Clozapine resistant schizophrenia: Newer avenues of management

Table 7 Scandinavian nationwide cohort studies of antipsychotic treatment

Ref.	Study details	Results
Tiihonen et al[105], 2006, Finland	2230 inpatients followed up for 3.6 yr	Significantly lower risks of rehospitalization or treatment discontinuation in patients on perphenazine LAI, clozapine, or olanzapine vs those on oral haloperidol.
Tiihonen et al[106], 2009, Finland	66881 outpatients followed up for 11 yr	Clozapine was associated with a substantially lower mortality than any other antipsychotics singly or in combination, with perphenazine as a comparator.
Tiihonen et al[107], 2011, Finland	2588 inpatients followed up for 2 mo after discharge	Significantly lower risks of rehospitalization with LAIs than oral medications. Clozapine and olanzapine were associated with significantly lower risk of rehospitalization than risperidone.
Tiihonen et al[108], 2017, Sweden	29823 patients followed up for 5.7 yr	Significantly lower risks of rehospitalization and of treatment failure1 with LAIs and clozapine vs no antipsychotic treatment.
Taipale et al[109], 2018, Finland	62250 inpatients followed up for 20 yr	Significantly lower risks of rehospitalization with LAIs and clozapine vs no antipsychotic treatment in first episode and chronic schizophrenia.
Tiihonen et al[77], 2019, Finland	62250 inpatients on antipsychotic monotherapy or antipsychotic combinations followed up for 14 yr	Combination of clozapine and aripiprazole was associated with significantly lower risk of rehospitalization and mortality than clozapine alone in first episode and chronic schizophrenia. Clozapine monotherapy was associated with the most favourable outcomes compared to other antipsychotics.
Luykx et al[82], 2020, Finland	2250 patients on clozapine treatment followed up for more than 1 yr before discontinuation	Compared to no antipsychotic treatment, significantly lower risks of rehospitalization with re-institution of clozapine alone, oral olanzapine, and antipsychotic combinations. Significantly lower risks of treatment failure1with aripiprazole LAI, re-institution of clozapine alone, and oral olanzapine.

¹Treatment failure included re-hospitalization, suicide attempt, treatment discontinuation, medication switch, or death.

LAI: Long-acting antipsychotic injection.