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Abstract
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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.; Results:There was no effect on the treatment outcome after 6 weeks with antidepressants (Anafranil vs. Des), prolactin response to fenfluramine (PRF) or baseline cortisol and no interactions between these factors. A significant effect of BLP (P=0.008) and a significant interaction between BLP and TRP/LNAA (P=0.003) was found. There was no significant correlation between outcome and BLP (P=0620) or between outcome and TRP/LNAA ratio (P=0.879). A significant correlation between BLP and outcome in the low TRP group (P=0.038) and a significant negative correlation between BLP and outcome in the high TRP group (P=0.022). Cortisol response to fenfluramine was not a significant co-variate (P=0.257). However, a significant effect of BLP and interaction between BLP and TRP/LNAA remained. A significant interaction between TRP/LNAA ratio and BLP (P=0.015) was observed. There was no main effect of BLP. None of the clinical variables (sex, severity, melancholia, weight loss or suicide attempt) showed significant interaction with the biological variables. There was no effect of phase of cycle (follicular/luteal) or interaction with the biological variables.; AdverseEffects:No adverse events were mentioned.; AuthorsConclusions:The PRF did not predict 6-week outcome. BLP and TRP/LNAA ratio measurement is easy and may be useful clinically. We hypothesize that failure to upregulate post synaptic 5HT [serotonin] receptors in response to low 5HT availability predicts a poor response to antidepressant treatment.; FreeText:Baseline measurements of prolactin, cortisol, L-TRP, and other large neutral amino acids (LNAAs) were taken and underwent fenfluramine challenge. Other test: Hamilton Depression Rating Scale (HDRS). Concomitant medications: oral contraceptive and 1 depo-provera.; Patients:104 inpatients. Anafranil group: 52 patients, 36 completed the study, 13 male and 23 female (mean age 31.9 years), 16 dropouts. Des group: 52 patients, 48 completed the study, 22 male and 26 female (mean age 13.0 years), 4 dropouts. Low TRP group (n=40). High TRP group (n=38).; Indications:52 patients with major depression.; TypeofStudy:A double-blind, randomized, comparative, controlled study investigating whether baseline prolactin (BLP), cortisol and levo-tryptophan (L-TRP) availability predict the overall treatment response of antidepressants desipramine (Des) or Anafranil in patients with major depression.; DosageDuration:75 to 250 mg daily (mean 144 mg daily) for 6 weeks.; ComparativeDrug:Desipramine dosage was 100 to 350 mg daily (mean 199 mg daily) for 6 weeks.
Language: en |