3 Clinical psychopharmacology3.4 Therapeutics
3.4.2.2 Managing poor response and treatment resistance
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Written by Resident Doctor Committee · Published
Defining response
Term | Criterion |
|---|---|
Non-response | Under 25% symptom reduction after an adequate trial |
Partial response | 25 to 49% reduction with substantial residual illness |
Response | 50% or greater reduction from baseline |
Treatment resistance | Failure of a defined number of adequate, adherent trials |
Pseudo-resistance
Adherence should be explored without judgement before any dose change, switch or augmentation, because covert or partial non-adherence is common.
Check the diagnosis, physical illness, substance use, dose, duration, drug interactions and unusual metabolism before concluding resistance.
Injections confirm administration but not an adequate dose, and a therapeutic plasma level shows exposure, not response.
Treatment-resistant schizophrenia
Treatment-resistant schizophrenia means persistent moderate symptoms despite two adequate antipsychotic trials, each usually at least six weeks at a therapeutic dose with verified adherence.
Clozapine should be offered after two adequate trials, and repeated ineffective trials that delay it should be avoided.
Treatment-resistant depression
Treatment-resistant depression commonly means inadequate response to at least two adequate antidepressant trials.
Bipolarity should be reassessed, including past activation or mixed symptoms.
Partial benefit favours optimising or augmenting, whereas minimal benefit or poor tolerability favours switching.
Next step | Detail |
|---|---|
Selective serotonin reuptake inhibitor (SSRI) or serotonin and noradrenaline reuptake inhibitor (SNRI) plus mirtazapine or mianserin | Evidence-supported after partial response to an adequate trial, for example venlafaxine plus mirtazapine |
Lithium, quetiapine or aripiprazole | Specialist augmentation |
Liothyronine (tri-iodothyronine) | The thyroid hormone with an established augmenting role |
Electroconvulsive therapy | Severe depression needing a rapid response, failed treatments, psychotic depression or catatonia |
Mirtazapine adds alpha-2, serotonin 5-HT2 and 5-HT3 receptor blockade to the reuptake inhibitor.
Lithium prophylaxis in bipolar disorder
Rapid cycling, four or more mood episodes in 12 months, predicts a poor prophylactic response to lithium, whereas classic features predict a good one.