Clozapine resistant schizophrenia: Newer avenues of management

Table 8 Steps for ensuring optimal clozapine treatment[65,81,110,111,120,123,132]

Steps for ensuring optimal clozapine treatment
Adequate assessment	Diagnosis should be established properly. Comorbid conditions should be looked for. Adherence should be determined. Symptoms and other outcome domains should be preferably rated using validated instruments. Caregiver burden and coping should be assessed. Stressors and adverse circumstances should be evaluated.
Proper dosing	Inter-individual and ethnic variability in optimal doses should be considered. If facilities for serum levels are available, doses should be titrated to ensure plasma levels > 350 ng/mL. Doses should be increased slowly with careful monitoring of side effects to reduce the burden of dose-dependent side effects.
Adequate duration	A minimum of 2-3 mo is considered necessary. Durations could be shorter in those with high risk of aggression or self-harm. Durations could be longer in those with negative or cognitive symptoms and in partial responders.
Managing side effects	Many of the common side effects of clozapine can be managed by slow titration, using the least effective dose, reducing doses when side effects develop, adding medications, or adopting lifestyle changes to counter side effects. Additionally, careful monitoring should be carried out for the more serious and idiosyncratic adverse reactions such as agranulocytosis and cardiopulmonary complications.
Managing non-adherence	Careful monitoring of adherence based on multiple sources is necessary. Managing side effects, educating patients to deal with negative attitudes to clozapine, developing a trusting alliance to improve motivation, caregiver education and support to increase their involvement in the patient’s care may help. These measures should ideally be initiated right at the beginning of treatment. Use of long-acting antipsychotic injections may be considered.
Collaboration with patients and caregivers	Both patients and caregivers should be the focus of treatment. Measures should be tailored according to their needs. Goals of treatment should be reduction of symptoms and distress, improving support, forging effective alliances, and promoting patient and caregiver engagement. Simple psychosocial measures including cognitive or behavioural strategies, psychoeducation, and emotional and practical support should be implemented at the start of treatment or as early as possible. More structured interventions can be tried depending on availability of resources and expertise.
Addressing clinician related barriers	Clinicians’ lack of awareness and experience of clozapine treatment and negative attitudes towards clozapine use should be addressed by proper education, dissemination of information, and dedicated facilities.