TABLE 1.

The 5 “Cs” assessment (correct diagnosis, comorbid conditions, compliance, concentration of antipsychotics, continuous psychosocial stressors)

Correct diagnosis	Ruling out pseudoresistance conditions, such as severe personality disorders, mania, or depressive disorders with psychotic features, and other brain diseases, such as anti-NMDA receptor encephalitis,61,62 will allow the determination of other treatable causes of the patient's condition.
Comorbid conditions	Determining the presence of substance abuse, affective disorders, and obsessive-compulsive disorder or personality disorders61 allows for the incorporation of additional therapeutic modalities that may be synergistic with the augmentation trial.
Compliance	Assessment of the patient's ability to comply with treatment is essential. Poor compliance has been associated with substance abuse, greater hostility, and lack of insight.63 If the patient is determined to have questionable compliance, it may be necessary to delay the augmentation trial until the compliance issues are resolved.
Concentration of antipsychotics	Determination of the clozapine and norclozapine plasma concentration is recommended prior to initiating an augmentation trial. In a study by McCutcheon et al,17 a third of treatment-resistant patients were found to have subtherapeutic plasma concentrations. In general, plasma concentrations of clozapine should be at a minimum of 350 to 600 ng/mL.64 An upper limit for the range is unclear at this time. In the case of low plasma concentration of clozapine, the concentration should be increased to the minimum therapeutic threshold for an appropriate duration of time to assess the effect on the patient's symptoms. In general, a trial of 3 to 6 mo at a therapeutic plasma concentration should occur prior to initiating an augmentation trial65-71
Continuous psychosocial stressors	Factors such as poor housing, little social support, isolation, and poverty may contribute to the appearance of a treatment refractory condition in patients with schizophrenia.71

NMDA = N-methyl-D-aspartate.