Pimozide augmentation for the treatment of schizophrenic patients who are partial responders to clozapine

Randomised controlled trials of conventional antipsychotic versus new atypical drugs, and new atypical drugs versus clozapine, in people with schizophrenia responding poorly to, or intolerant of, current drug treatment

“…Relevant published data are limited to a few recent case reports, case series and small studies. Adjunctive antipsychotics tested include pimozide, 54 sulpiride, 55 olanzapine, 56 loxapine 57 and amisulpride, 58 with reports of further clinical benefit. While the addition of risperidone in a couple of published cases failed to produce any improvement, 59,60 the majority of reports involving this drug have also been positive, 53,[61][62][63][64] For example, in a 4-week, open study, Henderson and Goff 62 assessed the safety and efficacy of risperidone as an adjunct in 12 patients with schizophrenia who continued to show positive and negative symptoms despite treatment with clozapine.…”

Treatment–Refractory Schizophrenia

“…The data derive mostly from case reports and open studies indicating improved efficacy of clozapine treatment following the addition of risperidone, [116][117][118][119][120][121][122] olanzapine, 123 or typical agents, such as pimozide and sulpiride. [124][125][126] However, the rationale behind this strategy remains elusive and the supportive data are doubtful. Selecting polypharmacy regimens according to specific symptoms or on the basis of a putative mechanism of action is way ahead of the current state of basic knowledge of schizophrenia pathophysiology and the recognized mechanism of action of drugs.…”

When Is Antipsychotic Polypharmacy Supported by Research Evidence? Implications for QI

“…51 We identified nine noncontrolled observational trials comparing antipsychotic polypharmacy to monotherapy in samples with established treatment resistance to trials of a single antipsychotic (Table 1). [53][54][55][56][57][58][59][60][61] All studies were of patients with schizophrenia or schizoaffective disorder. Eight of the trials reported significant improvement in reduced symptoms with the addition of a second antipsychotic.…”

“…Eight of the trials reported significant improvement in reduced symptoms with the addition of a second antipsychotic. 53,[55][56][57][58][59][60][61] Of the eight studies that examined side effects, four reported no change with the addition of a concurrent antipsychotic. 53,54,59,60 Three studies reported increased side effects with the addition of another antipsychotic, [56][57][58] whereas one study reported a decrease in sedation.…”

“…Of the nine trials, eight involved clozapine augmentation. [53][54][55][56][58][59][60][61] Clozapine was augmented with risperidone in three studies; 54,56,59 amisulpride (a second-generation drug not available in the United States) in two trials; 53,58 and pimozide 55 , aripiprazole, 60 and ziprasidone 61 each in one trial. The ninth trial reported on the nonspecific use of two SGAs in combination.…”