Clomipramine-induced serum prolactin as a marker for serotonin and dopamine turnover: results of an open label study

Abstract

Central nervous system (CNS) monoamine deficits have been linked to a number of pathological conditions such as major depressive disorder. Individual biological variations in 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) might account for the variation in responses of neurotransmitter systems observed after the administration of clomipramine. The prolactin response to clomipramine has been widely used to assess CNS functioning. This open label study investigates the prolactin response induced by clomipramine in the plasma of healthy volunteers and whether it is related to changes in monoamine metabolites. The effects of clomipramine challenge on prolactin, 5-HIAA, HVA and MHPG were measured in 12 healthy volunteers. Samples were drawn directly before and 50 min after clomipramine infusion. A statistically significant increase in serum prolactin concentrations was measured in women 50 min after CMI infusion, but not in men. We found no significant increases in the serum monoamine metabolite concentrations 50 min after CMI infusion. Changes in HVA and 5-HIAA correlated statistically significantly and positively with the amount of prolactin release in the whole sample. Furthermore, positive correlations were found between ∆(50-0 min) 5-HIAA and ∆(50-0 min) HVA, although we did not find a correlation between ∆(50-0 min) prolactin and ∆(50-0 min) MHPG after clomipramine challenge. The pronounced prolactin release in healthy adult women might indicate a higher physiological sensitivity. Correlations between intra-individual changes in HVA, 5-HIAA and serum prolactin might indicate a central nervous effect of clomipramine on monoamine turnover. We conclude that monoamine changes in relation to prolactin response after clomipramine challenge may be suitable for characterizing the relationship between central serotonergic and dopaminergic function.

Prolactin and oxytocin: potential targets for migraine treatment

“…Clinical studies in patients with hyperprolactinemia demonstrated that headache is decreased, in some cases diminished via downregulation of PRL [ 25 , 111 , 261 ]. It has been demonstrated that some migraine medications have an impact on PRL levels [ 22 , 152 , 153 ]. Acetaminophen, triptans and propranolol decrease PRL levels, while treatment with valproate increases PRL levels.…”

“…The group of PRL-lowering drugs includes direct acting dopamine agonist (e.g., dopamine, apomorphine), indirect acting dopamine agonist (e.g., methylphenidate, amphetamine), drugs that impair serotonergic neurotransmission (e.g., methysergide), gamma-aminobutytic acid mimetic drugs (e.g., sodium valproate), histamine H2-receptors agonist and cholinergic receptor agonist. Major prolactin-stimulating agents are dopamine receptor antagonists (atypical antipsychotic drugs), drugs capable of central nervous system dopamine function (carbidopa/benserazide), drugs enhancing serotonergic neurotransmission, 5-HT reuptake blockers, H1-receptors agonist and H2-receptors antagonists [ 22 , 152 , 153 , 156 ].…”

“…The dopamine receptor blockade by antipsychotic drugs increases PRL secretion in animals and humans. This effect is due to direct blockade of dopamine receptors on pituitary lactotrophs through the hypophyseal portal vessels [ 22 , 152 ].…”

Mood disorders in the light of genes, comorbidity and contemporary treatment

“…New treatment approaches should selectively improve these different components of sleep homeostasis. In a study by Cordes et al [5], antidepressant therapy with clomipramine has shown to induce a significant increase in serum prolactin levels in women, but not in men with major depression, indicating effects of clomipramine on the central monoaminergic system. In line with a glutamate hypothesis of depression, the N-methyl-Daspartate (NMDA) receptor antagonist ketamine has been shown to be therapeutically effective in unipolar and bipolar depression.…”