefly. Experiencing such a lack of (often desperately hoped for) clinical efficacy can give rise to intense negative emotions such as frustration, disappointment and hopelessness, which might further deteriorate a person's mental state.

3.3.1. Subtheme 3.1: Impact of Ketamine Treatment on Clinical Symptoms of Psychiatric Disorders

Across included studies, ketamine treatment is linked to rapid improvements of various psychiatric symptoms. Unsurprisingly, study participants repeatedly report an improvement of depressed mood as an effect of treatment, though the extent and sustainability of this effect shows considerable variation among individuals. Related to this, some individuals report that, following treatment, emotionality shifts towards positivity, i.e. they experience more positive and fewer negative emotions. Improvements in thinking (less intrusive thoughts/memories, less rumination, better organisation of thought process, more clarity of thought), decisiveness and concentration are also described. Furthermore, anxiety and fatigue appear to be reduced and experience of pleasure, interest, subjective energy and motivation seem to be improved by ketamine treatment. The positive changes induced by ketamine in some participants correlate with improvements in suicidality, though in others, suicidality also seems to get better independent of these changes. Where alcohol use was a problem prior to treatment, decreased and more controlled alcohol consumption, improved abstinence and reduced craving is reported. A range of different symptoms, for example, decreased libido, gastrointestinal symptoms, disturbed appetite or sleep difficulties is reportedly improved by ketamine treatment too, though these effects received less attention in the included literature. In addition, in some people, posttraumatic stress symptoms as well as symptoms of eating disorders (including binge eating and restrictive eating behaviours) were also described to improve with ketamine treatment.

3.3.2. Subtheme 3.2: Impact of Ketamine Treatment on the Individual Person and Their Day‐To‐Day Psychosocial Functioning

Ketamine treatment cannot only improve psychiatric symptoms but also seems to be able to positively impact on a person's day‐to‐day psychosocial functioning and their overall perspective on life. Participants in included studies indicate repeatedly that ketamine treatment feels like it has an important and fast effect on their brain—resetting, rewiring or repairing it somehow in beneficial ways. They can adopt new ways of thinking and relating to themselves and others, their life, their future and their problems—changes that are at times described as profound and life changing. In several cases, people speak of feeling transformed or like themselves again, being able to live a normal life again, feeling more hopeful, motivated and optimistic and being able to take up occupational and leisure activities again. Another reported effect of ketamine is a restored ability to socialise, along with a feeling of increased social connectedness and better relationships with other people. The experience of an at least temporary improvement is seen, by some, as proof that their mental health problem is not an inescapable fate, thus sparking hope that things can eventually get better. Interestingly, some study participants indicate that, after ketamine sessions, deliberately recalling specific aspects of the acute treatment experience allows them to reactivate positive feelings associated with the treatment and to better cope with difficulties they encounter in their day‐to‐day life.

3.3.3. Subtheme 3.3: Nothing Improved or Improvements Did Not Stay—Now What?

Some participants report not benefitting from ketamine treatment at all, or beneficial effects (both in terms of symptom improvements and psychosocial functioning) dissipating quickly over time. In these cases, individuals can develop frustration and disappointment about having undergone (yet another) unsuccessful treatment trial. Some also report feeling even more hopeless about their condition given the observed inefficacy of ketamine treatment.

4. Discussion

We conducted a systematic literature search and a meta‐synthesis of qualitative studies investigating the subjective experience of people undergoing ketamine treatment for psychiatric problem. Our findings suggest that the lived experience of ketamine treatment in a psychiatric context can be conceptualised as a three‐stage journey—moving towards ketamine treatment, receiving it, and eventually departing from it again—where at each stage different clinically relevant facets become central to first‐person experience.

Utilising qualitative research methods to study ketamine treatment offers several advantages. Qualitative approaches allow access to information that can be difficult to collect using quantitative means. For substances like ketamine, that induce non‐ordinary states of consciousness, this becomes particularly pertinent, as the subjective experience of the effects of these substances is complex and cannot easily be captured in full depth and breadth using simple scale measurements. Furthermore, qualitative approaches give voice to people undergoing ketamine treatment and can highlight clinically and ethically relevant aspects in want of improvement. While several qualitative studies on the subjective experience of ketamine treatment in psychiatry have been published in recent years, this is, to our knowledge, the first systematic summary and analysis of their findings.

With regard to our three‐stage journey framework, it is interesting to note that the information available on each of the stages, is not equally distributed in the current literature. Hitherto, most qualitative work focuses on the subjective experience of acute ketamine effects (i.e., Stage 2 in the proposed framework) and the experience of the time after treatment (i.e., Stage 3). Relatively little information is currently available on the experience of the time leading up to ketamine treatment (i.e., Stage 1), including seeking, getting into and preparing for the intervention. Considering that various efforts to find clinically useful biological markers to predict ketamine efficacy and tolerability in individual patients have not proven successful to date (Kadriu et al. 2020; Medeiros et al. 2022), conducting more qualitative research on the pre‐treatment stage might help to identify potential novel clinical or psychological markers that could be used for these prediction purposes.

Subjectively experienced acute ketamine effects can vary considerably between individual study participants and different studies, and this can likely be traced to both, inter‐individual biological and psychological differences as well as variability in study contexts. Potential examples of modifiable personal and contextual variables that were encountered in our meta‐synthesis include personal and professional preparation prior to treatment (e.g., specific education about potential treatment effects, meditative/contemplative practices, digital media diet), presence of an emotionally supporting person in the treatment room, the use of pleasant or meaningful perceptual stimuli (e.g., scents, music) during treatment and sharing, discussing and integrating ketamine experiences with others following treatment. As with other psychedelic substances, administering psychotherapy alongside ketamine treatment could also be an effective method to shape the experience of ketamine treatment in a clinically useful way (Crowe et al. 2023; Drozdz et al. 2022; Joneborg et al. 2022; Kew et al. 2023; Lakeman, Ryan, and Emeleus 2023).

As reflected by the third theme of our meta‐synthesis, in some people ketamine treatment can considerably improve both mental health symptoms as well as overall life quality and psychosocial functioning. This is well‐documented in the quantitative literature using scale‐based symptom measures and reflected in various qualitative reports. Interestingly, sometimes people qualitatively describe significant subjective improvements in mental health following ketamine treatment even when these improvements are not captured by quantitative measurements (Lapidos et al. 2023). This strengthens the case for combining quantitative and qualitative assessments of treatment effects when studying ketamine's efficacy for psychiatric disorders in clinical trials.

Another aspect, that has received relatively little attention to date, is the question of how people who do not benefit from ketamine treatment perceive their condition. Some reports suggest that in this case, having undergone yet another unsuccessful treatment trial, patients can develop frustration, disappointment and hopelessness. Theoretically, this could cause further psychological distress and aggravate a pre‐existing mental disorder. While the risk of such a dynamic is covered briefly in some qualitative studies (Lapidos et al. 2023; Lascelles et al. 2020; Sumner et al. 2021), this idea has not been comprehensively investigated yet. Thus, more work is needed to better understand how pre‐treatment expectations regarding ketamine and their subsequent nonfulfilment can influence a patient's mental state.

There are several limitations to our work that deserve highlighting. First, the researchers' subjective perspective—including their social and professional identities, their relationship to study participants and the data collection context—was reflected on poorly across included studies. Being based on these studies, our meta‐synthesis is also affected by this weakness. Since reflexivity is vital for nuance and depth in qualitative data analyses, future studies on the subjective experience of ketamine treatment should incorporate this aspect better. Furthermore, given the limited amount of available data, our meta‐synthesis included participants' quotes as well as authors' descriptions of analysis results and made no specific distinction between these two types of data. Although this merges first‐order and second‐order constructs, none of the themes were based exclusively on either type of data. Finally, we included a range of different studies with variations in study populations, treatment contexts, data collection methods and analysis approaches. This can be seen as a source of heterogeneity that complicates interpretability of results; however, we believe it also allows for a more nuanced, multifaceted and richer picture of the first‐person experience of psychiatric ketamine treatment. Future work should evaluate whether ketamine treatment experiences might differ depending on specific characteristics of treatment populations and treatment contexts.

5. Relevance for Clinical Practice

This is, to our knowledge, the first systematic meta‐synthesis of existing qualitative research exploring the subjective experience of people undergoing ketamine treatment for a psychiatric problem. We propose a three‐stage journey model that highlights different aspects relevant to the first‐person experience of moving towards ketamine treatment, receiving it and eventually departing from it again. This model allows mental health professionals to better understand what it means for patients to undergo ketamine treatment and what support they might need. Furthermore, the model can be used as a guiding conceptual framework along which further qualitative and quantitative research can be conducted to improve ketamine treatment for patients in a psychiatric context.

Author Contributions

All authors listed meet the authorship criteria according to the latest guidelines of the International Committee of Medical Journal Editors. All authors are in agreement with the manuscript.

Conflicts of Interest

The authors declare no conflicts of interest.

Supporting information

Data S1.

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.