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

详细信息    查看全文

• 作者：Heike E. Kü ; nzel ; Nibal Ackl ; Martin Hatzinger ; Katja Held ; Edith Holsboer-Trachsler ; Marcus Ising ; Wolfgang Kaschka ; Siegfried Kasper ; Anastasios Konstantinidis ; Annette Sonntag ; Manfred Uhr ; Ale
• 关键词：Delusional depression ; Trimipramine ; Amitriptyline ; Haloperidol ; Dex/CRH test
• 刊名：Journal of Psychiatric Research
• 出版年：2009
• 出版时间：April 2009
• 年：2009
• 卷：43
• 期：7
• 页码：702-710
• 全文大小：218 K

文摘

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.