Prolactin monitoring in schizophrenia should be indicated by symptomatology not time

First, we would like to congratulate the College on the release of the updated version of the clinical practice guidelines for the treatment of schizophrenia and related disorders (Galletly et al., 2016). We note that the guidelines are quite comprehensive; however, they are overly comprehensive with regard to the measurement of prolactin. Prolactin is a hormone secreted by the pituitary gland; it is strongly tied to circadian rhythms (Ajmal et al., 2014). Historically, prolactin has been associated with lactation and the female reproductive system, since that time, the role of prolactin in the male reproductive system, bone and metabolic health has also become evident (Ajmal et al., 2014).

Prolactin is a hormone that displays both high levels of individual variation and intra-individual variation with levels fluctuating over time (Henderson and Doraiswamy, 2008). Although there are high levels of variability in the hormone, normal readings for men and women are considered to be 10–20 and 10–25 µg/L, respectively (Henderson and Doraiswamy, 2008). Elevated levels of prolactin in the blood can lead to symptoms such as gynecomastia, galactorrhea, sexual dysfunction, infertility, oligomenorrhea and amenorrhea indicative of hyperprolactinemia (Henderson and Doraiswamy, 2008). Hyperprolactinemia is generally indicated by levels greater than 100 µg/L; however, not all individuals with high levels of prolactin exhibit symptoms of hyperprolactinemia (Henderson and Doraiswamy, 2008). It should be noted that hyperprolactinemia and the associated symptomatology are distinct between the sexes (Ajmal et al., 2014). However, younger females are at an increased risk in comparison with older males (Gupta et al., 2017).

Prolactin levels rise as a result of many factors such as sleep, exercise, stress and eating. Further certain antipsychotics can also elevate levels of prolactin (Halbreich et al., 2003; Henderson and Doraiswamy, 2008). As such the recently published guidelines, the primary focus of this commentary indicates that prolactin levels should be measured at baseline, 24 weeks and annually (Galletly et al., 2016); however, it is asserted that the measurement of prolactin at 24 weeks and annually is unnecessary when patients are not exhibiting any symptoms of hyperprolactinemia. As what are elevated levels of prolactin indicating when an individual is not exhibiting any symptomatology?

Recently, Gupta et al. (2017) noted that currently no consensus exists regarding the routine monitoring of prolactin levels in antipsychotic therapy. Rather they noted most guidelines do not endorse the routine monitoring of prolactin in patients undergoing antipsychotic treatment (Gupta et al., 2017). Specifically, the NICE guidelines advocate baseline measurement of prolactin levels with no follow-up measurement specified (Gupta et al., 2017). Thus, time and resources could be better utilized; rather a thorough history should be taken specifically probing for any possible symptoms of hyperprolactinemia with a focus upon symptoms that are under-reported due to their nature specifically, sexual symptoms (Ajmal et al., 2014). Structured questionnaires are available for the assessment of sexual symptoms to assist patients in divulging information that may make them feel uncomfortable and embarrassed (Gupta et al., 2017).

Therefore, measurement of prolactin levels should only be indicated by symptomatic hyperprolactinemia; rather than a pre-specified time period as the level of prolactin alone is not indicative of a problem. Prolactin levels differ throughout the day and there is vast individual variation in prolactin levels and genetic susceptibility to hyperprolactinemia. Furthermore, there is excessive concern pertaining to one of the long-term consequences of elevated prolactin levels, specifically osteoporosis. Osteoporosis can result from a myriad other factors and is not simply a result of elevated prolactin levels. Specifically, osteoporosis can result from lack of exercise, poor dietary habits, smoking, alcohol use and lack of vitamin D: factors that are common in the general population and even more common in a population with serious mental illness (SMI).

More recently, some clinicians have expressed concern regarding the potential relationship between chronically elevated prolactin levels and breast cancer; however, there remains no conclusive evidence that antipsychotics and increased prolactin contribute to the pathogenesis of breast cancer (Ajmal et al., 2014; De Hert et al., 2016). Furthermore, the results are merely correlative, from which causation cannot be extrapolated (De Hert et al., 2016). Rather lifestyle factors similar to those implicated in osteoporosis with the addition of nulliparity for females: factors which are overly represented in an SMI population are more detrimental (De Hert et al., 2016).

In the context of schizophrenia and antipsychotic use, this unnecessary testing of prolactin levels when not indicated by symptomatology is a waste of both time and resources. Both of which would be better utilized by a thorough history taken with regard to hyperprolactinemia symptoms as well as trying to motivate clients to consider and implement healthier lifestyle practices that contribute to a myriad of chronic illnesses that are overly represented in an SMI population. Furthermore, this unnecessary testing may lead to the unwarranted switching of antipsychotics to prolactin-sparing agents or the addition dopamine agonists, both of which can have a detrimental impact to the patient’s mental health and stability. Therefore, it is asserted that even if prolactin levels increase from baseline up to 2000 µg/L, if the patient is not exhibiting symptoms of hyperprolactinemia, nothing should be done. Beyond this level, further investigation is indicated.

See Guidelines by Galletly et al., 50: 410–472