title: A randomized clinical trial of histamine 2 receptor antagonism in treatment-resistant schizophrenia.
abstract: Histamine has important functions as regulator of several other key neurotransmitters. Patients with schizophrenia have lower histamine H1 receptor levels. Since a case report in 1990 of an effect of the H2 antagonist famotidine on negative symptoms in schizophrenia, some open-label trials have been performed, but no randomized controlled trial. Recently, it was shown that clozapine is a full inverse agonist at the H2 receptor. We performed a researcher-initiated, academically financed, double-blind, placebo-controlled, parallel-group, randomized trial with the histamine H2 antagonist famotidine in treatment-resistant schizophrenia. Thirty subjects with schizophrenia were randomized to have either famotidine (100 mg twice daily, n = 16) or placebo (n = 14) orally, added to their normal treatment regimen for 4 weeks. They were followed up weekly with the Scale for the Assessment of Negative Symptoms (SANS), the PANSS (Positive and Negative Syndrome Scale), and Clinical Global Impression (CGI) Scale. In the famotidine group, the SANS score was reduced by 5.3 (SD, 13.1) points, whereas in the placebo group the SANS score was virtually unchanged (mean change, +0.2 [SD, 9.5]). The difference did not reach statistical significance (P = 0.134) in Mann-Whitney U analysis. However, the PANSS Total score and the General subscore as well as the CGI showed significantly (P < 0.05) greater change in the famotidine group than in the placebo group. No significant adverse effects were observed. This is the first placebo-controlled, randomized clinical trial showing a beneficial effect of histamine H2 antagonism in schizophrenia. H2 receptor antagonism may provide a new alternative for the treatment of schizophrenia.
authors.affiliation: University of Helsinki, Department of Psychiatry and Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Katarina
authors.initials: K
authors.lastname: Meskanen
authors.forename: Heidi
authors.initials: H
authors.lastname: Ekelund
authors.forename: Jarmo
authors.initials: J
authors.lastname: Laitinen
authors.forename: Pertti J
authors.initials: PJ
authors.lastname: Neuvonen
authors.forename: Jari
authors.initials: J
authors.lastname: Haukka
authors.forename: Pertti
authors.initials: P
authors.lastname: Panula
authors.forename: Jesper
authors.initials: J
authors.lastname: Ekelund
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D004311:Double-Blind Method; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D015738:Famotidine / Q000627:therapeutic use*; D005260:Female; D005387:Finland; D006635:Histamine H2 Antagonists / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008390:Markov Chains; D008875:Middle Aged; D009010:Monte Carlo Method; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D006635:Histamine H2 Antagonists; D015738:Famotidine