This retrospective analysis (n=431) of at-home ketamine treatments (1x p/w, 50-400mg lozenges) for depression, generalized anxiety, and social anxiety found statistically significant improvements in symptoms measured via PHQ-9, GAD-7, and SAD-D-10 at all follow-up time points (1-2-3 months). Minor side effects were reported by 18.8% of patients, resolving within 24 hours, and the majority concluded treatment within ≤ 6 months. No significant differences were observed between treatment-resistant and non-resistant depression outcomes.
Objective
To evaluate the effectiveness of repeated at-home ketamine treatments for depression, generalized anxiety, and social anxiety and assess safety in terms of adverse effects and tendency towards long-term use.
Methods
This retrospective analysis included patients with depression, generalized anxiety, and/or social anxiety who received ketamine treatment (delivered at-home via low-dose, sublingual lozenges) through a private telehealth provider. Data was collected between May 2022 and April 2023. The primary outcome was change in depression, generalized anxiety, and social anxiety symptoms from baseline to three follow-up time points, measured via Patient Health Questionnaire (PHQ-9), Generalized Anxiety Disorder Assessment (GAD-7), and Social Anxiety Disorder Severity Scale (SAD-D-10), with analysis subgroups established based on baseline diagnosis. Secondary outcomes included side effects, adverse events, long-term use, well-being improvements, and comparison of outcomes between treatment-resistant and non-resistant depression cases.
Results
Of 431 patients (mean [SD] age, 43.6 [10.9] years; 49.2% women), 81 (18.8%) reported minor side effects resolving within 24 hours, and 397 concluded treatment in ≤ 6 months. Statistically significant improvement on the primary outcome was observed at all follow-ups in all three subgroups (p < 0.001). No significant differences were found between treatment-resistant and non-resistant depression outcomes.
Conclusions
Repeated sublingual ketamine significantly reduced depression, generalized anxiety, and social anxiety with no major adverse events and minimal tendency towards long-term use observed. These findings prompt further exploration of ketamine as an alternative or adjunct to medications such as SSRIs and benzodiazepines to minimize response delays and dependence risk.
Papers cited by this study that are also in Blossom
Taylor, J. H., Landeros-Weisenberger, A., Coughlin, C. et al. · Neuropsychopharmacology (2017)
Mcintyre, R. S., Rosenblat, J. D., Nemeroff, C. B. et al. · American Journal of Psychiatry (2021)
Sanacora, G., Frye, M. A., McDonald, W. et al. · JAMA Psychiatry (2017)
Depressive and anxiety disorders cause substantial disability and reduced quality of life, and current pharmacotherapies have important limitations: selective serotonin reuptake inhibitors (SSRIs) are slow to act and ineffective in a sizeable minority, while benzodiazepines produce more rapid symptomatic relief but carry sedation, cognitive effects and a high risk of long-term dependence. Ketamine has emerged as a rapidly acting antidepressant with growing evidence of benefit in treatment-resistant depression and preliminary signals for efficacy in generalized anxiety disorder (GAD) and social anxiety disorder (SAD). Most clinical research has used intravenous administration, leaving questions about the feasibility, safety and effectiveness of less invasive, at‑home delivery methods such as sublingual lozenges. Swanson and colleagues designed the present study to examine real-world clinical outcomes following repeated, at-home subanesthetic sublingual ketamine provided through a private telehealth service. The primary aim was to evaluate changes in depression, generalized anxiety and social anxiety symptoms over three follow-up time points. Secondary aims included describing safety (side effects and adverse events), the tendency toward longer‑term use, patient-reported changes in functioning and a comparison of outcomes between treatment-resistant and non-resistant depression cases. The investigators frame this work as a retrospective assessment of routine clinical care to inform feasibility and signal detection for future controlled trials.
This study is a retrospective secondary analysis of de-identified patient records from a private telehealth practice (Wondermed) offering at‑home sublingual ketamine for adults with depression, GAD and/or SAD. Records were eligible if the patient was prescribed ketamine between May 2022 and April 2023 and completed at least one post-treatment assessment within 60 days of baseline. The University of California, Los Angeles IRB determined the analysis did not meet the definition of human subjects research and granted exemption. Patients underwent a clinical evaluation by trained physician assistants and nurse practitioners who applied eligibility screening and contraindication checks; prescription was limited to those judged low-risk by the providers. The typical prescription was a 1‑month supply of sublingual lozenges, most commonly 150–200 mg once weekly; clinicians could individualise dosing within a 50–400 mg range and a maximum frequency of twice weekly. Renewal required completion of a post-treatment questionnaire and a remote follow-up consultation. The intervention package also included an integration programme of daily exercises (journaling, meditation, breathwork, cognitive exercises) and hour-long soundscapes to use during sessions. Outcome data included baseline demographics and clinical characteristics and up to three follow-ups at approximately 30, 60 and 90 days. Primary outcomes were changes in PHQ-9 (depression), GAD-7 (generalised anxiety) and SAD-D-10 (social anxiety) scores. Secondary outcomes were safety (side effects/adverse events as reported after the first month and at follow-ups), prevalence of long-term use (ongoing treatment past 6 months measured by prescriptions dispensed), and patient-reported well-being changes. For subgroup analyses, the sample was divided by baseline severity thresholds: PHQ-9 ≥ 10 for depression, GAD-7 ≥ 10 for GAD, and SAD-D-10 ≥ 15 for SAD. Within the depression subgroup, treatment‑resistant depression (TRD) was defined as prior use of two or more antidepressants without adequate response; a non-resistant cohort included those with one prior inadequate trial, discontinuation for side effects, or no prior antidepressant use. The investigators note that detailed dose/duration data for prior antidepressant trials were not available. Because the outcome data did not meet assumptions for parametric tests, nonparametric methods were used. The Skillings–Mack test assessed changes from baseline to 1, 2 and 3 months while accounting for missing repeated measures, with Dunn's post hoc corrections; Friedman's ANOVA was applied for the subset completing all three follow-ups. Effect sizes (Cohen's d with 95% confidence intervals), and categorical endpoints—response (≥50% symptom reduction), remission (follow-up score < 5), deterioration (increase ≥5 points), and meaningful clinical improvement (MCI, ≥20% reduction)—were reported. Descriptive statistics summarised side effects, prescription counts and patient-reported well-being. Analyses were performed in R.
From 1,028 screened records, 431 patients met inclusion criteria after excluding those without post-treatment assessments, late follow-ups, or invalid data. The analysed sample had mean age 43.6 (SD 10.9) years and was 49.2% female. The mean interval between assessments was about 34 days. Based on baseline severity thresholds, 249 patients met criteria for the depression subgroup, 271 for generalized anxiety and 194 for social anxiety, although the extracted text contains inconsistent denominators for the social anxiety subgroup in some tables (see note below). Safety: Eighty-one of 431 patients (18.8%) reported minor side effects, most commonly dizziness, headache and nausea; all side effects resolved within 24 hours without medical assistance. One patient reported transient increased anxiety/depression that resolved within 24 hours. There were no reports of misuse, addiction, diversion, or serious adverse events (including suicidal behaviour or self-harm) in the analysed records. Regarding treatment duration, 285 of 431 patients (66.1%) received three or fewer prescriptions before stopping, and 397 of 431 (92.1%) stopped after six or fewer prescriptions, indicating limited continuation beyond six months for most patients. Primary clinical outcomes: Across all three subgroups, statistically significant improvements from baseline were observed at each follow-up (p < 0.001). Reported meaningful clinical improvement (MCI, ≥20% reduction) rates in the depression subgroup were 188 of 249 (75.5%) at 1 month, 85 of 106 (80.2%) at 2 months and 47 of 53 (88.7%) at 3 months. In the generalized anxiety subgroup MCI rates were 225 of 271 (83.0%) at 1 month, 108 of 119 (90.8%) at 2 months and 39 of 49 (80.3%) at 3 months. For social anxiety the paper reports 196 of 237 (82.7%) at 1 month, 89 of 102 (87.3%) at 2 months and 47 of 56 (83.9%) at 3 months; however, earlier in the results the social anxiety subgroup size is given as 194, so the denominators for social anxiety outcomes are inconsistent in the extracted text. Treatment response rates were highest at the 3‑month follow-up across subgroups, remission rates rose over time, and deterioration was uncommon (less than 3% overall). The authors note that no deterioration was directly attributed to treatment and that some patients who initially worsened later improved. Functioning and well-being: Self-reported positive changes were common: 391 of 431 (90.7%) reported overall improvements at 1 month, with 188 of 194 (96.9%) at month 2 and 100 of 101 (99.0%) at month 3. Commonly endorsed changes included improved ability to calm down under stress and increased hopefulness about the future. Treatment‑resistant status comparison: Within the depression subgroup, 38 patients met the study's TRD definition and 101 were classified as non-resistant; 110 patients lacked the necessary prior-treatment information and were excluded from this comparison. The extracted text states there was no significant difference in baseline depression severity between TRD and non-resistant cohorts but does not provide the baseline means in the available extraction. Outcomes appeared comparable between cohorts. Long-term treatment beyond six months was infrequent in both groups (3 of 101 non-resistant patients and 5 of 38 TRD patients continued past six months).
Swanson and colleagues interpret their findings as indicating that repeated, at‑home sublingual ketamine was associated with statistically and clinically meaningful reductions in symptoms of depression, generalized anxiety and social anxiety across three follow-up time points in this real-world telehealth cohort. Dosing sessions were generally well tolerated, with only transient, minor side effects and no serious adverse events reported in the analysed records. The investigators suggest that careful patient selection and remote monitoring practices used by the provider may have contributed to the favourable safety profile. The authors emphasise the relevance of the observed benefits for GAD and SAD given limited prior data, and note that care delivered by trained physician assistants and nurse practitioners appeared feasible and safe—an important point in light of workforce shortages. They further propose that ketamine's rapid onset could justify earlier consideration in selected patients rather than reserving it solely for treatment‑resistant cases, particularly when rapid reduction of suicidal ideation is clinically desirable. The study team also highlights that many patients reported improved functioning and well‑being, and they posit that the adjunctive integration resources (meditation, journaling, breathwork and soundscapes) may have supported these outcomes; they recommend further work to define optimal ways to combine ketamine with supportive therapies. The authors acknowledge key limitations: the retrospective observational design, absence of a comparator or control group, and limited generalisability given recruitment from a single private telehealth provider. They note an important selection effect introduced by the provider’s follow-up procedures—post‑treatment assessments were performed as part of prescription renewal, which excluded patients who completed only one month of treatment from outcome analyses and may bias results. Other limitations include incomplete data on prior antidepressant trial dose/duration and heterogeneity in dosing regimens. Finally, the investigators call for prospective randomised trials and longer-term studies to better establish optimal dosing, duration, candidate selection and the abuse/misuse risk of repeated at‑home sublingual ketamine.
In this retrospective, real-world cohort, repeated low-dose sublingual ketamine delivered for at‑home use via a telehealth service was associated with significant reductions in depression, generalized anxiety and social anxiety symptoms, high rates of patient‑reported functional improvement, and a low incidence of transient side effects. No serious adverse events were recorded in the analysed sample. The authors conclude that further controlled and long-term research is needed to define optimal dosing strategies, duration of treatment, patient selection criteria and the longer-term safety and misuse risks of this mode of ketamine delivery.
Depressive and anxiety disorders are highly prevalent, debilitating conditions with considerable negative impacts on global disability and health-related quality of life.Severe depression and anxiety represent major risk factors for suicide, the second leading cause of death in Americans younger than 35.Despite the staggering burden of these conditions, treating them remains challenging.Selective serotonin reuptake inhibitors (SSRIs) are indicated as first-line medications, but lack widespread effectiveness, with roughly 40% of patients failing to meaningfully respond, and come with long delays before onset of therapeutic benefit and a range of undesirable side effects.Benzodiazepines are another class of medications used for managing anxiety disorders, and while they elicit a more rapid response than SSRIs, they are linked to a variety of adverse effects, including sedation/drowsiness/fatigue; emotional numbness; and impaired cognition, memory, and judgment.Long-term use carries high risk of physical dependence (i.e., tolerance and/or withdrawal) and high potential for abuse and addiction.Ketamine has been identified as a promising new treatment option that addresses some of the limitations of current medications, delivering rapid and robust antidepressant effects within hours following a single dose, notably in cases of treatment-resistant depression (TRD).Preliminary evidence suggests therapeutic benefits across diverse conditions, including generalized anxiety disorder (GAD) and social anxiety disorder (SAD).To date, the majority of studies have investigated ketamine delivered intravenously (IV), but less invasive routes, such as sublingual administration, are of interest to improve accessibility.The ability of sublingual ketamine to be self-administered allows for dosing in an at-home setting, which-assuming the presence of rigorous safety measures-could provide an attractive alternative to in-clinic infusions for select patients.While the efficacy and safety of ketamine have been well-established in depression, most research has focused primarily on its use in more severe, treatment-resistant cases,and clinical data on GAD and SAD is also limited.The aim of the present study was to examine clinical outcomes of a large group of patients with depression, generalized anxiety, and social anxiety treated with repeated, subanesthetic doses of sublingual ketamine in an at-home setting to assess effectiveness, safety, and feasibility.
Data was obtained from a private telehealth practice that offered at-home ketamine treatment in the form of low-dose, sublingual lozenges for adults with depression, GAD, and SAD. All patients who were prescribed ketamine through the telehealth practice, Wondermed, between May 2022 and April 2023 were assessed for eligibility. All patients signed a detailed informed consent form granting the use of their personal health information for research purposes, subject to the requirements of applicable law. The study protocols were limited to secondary analysis of existing, de-identified patient data and involved no intervention or interaction with subjects. The institutional review board (IRB) of the University of California, Los Angeles, determined this study did not meet the definition of human subjects research, and as such, exemption from IRB review was granted.
Patients seeking treatment through the practice underwent thorough evaluation by a licensed clinician to ensure the clinical appropriateness of at-home ketamine treatment. This included an eligibility questionnaire to screen for contraindications and an intake questionnaire that included symptom severity screens in preparation for a psychiatric consultation. Clinicians included physician assistants (PAs) and nurse practitioners (NPs) that underwent training by the telehealth practice on how to safely and effectively prescribe sublingual ketamine. Providers made the final determination as to whether the patient was well-suited for at-home ketamine treatment, and prescription issuance was limited to patients assessed as low-risk. Criteria used by Wondermed to determine eligibility for ketamine treatment are detailed in the eAppendix (Supplementary Material). Study participants represent patients treated by the telehealth practice who completed at least one post-treatment assessment within 60 days of their baseline assessment.
For analysis of primary outcomes, the sample was split into three subgroups according to the indication(s) for which they received treatment, defined by baseline scores that met or exceeded established thresholds for moderate disease severity (depression subgroup, PHQ-9 score ≥ 10; generalized anxiety subgroup, GAD-7 score ≥ 10; social anxiety subgroup, SAD-D-10 score ≥ 15).While most participants had comorbidities, resulting in substantial overlap between subgroups (Table), the rationale for further division was to prevent primary outcomes from being skewed by patients without comorbidities who presented with minimal symptoms of one or more disorders. Patients in the depression subgroup were further classified into two cohorts based on treatment-refractory status to compare outcomes. The TRD cohort was defined as patients who reported prior use of two or more antidepressants without adequate response.While some TRD definitions include requirements related to dose and duration of previous trials, this data was not available in the present sample. The non-resistant cohort consisted of patients who: 1) reported inadequate response to only one previous antidepressant medication, 2) reported discontinuation of previous antidepressant(s) due to side effect intolerability, rather than lack of response, or 3) did not report previous antidepressant use. The full flowchart of sample selection and subgroup designation is presented in Figure.
Patients determined to be good candidates for at-home treatment were prescribed a 1-month supply of ketamine. Most patients received the standard dose of 150-200 mg/lozenge at a once-weekly frequency, but dose could vary from 50-400mg at a maximum frequency of twice-weekly based on clinician discretion. Full data on medication prescription patterns is reported in Supplementary Table. Patients wishing to renew their prescription for an additional month were required to complete a post-treatment assessment questionnaire and attend a remote follow-up consultation with their provider. Providers assessed the benefit of continued treatment, and dose was adjusted for follow-up prescriptions when appropriate. The intervention also included an integration program with daily exercises designed to help patients improve awareness of negative thought patterns and create new positive habits. Daily practices included journaling, meditation, breathwork, and therapy-based cognitive challenges. Hour-long soundscapes to listen to during treatment sessions were also provided.
The study included all data collected from baseline, up to and including the first three follow-up assessments (occurring approximately 30, 60, and 90 days after baseline). The number of follow-ups included was limited to three due to patient numbers becoming much smaller thereafter (n < 50 in each subgroup). Demographic and clinical characteristics were collected at baseline. The study's primary outcome was change in depression, generalized anxiety, and social anxiety symptoms from baseline to three follow-up time points, measured using the 9-item Patient Health Questionnaire (PHQ-9), the 7-item Generalized Anxiety Disorder Assessment (GAD-7), and the 10-item Social Anxiety Disorder Severity Scale (SAD-D-10). Secondary outcomes included safety, assessed using 1) data on side effects and adverse events (collected in a questionnaire administered after the first month of treatment, and at follow-up consultations), and 2) prevalence of long-term use (defined as ongoing treatment past 6 months, which was measured by number of prescriptions dispensed); as well as patient-reported changes across various well-being domains (collected at each follow-up). A final secondary outcome was comparison of treatment effects between treatment-resistant and non-resistant patients within the depression subgroup.
The data did not meet the assumptions required for the general linear model, thus necessitating nonparametric statistics for analysis of primary outcomes. To assess the statistical difference in scores at 1-, 2-, and 3-month follow-ups compared to baseline, the Skillings-Mack test was used, as it can account for missing data in analyses with repeated measurements.Dunn's post hoc test was used to correct for multiple comparisons. Friedman's ANOVA test was used for a subset of patients who completed three follow-ups (Supplementary Figure). In addition to statistical significance, effect size (Cohen's d, 95% confidence intervals) was also reported, along with other primary endpoints, including treatment response (50% or greater reduction in symptoms as reported on outcome measures from baseline to follow-up), remission (follow-up score less than 5), deterioration (score increase of 5 or greater), and meaningful clinical improvement (MCI), defined as a 20% or greater reduction in score compared to baseline (established in previous research for both PHQ-9 and GAD-7).While clinically meaningful change on the SAD-D-10 has not been established, prior work suggests this 20% threshold may be relevant across various psychiatric disorders.Descriptive analyses were conducted to determine the frequencies and distributions of sample population characteristics (e.g., age, sex, psychiatric disorder diagnoses); side effects and adverse events; and number of prescriptions dispensed. Changes in measures of well-being were also summarized using absolute frequencies and percentages of patients. For the treatment-resistant versus non-resistant depression analysis, a nonparametric independent t-test was used to compare PHQ-9 scores at each time point between the two cohorts. All analyses were performed in R (Version 4.
A total of 1,028 patient records were screened for eligibility. Of these, 597 patients were excluded from analysis due to: failure to complete at least one post-treatment assessment (n=460), completion of first post-treatment assessment > 60 days after completion of baseline assessment (n=112), and invalid data (n=25). A total of 431 patients met criteria for inclusion into the final study sample (Figure), of which 212 (49.2%) were women, with mean [SD] age of 43.6 [10.9] years (Table). The mean (SD) time interval between each assessment for all participants was 33.9 (9.7) days. Based on baseline severity scores, 249 patients met the criteria for inclusion in the depression subgroup, 271 met criteria for generalized anxiety, and 194 met criteria for social anxiety (Figure).
Minor side effects were reported by 81 of 431 patients (18.8%), the most common being dizziness, headache, and nausea (Supplementary Table). One patient (0.02%) reported increased anxiety/depression, which was resolved within 24 hours of dosing. All side effects were resolved without reported medical assistance and did not persist for longer than 24 hours. No late-onset side effects were reported. There were no reports of misuse, development of addiction, or diversion, and no serious adverse events (suicidal ideation, suicides or attempted suicides, or self-harm behaviors) were observed. The majority of the sample (285 of 431) received ≤ 3 prescriptions before stopping treatment (66.1%), with 92.1% of patients (397 of 431) stopping treatment after ≤ 6 prescriptions.
In the depression subgroup, significant improvement in PHQ-9 score was found at all three follow-up time points compared to baseline (p < 0.001) (Figure). Meaningful clinical improvement (MCI) was observed in 188 of 249 patients (75.5%) at 1 month, 85 of 106 patients (80.2%) at 2 months, and 47 of 53 patients (88.7%) at 3 months (Table). The generalized anxiety subgroup also demonstrated statistically significant improvement from baseline at each follow-up (p < 0.001) (Figure), with MCI achieved by 225 of 271 (83.0%), 108 of 119 (90.8%), and 39 of 49 (80.3%) of patients at months 1, 2, and 3, respectively (Table). Statistically significant improvement across all three follow-ups was also observed within the social anxiety subgroup (Figure). At 1 month, 196 of 237 patients (82.7%) achieved MCI, with 89 of 102 (87.3%) and 47 of 56 patients (83.9%) meeting criteria for MCI at months 2 and 3 (Table). Across all subgroups, the highest rate of treatment response was observed at 3-month follow-up (Table). Patients meeting remission criteria increased at each follow-up time point, and deterioration was minimal (less than 3% of all patients) (Table), with no reports of patients or clinicians directly attributing deterioration to treatment. Several patients who deteriorated reported challenges in their personal lives or extra stress at work to their clinicians during follow-up appointments. Four patients who continued treatment after deteriorating demonstrated significant improvement at subsequent follow-ups, with 3 concluding treatment with mild symptoms and 1 achieving remission at final follow-up. Data on the percentage of patients within each severity level category for each time point is presented in Supplementary Table.
Of the full study sample (n=431), 90.7% (391 patients) self-reported positive change(s) in their overall well-being and functioning at 1 month, with higher numbers at months 2 (188 of 194, 96.9%) and 3 (100 of 101; 99.0%). Commonly reported changes included better ability to calm down when stressed (258 patients, 59.9%) and feeling more hopeful for the future (286 patients, 66.36%). Full data on patient-reported positive changes is presented in Table.
Of the 249 patients in the depression subgroup, 38 patients met criteria for TRD, and 101 met the criteria for the non-resistant cohort, with 110 patients excluded due to: (1) no previous depression diagnosis (n=88), (2) unknown TRD status (n=22) (Figure). There was no significant difference in baseline depression severity between the treatment-resistant (mean These findings suggest comparable therapeutic effects regardless of treatment-resistant status. Prevalence of long-term treatment was minimal in both cohorts, with just 3 of 101 non-resistant patients and 5 of 38 treatment-resistant patients continuing treatment past 6 months.
In the present study, repeated sublingual ketamine was associated with significant improvement in symptoms of depression, GAD, and SAD at three follow-up time points in an outpatient telehealth setting. Dosing sessions were well-tolerated, and no serious adverse events were reported within the study sample for the duration of the data collection period. Cases of significant symptomatic worsening were minimal. The rigorous eligibility criteria for treatment used by the telehealth provider may have contributed to these positive safety outcomes. These findings suggest that with appropriate patient selection and monitoring, sublingual ketamine in an at-home setting can be a safe, practical, and clinically effective treatment option for patients with anxiety and depression. The clinical benefits observed in generalized and social anxiety symptoms are particularly noteworthy given the limited research on these indications.Also of note is the successful utilization of PAs and NPs as the lead care providers for this intervention, demonstrating the potential for advanced practice practitioners like PAs and NPs to proficiently, effectively, and safely prescribe ketamine. In light of a worsening physician shortage, increased utilization of PAs and NPs to deliver ketamine treatment may represent an effective strategy to improve access to care and decrease costs.Future studies should investigate ketamine's therapeutic potential across various psychiatric conditions in both open-label and randomized controlled trials. While most consensus groups recommend consideration of ketamine only after other antidepressant options have been exhausted,our findings provide evidence that ketamine's antidepressant efficacy is not exclusive to advanced cases of treatment-resistance. Earlier intervention with ketamine could be advantageous for select patients as a strategy to reduce the negative consequences of protracted ineffective treatment.For patients with suicidal ideation, ketamine's rapid onset of effectiveness is especially crucial, reflecting a distinct advantage over the delayed efficacy of SSRIs. At all three follow-ups, patients reported positive changes in functional outcomes and general well-being, including improved ability to regulate and manage emotions, increased productivity, and a more optimistic attitude about the future. Patients' perceived benefits may have been mediated by the therapeutic integration resources included in the program (e.g., meditation, breathwork, and journaling exercises), as the value of integrating ketamine treatment with nonmedicinal therapeutic modalities and mindfulness-based practices has also been previously described.Further research should seek to clarify how to most effectively integrate ketamine with other supportive therapeutic practices to optimize treatment outcomes. Previous studies found intermittent, repeated dosing regimens can prolong ketamine's therapeutic effects; however, concerns exist about the safety and abuse potential of this approach, particularly in at-home treatment settings. In the present study, low inclination for continuous long-term treatment was observed, with 66.1% of patients concluding treatment within three months, and 92.1% within six months. Of note, as many as 83% of individuals prescribed a benzodiazepine for anxiety use the drug for longer than 6 months, despite clinical guidelines establishing treatment should not exceed 8-12 weeks.Given the high dependence and addiction potential of benzodiazepines, as well as the severe and potentially life-threatening effects associated with withdrawal,our findings provide preliminary evidence for the potential of ketamine as a safer alternative in specific contexts. We recommend that additional long-term studies be conducted to confirm the low abuse and misuse potential of repeated sublingual ketamine treatments in this patient population. We acknowledge several limitations, including the retrospective observational design and the lack of a comparison group, resulting in within-subjects comparisons only. Generalizability is also limited by the characteristics of participants, all of whom actively sought at-home ketamine treatment through one private telehealth provider. Another notable limitation was that follow-up assessments were only administered by the telehealth practice when patients sought a prescription renewal. As a result, no post-treatment outcome data was available for patients who completed 1-month of treatment only, automatically excluding them from analysis. Individual reasons for treatment discontinuation could range from inadequate response, side effects, lack of perceived benefit, or symptomatic remission.
This retrospective observational study evaluated the use of at-home sublingual ketamine in the context of real-world clinical practice, finding statistically significant benefits across depression, generalized anxiety, and social anxiety symptoms. Repeated dosing was well-tolerated, with no major adverse events reported. Future research is warranted to understand optimal dose, dosing frequency, duration of treatment, candidate selection, and the long-term outcomes and risks associated with treatment. a Of the 431 patients included in the study, 249 met the criteria for inclusion in the depression subgroup (baseline PHQ-9 score ≥ 10), 271 met the criteria for the generalized anxiety subgroup (baseline GAD-7 score ≥ 10), and 237 met the criteria for inclusion in the social anxiety subgroup (baseline SAD-D-10 score ≥ 15). Most (265 of 431; 61.5%) had comorbidities between 2 or three conditions based on baseline screening scores, resulting in overlap between the subgroups. A total of 84 patients did not meet the baseline score required for inclusion in any of the three subgroups and thus were excluded from primary outcome analysis and included in analysis of secondary outcomes only. a Values in each column reflect the number of patients reporting each change at each follow-up time point. b Examples of other benefits noted by patients included increased ability to process repressed emotions, feeling more gratitude in day-to-day life, less frequent social media use, reduced food cravings associated with emotional eating, and more consistently engaging in self-care.
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