Outcome in delusional depression comparing trimipramine monotherapy with a combination of amitriptyline and haloperidol – A double-blind multicenter trial

• Published in: Journal of psychiatric research Vol. 43; no. 7; pp. 702 - 710
• Main Authors: Künzel, Heike E, Ackl, Nibal, Hatzinger, Martin, Held, Katja, Holsboer-Trachsler, Edith, Ising, Marcus, Kaschka, Wolfgang, Kasper, Siegfried, Konstantinidis, Anastasios, Sonntag, Annette, Uhr, Manfred, Yassouridis, Alexander, Holsboer, Florian, Steiger, Axel
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 01-04-2009; Elsevier
• Subjects: Adrenocorticotropic Hormone - blood; Adult; Adult and adolescent clinical studies; Amitriptylene; Amitriptyline; Amitriptyline - therapeutic use; Anti-Dyskinesia Agents - therapeutic use; Antidepressive Agents, Tricyclic - therapeutic use; Biological and medical sciences; Corticotropin-Releasing Hormone; Delusional depression; Delusions - diagnosis; Delusions - drug therapy; Delusions - psychology; Depression; Depressive Disorder - diagnosis; Depressive Disorder - drug therapy; Depressive Disorder - psychology; Dex/CRH test; Dexamethasone; Dosage; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Electrocardiography; Electroencephalography; Female; Haloperidol; Haloperidol - therapeutic use; Humans; Hydrocortisone - blood; Hypothalamic-pituitary-adrenal axis; Hypothalamo-Hypophyseal System - drug effects; Hypothalamo-Hypophyseal System - physiopathology; Male; Medical sciences; Middle Aged; Mood disorders; Neuropharmacology; Pharmacology. Drug treatments; Pituitary-Adrenal System - drug effects; Pituitary-Adrenal System - physiopathology; Psychiatric Status Rating Scales; Psychiatry; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psycholeptics: tranquillizer, neuroleptic; Psychology. Psychoanalysis. Psychiatry; Psychomotor Agitation - etiology; Psychomotor Agitation - physiopathology; Psychopathology. Psychiatry; Psychopharmacology; Treatment Outcome; Trimipramine; Trimipramine - administration & dosage; Trimipramine - adverse effects; Trimipramine - therapeutic use; Amitriptyline; Delusional depression; Dex/CRH test; Haloperidol; Trimipramine; Neuroleptic; Psychotropic; Multicenter study; Corticotropin releasing factor; Delusion; Reuptake inhibitor; Antidepressant agent; Hormone releasing factor; Mood disorder; Serotonin; Dopamine antagonist; Depression; Butyrophenone derivatives; Catecholamine; Tricyclic compound; Hypothalamic hormone; D2 Dopamine receptor; Neurotransmitter; Double blind study; Norepinephrine
• ISSN: 0022-3956; 1879-1379
• DOI: 10.1016/j.jpsychires.2008.10.004

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 100 mg up to 400 mg trimipramine and from 100 mg up to 200 mg amitriptyline combined with 2 mg up to 7.5 mg 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 ± 61.2 mg 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 ⩽ 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. Conclusion In all, trimipramine monotherapy appears to be an effective treatment in delusional depression.