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Psychiatry Xagena

Novel and newly approved antipsychotics : the effects on serum prolactin levels


Since the 1970s, clinicians have increasingly become more familiar with hyperprolactinemia ( HPRL ) as a common adverse effect of antipsychotic medication, which remains the cornerstone of pharmacological treatment for patients with schizophrenia.
Although treatment with second-generation antipsychotics ( SGAs ) as a group is, compared with use of the first-generation antipsychotics, associated with lower prolactin ( PRL ) plasma levels, the detailed effects on plasma PRL levels for each of these compounds in reports often remain incomplete or inaccurate.
Moreover, at this moment, no review has been published about the effect of the newly approved antipsychotics Asenapine ( Saphris ), Iloperidone ( Fanapt ) and Lurasidone ( Latuda ) on prolactin levels.

A literature search was conducted to identify relevant publications to report on the state of the art of hyperprolactinemia and to summarize the available evidence on newly approved antipsychotics to elevate prolactin levels.

The review has shown that although hyperprolactinemia usually is defined as a sustained level of prolactin above the laboratory upper limit of normal, limit values show some degree of variability in clinical reports, making the interpretation and comparison of data across studies difficult.
Moreover, many reports do not provide much or any data detailing the measurement of prolactin.

Although the highest rates of hyperprolactinemia are consistently reported in association with Amisulpride, Risperidone and Paliperidone, while Aripiprazole and Quetiapine have the most favorable profile with respect to this outcome, all second-generation antipsychotics can induce prolactin elevations, especially at the beginning of treatment, and have the potential to cause new-onset second-generation antipsychotics.

Considering the prolactin-elevating propensity of the newly approved antipsychotics, evidence seems to indicate these agents have a prolactin profile comparable to that of Clozapine ( Asenapine and Iloperidone ), Ziprasidone and Olanzapine ( Lurasidone ).
Prolactin elevations with antipsychotic medication generally are dose dependant.

However, antipsychotics having a high potential for prolactin elevation ( Amisulpride, Risperidone and Paliperidone ) can have a profound impact on prolactin levels even at relatively low doses, while prolactin levels with antipsychotics having a minimal effect on prolactin, in most cases, can remain unchanged ( Quetiapine ) or reduce ( Aripiprazole ) over all dosages.

Although tolerance and decreases in prolactin values after long-term administration of prolactin-elevating antipsychotics can occur, the elevations, in most cases, remain above the upper limit of normal.

Prolactin profiles of antipsychotics in children and adolescents seem to be the same as in adults.

The hyperprolactinemic effects of antipsychotic medication are mostly correlated with their affinity for dopamine D2 receptors at the level of the anterior pituitary lactotrophs ( and probably other neurotransmitter mechanisms ) and their blood-brain barrier penetrating capability.
Even though antipsychotics are the most common cause of pharmacologically induced hyperprolactinemia, recent research has shown that hyperprolactinemia can be pre-existing in a substantial portion of antipsychotic-naïve patients with first-episode psychosis or at-risk mental state. ( Xagena )

Peuskens J et al, CNS Drugs 2014;28:421-453

XagenaMedicine_2014



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