Early coadministration of clonazepam with sertraline for panic disorder

Arch Gen Psychiatry. 2001 Jul;58(7):681-6. doi: 10.1001/archpsyc.58.7.681.


Background: There is debate about combining benzodiazepines with selective serotonin reuptake inhibitors in the acute treatment of panic disorder. Although this medication combination is widely used in clinical practice, there is no well-tested, optimal method of coadministering these medications for the treatment of panic disorder. The purpose of this study was to test the efficacy of early coadministration of clonazepam with sertraline in the treatment of panic disorder.

Methods: Fifty patients with panic disorder were randomized into a double-blind clinical trial. Patients received open-label sertraline for 12 weeks (target dose, 100 mg/d), and in addition were randomized to groups receiving either 0.5 mg of active clonazepam 3 times daily or placebo clonazepam for the first 4 weeks of the trial. The clonazepam dose was then tapered during 3 weeks and discontinued.

Results: Thirty-four (68%) of 50 patients completed the trial. Drop-out rates were similar in the sertraline/placebo vs the sertraline/clonazepam group (38% vs 25%) (P =.5). An intent-to-treat analysis (on last observation carried forward data) revealed a much greater proportion of responders in the sertraline/clonazepam compared with the sertraline/placebo group at the end of week 1 of the trial (41% vs 4%) (P =.003). There was also a significant between-group difference at the end of week 3 with 14 (63%) of 22 of the sertraline/clonazepam group responding to treatment vs 8 (32%) of 25 of the sertraline/placebo group (P =.05). This difference was not observed at other times during the trial.

Conclusion: These data indicate that rapid stabilization of panic symptoms can be safely achieved with a sertraline/clonazepam combination, supporting the clinical utility of this type of regimen for facilitating early improvement of panic symptoms relative to sertraline alone.

Publication types

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

MeSH terms

  • Adult
  • Anticonvulsants
  • Clonazepam / therapeutic use*
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Humans
  • Male
  • Panic Disorder / diagnosis
  • Panic Disorder / drug therapy*
  • Panic Disorder / psychology
  • Placebos
  • Psychiatric Status Rating Scales / statistics & numerical data
  • Selective Serotonin Reuptake Inhibitors / therapeutic use*
  • Sertraline / therapeutic use*
  • Treatment Outcome


  • Anticonvulsants
  • Placebos
  • Serotonin Uptake Inhibitors
  • Clonazepam
  • Sertraline