Practice choices

There is no evidence that any one drug is better than any other for long-term maintenance if one's 'endpoint' is relapse, although there is persuasive, if largely anecdotal, evidence that in terms of quality-of-life parameters, clozapine offers superior benefits. (57)

There is powerful evidence that the choice of a depot formulation is associated with substantial improvements in relapse prevention. Support for the value of depot over oral administration comes largely form 'mirror-image' studies, which compare a period on depot with a corresponding period prior to starting depot, in terms of, primarily, time spent in hospital. Six such studies were unanimous in showing a substantial reduction of time spent in hospital after the switch to depot (range 55-90 per cent; average 77.8 per cent).(58) There is no evidence that depots are themselves inherently more efficacious in maintenance. Their advantage seems to spring entirely from the enhanced compliance that ensues from their long-term use.

The other treatment practice variable is dosage. There is substantial evidence that long-term, low-dose antipsychotic regimens are associated with an increased risk of relapse. This has been investigated mainly in relation to depots, particularly fluphenazine decanoate. Kane et al.(59) found 1.25 to 5 mg every two weeks to be significantly less effective than 25 mg, a finding supported by other authors and with other preparations. (6,6!,62 and 63>

Interpretation of such data is, nonetheless, not clear, and applying a dose-response model, Baldessarini et al.(47) have argued that in long-term treatment the half-maximal effective doses (ED5C) may be as low as one-fifth to one-tenth those normally employed. Even the statistical findings of the studies above indicate that some individual patients may be successfully maintained on low-dose depot regimens. Kane and colleagues showed that while relapse rates were higher in the low-dose group, neurological adverse effects and psychosocial/quality-of-life parameters were superior. (59> Similarly, the Northwick Park First Episodes Study found that at endpoint, significantly fewer of those treated with active drug achieved some specific advance or attainment in their life than those on placebo. (64> This raises concern that maintenance antipsychotic treatment may have hidden costs.

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