Objective: Whether for spiritual, recreational, or potential therapeutic use, interest in ayahuasca has grown remarkably. Ayahuasca’s main active substances are N,N-dimethyltryptamine and certain monoamine oxidase inhibitor β-carbolines. Possible drug interactions are a major concern, and research is lacking in this area. The objective of this study was to evaluate the safety of ritual ayahuasca use regarding adverse effects and risk factors.
Methods: In this cross-sectional study, ayahuasca users from a religious institution answered an online questionnaire about its safety. Adverse effects, safety measures, and possible risk factors (psychiatric diagnosis and medications) were investigated.
Results: The most frequent adverse effects among the 614 participants were transient gastrointestinal effects (nausea and vomiting). Fifty participants self-reported a psychiatric diagnosis (depression and anxiety were the most prevalent), and these participants experienced adverse effects more frequently. Psychiatric medication use was reported by 31 participants. No indication of increased adverse effects due to drug-drug interactions was found.
Conclusion: A minority of participants reported being very negatively affected by persistent adverse effects. Psychiatric medication use while participating in ayahuasca rituals was not associated with increased adverse effects. For the most part, the institution’s practices seem sufficient to prevent exacerbated reactions. Future studies may focus on negatively affected users.
Durante, Í., Dos Santos, R. G., Bouso, J. C., & Hallak, J. E. (2021). Risk assessment of ayahuasca use in a religious context: self-reported risk factors and adverse effects. Revista brasileira de psiquiatria (Sao Paulo, Brazil : 1999), 43(4), 362–369. https://doi.org/10.1590/1516-4446-2020-0913
Background: Ketamine’s potent and rapid antidepressant properties have shown great promise to treat severe forms of major depressive disorder (MDD). A recently hypothesized antidepressant mechanism of action of ketamine is the inhibition of N-methyl-D-aspartate receptor-dependent bursting activity of the habenula (Hb), a small brain structure that modulates reward and affective states.
Methods: Resting-state functional magnetic resonance imaging was conducted in 35 patients with MDD at baseline and 24 hours following treatment with i.v. ketamine. A seed-to-voxel functional connectivity (FC) analysis was performed with the Hb as a seed-of-interest. Pre-post changes in FC and the associations between changes in FC of the Hb and depressive symptom severity were examined.
Results: A reduction in Montgomery-Åsberg Depression Rating Scale scores from baseline to 24 hours after ketamine infusion was associated with increased FC between the right Hb and a cluster in the right frontal pole (t = 4.65, P = .03, false discovery rate [FDR]-corrected). A reduction in Quick Inventory of Depressive Symptomatology-Self Report score following ketamine was associated with increased FC between the right Hb and clusters in the right occipital pole (t = 5.18, P < .0001, FDR-corrected), right temporal pole (t = 4.97, P < .0001, FDR-corrected), right parahippocampal gyrus (t = 5.80, P = .001, FDR-corrected), and left lateral occipital cortex (t = 4.73, P = .03, FDR-corrected). Given the small size of the Hb, it is possible that peri-habenular regions contributed to the results.
Conclusions: These preliminary results suggest that the Hb might be involved in ketamine’s antidepressant action in patients with MDD, although these findings are limited by the lack of a control group.
Rivas-Grajales, A. M., Salas, R., Robinson, M. E., Qi, K., Murrough, J. W., & Mathew, S. J. (2021). Habenula Connectivity and Intravenous Ketamine in Treatment-Resistant Depression. The international journal of neuropsychopharmacology, 24(5), 383–391. https://doi.org/10.1093/ijnp/pyaa089
The promising results of psychedelic treatments in small scale clinical trials are feeding an emergent health and wellness industry around these substances. The Netherlands, where psilocybin truffles remain unregulated, has become fertile ground for entrepreneurs aiming to position themselves at the cutting-edge of the psychedelic medicine market. Even though most of these psychedelic retreats cater to healthy participants, an increasing number of companies are planning to offer truffle sessions as psychedelic therapy to psychiatric patients. At the current stage, when scientific evidence proves promising but not yet conclusive, researchers are worried about the risks of commercial providers running ahead of the ongoing research. Should companies tread more carefully and let clinical researchers take the lead in the development of psychedelic therapy?
Psilocybin in the Netherlands
Psilocybin is a controlled substance in the Netherlands and the possession and sale of any species of psilocybin containing mushrooms is forbidden. However, this regulation does not apply to truffles, given that these are not strictly mushrooms but a different part of the fungus. This legal loophole has allowed the spread of psychedelic retreat centers offering truffle ceremonies for self-development or spiritual purposes.
Even though truffles qualify as a legal food in the Netherlands, they cannot be advertised as a medical treatment. The Dutch Health and Youth Care Inspectorate (IGJ) states that truffles may fall under the regulatory scope of the Medicines Act if medical claims are made. “In that case, we qualify the truffles as a medicine, for which no trade permit has been granted in the Netherlands”, an IGJ spokesperson declared.
Most entrepreneurs, aware of the existing regulation, avoid making explicit medical claims when advertising their services and try to use terms like “inner healing” and “personal development” instead. Many also warn that their ceremonies are not meant to substitute medical or psychotherapeutic care and make an effort to exclude clients with mental diagnoses and possible physical risks from participating through careful health screening.
This is, however, not always the case. The clinical director of a new truffle clinic recently declared to Dutch media: “We administer truffles to people in order to make them feel better and to overcome psychological disorders such as depression, anxiety and stress”. Others openly claim to provide “psychedelic-assisted therapy” on their websites and display the available scientific evidence to illustrate its efficacy in the treatment of depression, addiction or PTSD. We asked Nick (whose real name is not disclosed) about the apparent targeting of mental health patients on his retreat center’s website. “We are not pretending to treat or cure PTSD”, he assured, “we are acknowledging that there are people who have PTSD and that those clients that we have received (and not targeted) had very beneficial experiences”.
The hype around psychedelics is sparking a race among startups to become pioneers of a new therapeutic or wellness market, the boundaries are not always clear. But the emergence of truffle therapy is not just about opportunistic entrepreneurship. The mainstreaming of psychedelics is also bringing some of the underground therapists to the surface and from their perspective, there might not be meaningful reasons to wait for approval and regulation. Peter (whose real name is not disclosed) has conducted truffle therapy for the last eight years and more recently decided to start advertising their services online. “Back then we also thought we were moving too fast but people were really searching for this. We just couldn’t wait. Regulation can be helpful, but for a lot of us who already walked that path it’s not that great, especially for the ones who believe more in alternative therapies”.
The lack of formal regulation governing the profession has led some psychedelic guides in the Netherlands to found the Guild of Guides. This professional association is developing its own ethical codes in order to ensure best practices during psychedelic sessions. Peter also acknowledges the importance of the guild in the self-regulation of psychedelic facilitators. When it comes to offering therapy, however, their guidelines are unequivocal: “Guides do not claim to be psychedelic therapists nor offer ‘therapeutic’ services when they lack the appropriate accreditation.”
Scientists’ call for caution
A number of Dutch researchers and therapists are currently working on trials investigating the safety and efficacy of psilocybin for patients with treatment-resistant depression. They are concerned about commercial providers rushing to open up the market even before the scientific evidence is established. Clinical psychologist Jan Mars, therapist at the University Medical Centre Groningen (UMCG), says: “I am not a supporter of this practice because we are still doing research right now and you don’t want to run ahead of the science”. Joost Breeksema, researcher at the UMCG and director of the OPEN Foundation, echoed similar concerns: “The main problem is that we don’t know yet if this can be done safely and if so, which patients might benefit and which may be more at risk. And we’re only talking about the treatment of depression, where clinical research with psilocybin is relatively advanced. Offering psilocybin truffles to treat PTSD is even more problematic, not just because of the nature of this disorder, but also because we lack solid research. I understand the need for better treatments, and the impatience of patients who’ve sometimes suffered for decades, but it’s unethical, unwise and irresponsible to experiment blindly with these powerful treatments.”
It is important to remark that most scientists and therapists see no harm in conducting truffle ceremonies with experienced guides outside the medical realm. Renske Blom, psychiatrist at GGZ Centraal and therapist at UMC Utrecht, noted: “Truffles are legally available in the Netherlands so they can be and are being offered for spiritual care, wellbeing and self-improvement”.
While there are signs to be hopeful about the potential of psychedelics for the future of mental health treatments, research has not yet offered conclusive evidence that would warrant safe and efficacious provision of psilocybin therapy. Two psilocybin trials so far have shown significant and long-term improvements for depression. However, these trials lacked placebo controls and the samples were pretty small. Several ongoing multisite trials with hundreds of participants will be able to give more reliable evidence about the therapeutic value of psilocybin. Nonetheless, these studies have not yet been completed and experts warn that it is precisely at this stage of drug development where most new pharmaceuticals fail. In the case of PTSD, larger studies are proving that MDMA-assisted psychotherapy may be useful, but not a single clinical trial has investigated psilocybin for this indication yet. In general, there are still a number of incognitas around safety, short- and long-term efficacy, relapse rates and the optimal amount of integration sessions.
One of the main concerns of researchers relates to the qualifications and therapeutic experience of these truffle providers. This is a complicated issue given that clinicians and researchers are still debating the adequate standards and training requirements for the certification of future psychedelic therapists. Some companies currently offering truffle therapy have a team of professionals with a background in mental health. In other cases, the psychotherapeutic and medical credentials of guides and their experience with disorders such as PTSD or depression are dubious.
The exposure of these sensitive populations to the intensity of the psychedelic experience can be risky if guides are not able to respond to the particular needs of psychiatric patients. In working with depression and psychedelics, Jan Mars emphasizes that “supporting a psychedelic journey is a humbling experience. You don’t know what is going to happen during the session. You can expect anything to happen,” and therefore, he adds, “It’s important that therapists know how to provide a safe environment. We still need much more experience and knowledge about how to work with patients who suffer from chronic psychological conditions. Trauma often lies beneath the surface and pops up during a session with psychedelics”. In regard to trauma therapy with these substances, Joost Breeksema adds: “Patients may relive traumatic moments, completely dissociate or become overwhelmed with fear and anxiety. This can be hard to handle even for an experienced therapist. Now imagine what happens with well-intended, but under-qualified and unprepared guides”.
Although these treatments are known to be generally safe in terms of toxicology and no serious adverse events are commonly reported in trials, their safety profile resides precisely in the close psychotherapeutic support and monitoring performed before, during and after psilocybin administration. Jan Mars hopes that in future clinical practice, “psychedelic journeys will be embedded in a safe and trusting therapeutic environment. These journeys are no magic bullets.”
In general, truffle providers understand the concerns of scientists, but they feel that the benefits of psilocybin treatment outweigh its risks. According to the clinical director of a truffle clinic, clients with depression may be thinking: “Damned! Science says that this can help me. It is not yet approved but there are places where it can be done safely so I am going to try”. From his own experience guiding sessions, Peter concluded that: “It all comes down to a balance between safety and effectiveness. We are all trying to find out, but at the moment psychedelic sessions do more to help people than to harm them”.
For psychiatric patients for whom other treatments have failed, this call for patience and caution may be difficult to accept. At the same time, they should be able to make informed decisions. Given the current exclusion criteria in psychedelic trials, researchers discourage patients with a history of personality or psychotic disorders from seeking these treatments at all. Jan Mars sends a piece of advice to those other patients without complex comorbidities who, despite potential risks, decide to seek truffle therapy: “Involve a loved one in the journey that you are about to embark on, for support before and after. Do some research on who is guiding it, what the setting will be like and whether there is enough time dedicated to the preparation of the session. Make sure that you feel you can trust the guide. If you have doubts, then there is probably a good reason for it, and it might not be a good idea.”
The relation between retreat and research
Truffle therapists in the Netherlands definitely have clinical research on psilocybin as their reference of best practice. Nick explained: “We frame it in a therapeutic setting to optimize positive outcomes and keep clients safe”. Nonetheless, researchers remain sceptical about the degree to which truffle providers actually manage to screen out participants with mental diagnoses or maintain high standards of care. To be fair, even some research protocols could be criticized for including the minimal amount of preparation and integration sessions.
Besides the potential harm to patients, researchers also seem to be worried about the future of research itself. The controversial history of the field has made psychedelic scientists generally cautious about avoiding any kind of social backlash. An unfortunate incident with a patient could set back the progress made in the last years. Renske Blom added: “If a major incident happens in the context of these therapy sessions, inside or outside clinical trials, it could influence upcoming research as well”.
While acknowledging the importance of further research, Nick also stressed that “truffles were never researched. They cannot say that psilocybin session guides are too early. Actually, the research is late because more people trip on naturals than on lab-grade psilocybin”. Bearing in mind the likely pharmacological difference between the synthetic compound and whole truffles, the current research agenda may not represent the interests of truffle therapists. In other words, it is unclear whether research with pure psilocybin would ever be considered valid evidence to justify their practice. Joost Breeksema said: “We don’t really know what truffles contain because they haven’t been standardized or analyzed in the laboratory, but I do think that if psilocybin goes through the approval process, it is likely that people and investors will get interested in the whole product as well.”
Despite the rather marginal position of truffles in current research, some investigators have realized the potential role that the retreat ecosystem can play in psychedelic science. In collaboration with retreat centers, several research projects have administered questionnaires to participants to learn more about the effects of these substances and their ritual use on healthy people. These centers could also become a place where all kinds of alternative models of psychedelic care can develop. The rigid regulatory and scientific frameworks within which researchers operate may limit the possible treatment conditions. In contrast, retreats offer the chance to explore new experimental protocols such as group sessions or natural settings. Joost Breeksema said: “The retreats may offer an infrastructure that is better suited to the psychedelic experience than clinical hospital settings”.
Nick is enthusiastic about future collaborations: “We want to set up research at our centers and we would love to count on scientific organizations, so we can actually build up the science needed and move beyond this internal dialogue about truffle therapy.” Joost Breeksema adds: “If they do proper data collection and analysis, they can contribute to the body of knowledge about the potential effects and risks of psychedelics. There are definitely options for collaboration but it has to be done judiciously and cautiously.”
The medicalization of psilocybin appears to raise tensions among different stakeholders in the psychedelic field. In the eyes of researchers, the underground therapy scene and the booming industry around psychedelic medicine may entail risks for patients and for the public image of ongoing research. Hopefully, future collaborations between retreat centers and research teams may offer a way forward to generate the evidence needed for an eventual regulation of the medical, as well as the non-medical uses of psilocybin truffles. However, at this stage, the open commercialization of psychedelic therapy to potentially vulnerable patients may be an unwise step ahead.
Written by Alberto Cantizani López Art by Anna Temczuk *The names of all informants involved in the commercial provision of truffles as therapy have been omitted or replaced by pseudonyms
Yaden, D. B., Yaden, M. E., & Griffiths, R. R. (2021). Psychedelics in Psychiatry-Keeping the Renaissance From Going Off the Rails. JAMA psychiatry, 78(5), 469–470. https://doi.org/10.1001/jamapsychiatry.2020.3672
Importance: Major depressive disorder (MDD) is a substantial public health burden, but current treatments have limited effectiveness and adherence. Recent evidence suggests that 1 or 2 administrations of psilocybin with psychological support produces antidepressant effects in patients with cancer and in those with treatment-resistant depression.
Objective: To investigate the effect of psilocybin therapy in patients with MDD.
Design, setting, and participants: This randomized, waiting list-controlled clinical trial was conducted at the Center for Psychedelic and Consciousness Research at Johns Hopkins Bayview Medical Center in Baltimore, Maryland. Adults aged 21 to 75 years with an MDD diagnosis, not currently using antidepressant medications, and without histories of psychotic disorder, serious suicide attempt, or hospitalization were eligible to participate. Enrollment occurred between August 2017 and April 2019, and the 4-week primary outcome assessments were completed in July 2019. A total of 27 participants were randomized to an immediate treatment condition group (n = 15) or delayed treatment condition group (waiting list control condition; n = 12). Data analysis was conducted from July 1, 2019, to July 31, 2020, and included participants who completed the intervention (evaluable population).
Interventions: Two psilocybin sessions (session 1: 20 mg/70 kg; session 2: 30 mg/70 kg) were given (administered in opaque gelatin capsules with approximately 100 mL of water) in the context of supportive psychotherapy (approximately 11 hours). Participants were randomized to begin treatment immediately or after an 8-week delay.
Main outcomes and measures: The primary outcome, depression severity was assessed with the GRID-Hamilton Depression Rating Scale (GRID-HAMD) scores at baseline (score of ≥17 required for enrollment) and weeks 5 and 8 after enrollment for the delayed treatment group, which corresponded to weeks 1 and 4 after the intervention for the immediate treatment group. Secondary outcomes included the Quick Inventory of Depressive Symptomatology-Self Rated (QIDS-SR).
Results: Of the randomized participants, 24 of 27 (89%) completed the intervention and the week 1 and week 4 postsession assessments. This population had a mean (SD) age of 39.8 (12.2) years, was composed of 16 women (67%), and had a mean (SD) baseline GRID-HAMD score of 22.8 (3.9). The mean (SD) GRID-HAMD scores at weeks 1 and 4 (8.0 [7.1] and 8.5 [5.7]) in the immediate treatment group were statistically significantly lower than the scores at the comparable time points of weeks 5 and 8 (23.8 [5.4] and 23.5 [6.0]) in the delayed treatment group. The effect sizes were large at week 5 (Cohen d = 2.5; 95% CI, 1.4-3.5; P < .001) and week 8 (Cohen d = 2.6; 95% CI, 1.5-3.7; P < .001). The QIDS-SR documented a rapid decrease in mean (SD) depression score from baseline to day 1 after session 1 (16.7 [3.5] vs 6.3 [4.4]; Cohen d = 2.6; 95% CI, 1.8-3.5; P < .001), which remained statistically significantly reduced through the week 4 follow-up (6.0 [5.7]; Cohen d = 2.3; 95% CI, 1.5-3.0; P < .001). In the overall sample, 17 participants (71%) at week 1 and 17 (71%) at week 4 had a clinically significant response to the intervention (≥50% reduction in GRID-HAMD score), and 14 participants (58%) at week 1 and 13 participants (54%) at week 4 were in remission (≤7 GRID-HAMD score).
Conclusions and relevance: Findings suggest that psilocybin with therapy is efficacious in treating MDD, thus extending the results of previous studies of this intervention in patients with cancer and depression and of a nonrandomized study in patients with treatment-resistant depression.
Davis, A. K., Barrett, F. S., May, D. G., Cosimano, M. P., Sepeda, N. D., Johnson, M. W., Finan, P. H., & Griffiths, R. R. (2021). Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial. JAMA psychiatry, 78(5), 481–489. https://doi.org/10.1001/jamapsychiatry.2020.3285
In the last 2 decades, there is a renaissance in the scientific investigation of the therapeutic potential of psychedelic compounds. It is studied for the treatment of many psychiatric disorders, including posttraumatic stress disorder. The treatment is always done in the setting of psychedelic-assisted psychotherapy. A little is known about the potential effects, outside of the setting of psychedelic-assisted psychotherapy, on people diagnosed with a mental disorder or have a significant trauma history. In this case report, we present a young man who developed posttraumatic stress disorder after a psychedelic experience, induced by both Lysergic Acid Diethylamide (LSD) and N, N Dimethyltryptamine (DMT). In the psychedelic experience, a repressed memory of childhood sexual abuse was recovered. To our knowledge, this is the first report on posttraumatic stress disorder onset after a psychedelic experience. We believe that this case report is important since the history of trauma is prevalent among individuals with substance use disorder. Medical staff that treat people with either substance use disorder or trauma should be familiar with irregular presentations, such as the one described in this case.
Rubin-Kahana, D. S., Hassan, A. N., & Le Foll, B. (2021). Posttraumatic Stress Disorder After a Psychedelic Experience, a Case Report. Journal of addiction medicine, 15(3), 248–251. https://doi.org/10.1097/ADM.0000000000000734
Objective: To use the Clinical Global Impression-Severity (CGI-S) scale to estimate clinically meaningful and clinically substantial changes as measured using the Montgomery-Åsberg Depression Rating Scale (MADRS), the Sheehan Disability Scale (SDS), and the Patient Health Questionnaire-9 (PHQ-9) in patients with treatment-resistant depression (TRD).
Methods: Pooled data were derived from two 4-week, randomized, active-controlled studies evaluating esketamine nasal spray (ESK) plus oral antidepressant (OAD) or OAD plus placebo nasal spray (PBO) in adults with TRD (N = 565). CGI-S, MADRS, SDS, and PHQ-9 scores were obtained at baseline and over 4 weeks of treatment. In this post hoc analysis, change scores on the MADRS, SDS, and PHQ-9 that corresponded to a clinically meaningful (1-point) or clinically substantial (2-point) change on the CGI-S scale were identified.
Results: Clinically meaningful changes in CGI-S scores after 28 days corresponded to 6-, 4-, and 3-point changes from baseline on the MADRS, SDS, and PHQ-9, respectively. Similarly, a 2-point CGI-S score change (clinically substantial change) corresponded to a 12-, 8-, and 6-point change on the MADRS, SDS, and PHQ-9, respectively. The proportion of patients showing substantial clinical improvement in the ESK plus OAD group versus the OAD plus PBO group after 28 days of treatment favored ESK plus OAD: 69.0% vs 55.3% (MADRS), 64.5% vs 48.9% (SDS), and 77.1% vs 64.7% (PHQ-9).
Conclusion: We provide a basis for identifying clinically meaningful and clinically substantial changes as assessed with commonly used outcome measures for depression to facilitate the translation of clinical trial results into clinical practice.
Turkoz, I., Alphs, L., Singh, J., Jamieson, C., Daly, E., Shawi, M., Sheehan, J. J., Trivedi, M. H., & Rush, A. J. (2021). Clinically meaningful changes on depressive symptom measures and patient-reported outcomes in patients with treatment-resistant depression. Acta psychiatrica Scandinavica, 143(3), 253–263. https://doi.org/10.1111/acps.13260
Background: The glutamatergic modulator ketamine has created a blueprint for studying novel pharmaceuticals in the field. Recent studies suggest that “classic” serotonergic psychedelics (SPs) may also have antidepressant efficacy. Both ketamine and SPs appear to produce rapid, sustained antidepressant effects after a transient psychoactive period.
Methods: This review summarizes areas of overlap between SP and ketamine research and considers the possibility of a common, downstream mechanism of action. The therapeutic relevance of the psychoactive state, overlapping cellular and molecular effects, and overlapping electrophysiological and neuroimaging observations are all reviewed.
Results: Taken together, the evidence suggests a potentially shared mechanism wherein both ketamine and SPs may engender rapid neuroplastic effects in a glutamatergic activity-dependent manner. It is postulated that, though distinct, both ketamine and SPs appear to produce acute alterations in cortical network activity that may initially produce psychoactive effects and later produce milder, sustained changes in network efficiency associated with therapeutic response. However, despite some commonalities between the psychoactive component of these pharmacologically distinct therapies-such as engagement of the downstream glutamatergic pathway-the connection between psychoactive impact and antidepressant efficacy remains unclear and requires more rigorous research.
Conclusions: Rapid-acting antidepressants currently under investigation may share some downstream pharmacological effects, suggesting that their antidepressant effects may come about via related mechanisms. Given the prototypic nature of ketamine research and recent progress in this area, this platform could be used to investigate entirely new classes of antidepressants with rapid and robust actions.
Kadriu, B., Greenwald, M., Henter, I. D., Gilbert, J. R., Kraus, C., Park, L. T., & Zarate, C. A. (2021). Ketamine and Serotonergic Psychedelics: Common Mechanisms Underlying the Effects of Rapid-Acting Antidepressants. The international journal of neuropsychopharmacology, 24(1), 8–21. https://doi.org/10.1093/ijnp/pyaa087
Background: Subanesthetic ketamine infusion therapy can produce fast-acting antidepressant effects in patients with major depression. How single and repeated ketamine treatment modulates the whole-brain functional connectome to affect clinical outcomes remains uncharacterized.
Methods: Data-driven whole brain functional connectivity (FC) analysis was used to identify the functional connections modified by ketamine treatment in patients with major depressive disorder (MDD). MDD patients (N = 61, mean age = 38, 19 women) completed baseline resting-state (RS) functional magnetic resonance imaging and depression symptom scales. Of these patients, n = 48 and n = 51, completed the same assessments 24 h after receiving one and four 0.5 mg/kg intravenous ketamine infusions. Healthy controls (HC) (n = 40, 24 women) completed baseline assessments with no intervention. Analysis of RS FC addressed effects of diagnosis, time, and remitter status.
Results: Significant differences (p < 0.05, corrected) in RS FC were observed between HC and MDD at baseline in the somatomotor network and between association and default mode networks. These disruptions in FC in MDD patients trended toward control patterns with ketamine treatment. Furthermore, following serial ketamine infusions, significant decreases in FC were observed between the cerebellum and salience network (SN) (p < 0.05, corrected). Patient remitters showed increased FC between the cerebellum and the striatum prior to treatment that decreased following treatment, whereas non-remitters showed the opposite pattern.
Conclusion: Results support that ketamine treatment leads to neurofunctional plasticity between distinct neural networks that are shown as disrupted in MDD patients. Cortico-striatal-cerebellar loops that encompass the SN could be a potential biomarker for ketamine treatment.
Sahib, A. K., Loureiro, J. R., Vasavada, M., Anderson, C., Kubicki, A., Wade, B., Joshi, S. H., Woods, R. P., Congdon, E., Espinoza, R., & Narr, K. L. (2020). Modulation of the functional connectome in major depressive disorder by ketamine therapy. Psychological medicine, 1–10. Advance online publication. https://doi.org/10.1017/S0033291720004560
Background: Higher body mass index (BMI) has been found to predict greater antidepressant response to intravenous (IV) ketamine treatment. We evaluated the association between BMI and response to repeat-dose IV ketamine in patients with treatment-resistant depression (TRD).
Methods: Adults (N = 230) with TRD received four infusions of IV ketamine at a community-based clinic. Changes in symptoms of depression (ie, Quick Inventory for Depressive Symptomatology-Self-Report 16; QIDS-SR16), suicidal ideation (SI; ie, QIDS-SR16 SI item), anxiety (ie, Generalized Anxiety Disorder-7 Scale), anhedonic severity (ie, Snaith-Hamilton Pleasure Scale), and functioning (ie, Sheehan Disability Scale) following infusions were evaluated. Participants were stratified by BMI as normal (18.0-24.9 kg/m2; n = 72), overweight (25-29.9 kg/m2; n = 76), obese I (30-34.9 kg/m2; n = 47), or obese II (≥35.0 kg/m2; n = 35).
Results: Similar antidepressant effects with repeat-dose ketamine were reported between BMI groups (P = .261). In addition, categorical partial response (P = .149), response (P = .526), and remission (P = .232) rates were similar between the four BMI groups.
Conclusions: The findings are limited by the observational, open-label design of this retrospective analysis. Pretreatment BMI did not predict response to IV ketamine, which was effective regardless of BMI.
Lipsitz, O., McIntyre, R. S., Rodrigues, N. B., Lee, Y., Gill, H., Subramaniapillai, M., Kratiuk, K., Nasri, F., Mansur, R. B., & Rosenblat, J. D. (2020). Does body mass index predict response to intravenous ketamine treatment in adults with major depressive and bipolar disorder? Results from the Canadian Rapid Treatment Center of Excellence. CNS spectrums, 1–9. Advance online publication. https://doi.org/10.1017/S1092852920002102