Rationale: 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.
Method: 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.
Results: 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.
Conclusion: 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.