Porter Richard J, Mulder Roger T, Joyce Peter R
Department of Psychological Medicine, Christchurch School of Medicine and Health Sciences, P.O. Box 4345, Christchurch, New Zealand.
Psychopharmacology (Berl). 2003 Jan;165(3):216-21. doi: 10.1007/s00213-002-1282-0. Epub 2002 Nov 19.
Depression may be associated with a hypofunction of central serotonin (5HT) systems. The prolactin response to fenfluramine (PRF) is an indicator of 5HT activity. It has been suggested that the PRF may predict response to different forms of treatment. Baseline cortisol, prolactin, and L-tryptophan ( L-TRP) availability may affect PRF and may also influence response to treatment.
In this study, 46 males and 58 females with a DSM-III-R diagnosis of major depression underwent a detailed clinical evaluation and prior to treatment had baseline measures of prolactin, cortisol, L-TRP, and other large neutral amino acids (LNAAs) taken and underwent a fenfluramine challenge. The subjects with major depression entered a 6-week double-blind treatment trial comparing clomipramine and desipramine.
There was no effect on the 6-week outcome of treatment (clomipramine versus desipramine), PRF or baseline cortisol and no interactions between these factors. However, there was a significant effect of baseline prolactin (BLP) and a significant interaction between TRP/LNAA ratio and BLP. Post-hoc analysis revealed that at low TRP/LNAA values, outcome improved as prolactin levels increased while at high TRP/LNAA values the opposite was the case.
The PRF did not predict 6-week outcome. BLP and TRP/LNAA ratio measurement is easy and may be useful clinically. We hypothesise that failure to upregulate post-synaptic 5HT receptors in response to low 5HT availability predicts a poor response to antidepressant treatment.
抑郁症可能与中枢5-羟色胺（5-HT）系统功能低下有关。对芬氟拉明的催乳素反应（PRF）是5-HT活性的一个指标。有人提出，PRF可能预测对不同治疗形式的反应。基线皮质醇、催乳素和L-色氨酸（L-TRP）的可用性可能影响PRF，也可能影响治疗反应。
在本研究中，46名男性和58名女性被诊断为符合《精神疾病诊断与统计手册》第三版修订版（DSM-III-R）标准的重度抑郁症，他们接受了详细的临床评估，在治疗前测量了催乳素、皮质醇、L-TRP和其他大中性氨基酸（LNAAs）的基线水平，并接受了芬氟拉明激发试验。重度抑郁症患者进入一项为期6周的双盲治疗试验，比较氯米帕明和地昔帕明的疗效。
治疗6周的结果（氯米帕明与地昔帕明）、PRF或基线皮质醇没有影响，这些因素之间也没有相互作用。然而，基线催乳素（BLP）有显著影响，TRP/LNAA比值与BLP之间有显著相互作用。事后分析显示，在低TRP/LNAA值时，随着催乳素水平升高，结果改善，而在高TRP/LNAA值时情况相反。
PRF不能预测6周的治疗结果。测量BLP和TRP/LNAA比值简单易行，可能在临床上有用。我们假设，由于5-HT可用性低而未能上调突触后5-HT受体预示着对抗抑郁治疗反应不佳。
