CLINICAL RISK FOLLOWING ABRUPT AND GRADUAL WITHDRAWAL OF MAINTENANCE NEUROLEPTIC TREATMENT

Background: Abrupt discontinuation of long-term psychotropic medicatio n can be followed by a high risk of early relapse. This study aimed to quantify the relapse risk over time in patients with schizophrenia fo llowing discontinuation of maintenance neuroleptic treatment. Methods: Data on the timing of relapses in patients with schizophrenia after w ithdrawal from neuroleptic therapy were located by a computerized lite rature. search, combined with new data, and evaluated by survival anal ysis. Results: Data were found for 1210 schizophrenic subjects: 1006 ( 795 inpatients and 211 outpatients) were withdrawn abruptly from oral; neuroleptic therapy, and 204 discontinued treatment gradually (greater than or equal to 3 weeks) or stopped treatment with depot neuroleptic drugs. After abrupt discontinuation of oral medication, the risk of r elapse reached 50% within 30 weeks, with remarkably little additional risk thereafter to 3.7 years; inpatients relapsed more rapidly than di d outpatients (10 vs 18 weeks to a 25% relapse risk). In studies inclu ding subjects whose drug therapy was withdrawn abruptly (n=49) vs grad ually (n=58), relapse was earlier after abrupt discontinuation (25% ri sk in 6 vs 10 weeks), with a persistent difference for at least 6 mont hs. Conclusions: The relapse risk was high within 6 months of disconti nuing oral neuroleptic therapy, particularly in hospitalized patients. Most patients who remained stable for 6 months continued to do so for long periods without medication, indicating clinical heterogeneity. D rug-withdrawal stressors, related to long-term pharmacodynamic adaptat ions, are implicated. Since the risk was lower after gradually discont inuing oral neuroleptic therapy or stopping depot injections, early re lapse may be spared by a slow removal of drugs.