Polypharmacy, or the use of multiple drugs in the therapy of psychiatric disorders, is not recommended. However, appropriate combinations of pharmacologic mechanisms may enhance the efficacy of antipsychotic drugs and alter the course of schizophrenia. In recent years, some articles have been published about the successful use of clozapine and risperidone in combination for the treatment of patients with resistant schizophrenic and schizoaffective disorders. However, safety of this drug combination is open to discussion. This report presents the results of a preliminary study of five patients with resistant schizophrenia successfully treated with risperidone-olanzapine combination. The results suggest that this combination may be useful. In the future, the efficacy of risperidone-olanzapine combination should be confirmed in larger study populations before its clinical application is considered.
Coadministration of olanzapine, an atypical neuroleptic, with sulpiride, a selective D2 antagonist, is suggested as an efficient strategy for treating patients with resistant unremitting schizophrenia. The psychopharmacologic rationale that may account for the enhanced clinical efficacy of combining sulpiride with olanzapine and vice versa is the difference in affinity of the two drugs to brain receptors. Olanzapine affinity is related more to serotonin 5-HT2 than to dopamine-2, whereas sulpiride is considered a selective D2 blocker. The adjunction of a selective D2 antagonist to olanzapine may act as the olanzapine's augmentor by enhancing D2 blockage. This mode of treatment was introduced to six patients with chronic schizophrenia who showed noteworthy and rapid clinical improvement, supported by a decrease in their scores on the Positive and Negative Syndrome Scale and Brief Psychiatric Rating Scale. No bothersome side effects were noticed. This clinical approach is in accordance with the findings of previous reports assessing the efficacy of the combined treatment of clozapine and sulpiride. The grounds for this treatment regimen using olanzapine rather than clozapine are discussed, calling for further studies to affirm the hypothesis and clinical results.
Hypothesized that a combined regimen of clozapine, a relatively weak D₂-dopaminergic antagonist, and sulpiride, a selective D₂ blocker, would demonstrate a greater antipsychotic efficacy by enhancing the D₂ blockade of clozapine. 28 adults with schizophrenia, previously unresponsive to atypical antipsychotics and only partially responsive to current treatment with clozapine, received, double-blind, 600 mg/day sulpiride or placebo, in addition to an ongoing clozapine treatment. The clinical status was evaluated before, during, and at the end of 10 wks of sulpiride addition using the Brief Psychiatric Rating Scale (BPRS), Scale for the Assessment of Positive Symptoms (SAPS), Scale for the Assessment of Negative Symptoms, and Hamilton Rating Scale for Depression. The clozapine-sulpiride group exhibited substantially greater and significant improvements in positive and negative psychotic symptoms. About half of them, characterized by a younger age and lower baseline SAPS scores, had a mean reduction of 42.4% and 50.4% in their BPRS and SAPS scores, respectively. (PsycInfo Database Record (c) 2021 APA, all rights reserved)
BACKGROUND: Some treatment-resistant schizophrenic patients improve enough to remain out of the hospital but continue to have significant positive or negative symptoms.
METHOD: The goal of this study was to assess the safety and potential efficacy of risperidone as an adjunct for schizophrenic patients treated with clozapine. In an open 4-week trial involving 12 DSM-III-R-diagnosed patients, the addition of risperidone to clozapine was well tolerated and did not affect serum clozapine concentrations significantly.
RESULTS: Total Brief Psychiatric Rating Scale (BPRS) scores and subscales measuring positive symptoms, negative symptoms, and depressive symptoms were significantly reduced from baseline. Ten of 12 participants had a 20% or greater reduction in the total BPRS score.
CONCLUSION: In this open trial, the addition of risperidone to clozapine was well tolerated and produced significant reduction of symptoms, suggesting that this may be a useful clinical approach. Because this was an open trial, the improvement we observed must be replicated in a controlled trial.
The purpose of this trial was to assess the potential utility of adjunctive treatment with a typical neuroleptic for patients with refractory psychosis insufficiently responsive to clozapine alone. Seven chronic schizophrenic or schizoaffective patients who remained stabilized for at least 9 months on clozapine received open clinical trials with adjunctive loxapine lasting from 18 to 50 weeks. Their symptoms were documented with periodic Brief Psychiatric Rating Scale assessments. All patients improved at least somewhat and two improved remarkably. In the four cases in which the assessment was made, the loxapine had no apparent effect on plasma clozapine levels. We conclude that adjunctive treatment with typical neuroleptics for patients with an incomplete response to clozapine merits further investigation.
