Hyperprolactinemia in response to antipsychotic drugs: characterization across comparative clinical trials

Kinon, Bruce J.; Gilmore, J.A.; Liu, Hong; Halbreich, Uriel

doi:10.1016/s0306-4530(02)00128-2

Cited by 133 publications

(111 citation statements)

References 30 publications

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“…All subjects had normal basal PRL levels, implicating loss of normal pulsatility in fertility problems (Subramanian et al, 1997). Consistent with this, altered fertility associated with only modestly elevated PRL levels is well recognized with antipsychotic drug use (Dickson and Glazer, 1999;Kinon et al, 2003;Smith, 2003), but has not been studied with respect to SSRIs. Aberrant PRL levels can interfere with female fertility through both CNS and peripheral mechanisms.…”

Section: Altered Fertilitymentioning

confidence: 64%

From Galactorrhea to Osteopenia: Rethinking Serotonin–Prolactin Interactions

Emiliano

Fudge

2004

Neuropsychopharmacol

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The widespread use of the selective serotonin reuptake inhibitors (SSRIs) has been accompanied by numerous reports describing a potential association with hyperprolactinemia. Antipsychotics are commonly known to elevate serum prolactin (PRL) through blockade of dopamine receptors in the pituitary. However, there is little awareness of the mechanisms by which SSRIs stimulate PRL release. Hyperprolactinemia may result in overt symptoms such as galactorrhea, which may be accompanied by impaired fertility. Long-term clinical sequelae include decreased bone density and the possibility of an increased risk of breast cancer. Through literature review, we explore the possible pathways involved in serotonin-induced PRL release. While the classic mechanism of antipsychotic-induced hyperprolactinemia directly involves dopamine cells in the tuberoinfundibular pathway, SSRIs may act on this system indirectly through GABAergic neurons. Alternate pathways involve serotonin stimulation of vasoactive intestinal peptide (VIP) and oxytocin (OT) release. We conclude with a comprehensive review of clinical sequelae associated with hyperprolactinemia, and the potential role of SSRIs in this phenomenon.

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Section: Altered Fertilitymentioning

confidence: 64%

From Galactorrhea to Osteopenia: Rethinking Serotonin–Prolactin Interactions

Emiliano

Fudge

2004

Neuropsychopharmacol

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“…Antipsychotics produce an elevation in circulating prolactin levels in rats and humans Kinon et al, 2003). The prolactin elevation in patients for olanzapine is lower in magnitude and more transient compared with Fig.…”

Section: Discussionmentioning

confidence: 90%

Preclinical Pharmacology of FMPD [6-Fluoro-10-[3-(2-methoxyethyl)-4-methyl-piperazin-1-yl]-2-methyl-4H-3-thia-4,9-diaza-benzo[f]azulene]: A Potential Novel Antipsychotic with Lower Histamine H₁Receptor Affinity Than Olanzapine

Rasmussen

Benvenga²,

Bymaster³

et al. 2005

J Pharmacol Exp Ther

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FMPD [6-fluoro-10-[3-(2-methoxyethyl)-4-methyl-piperazin-1-yl]-2-methyl-4H-3-thia-4,9-diaza-benzo[f]azulene] is a potential novel antipsychotic with high affinity for dopamine D 2 (K i ϭ 6.3 nM), 5-HT 2A (K i ϭ 7.3 nM), and 5-HT 6 (K i ϭ 8.0 nM) human recombinant receptors and lower affinity for histamine H 1 (K i ϭ 30 nM) and 5-HT 2C (K i ϭ 102 nM) human recombinant receptors than olanzapine. Oral administration of FMPD increased rat nucleus accumbens 3,4-dihyroxyphenylacetic acid concentrations (ED 200 ϭ 6 mg/kg), blocked 5-HT 2A agonist-induced increases in rat serum corticosterone levels (ED 50 ϭ 1.8 mg/kg), and inhibited the ex vivo binding of [ 125 I]SB-258585 [4-iodo-N-[4-methoxy-3-(4-methyl-piperazin-1-yl)-phenyl]-benzenesulfonamide] to striatal 5-HT 6 receptors (ED 50 ϭ 10 mg/kg) but failed to inhibit ex vivo binding of [ 3 H]pyrilamine to hypothalamic histamine H 1 receptors at doses of up to 30 mg/kg. In electrophysiology studies, acute administration of FMPD selectively elevated the number of spontaneously active A10 (versus A9) dopamine neurons and chronic administration selectively decreased the number of spontaneously active A10 (versus A9) dopamine neurons. FMPD did not produce catalepsy at doses lower than 25 mg/kg p.o. In Fos-induction studies, FMPD had an atypical antipsychotic profile in the striatum and nucleus accumbens and increased Fos expression in orexin-containing neurons of the hypothalamus. FMPD produced only a transient elevation of prolactin levels. These data indicate that FMPD is an orally available potent antagonist of dopamine D 2 , 5-HT 2A , and 5-HT 6 receptors and a weak antagonist of H 1 and 5-HT 2C receptors. FMPD has the potential to have efficacy in treating schizophrenia and bipolar mania with a low risk of treatmentemergent extrapyramidal symptoms, prolactin elevation, and weight gain. Clinical trials are needed to test these hypotheses.Olanzapine is effective in treating schizophrenia and bipolar mania (Beasley et al., 1996;Tohen et al., 2000). It is classified as an atypical antipsychotic in that it has therapeutic effects on the positive, negative, and cognitive symptoms of schizophrenia while having a low propensity to produce extrapyramidal symptoms (EPS) and prolactin elevation. However, many patients have observed weight gain associated with the treatment of olanzapine and other atypical antipsychotics (Wirshing, 2001).It has been hypothesized that blockade of the histamine H 1 receptor plays a critical role in antipsychotic treatmentemergent weight gain. Histamine has long been associated with the control of food intake. Histamine activates postsynaptic H 1 receptors in the ventromedial and para-ventricular nucleus of the hypothalamus to suppress feeding (Sakata et al., 1988;Ookuma et al., 1989), and H 1 knock-out mice develop diet-induced and age-related obesity (Masaki et al., 2001). In addition, a significant correlation between affinity for the human H 1 receptor and weight gain has been reported for antipsychotics (Kroeze et al., 2003). Thus, an a...

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“…The synthesis and release of prolactin in inhibited by hypothalamic dopamine, which acts which acts on D 2 receptors located on the surface of the lactotroph cells. Any process that results in a reduction in the dopamine influence of the lactotroph cell D 2 receptors would increase prolactin levels [6].The relative risk of an elevated prolactin level needs to be considered in the treatment decision process. All antipsychotic drugs may affect serum prolactin levels to some degree.…”

Section: Applicationmentioning

confidence: 99%

A Mathematical Model ForProlactin Levels In Olanzapine Treatment Of Schizophrenia Patients

Lakshmi¹

2014

IOSRJEN

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Hyperprolactinemia in response to antipsychotic drugs: characterization across comparative clinical trials

Cited by 133 publications

References 30 publications

From Galactorrhea to Osteopenia: Rethinking Serotonin–Prolactin Interactions

From Galactorrhea to Osteopenia: Rethinking Serotonin–Prolactin Interactions

Preclinical Pharmacology of FMPD [6-Fluoro-10-[3-(2-methoxyethyl)-4-methyl-piperazin-1-yl]-2-methyl-4H-3-thia-4,9-diaza-benzo[f]azulene]: A Potential Novel Antipsychotic with Lower Histamine H₁Receptor Affinity Than Olanzapine

A Mathematical Model ForProlactin Levels In Olanzapine Treatment Of Schizophrenia Patients

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Hyperprolactinemia in response to antipsychotic drugs: characterization across comparative clinical trials

Cited by 133 publications

References 30 publications

From Galactorrhea to Osteopenia: Rethinking Serotonin–Prolactin Interactions

From Galactorrhea to Osteopenia: Rethinking Serotonin–Prolactin Interactions

Preclinical Pharmacology of FMPD [6-Fluoro-10-[3-(2-methoxyethyl)-4-methyl-piperazin-1-yl]-2-methyl-4H-3-thia-4,9-diaza-benzo[f]azulene]: A Potential Novel Antipsychotic with Lower Histamine H1Receptor Affinity Than Olanzapine

A Mathematical Model ForProlactin Levels In Olanzapine Treatment Of Schizophrenia Patients

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Preclinical Pharmacology of FMPD [6-Fluoro-10-[3-(2-methoxyethyl)-4-methyl-piperazin-1-yl]-2-methyl-4H-3-thia-4,9-diaza-benzo[f]azulene]: A Potential Novel Antipsychotic with Lower Histamine H₁Receptor Affinity Than Olanzapine