A randomized controlled trial of venlafaxine ER and paroxetine in the treatment of outpatients with panic disorder
Few randomized, placebo-controlled trials have evaluated the comparative efficacy and tolerability of more than one pharmacological agent for panic disorder.
The primary objective of this study was to compare the efficacy and tolerability of venlafaxine extended release (ER) with placebo in treating panic disorder. Secondary objectives included comparing paroxetine with venlafaxine ER and placebo.
Outpatients aged ≥18 years (placebo, n = 157; venlafaxine ER 75 mg, n = 156; venlafaxine ER 225 mg, n = 160; paroxetine, n = 151), with a primary diagnosis of panic disorder (±agoraphobia) based on the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) criteria for ≥3 months were randomly assigned to receive venlafaxine ER (titrated to 75 mg/day or 225 mg/day), paroxetine (titrated to 40 mg/day), or placebo for 12 weeks. The primary efficacy measure was the percentage of patients free of full-symptom panic attacks (≥ four symptoms) at endpoint. Key secondary outcomes included the Panic Disorder Severity Scale (PDSS) mean score change and response.
At endpoint, all active treatment groups showed a significantly (P < 0.01) greater proportion of patients free of full-symptom panic attacks, compared with placebo, and were superior (P < 0.05) on most secondary measures. The venlafaxine ER 225 mg group had significantly (P < 0.05) greater mean PDSS score improvement than the paroxetine group (−12.58 vs −11.87) and a significantly higher proportion of patients free of full symptom panic attacks (70.0 vs 58.3%). Both drugs were generally well tolerated.
Venlafaxine ER 75 mg/days and 225 mg/days and paroxetine 40 mg/day were both well tolerated and effective for short-term treatment of panic disorder.
KeywordsVenlafaxine Paroxetine Panic disorder Agoraphobia Pharmacotherapy Panic attack
The authors would like to acknowledge Michael Rennert, PhD for his editorial assistance on this manuscript. Funding for this study was provided by Wyeth Research, Collegeville, Pennsylvania.
Mark Pollack, MD
Advisory boards and consultation
AstraZeneca, Brain Cells, Bristol Myers Squibb, Cephalon, Forest Laboratories, GlaxoSmithKline, Janssen, Jazz Pharmaceuticals, Eli Lilly, Medavante, Neurocrine, Neurogen, Novartis, Otsuka Pharmaceuticals, Pfizer, Predix, Roche, Laboratories, Sanofi, Sepracor, Solvay, Tikvah Therapeutics, Transoral Pharmaceuticals, UCB Pharma, Wyeth
Bristol Myers Squibb, Cephalon, Forest Laboratories, GlaxoSmithKline, Janssen, Eli Lilly, NARSAD, NIDA NIMH, Pfizer, Sepracor, UCB Pharma, Wyeth
Bristol Myers Squibb, Forest Laboratories, GlaxoSmithKline, Janssen, Lilly, Pfizer, Solvay, Wyeth
Naomi Simon, MD, MSc
Astra Zeneca, Cephalon, Forest Laboratories, Glaxo SmithKline, Janssen, Eli Lilly Inc., NARSAD, NIMH, Pfizer, Inc., UCB- Pharma, Sepracor
Paramount Biosciences, Solvay
Forest Laboratories, Janssen, Eli Lilly Inc., Pfizer, Inc., UCB- Pharma, Sepracor
Richard Entsuah, PhD and Evan Tzanis are employees of Wyeth. Richard Mangano, PhD is a former Wyeth employee but was an employee of Wyeth at the time the study was conducted and the manuscript was written.
All authors confirm that they have provided significant input in the study design, collection, analysis, and interpretation of data and writing the reports. They have had full control of all primary data and agree to allow the journal to review the data if requested.
- American Psychiatric Association (1994) Diagnostic and statistical manual of mental disorders (DSM-IV), 4th edn (revised). Washington, DCGoogle Scholar
- American Psychiatric Association (1998) Practice guideline for the treatment of patients with panic disorder. Work Group on Panic Disorder. Am J Psychiatry 155:1–34Google Scholar
- Baldwin DS,Anderson IM, Nutt DJ, Bandelow B, Bond A, Davidson JR, den Boer JA, Fineberg NA, Knapp M, Wittchen HU, British Association for Psychopharmacology (2005) Evidence-based guidelines for the pharmacological treatment of anxiety disorders: recommendations from the British Association for Psychopharmacology. J Psychopharmacol 19:567–596PubMedCrossRefGoogle Scholar
- Guy W (ed) (1976) ECDEU Assessment Manual for Psychopharmacology (revised). National Institute of Mental Health, Psychopharmacology Research Branch, Rockville, MDGoogle Scholar
- Michelson D, Lydiard RB, Pollack MH, Tamura RN, Hoog SL, Tepner R, Demitrack MA, Tollefson GD (1998) Outcome assessment and clinical improvement in panic disorder: evidence from a randomized controlled trial of fluoxetine and placebo. The Fluoxetine Panic Disorder Study Group. Am J Psychiatry 155:1570–1577PubMedGoogle Scholar
- Michelson D, Allgulander C, Dantendorfer K, Knezevic A, Maierhofer D, Micev V, Paunovic VR, Timotijevic I, Sarkar N, Skoglund L, Pemberton SC (2001) Efficacy of usual antidepressant dosing regimens of fluoxetine in panic disorder: randomised, placebo-controlled trial. Br J Psychiatry 179:514–518PubMedCrossRefGoogle Scholar
- Sheehan DV (1983) The anxiety disease. Charles Scribners Sons, New York, NYGoogle Scholar
- Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janavs J, Weiller E, Hergueta T, Baker R, Dunbar GC (1998) The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry 59:22–33PubMedGoogle Scholar
- Smith D (2001) The efficacy and tolerability of venlafaxine compared with other antidepressants in depression: a meta-analysis. J Psychopharmacol 15:A11Google Scholar
- Tiller JW, Bouwer C, Behnke K (1999) Moclobemide and fluoxetine for panic disorder. International Panic Disorder Study Group. Eur Arch Psychiatry Clin Neurosci 249(Suppl 1):7–10Google Scholar