Long-term maintenance and discontinuation of imipramine therapy in panic disorder with agoraphobia

Arch Gen Psychiatry. 1999 Sep;56(9):821-7. doi: 10.1001/archpsyc.56.9.821.


Background: There has been little systematic work done regarding the long-term treatment of panic disorders. The aim of the present study was to assess the 12-month cumulative risk of relapse specifically due to discontinuation of imipramine and to test the hypothesis that maintenance treatment with imipramine protects patients with panic disorder and agoraphobia from such reversals.

Method: Following an acute-phase open trial with imipramine (2.25 mg/kg per day) involving 110 patients for 6 months, the 56 patients who were in stable remission, did not require additional treatment, and consented to be randomly assigned to double-blind maintenance (n = 29) or discontinuation (n = 27) conditions were followed up with planned assessments every 2 months during a 1-year period. There were no behaviorally oriented interventions or instructions at any time during the 18 months of the study.

Results: Maintenance treatment (1 relapse) and discontinuation (10 relapses) conditions had significantly different survival curves (Mantel-Cox statistic chi(2)1 = 10.47, P = .001). None of the additional 10 variables from demographic, clinical, and open-treatment domains considered in the proportional hazard model disrupted the significant relationship between experimental drug condition and relapse; other things being equal, a patient receiving imipramine maintenance was 92.5% lower in the hazard rate of relapse than a patient receiving placebo.

Conclusion: The results confirm the very high degree of prophylactic effectiveness of maintenance imipramine treatment and demonstrate that relapse, although substantial, occurs in a minority of patients with panic disorder and agoraphobia who are in stable remission prior to treatment discontinuation.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Agoraphobia / diagnosis
  • Agoraphobia / drug therapy
  • Agoraphobia / prevention & control*
  • Antidepressive Agents, Tricyclic / therapeutic use*
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Follow-Up Studies
  • Humans
  • Imipramine / therapeutic use*
  • Male
  • Panic Disorder / diagnosis
  • Panic Disorder / drug therapy
  • Panic Disorder / prevention & control*
  • Proportional Hazards Models
  • Psychiatric Status Rating Scales
  • Secondary Prevention
  • Substance Withdrawal Syndrome / etiology
  • Substance Withdrawal Syndrome / prevention & control
  • Treatment Outcome


  • Antidepressive Agents, Tricyclic
  • Imipramine