title: Hemodynamic and cognitive effects of lofexidine and methadone coadministration: a pilot study.
abstract: OBJECTIVE
  To determine the hemodynamic and cognitive effects of lofexidine and methadone coadministration.
  
  
  METHODS
  Prospective, double-blind study.
  
  
  METHODS
  Outpatient drug treatment research clinic.
  
  
  METHODS
  Fourteen participants (aged 18-45 yrs) with physical dependence on opioids.
  
  
  METHODS
  Subjects were stabilized on methadone maintenance therapy, starting with 30 mg/day and increasing by 10-mg/day increments, based on each subject's tolerability to achieve a target dose of 80 mg/day. After 3 weeks of methadone stabilization, lofexidine 0.4 mg/day or matching placebo were coadministered with methadone, in doses escalating by 0.2-mg/week increments, to achieve a target dose of 1.6 mg/day over the next 8 weeks.
  
  
  RESULTS
  Acute orthostatic vital signs and neuropsychological effects of lofexidine and methadone coadministration were monitored for 5 hours after the dose on the first day of each new lofexidine dose. Orthostatic vital signs and adverse events were assessed daily thereafter to determine the effects of repeated doses. Lofexidine significantly decreased sitting systolic and diastolic blood pressure (p=0.045 and p=0.033, respectively) compared with placebo (i.e., methadone alone). With lofexidine 0.4 mg/day, mean decreases in systolic and diastolic blood pressure were 27 +/- 17 and 15 +/- 16 mm Hg, respectively. No significant association was noted between changes in orthostatic vital signs and lofexidine dose. Decreased cognitive efficiency was associated with lofexidine administration, and higher lofexidine doses adversely affected performance on a mathematical task compared with placebo (p=0.0035). The rate of adverse events was no higher with lofexidine than with placebo; the majority (54.3%) were common adverse effects of lofexidine.
  
  
  CONCLUSIONS
  Significant changes in hemodynamic and cognitive efficiency were observed with coadministration of lofexidine and methadone compared with methadone alone. When patients receiving methadone are prescribed lofexidine, they should be closely monitored for cardiovascular and cognitive changes.
authors.affiliation: Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21224, USA.
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Schroeder
authors.forename: John
authors.initials: J
authors.lastname: Schmittner
authors.forename: Joseph
authors.initials: J
authors.lastname: Bleiberg
authors.forename: David H
authors.initials: DH
authors.lastname: Epstein
authors.forename: Mori J
authors.initials: MJ
authors.lastname: Krantz
authors.forename: Kenzie L
authors.initials: KL
authors.lastname: Preston
mesh_terms: D000293:Adolescent; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D003071:Cognition / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D008691:Methadone / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D008875:Middle Aged; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D009294:Narcotics / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D010865:Pilot Projects; D011446:Prospective Studies; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy
chemical_list: D009292:Narcotic Antagonists; D009294:Narcotics; D003000:Clonidine; D008691:Methadone; C025655:lofexidine