Schizophrenia is considered to be among the most severe, debilitating and persistent of all psychiatric disorders. Although the adult prevalence is approximately 1%, studies have indicated that sufferers constitute close to 10% of the permanently disabled population. (1) As such, schizophrenia is a major public health problem and the negative economic consequences underscore the urgent need to develop strategies to improve treatment effectiveness. (2)
Despite great advances in the understanding and management of the disease, a significant portion of individuals with schizophrenia do not respond well to drug treatment. (3) Management of these treatment-refractory patients is particularly challenging as they often require longer periods of hospitalisation, with their care ultimately amounting to a disproportionately high share of the total cost of schizophrenia. (1) Although the advent of the second-generation antipsychotic drugs has been regarded as a breakthrough owing to improved side-effect profiles and patient satisfaction, claims of their superior efficacy in treatment-refractory patients still remain unproven. (4) To date, in terms of evidence base, clozapine remains the undisputed treatment of choice for patients with severe treatment-refractory schizophrenia. (5-7)
Unfortunately, even though clozapine remains the gold standard, recent data show that 40 - 70% of sufferers from treatment-refractory schizophrenia treated with clozapine monotherapy, of adequate dosage and duration will continue to experience cognitive deficits and disabling symptoms, i.e. positive, negative or residual symptoms. (4-6,8) Several factors have been implicated in patient failure to respond to clozapine monotherapy, including patient non-compliance and intolerable and/or serious side-effects such as agranulocytosis, seizures, sedation, hypersalivation and metabolic issues. (3,9) However, for patients in whom these can be managed and who show at least partial response to monotherapy, effective clozapine augmentation treatment strategies need to be developed. (4)
Numerous different clozapine augmentation strategies have been described in the literature, but there is currently no actual evidence supporting one strategy over another, with research consisting mostly of case reports and small open-label, unreplicated studies. (6,10-15) Strategies include adjunctive antipsychotic medications, mood stabilisers and novel anticonvulsants, antidepressants such as selective serotonin re-uptake inhibitors and others, glycinergic agents, dopamine agonists, mazindol, omega-3 fatty acids and electroconvulsive therapy (ECT).
The combined use of clozapine and ECT was first proposed in 1990 by Fink and reported on in 1991. (9,15,16) A recent literature review on ECT-clozapine bitherapy in patients with treatment-refractory schizophrenia previously treated with clozapine monotherapy revealed 72% of reported cases to have had a beneficial response on the combination treatment. (17) To date, the largest single study reported on in the literature is an open-label study evaluating ECT-clozapine bitherapy in 11 clozapine non-responders, with 8 meeting remission criteria after treatment. (18)
Safety issues could be regarded as one potential concern when considering the use of ECT-clozapine bitherapy. It is known that clozapine use may lead to an increased risk of seizures or even prolonged seizures due to the threshold-lowering effects of clozapine. (19,20) Both ECT and clozapine may also cause cardiac arrhythmias, and memory effects have been described. (21-23) However, a recent review article on somatic augmentation strategies in clozapine-refractoriness by Tranulis et al. found that only seven incidences of significant side-effects in ECT-clozapine bitherapy had been described, with no fatalities. (24) They concluded ECT to be a safe and tolerable clozapine augmentation strategy. …