Prolonged Grief Disorder and Ketamine: What Mindbloom's Research Found

What Is Prolonged Grief Disorder and Why Doesn't It Get Better on Its Own?

Grief is a natural response to loss. Prolonged grief disorder (PGD) is something different.

PGD is a recognized clinical condition, now formally included in both the DSM-5-TR and ICD-11, characterized by grief that persists well beyond what most people experience and that significantly impairs daily functioning. Under DSM-5-TR criteria, the diagnosis requires symptoms lasting at least 12 months after the loss; ICD-11 sets the threshold at 6 months. Approximately 7–10% of bereaved adults develop PGD.¹

The core symptoms are distinct from ordinary sadness. People with PGD experience persistent, intense yearning for the person they lost; a disrupted sense of identity; difficulty accepting the reality of the loss; emotional numbness; an inability to re-engage with daily life; and a pervasive sense that life has lost its meaning. These aren't signs of grieving too much — they're signs that the grief has become clinically stuck.

While PGD frequently co-occurs with depression, it remains a distinct condition requiring specialized care.¹

Chronic grief physically changes brain structure and function, meaning it is not a failure of willpower. Prolonged grief dysregulates the HPA axis, elevates cortisol levels, and causes synaptic atrophy in the prefrontal cortex and hippocampus.³ The default mode network has been implicated in self-referential rumination and autobiographical memory, making it a plausible mechanism of interest in prolonged grief.⁴ The brain has essentially reorganized itself around the loss.

Identity disruption serves as a core dimension of the condition. When someone central to your life dies, you often lose the version of yourself that existed with them. Prolonged grief disorder is not just profound sadness; it is a fundamental loss of self. Identity loss sets the stage for understanding treatment outcomes, where role confusion often shows the greatest gains.

Most people experiencing prolonged grief have been told that time will heal their pain, but by definition, the condition is the grief that time did not heal. In the evaluated cohort, the median time since loss was 18 months, and 64% of participants had been grieving for over a year.

The core symptom dimensions of prolonged grief disorder include:

• Persistent yearning: An intense, consuming longing for the deceased person.
• Identity and role confusion: Feeling like you no longer know who you are.
• Emotional numbness: A blunted capacity to feel emotions.
• Difficulty accepting the loss: An inability to integrate the reality of the death.
• Preoccupation with the deceased: Grief crowds out daily functioning and thoughts.
• Difficulty re-engaging with life: Withdrawal from activities, hobbies, and relationships.
• Loneliness: A specific, profound aloneness tied directly to the absence.
• Meaninglessness: A persistent feeling that life is purposeless.
• Avoidance of reminders: Needing to avoid people, places, or things associated with the loss.
• Emotional pain: Bitterness, sorrow, or anger related to the death.

About Mindbloom's Research

Mindbloom's grief research evaluated 503 bereaved adults. Prior grief therapy research has typically been conducted primarily in specialty academic clinics with specially trained therapists, whereas the current analysis reflects at-home telehealth care. The findings were published as a preprint on Research Square (https://doi.org/10.21203/rs.3.rs-9839240/v1), making the data accessible to the public and the medical community.⁵

The analysis evaluated 503 bereaved adults who received care at home via telehealth using the Mindbloom protocol. Participants received sublingual or subcutaneous racemic ketamine and were all concurrently treated for depression. The median age was 45, 68% were female, and the median time since loss was 18 months. Eligibility required a PGD-13 score of 30 or higher at baseline, indicating significantly elevated grief.

Participants completed six guided sessions over approximately four to six weeks. The protocol included medical oversight, guide coaching, and integration support. Outcomes were measured using the PGD-13, which is a validated grief-specific instrument. A positive response was defined strictly as a reduction of 5 or more points from the baseline score.

The research is a real-world retrospective cohort analysis, meaning outcomes are observed in a care setting rather than proven caused in a randomized controlled trial. The headline outcomes are based on 121 completers who finished all six sessions and provided post-session 6 data out of the 503 enrolled participants.

What the Research Found: Overall Outcomes

In the published outcomes, 90% of completers reported improvement in their grief symptoms, with 76% meeting the study-specified threshold for a meaningful reduction. A meaningful response was defined strictly as a 5-point or greater reduction on the PGD-13 scale.

Among those who started with diagnosable prolonged grief disorder, 73% no longer met ICD-11 diagnostic criteria after treatment. Similarly, 71% no longer met DSM-5-TR criteria following the protocol. Meaning, for most people who started with a diagnosable grief condition, it was no longer diagnosable afterward. Furthermore, 64% dropped below the initial PGD-13 eligibility threshold of 30.

By session 2, typically within the first two weeks of treatment, 52% of participants with session-2 data had already responded, marking the biggest single-interval change in the analysis. Scores continued to decrease steadily through session 6, meaning people who had been grieving for a median of 18 months were already feeling measurably better within two weeks.

Ketamine therapy has a well-documented safety profile across hundreds of thousands of supervised sessions. Side effects in the population were uncommon and declined over the course of treatment, dropping from 7.4% at session 2 to 4.1% by session 6. In Mindbloom's broader published safety data, serious adverse events occurred in fewer than 0.1% of sessions.⁶

What Changed: Symptom by Symptom

The symptom that shifted most was identity and role confusion, which is the feeling of finally being like yourself again. Data showed that 77% of completers scored better on this item, the highest improvement rate of any symptom; the average drop on the item was 35.9%. Grief does not just make you sad; it makes you lose yourself, and the most notable change was people reclaiming their sense of identity.

Many participants reported progress on symptoms associated with feeling frozen or stuck in their grief. People did not just feel less pain; they started moving forward again.

• Identity and role confusion: 77% reported gains. Identity confusion involves the sense of not knowing who you are without the person you lost.
• Preoccupation and inability to function: 74% showed progress. Preoccupation reflects grief crowding out the ability to get through the day.
• Emotional numbness: 73% reported relief. Emotional numbness is a blunted capacity to feel anything at all.
• Re-engaging with life: 71% showed gains. Re-engaging involves starting to step back into activities, relationships, and the world.

A common fear is not wanting to stop missing a loved one, but the data show that yearning eased while people simultaneously re-engaged with life.

• Yearning: 71% reported easing. The consuming longing for the deceased softened.
• Emotional pain, bitterness, and sorrow: 65% reported reduction. The sharp emotional edges softened.
• Loneliness: 63% experienced lessening. The specific aloneness tied to the absence lessened.

Existential symptoms related to purpose and reality also showed notable movement.

• Meaninglessness: 59% reported a shift. Nearly 6 in 10 participants improved on the feeling that life is meaningless.
• Avoidance of reminders: 52% showed reduction. Over half stopped needing to avoid the reminders that used to be unbearable.
• Acceptance: 50% reported progress. Half found it easier to accept the reality of the loss.

These results are particularly notable given that participants had been grieving for a median of 18 months, with many stuck for years. The brutal psychology of prolonged grief often leads to resignation that life will always feel painful. The data provides a stark contrast to the resignation, showing that after years of living with profound grief, people started feeling better after just two sessions.

How Ketamine Targets the Mechanisms Behind Prolonged Grief

Ketamine has been FDA-approved as an anesthetic since 1970 and has been on the World Health Organization List of Essential Medicines since 1985, establishing a long medical history before its application to grief.² Ketamine is an NMDA receptor antagonist with known effects on neuroplasticity, glutamate signaling, and large-scale brain networks. These effects may be relevant to mechanisms involved in prolonged grief, including rumination, cognitive rigidity, identity disruption, and difficulty re-engaging with life.

Ketamine temporarily modulates NMDA receptor signaling, triggering a downstream surge in glutamate release. AMPA receptor activation follows, triggering rapid BDNF release and synaptogenesis that directly reverses the synaptic atrophy caused by chronic grief.^7,8 Restored synaptic density translates into improved cognitive flexibility, emotional regulation, and prefrontal function. These pathways help explain why improvement can begin within sessions rather than over weeks.

Prefrontal hypofunction impairs the sense of self, executive function, and the capacity to imagine a future. Restoring prefrontal connectivity offers a direct biological explanation for why feeling like yourself again was the top-moving symptom in the analysis.

Ketamine also reduces default mode network hyperconnectivity during sessions. That reduced connectivity underlies the dissociative state, which is therapeutically meaningful: it temporarily loosens the grip of habitual thought patterns.⁴ The marked gains in preoccupation and rumination likely trace to this effect, as the brain becomes less prone to looping on the loss.

Preclinical evidence suggests ketamine may normalize stress-hormone signaling along the HPA axis. Easing that hormonal imbalance may allow the brain to move out of a chronic stress response.³ Interrupting cortisol dysregulation could, in turn, help restore the energy and forward momentum that chronic grief depletes.

What Treatment Looks Like: The Mindbloom Protocol

The outcomes observed in the research came from a specific, supervised program rather than generic ketamine use. As described in the research protocol above, the program involves six guided sessions over four to six weeks. What distinguishes the protocol is how each component works together.

The program structure includes several core components designed to maximize safety and therapeutic benefit:

• Medical evaluation and personalized treatment plan: A licensed provider evaluates each person individually and determines eligibility.
• At-home sessions with a peer treatment monitor present: A peer treatment monitor, whom the client arranges, is required to be present during every session.
• App-guided preparation and integration: Protocol-driven content is provided before and after each session.
• Guide coaching sessions: One-on-one sessions with a trained guide help with preparation and integration.
• Unlimited guide messaging: Clients have ongoing access to their guide between sessions.
• Group Integration Circles: Community-based integration support connects participants with others.
• Ongoing medical oversight and dosage support: Provider-guided scheduling continues throughout the program.

Integration is the process of reflecting on, making sense of, and applying insights from ketamine sessions to daily life. The neuroplastic window that ketamine opens is where the behavioral and psychological work happens. For prolonged grief specifically, integration support helps people identify new ways of carrying the loss, rebuild engagement with life, and address identity disruption. Participating in Group Integration Circles further amplifies the progress.

The outcomes were achieved in a home environment, not a specialty clinic. The at-home ketamine therapy model provided a comfortable, familiar setting for participants to process their grief.

Mindbloom offers programs of 6, 12, or 18 sessions. After you select a program, a licensed provider conducts a comprehensive medical evaluation to confirm your eligibility and personalize your care plan. Mindbloom's at-home ketamine therapy starts at $165 per guided session for new clients, with programs billed in monthly installments. Returning clients pay as little as $129 per session with an 18-session program.

Who This May Be Right For

Prolonged grief disorder is the primary target for the therapeutic approach evaluated in the analysis. The condition applies to grief that has persisted for 12 or more months under DSM-5-TR criteria, or 6 or more months under ICD-11 criteria, and is actively interfering with daily functioning. If grief still has its hooks in you after months or years, you are not failing at it; you may have a real and treatable condition.

The published outcomes found clinically meaningful improvement across a diverse participant population, while recognizing that this retrospective analysis cannot establish causation. The median time since loss was 18 months, and 64% had been grieving for over a year. Response rates were similar across time since loss, meaning completers were about equally likely to report a meaningful reduction in grief symptoms whether their loss was recent or years ago. Improvement was observed across age groups, in both men and women, and across both sublingual and subcutaneous delivery routes.

Standard contraindications for ketamine therapy include uncontrolled hypertension, active psychotic disorders, and active substance use disorders. A qualified provider evaluates each person individually to determine if treatment is medically appropriate. Ketamine is FDA-approved as an anesthetic, and its use for grief represents off-label prescribing by licensed physicians based on medical judgment. Off-label prescribing is a widespread, legally accepted medical practice.⁹

Conclusion

Across 503 bereaved adults, Mindbloom's research showed a pre-specified response in 76% of completers, diagnostic remission in over 70%, and the largest gains in identity disruption and the frozen, stuck symptoms of grief.

The research is a retrospective analysis, and individual results may vary based on personal medical history and adherence to the treatment plan. If you recognize yourself in the data and feel stuck in your grief, speaking with a specialist can help you understand your options.

Important Safety Information

Ketamine is not FDA-approved for PTSD, depression, or anxiety. Common side effects include dissociation, increased blood pressure, nausea, dizziness, and cognitive impairment. Ketamine has abuse potential and is not appropriate for patients with uncontrolled hypertension, psychotic disorders, or substance use disorders. Do not drive or operate machinery until the day after treatment. Individual results may vary. Full safety information: www.mindbloom.com/safety-information

Off-Label Use Disclosure

Ketamine is FDA-approved only as an anesthetic. Use for mental health conditions represents off-label prescribing by licensed clinicians based on clinical judgment. Schedule III Controlled Substance - DEA regulations apply.