Table 1. Recommendations for when to consider that a patient’s illness is treatment resistant used in international guidelines.

Guideline	Requirements of previous treatment				Severity of illness	Other
	Minimum number of failed APs	Specified AP	Adequate treatment episode duration	Dose
APA(6)	2	“At least one of which is a second-generation AP”	≥6 weeks	Therapeutic range	“a clinically inadequate response” “and for patients with persistent suicidal ideation or behaviour that has not responded to other treatments”	Nil
RANZCP (90)	2	Recommends both first and second trial to be of an atypical	6-8 weeks	Dosages specified for	“Poor response”	“If poor… adherence, or persistent suicide risk, positively offer trial of clozapine.”
BAP(91)	2	“One of the trials should be of an antipsychotic with an established, favourable, efficacy profile in comparison with other antipsychotics”	‘Adequate’	‘Adequate’	‘schizophrenic illness has shown a poor response to, or intolerance of the neurological side effects of [previous treatment]’	“Poor…adherence and …substance use should be excluded as causes of the …poor response to AP “
IPAP(92)	2	“…a typical or, if not available a trial of haloperidol, chlorpromazine or other typical antipsychotic”	4-6 weeks	‘Adequate’	Psychosis or mod-to-severe TD or tardive dystonia after adjusting dose”	Nil
Maudsley (79)	2	Consider use of either first generation or second generation AP	2-3 weeks for trial of first AP in FEP. 6 week trial for subsequent 2nd AP before clozapine.	At least minimum effective dose, then titrated to response	Not specified	Nil
MOHS(93)	2	No	Adequate	Adequate	“illness has not responded adequately to treatment”	2 trials should be given “sequentially”
NICE(5)	2	“One of the drugs should be a non-clozapine second-generation AP”	Not specified	Adequate	“illness has not responded adequately to treatment”	2 trials should be given “sequentially”
WFSBP(7)	2	“one of which should be an atypical antipsychotic”	6-8 weeks	Recommended dosage	no improvement at all or only insufficient improvement in the target symptoms	Compliance should be ensured, if necessary by checking drug concentrations

AP – Antipsychotic; APA – American Psychiatric Assocation; BAP – British Association for Psychopharmacology; FEP – First Episode Psychosis; IPAP - The International Psychopharmacology Algorithm Project; MOHS – Ministry of Health Singapore; NICE – National Institute for Clinical Excellence; RANZCP - Royal Australian and New Zealand College of Psychiatrists; WFSBP - World Federation of Societies of Biological Psychiatry.