Clinical risk following abrupt and gradual withdrawal of maintenance neuroleptic treatment

Arch Gen Psychiatry. 1997 Jan;54(1):49-55. doi: 10.1001/archpsyc.1997.01830130055011.

Abstract

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Results: Data were found for 1210 schizophrenic subjects: 1006 (795 inpatients and 211 outpatients) were withdrawn abruptly from oral neuroleptic therapy, and 204 discontinued treatment gradually (> or = 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 In studies including subjects whose drug therapy was withdrawn abruptly (n = 49) vs gradually (n = 58), relapse was earlier after abrupt discontinuation (25% risk in 6 vs 10 weeks), with a persistent difference for at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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Oral
  • Ambulatory Care
  • Antipsychotic Agents / administration & dosage
  • Antipsychotic Agents / adverse effects*
  • Delayed-Action Preparations
  • Drug Administration Schedule
  • Female
  • Follow-Up Studies
  • Hospitalization
  • Humans
  • Injections, Intramuscular
  • Male
  • Recurrence
  • Risk Factors
  • Schizophrenia / drug therapy*
  • Schizophrenia / etiology
  • Schizophrenic Psychology
  • Substance Withdrawal Syndrome / diagnosis
  • Substance Withdrawal Syndrome / etiology*
  • Substance Withdrawal Syndrome / psychology
  • Survival Analysis

Substances

  • Antipsychotic Agents
  • Delayed-Action Preparations