Treatment-resistant schizophrenia (TRS) presents serious problems and unmet needs for clinicians, families, social, and legal services. Existing preliminary neurophysiological and clinical data confirm the hypothesis that ECT and dibenzodiazepine antipsychotics may have synergistic effects in TRS.

To evaluate efficacy and tolerability of two combination therapy options (ECT with clozapine [CLZ] and ECT with olanzapine [OLZ]) in TRS, as well as to differentiate clinical indications of the aforementioned methods in TRS.

80 TRS patients were randomised into four treatment groups: CLZ+ECT (n=19); OLZ+ECT (n=19); OLZ (n=21); CLZ (n=21), with dosage ranging 10–20mg OLZ and 200–900mg CLZ. ECT was administered 8-18 times in a twice weekly regimen. Patients (44 male, 36 female; mean age 32.2±11.6) were treated for 10 weeks and assessed using PANSS (total score [TS] and subscores), CGI and MOSES scales.

At the 10-week end-point, the number of responders (>30% PANSS TS reduction) in combination treatment groups was significantly higher compared to antipsychotic monotherapy: CLZ+ECT 53%, CLZ 14% (p<.05); OLZ+ECT 58%, OLZ 19% (p<.05); as was the mean PANSS TS reduction: CLZ+ECT 28.3%, CLZ 25.7% (p<.05); OLZ+ECT 37.6%, OLZ 26.3% (p<.01). Moreover, in combination groups the response threshold was generally observed 2–4 weeks earlier than in monotherapy groups.

Combining ECT with CLZ or OLZ improves and accelerates treatment response, and its efficacy is directly correlated with the number of ECT sessions. Specific indications include TRS with predominant catatonic, hebephrenic, negative and depressive symptoms. Combination options also demonstrated similar tolerability as CLZ and OLZ monotherapy.