title: Outcome in delusional depression comparing trimipramine monotherapy with a combination of amitriptyline and haloperidol--a double-blind multicenter trial.
abstract: BACKGROUND
  Patients with delusional depression are difficult to treat. The atypical antidepressant trimipramine was effective in a previous 4-week open label pilot study in patients with this disorder. The major neurobiological effect of trimipramine is the inhibition of the hypothalamic-pituitary-adrenocortical (HPA) system. In delusional depression HPA overactivity is more distinct than in other subtypes of depression. HPA suppression is thought to contribute to the action of trimipramine.
  
  
  METHODS
  In a double-blind, randomized, placebo controlled multicenter trial we compared the effects of trimipramine monotherapy versus a combination of amitriptyline and haloperidol. Dosage was increased stepwise from 100mg up to 400mg trimipramine and from 100mg up to 200mg amitriptyline combined with 2mg up to 7.5mg haloperidol. The average dose of trimipramine was higher than that of amitriptyline throughout the trial. During sixth week mean dosage (+/-standard deviation) were 356.1+/-61.2mg trimipramine, 184.0+/-23.6 mg amitriptyline and 6.3+/-1.8 mg haloperidol. During six weeks psychometric assessments were performed weekly. For HPA monitoring a dexamethasone/corticotropin-releasing hormone (Dex/CRH) test was performed before active medication and at the end of treatment. Additionally tolerability was monitored by ECG, EEG assessment of extrapyramidal symptoms and akathisia, clinical laboratory routine and recording of blood pressure and heart rate. Adverse events were documented.
  
  
  RESULTS
  94 patients were enclosed into the study. The per protocol sample consisted of 33 patients of the trimipramine group and of 24 patients of the amitriptyline/haloperidol group. The decrease of the Hamilton depression (HAMD) score (24 items) showed non-inferiority of trimipramine compared to amitriptyline/haloperidol. Twenty-eight patients (84.84%) in the trimipramine arm and 17 patients (70.83%) in the amitriptyline/haloperidol arm were responders (HAMD <or=50%). Remission (HAMD<8) was found in 18 (54.55%) patients after trimipramine and in 11 (45.83%) patients after amitriptyline/haloperidol. No significant differences were found concerning response and remission. The cortisol and ACTH response in the Dex/CRH test decreased between days 1 and 42 in both groups. Serious side effects were not reported.
  
  
  CONCLUSIONS
  In all, trimipramine monotherapy appears to be an effective treatment in delusional depression.
authors.affiliation: Department of Psychiatry, Max Planck Institute of Psychiatry, Kraepelinstrasse 10, 80804 Munich, Germany.
authors.forename: Heike E
authors.initials: HE
authors.lastname: Künzel
authors.forename: Nibal
authors.initials: N
authors.lastname: Ackl
authors.forename: Martin
authors.initials: M
authors.lastname: Hatzinger
authors.forename: Katja
authors.initials: K
authors.lastname: Held
authors.forename: Edith
authors.initials: E
authors.lastname: Holsboer-Trachsler
authors.forename: Marcus
authors.initials: M
authors.lastname: Ising
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kaschka
authors.forename: Siegfried
authors.initials: S
authors.lastname: Kasper
authors.forename: Anastasios
authors.initials: A
authors.lastname: Konstantinidis
authors.forename: Annette
authors.initials: A
authors.lastname: Sonntag
authors.forename: Manfred
authors.initials: M
authors.lastname: Uhr
authors.forename: Alexander
authors.initials: A
authors.lastname: Yassouridis
authors.forename: Florian
authors.initials: F
authors.lastname: Holsboer
authors.forename: Axel
authors.initials: A
authors.lastname: Steiger
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D000639:Amitriptyline / Q000627:therapeutic use*; D018726:Anti-Dyskinesia Agents / Q000627:therapeutic use*; D000929:Antidepressive Agents, Tricyclic / Q000627:therapeutic use*; D003346:Corticotropin-Releasing Hormone; D003702:Delusions / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D003866:Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D003907:Dexamethasone; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004562:Electrocardiography; D004569:Electroencephalography; D005260:Female; D006220:Haloperidol / Q000627:therapeutic use*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000503:physiopathology; D011569:Psychiatric Status Rating Scales; D011595:Psychomotor Agitation / Q000209:etiology / Q000503:physiopathology; D016896:Treatment Outcome; D014299:Trimipramine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D018726:Anti-Dyskinesia Agents; D000929:Antidepressive Agents, Tricyclic; D000639:Amitriptyline; D014299:Trimipramine; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D006220:Haloperidol; D006854:Hydrocortisone