Abstract
I wish to document the fact that, at least in some cases, it is possible to electively withdraw clozapine without relapse of (previously treatment resistant) schizophrenia by substituting another atypical antipsychotic for clozapine with a lengthy withdrawal period.
The possibility of successful withdrawal is important because it reduces the deterrent impact, for both doctors and patients, of the idea that commencing clozapine means accepting a life-time sentence (a commitment to monthly blood tests and endless acceptance of troublesome side-effects). Also, it is important for doctors to be aware that elective withdrawal, with no relapse of psychosis, is possible when ceasing clozapine becomes almost mandatory in the presence of medically serious complications.
Although much attention has been given to the association of clozapine with serious complications and to addressing obesity in persons using clozapine, there is no literature about the optimal mode of withdrawal. The dangers of abruptly withdrawing clozapine have been extensively reported (see Goudie [1] and Moncrieff [2]) but official advice concerning elective withdrawal (Approved Clozaril product information; Novartis Pharmaceuticals Australia, amended 12 June 2009) is simply that, in ‘planned termination’ of clozapine, ‘reducing the dose gradually over one to two weeks is recommended’. Previously (Stanitta et al. [3] and Berecz et al. [4]) suggested cross-tapering clozapine with an alternative antipsychotic over a few weeks.
More cautiously, extending the cross-over period to about six months to allow for a return to clozapine if symptoms escalate, over the last ten years I have successfully withdrawn seven patients who requested to be free of clozapine because of side-effects or because of their intolerance of the blood monitoring regime. These patients were selected, from about sixty patients whom I have maintained on clozapine for eighteen months or more, because their psychosis, and clozapine dose, had been stabilized.
Each patient had a well documented history of years of treatment-resistant psychosis, with exposure to a number of antipsychotics before embarking on clozapine. All did well whilst on clozapine and all have continued to do well since ceasing clozapine. In only one (very recent) patient has this process failed.
I used a range of alternative antipsychotics with no special preference, as there is no convincing evidence of differential efficacy.
I do not claim that my methods of patient selection and clozapine withdrawal are ideal. I hope, only, to interest doctors in the idea of withdrawal and attempts to define best practice.