Treatment Resistance

Failure to respond to medication, sometimes termed ''treatment resistance'', is not always due to a failure of the medication itself or an inadequate dose. The lack of response might be explained by factors such as nonadherence, unusual metabolism of the medication or poor absorption [11]. If nonadherence is a problem, then more intensive and sophisticated psycho-education treatment can be helpful, as can administering the medication in liquid oral form or parenterally if ultimately essential (and if appropriate formulations are available).

If the patient has complied with treatment for an adequate time but psychotic symptoms have failed to improve, then alternative treatment approaches should be considered. If the patient can tolerate a higher dose without significant side effects, then raising the dose for a limited period, such as 4-6 weeks, can be tried, although it is rarely beneficial [11]. If this does not result in an adequate response, a second atypical antipsychotic medication should be considered.

A trial of clozapine should be considered for patients who have positive (and perhaps negative and cognitive) symptoms that do not fully respond to an adequate trial of at least one and probably two other antipsychotic medications within the first few months of treatment. Clozapine treatment requires patients to be free of special risk factors such as cardiac arrhythmia, and to be willing and able to cooperate with regular monitoring, including blood tests for haematological side effects and glucose intolerance, and cardiac monitoring. Cognitive-behaviour therapy may also be a useful adjunctive strategy, when positive symptoms are persistent [61].

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