MADRS vs PHQ-9: How Ketamine Trials Measure Response

MADRS and PHQ-9 are the two depression rating scales most often used to judge whether low-dose ketamine is working, but they measure response differently enough that a patient can look like a responder on one and not the other. The Montgomery-Åsberg Depression Rating Scale (MADRS) is a 10-item, clinician-administered interview used as the primary outcome in the pivotal trials that led to FDA approval of esketamine (Spravato) for treatment-resistant depression in 2019. The Patient Health Questionnaire-9 (PHQ-9) is a 9-item self-report checklist many ketamine clinics use instead, because a patient can complete it in under two minutes without a trained rater. Understanding how the two scales diverge matters practically: if your clinic tracks PHQ-9 and you're trying to compare your results to published MADRS-based trial data, you need to know where the thresholds line up and where they don't.

What MADRS Measures

The MADRS was developed by psychiatrists Stuart Montgomery and Marie Åsberg and first described in a 1979 paper in the British Journal of Psychiatry, where the authors designed it specifically to be sensitive to short-term symptom change, the kind a clinician needs to track across weekly ketamine sessions (Montgomery & Åsberg, 1979). A trained rater, usually a psychiatrist, nurse, or research coordinator, asks structured questions and scores 10 items, including apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts, each on a 0 to 6 scale. Total scores range from 0 to 60, with higher scores indicating more severe depression. Because a clinician is also observing you, MADRS can pick up on signs you might not report yourself, such as psychomotor slowing, but your score can also shift somewhat depending on which rater is asking the questions.

What PHQ-9 Measures

The PHQ-9, developed by Kurt Kroenke, Robert Spitzer, and Janet Williams and validated in a 2001 study in the Journal of General Internal Medicine, is a self-report questionnaire built directly from the nine DSM symptom criteria for a major depressive episode (Kroenke et al., 2001). You rate how often each symptom, such as poor appetite, trouble sleeping, or feeling like a failure, bothered you over the past two weeks, scoring each item 0 (not at all) to 3 (nearly every day), for a total range of 0 to 27. Because there's no rater involved, PHQ-9 is faster to administer and easier to repeat at every visit, which is why outpatient ketamine clinics lean on it for session-to-session tracking. See our guide on ketamine PHQ-9 score change meaningful improvement for what a clinically meaningful drop in points actually looks like.

Why Response and Remission Thresholds Don't Line Up

Both scales typically define treatment response the same way: a 50% or greater reduction from your baseline score. That part is consistent. The mismatch shows up at remission, the threshold for being back to essentially well. Published depression-scale literature commonly sets MADRS remission at a score of 10 or below and PHQ-9 remission at 4 or below, sometimes defined as under 5, but these are not the same severity line translated into two units. MADRS's clinician-rated design and PHQ-9's self-report design can produce different scores for the same underlying mood state, especially for symptoms like psychomotor retardation or anhedonia that a trained observer may weight differently than a patient filling out a checklist alone. Our full breakdown of ketamine remission criteria for depression covers how remission is defined across different scales and trials.

This matters for low-dose ketamine protocols because the pivotal esketamine trials, TRANSFORM-1, TRANSFORM-2, TRANSFORM-3, and SUSTAIN-1, that supported the FDA's 2019 approval of Spravato for treatment-resistant depression used MADRS as the primary efficacy measure, according to the FDA's approval announcement (FDA, March 2019). If your own clinic only tracks PHQ-9, you cannot directly map your score onto those trial results; you can only use PHQ-9's own published response and remission cutoffs. Remember that low-dose intravenous or intramuscular ketamine for depression remains an off-label use, meaning the FDA has not evaluated it for this indication the way it evaluated esketamine; only esketamine (Spravato) carries that approval. For background on how eligibility and baseline severity factor into whether this treatment fits your situation, see our page on low-dose ketamine clinical eligibility criteria.

When the Two Scales Disagree

A patient can score well into remission range on PHQ-9 while MADRS, administered the same week, still reflects residual symptoms a clinician picked up on, such as mild psychomotor slowing or blunted affect. This is a documented limitation of comparing self-report and clinician-administered depression scales: they tend to correlate reasonably well at the group level but disagree often enough at the individual level, particularly near a response or remission cutoff, that neither scale alone should be treated as the final word on how you're doing. Scale choice can matter even more in ketamine therapy for older adults safety considerations, where overlapping medical symptoms like fatigue and sleep changes can inflate PHQ-9's somatic items in ways that aren't necessarily about mood. If you track your own symptoms with a journal between visits, pairing it with whichever structured scale your prescriber uses, rather than switching scales or comparing across scales, gives a cleaner signal of real change. Our ketamine dosing journal template and guide to how to track symptoms between ketamine treatments walk through what to log alongside whatever rating scale your clinic has chosen.

Dissociative side effects during and shortly after a low-dose ketamine session can also color same-day self-report scores if a PHQ-9 is completed too soon after dosing; most clinics wait until dissociative effects have resolved before administering any outcome measure. For more on how acute dissociation relates to longer-term antidepressant response, see ketamine dissociation and antidepressant response.