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Clinical Risk Following Abrupt and Gradual Withdrawal of Maintenance Neuroleptic Treatment

Adele C. Viguera, MD; Ross J. Baldessarini, MD; James D. Hegarty, MD, MPH; Daniel P. van Kammen, MD, PhD; Mauricio Tohen, MD, DrPH
Arch Gen Psychiatry. 1997;54(1):49-55. doi:10.1001/archpsyc.1997.01830130055011.
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Background:  Abrupt discontinuation of long-term psychotropic medication can be followed by a high risk of early relapse. This study aimed to quantify the relapse risk over time in patients with schizophrenia following discontinuation of maintenance neuroleptic treatment.

Methods:  Data on the timing of relapses in patients with schizophrenia after withdrawal from neuroleptic therapy were located by a computerized literature search, combined with new data, and evaluated by survival analysis.

Results:  Data were found for 1210 schizophrenic subjects: 1006 (795 inpatients and 211 outpatients) were withdrawn abruptly from oral neuroleptic therapy, and 204 discontinued treatment gradually (≥3 weeks) or stopped treatment with depot neuroleptic drugs. After abrupt discontinuation of oral medication, the risk of relapse reached 50% within 30 weeks, with remarkably little additional risk thereafter to 3.7 years; inpatients relapsed more rapidly than did outpatients (10 vs 18 weeks to a 25% relapse risk). In studies including subjects whose drug therapy was withdrawn abruptly (n=49) vs gradually (n=58), relapse was earlier after abrupt discontinuation (25% risk in 6 vs 10 weeks), with a persistent difference for at least 6 months.

Conclusions:  The relapse risk was high within 6 months of discontinuing 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. Drug-withdrawal stressors, related to long-term pharmacodynamic adaptations, are implicated. Since the risk was lower after gradually discontinuing oral neuroleptic therapy or stopping depot injections, early relapse may be spared by a slow removal of drugs.

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