This is a fictional, illustrative case created for education. It is not medical advice, diagnosis, or treatment, and does not describe a real person.

Eight years. Four SSRIs. None of them worked. Here's why.

Kofi, 36, was told his depression was treatment-resistant after four antidepressants failed. His genetics suggested a simpler story: the same dose was not behaving the same way in his body.

Persona

Kofi, 36, Male, Ghanaian-British, Secondary school teacher.

Eight years of depression. He has tried sertraline, fluoxetine, citalopram, and escitalopram. None helped at standard doses, and two caused severe side effects when the dose was raised. He is on no antidepressant now because he gave up. His family doctor called it treatment-resistant depression. Kofi is not convinced.

Family history: Mother: depression, on mirtazapine — works well for her. No one in the family has done well on SSRIs.

Clinical picture

Symptoms

Labs

Medications

Supplements

Lifestyle

Genetics

Four prescriptions told the same story

Kofi is 36, a secondary school teacher, and has been depressed since his late twenties. He tried sertraline, fluoxetine, citalopram, and escitalopram. Each time, the standard dose did almost nothing. When two doses were raised, the side effects became too much. He stopped trying two years ago. Then his family doctor called the depression treatment-resistant. But one family clue kept bothering him: his mother does well on mirtazapine, and no one in the family seems to do well on SSRIs.

The label assumed the dose had a fair chance

'Treatment-resistant depression' means depression that has not responded to two or more antidepressant trials. But the label assumes each drug reached the right level in the blood and stayed there long enough to work. If someone clears the drug unusually fast, a normal dose may never get a fair chance. The chart says the drug failed. The body may be saying the dose never behaved normally.

The same dose was not the same dose for him

Kofi's results show that his body makes extra CYP2D6 enzyme, which breaks down many antidepressants. At standard doses, the medication may have cleared before it built up enough to help. When the dose was raised, the system may have become less predictable, creating spikes that felt like side effects instead of steady treatment. He may not have failed four medications. Four standard doses may have failed to match his biology.

The family clue finally mattered

Two of his four trials — citalopram and escitalopram — also depend on CYP2C19, and Kofi clears that pathway quickly too. A third result points to a serotonin system that may not respond well to the SSRI mechanism even when dosing is solved. That makes his mother's response to mirtazapine more than a coincidence: it works through a different route and avoids the main problem pathways. The family pattern was a clue the whole time.

Five things to do with this information

Kofi's 14-day check-in on mirtazapine

Daily mood, sleep & motivation — on mirtazapine. Kofi started mirtazapine after reviewing his pharmacogenomics results with his clinician. The first few days were sedating, which is common. By day 9, the grogginess eased and the mood shift was clear.