3 Clinical psychopharmacology3.4 Therapeutics
3.4.2.3 Defining treatment resistance
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Written by Resident Doctor Committee · Published
New in the 2027 syllabus
The College added this topic for exams from January 2027.
Check the treatment was adequate first
Treatment resistance means the illness persists despite trials of treatment that meet a stated standard of adequacy. Counting how many prescriptions someone has had does not establish it.
Pseudo-resistance is when treatment only appears to have failed. Common causes are too little drug exposure, poor adherence, the wrong diagnosis or a comorbidity that has not been treated.
Before calling an illness treatment resistant, document each of the following.
Check | What to document |
|---|---|
Diagnosis | The current syndrome, other possible diagnoses and any comorbidity |
Dose | A therapeutic dose, or a specified dose that was adequately tolerated |
Duration | How long the person actually spent at the adequate dose |
Adherence | Discussion with the patient, dispensing history, supervised administration or suitable drug levels |
Outcome | Symptoms, functioning, side effects and change from baseline |
Schizophrenia
Treatment-resistant schizophrenia usually means clinically significant symptoms that persist despite at least two adequate trials of different antipsychotics.
The TRRIP (Treatment Response and Resistance in Psychosis) consensus sets out more detail:
each antipsychotic trial lasts at least six weeks at a therapeutic exposure
clinically significant symptoms persist for at least 12 weeks
there is functional impairment
adherence is at least 80% over the required treatment period. This is part of the minimum TRRIP research criteria, and you should assess it systematically.
If you are unsure whether the person actually took the drug, a long-acting injection or a prospective observed trial can help. Giving the drug does not by itself prove that the dose or the duration was adequate.
Clozapine is the established treatment after two adequate antipsychotic trials have failed. Do not let repeated, similar trials put off considering it indefinitely.
Major depression
Treatment-resistant depression commonly means not responding well enough to at least two adequate antidepressant trials in the current depressive episode.
What counts as an adequate duration depends on the medicine, the dose, how the response is progressing and which definition you are using. Studies do not all use the same threshold.
Stopping because of side effects (intolerance) is different from stopping because the drug did not work (non-response). Record which applied. Do not treat every brief exposure as a failure of efficacy.
When depression persists, think again about bipolarity, substance use and physical illness.
Using the label
Response means improvement from baseline. Remission means symptoms have fallen below a defined threshold. Someone can improve and still have a lot of residual illness.
A documented treatment history should say which definition of resistance is being used and which criteria have been met.
The label alone does not decide the plan. Treatment still depends on severity, urgency, the person's preferences, psychological treatment and their social circumstances.