title: A double-blind, placebo-controlled trial of amantadine, propranolol, and their combination for the treatment of cocaine dependence in patients with severe cocaine withdrawal symptoms.
abstract: BACKGROUND
  This trial evaluated the efficacy of amantadine, propranolol and their combination in cocaine dependent patients with severe cocaine withdrawal symptoms.
  
  
  METHODS
  Cocaine withdrawal symptom severity was measured by the cocaine selective severity assessment (CSSA). One hundred and ninety-nine patients with high scores on the CSSA participated in a 10-week double-blind trial. Patients were randomly assigned to receive amantadine (300 mg/day), propranolol (100mg/day), a combination of amantadine (300 mg/day) and propranolol (100mg/day) or matching placebo capsules. The primary outcome measure was cocaine abstinence.
  
  
  RESULTS
  In the intent-to-treat sample, there were no significant differences between the four medication groups in treatment retention. The odds of cocaine abstinence showed a marginally significant increase over time in the propranolol group (p=0.06) but not in the other three groups. In highly medication-adherent patients, treatment retention was significantly better in the propranolol group compared to the placebo group (p=0.01) and the odds of cocaine abstinence increased significantly over time in the propranolol group but not in the other three groups.
  
  
  CONCLUSIONS
  In the intent-to-treat sample, none of the three active treatments (propranolol, amantadine or their combination) was significantly more effective than placebo in promoting abstinence from cocaine among patients who entered treatment with more severe cocaine withdrawal symptoms. Among patients highly adherent to study medication, propranolol treatment was associated with better treatment retention and higher rates of cocaine abstinence compared to placebo.
authors.affiliation: Department of Psychiatry, University of Pennsylvania School of Medicine, 3900 Chestnut Street, Philadelphia, PA 19104, USA. kampman_k@mail.trc.upenn.edu
authors.forename: Kyle M
authors.initials: KM
authors.lastname: Kampman
authors.forename: Charles
authors.initials: C
authors.lastname: Dackis
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Lynch
authors.forename: Helen
authors.initials: H
authors.lastname: Pettinati
authors.forename: Carlos
authors.initials: C
authors.lastname: Tirado
authors.forename: Peter
authors.initials: P
authors.lastname: Gariti
authors.forename: Thorne
authors.initials: T
authors.lastname: Sparkman
authors.forename: Michal
authors.initials: M
authors.lastname: Atzram
authors.forename: Charles P
authors.initials: CP
authors.lastname: O'Brien
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D000547:Amantadine / Q000009:adverse effects / Q000627:therapeutic use*; D018712:Analgesics, Non-Narcotic / Q000009:adverse effects / Q000627:therapeutic use*; D003042:Cocaine / Q000009:adverse effects* / Q000031:analogs & derivatives / Q000652:urine; D019970:Cocaine-Related Disorders / Q000534:rehabilitation*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D009460:Neurologic Examination / Q000187:drug effects; D010352:Patient Dropouts / Q000706:statistics & numerical data; D011433:Propranolol / Q000009:adverse effects / Q000627:therapeutic use*; D015813:Substance Abuse Detection; D013375:Substance Withdrawal Syndrome / Q000534:rehabilitation*
chemical_list: D000319:Adrenergic beta-Antagonists; D018712:Analgesics, Non-Narcotic; C005618:benzoylecgonine; D011433:Propranolol; D000547:Amantadine; D003042:Cocaine