title: A double-blind, placebo-controlled, efficacy, safety, and pharmacokinetic study of INN 00835, a novel antidepressant peptide, in the treatment of major depression.
abstract: BACKGROUND
  INN 00835 is a synthetic pentapeptide with a potential for rapid onset of action as an antidepressant. Its efficacy was investigated in a pilot study in patients diagnosed with major depression.
  
  
  METHODS
  Fifty two patients received either active drug - INN 00835 (26 patients) - or placebo (26 patients), subcutaneously at 0.2 mg/kg for 5 consecutive days. The patients were evaluated for an additional 4 weeks after treatment. Efficacy was evaluated by the following psychiatric rating scales: HAMD, MADRS, CSRS, CGI, and VAS. The effect of treatment was also evaluated by using a biochemical marker: changes in blood platelet serotonin (5HT) uptake rates in drug-treated patients compared to those in the placebo group. Plasma concentrations of INN 00835 were measured by LC/MS.
  
  
  RESULTS
  Statistical analysis indicated a strong pharmacodynamic correlation between plasma drug concentrations at 1 h after dosing and the reduction in the severity of depression as measured by the psychiatric rating scales. A minimum effective plasma concentration (MEC) of INN 00835 was 5 ng/ml. Statistically significant differences in response to treatment (P<0.05) were found between patients with plasma concentrations above MEC and those in the placebo group, as well as between subjects with plasma concentrations above and below the MEC. The peak effect was observed after the 5-day treatment and the response to treatment persisted during the 4-week follow-up period. The change of 5HT uptake rates after treatment was significantly larger in the drug-treated group than in the placebo group.
  
  
  CONCLUSIONS
  This was a pilot study conducted in a relatively small population (52 patients) and the limited number of blood sampling times did not allow a comprehensive pharmacokinetic analysis. There was a relatively large placebo response. The results have to be confirmed in future, large scale studies.
  
  
  CONCLUSIONS
  INN 00835 appears to be a promising drug for the treatment of major depression.
authors: The Feighner Research Institute, San Diego, CA, USA.
authors: J P
authors: JP
authors: Feighner
authors: R H
authors: RH
authors: Ehrensing
authors: A J
authors: AJ
authors: Kastin
authors: B E
authors: BE
authors: Leonard
authors: L
authors: L
authors: Sverdlov
authors: G
authors: G
authors: Nicolau
authors: A
authors: A
authors: Patel
authors: J
authors: J
authors: Hlavka
authors: H
authors: H
authors: Abajian
authors: J F
authors: JF
authors: Noble
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D015415:Biomarkers; D003865:Major Depressive Disorder / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D011569:Psychiatric Status Rating Scales; D012189:Retrospective Studies; D012701:Serotonin / Q000378:metabolism; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D015415:Biomarkers; D009842:Oligopeptides; C406668:nemifitide ditriflutate; D012701:Serotonin