Ketamine Therapy and Depression Symptoms: What Mindbloom's PHQ-9 Research Found Across 36,847 Adults

Depression Is Nine Symptoms, Not One Score: Why Mindbloom Looked at Each

Depression affects millions of people, but anyone who has lived with it knows it does not look the same for everyone. Mindbloom's analysis set out to show which depression symptoms improve during ketamine therapy, by how much, and how quickly, measured only among the people who actually had each one.

One person may be stuck on feeling like a failure while sleeping fine. Another may concentrate without trouble but have lost interest in almost everything and have no energy to do anything about it. The research bears this out. In one study of 3,703 people starting depression treatment, researchers found 1,030 different combinations of symptoms, and even the most common combination described fewer than 2 in 100 patients (Fried and Nesse, 2015).²

Most outcome studies, including most research on ketamine therapy, still report one total score. A total can show that depression improved overall without showing which symptoms changed. It also mixes in people who never had a given symptom: someone who already concentrates well has no room to improve on concentration, so counting them blurs the result.

The analysis was built around those two problems. For each of the nine PHQ-9 symptoms, it followed only the patients who had that symptom on more than half the days when they started, and tracked how it changed over six sessions (Carter et al., 2026).¹ That answers a more useful question: for people who were struggling with this specific symptom, what changed during treatment?

About Mindbloom's PHQ-9 Research: Preprint Design, Participants, and Measures

Mindbloom's analysis is a preprint, posted on Preprints.org in October 2026, and it has not yet been peer reviewed (Carter et al., 2026).¹ It is a retrospective look at real-world, patient-reported outcomes from adults who started a new course of at-home ketamine-assisted therapy at Mindbloom between May 2021 and November 2025.

Who was included. The full cohort was 36,847 adults, with an average age of about 45, and roughly half were women.¹ Most (88%) took ketamine as sublingual tablets and the rest (12%) by subcutaneous injection, and results were combined across the two.¹ For each symptom, the analysis included only patients who scored 2 or 3 on that question at the start, meaning they had it on more than half the days or nearly every day.¹

How symptoms were measured. Patients completed the PHQ-9 before their first session and again after Sessions 2, 4 and 6, at a median of about two, five and six and a half weeks.¹ Each question is scored from 0 (not at all) to 3 (nearly every day). A symptom counted as improved if it dropped by at least 1 point, and as resolved if it reached 0.¹

Who the results describe. Results on this page reflect patients who completed the Session 6 check-in, between 175 and 1,769 people depending on the symptom.¹

How Much Did Depression Symptoms Improve Overall?

Before breaking depression into its nine symptoms, the analysis looked at the overall PHQ-9 score for patients who started with at least moderate depression, a total of 10 or more out of 27 (Carter et al., 2026).¹ Their average score fell from 15.6 at the start to 9.5 by Session 2, 8.2 by Session 4 and 7.5 by Session 6, a 52% drop.¹

By Session 6, 59% had responded, meaning their score was cut at least in half, and 31% were in remission, with a score below 5.¹ About 72% had moved below 10, the threshold for moderate depression.¹

The symptom results in the rest of this article are measured a different way. Each one covers only the patients who had that symptom at the start, so a symptom-level drop and the overall drop are not directly comparable.

Which Depression Symptoms Did Ketamine Improve Most? The Full Ranking

Mindbloom's analysis ranked all nine PHQ-9 symptoms by how much their severity dropped on average by Session 6, among patients who had each symptom on more than half the days at the start (Carter et al., 2026).¹ Every symptom improved, and on every one, at least three in four patients improved by a point or more.¹

The two symptoms at the top also had the smallest groups: thoughts of being better off dead or of self-harm (175 people at Session 6) and moving or speaking noticeably slower or more restlessly than usual (434 people).¹ Among the seven symptoms reported by the most patients, self-worth improved most, and fatigue and sleep improved least.¹

Each PHQ-9 symptom is a single question rather than a full standalone measure of that symptom, so a change in one symptom may partly reflect improvement in mood overall.

Anhedonia: Getting Interest and Pleasure Back

Anhedonia, losing interest or pleasure in doing things, is one of the two core symptoms of depression. Among the 1,565 Mindbloom patients who had it on more than half the days at the start:

• Symptom severity dropped 58% on average by Session 6 (Carter et al., 2026).¹
• About 89% improved by at least a point.¹
• 21% no longer reported any loss of interest or pleasure.¹
• Severity was already down 42% by Session 2.¹

Self-Esteem: Feeling Like a Failure Less Often

This question asks how often people feel bad about themselves, or feel like a failure, a core part of low self-worth. Among the 1,329 Mindbloom patients who felt this way on more than half the days at the start:

• Symptom severity dropped 62% on average by Session 6, the largest drop among the seven most common symptoms (Carter et al., 2026).¹
• About 87% improved by at least a point.¹
• 31% no longer felt bad about themselves at all.¹
• Severity was already down 46% by Session 2.¹

Concentration: Thinking Clearly Again

This question asks about trouble concentrating on everyday things, like reading or watching TV. Among the 1,335 Mindbloom patients who had this on more than half the days at the start:

• Symptom severity dropped 56% on average by Session 6 (Carter et al., 2026).¹
• About 84% improved by at least a point.¹
• 28% no longer had trouble concentrating at all.¹
• Severity was already down 42% by Session 2.¹

Energy: Less Fatigue, More Capacity

Feeling tired or having little energy was the most common symptom in the analysis, reported on more than half the days by 24,533 patients at the start (Carter et al., 2026).¹ Among the 1,769 who completed the Session 6 check-in:

• Symptom severity dropped 49% on average.¹
• About 79% improved by at least a point.¹
• 15% no longer reported any fatigue, the smallest share of any symptom.¹
• Severity was already down 39% by Session 2.¹

The next section looks at why fatigue moved less than other symptoms.

Appetite: Eating Patterns Settling

This question covers appetite changes in either direction: eating too little or too much. Among the 1,100 patients who had this on more than half the days at the start:

• Symptom severity dropped 57% on average by Session 6 (Carter et al., 2026).¹
• About 83% improved by at least a point.¹
• 31% no longer reported any appetite problems.¹
• Severity was already down 46% by Session 2.¹

Sleep: Sleeping More Easily

This question covers trouble falling or staying asleep, or sleeping too much. Mindbloom's dedicated sleep analysis followed 13,963 adults with frequent sleep trouble. Among the 1,340 who reached the end of treatment:

• Symptom severity dropped about 49% on average (Swain et al., 2026).³
• About 77% improved by at least a point.³
• 21% no longer reported any sleep trouble.³
• 67% had already improved by Session 2.³

Suicidal Ideation: What the Data Shows

This question asks how often people have thoughts that they would be better off dead, or of hurting themselves. It asks about thoughts, not plans or actions, and it is not a suicide-risk assessment. At the start, 2,128 patients reported these thoughts on more than half the days (Carter et al., 2026).¹ Among the 175 who completed the Session 6 check-in:

• Symptom severity dropped 73% on average.¹
• About 95% improved by at least a point.¹
• 49% no longer reported these thoughts at all.¹
• None reported their score getting worse.¹

This is the smallest group in the analysis, so these figures are less precise than the others. Among patients who started with no or only occasional thoughts of this kind, no more than 1.4% reported them on more than half the days at any later check-in.¹

If you are having thoughts of suicide or self-harm, call or text 988 to reach the Suicide and Crisis Lifeline in the US.

Where Ketamine Therapy Helped Least in Mindbloom's Data

Fatigue and sleep moved least. For both, symptom severity dropped 49% on average by Session 6, compared with 56% to 62% for the other common symptoms (Carter et al., 2026).¹ They also had the lowest shares of patients improving by at least a point, 79% for fatigue and 77% for sleep, and fatigue had the smallest share of patients who no longer reported the symptom at all, 15%.¹

These are still real improvements: roughly four in five patients with frequent fatigue or sleep trouble improved on each by Session 6.¹ But they are smaller than the changes in mood, interest, self-worth and concentration, and fatigue in particular was the symptom patients were least likely to be fully free of.

Fatigue and sleep are often among the hardest symptoms of depression to shift. In one three-year study of 267 people with depression, lack of energy and sleep problems were among the three symptoms that persisted most, still present 39% to 44% of the time even after depression had eased (Conradi et al., 2011).⁴ Fatigue and poor sleep can also have causes outside depression, such as other health conditions, sleep disorders, medications or the demands of daily life, which a course of depression treatment may not address.

For people whose main struggle is exhaustion or sleep, this is useful to know going in: these symptoms tended to improve, but more slowly and less completely than the rest.

How Fast Each Symptom Improved: Session 2 Compared With Session 6

Improvement showed up early. By the Session 2 check-in, a median of about two weeks after starting, Mindbloom patients' symptom severity was already down 39% to 59% depending on the symptom, and 67% to 80% had improved by at least a point on each one (Carter et al., 2026).¹ Every symptom kept improving through Sessions 4 and 6.¹

Fewer patients had reached the Session 6 check-in, which was added to routine data collection partway through the study period, so each column describes the patients who completed that check-in.¹

_{Average drop in symptom severity from the start, among patients who had each symptom on more than half the days.}

Self-worth and thoughts of self-harm showed the largest gains after Session 2, adding 16 and 19 percentage points by Session 6.¹ Sleep and fatigue showed the smallest, adding 10 percentage points each.¹

How Ketamine May Affect These Symptoms

Unlike most antidepressants, which target serotonin, ketamine acts on glutamate, the brain's main excitatory messenger, setting off growth signaling that builds new connections between brain cells (Krystal et al., 2024).⁵ Where those changes happen may help explain how ketamine helps depression symptom by symptom.

• Interest and pleasure. In stressed mice, one dose of ketamine restored weakened connections in the brain's reward hub, the nucleus accumbens (Lucantonio et al., 2025).⁶ In people with treatment-resistant depression, a single infusion brought reward learning up to the level of healthy participants within 24 hours (Bogdanov et al., 2026).⁷
• Self-worth. Depression tends to lock in rigid, negative beliefs about the self (Dai et al., 2025).⁸ Researchers describe a window after ketamine when thinking is more flexible and those beliefs may be easier to update (Hardy et al., 2026).⁹
• Concentration. In rats and mice, chronic stress strips away connections in the prefrontal cortex, the region behind attention and planning, and ketamine rapidly grew new ones and restored many that were lost (Li et al., 2010; Moda-Sava et al., 2019).¹⁰⁻¹¹

What the Mindbloom Protocol Involves and Who It May Fit

The patients in this analysis were adults in Mindbloom's at-home ketamine therapy program for depression, and the results on this page reflect their first six sessions. Here is how the program works:

• Choose your plan. You start by choosing how many sessions you want: 6, 12 or 18.
• Clinical consult. A psychiatric clinician reviews your symptoms, medical history and medications over video and decides whether ketamine treatment is appropriate. If you are not a candidate, you receive a full refund. If you are, you and your clinician choose a route, sublingual tablets or a small subcutaneous injection, and your clinician sets your starting dose and session spacing.
• Your medication and Bloombox arrive. Your prescription and your Bloombox, a kit with a journal, eye mask and blood pressure monitor, are shipped to your home.
• Sessions at home, with support. Sessions last about one to two hours. A trained guide meets with you before and after your first session, and a peer treatment monitor is present for every session. Your clinician monitors your progress and adjusts your dose as needed.
• Preparation and integration. Guided programs and one-on-one coaching help you prepare for sessions and work through what comes up between them.

Ketamine therapy is not right for everyone. Uncontrolled high blood pressure, a history of psychosis or mania, serious heart or breathing problems, and pregnancy are among the conditions that rule out treatment, and your clinician will check for medications that interact with ketamine.

Conclusion

Mindbloom's PHQ-9 analysis of 36,847 adults found that all nine depression symptoms improved during at-home ketamine therapy, with severity dropping 49% to 73% on average by Session 6 (Carter et al., 2026).¹ Among the most common symptoms, self-worth, anhedonia and depressed mood improved most, and fatigue and sleep improved least.¹ The changes were visible by Session 2, about two weeks in, and kept building through Session 6.¹

These findings come from a retrospective analysis of real-world, patient-reported data. What it adds is a symptom-by-symptom view of how depression changed for people who started treatment struggling with each symptom.