Treatment-Resistant Depression
Sofia, 38, software engineer
Fictional teaching case
Compare the formulations ↓Presentation
Four years of persistent depression unresponsive to two SSRIs, one SNRI, and 16 sessions of CBT. Functional but describes life as 'gray.' Sleep disrupted, anhedonia, loss of creative interests. Says: 'I've done everything right: therapy, meds, exercise. Nothing reaches wherever this lives.'
Read the full case history and clinical context
No trauma history she identifies. Loving family, stable career. First depressive episode at 24. Meditation retreat at 30 was the only time she felt 'something break through.' Interested in psychedelic-assisted therapy after reading about psilocybin research. Physician supportive.
Compare how approaches understand this case
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Showing 2 of 7 formulations.
ACT
Four years of trying to fix the depression has become the problem. The struggle with depression (experiential avoidance, fusion with 'I'm broken,' the control agenda) is narrowing her life more than the depression itself.
Creative hopelessness (what has the struggle cost?). Cognitive defusion from the 'treatment-resistant' identity. Values clarification. Willingness to have difficult internal experiences while living fully.
"What if the depression isn't the problem? What if the problem is that you've spent four years at war with it. And the war is what's making your life gray?"
Compassion-Focused Therapy
Treatment resistance may reflect a deeply entrenched inner critic and self-blame system. The self-attack ('I've done everything right and I'm still broken') maintains the depressive cycle. The soothing/affiliation system has been offline.
Psychoeducation about three emotion systems. Compassionate mind training. Compassionate self-correction replacing self-criticism. Building capacity for self-warmth and receiving care.
"Notice the tone of 'I've done everything right.' There's frustration in it, and there's something harder than frustration aimed at yourself. That tone isn't your fault. You didn't design a brain that turns on itself when it feels threatened. What I want to know is whether anything in you knows how to be warm toward you, because that system looks like it's been offline for years."
Buddhist Psychology / Contemplative Psychotherapy
The meditation retreat 'broke through' because contemplative practice directly addresses the root of suffering: clinging to a fixed self. The depression may be what happens when the constructed self cannot sustain itself but there is no framework for what comes next.
Sitting practice, not as a relaxation technique but as the investigation itself. Look at the 'gray' directly: what is it made of, where does it start and stop, how long does any one piece of it last? Work with the three marks (impermanence, suffering, non-self). Alongside that, maitri, unconditional friendliness toward the grayness, which is the exact opposite of the four-year campaign to get rid of it.
"You said the meditation retreat was the only time something broke through. What if we go back to that, not as self-improvement, but as investigation? What is this grayness, when you look at it directly?"
Existential Psychotherapy
The 'grayness' is not a symptom to be eliminated but a signal: a confrontation with meaninglessness that medication and CBT cannot address because it is not a malfunction. The meditation retreat 'broke through' because it touched something real.
Take the grayness seriously as existential communication. Explore what vitality meant before the depression. Sit with meaninglessness rather than trying to solve it. What does she care about that she has lost contact with?
"You've treated this as something broken for four years. What if it's not broken? What if the grayness is telling you something true about how you're living?"
KAP
Treatment resistance suggests the depression is held in place by something monoamine antidepressants and talk therapy have not reached. Ketamine works on a different system: NMDA blockade followed by a glutamate surge and a burst of synaptogenesis. The proposal, and it remains a proposal, is that this opens a window of days in which new learning takes unusually well, which is what the therapy is there to use.
Preparation sessions exploring intention and relationship to the depression. Ketamine dosing session with therapist present, music, eyeshades. Integration sessions to make meaning of the experience and consolidate shifts.
"During the medicine session, you may experience unusual states: dissociation, visual imagery, emotional intensity, or deep stillness. Whatever comes, I'll be right here. Your only job is to stay open."
Psilocybin-Assisted Therapy
Psilocybin may disrupt the rigid self-referential processing that maintains depression. The mystical-type experience (ego dissolution, oceanic boundlessness, noetic quality) correlates with lasting antidepressant response.
2-3 preparation sessions building therapeutic alliance and setting intention. 1-2 high-dose psilocybin sessions (25mg) with trained therapists. Multiple integration sessions processing the experience.
"Many people describe a sense of connection, to themselves, to others, to something larger, that the depression had walled off. We'll have plenty of time afterward to make sense of whatever comes."
ISTDP
'Nothing reaches wherever this lives' suggests the depression may be a defense against unconscious affect: likely grief or rage that was never experienced. Treatment resistance often signals characterological depression maintained by unconscious defenses rather than neurochemical imbalance alone.
Trial therapy to assess unconscious anxiety pathway. Pressure to feeling. Identify the triangle of conflict (feeling, anxiety, defense). Break through the defensive barrier to access core grief/rage.
"You said nothing reaches wherever this lives, and you said it with a shrug. Look at what your hands just did. Something is here right now. Do we keep it at arm's length, or do you want to find out what it is?"
Philosophical Lenses
These are not treatment plans. They are ways of seeing — philosophical perspectives that illuminate aspects of this case that clinical modalities may not address directly.
Sofia's depression may not be a disorder at all. It may be lucidity. She has seen through the automated meanings that sustain most people (career, achievement, routine) and found them insufficient. The grayness she describes is the absurd: the confrontation between the human need for meaning and the world's silence. Camus would not try to restore the meanings that failed her. He would ask whether she can live without them: whether she can face the absurd and still choose engagement, pleasure, rebellion against the terms of existence. The question is not 'How do we make the gray go away?' but 'Can you live fully in a world that doesn't answer back?'
Weil would recognize Sofia's state as affliction (malheur): not ordinary suffering but the condition in which suffering has destroyed the sufferer's capacity to want anything, including recovery. Affliction is characterized by social degradation, physical suffering, and a sense of being crushed by impersonal force. The danger is not the depression itself but the spiritual temptation to fill the void with false consolation. Weil would say the therapeutic task is radical attention: learning to wait in the emptiness without grasping, because genuine transformation requires the soul to be bare. This is the opposite of problem-solving.
Sofia is not sick. She is exhausted, worn down by the achievement society that has replaced external discipline with internal compulsion. She is both the exploiter and the exploited, driving herself to perform while experiencing the failure of performance as personal inadequacy. Her depression is not the absence of meaning but the burnout of a subject who has internalized the imperative to optimize. The 'grayness' is what remains when the capacity for contemplation, rest, and genuine experience has been consumed by productivity. Therapy that aims to restore her 'functioning' simply returns her to the system that broke her.
Sources & Method
This is a composite fictional case — no real client is depicted. Formulations represent how each modality would typically conceptualize and approach a case with this presentation, based on published clinical literature and training materials. Each formulation draws on the modality's own theoretical framework, key texts, and clinical principles as documented on its modality page. Full source citations for every modality are available on the Sources page.