Antipsychotic-induced Hyperprolactinemia Research Articles

Assessment of Monitoring and Management Practices of Antipsychotic-Induced Hyperprolactinemia at a Medical City in Riyadh, Saudi Arabia: A Retrospective Cohort Study.

Hyperprolactinemia is a commonly underestimated adverse effect of antipsychotic medications. There are still no consensus guidelines for the optimal monitoring and treatment strategies. The aim of the study was to assess the monitoring and treatment practices of antipsychotic- induced hyperprolactinemia, in addition to the prevalence and risk factors associated with it. A retrospective cohort observational study was conducted among patients attending the psychiatric clinics at an academic tertiary hospital in Riyadh, Saudi Arabia, from May 2020 until May 2021, by reviewing each patient's medical record for up to five years. Among the 662 patients, 35 patients (5.3%) and 242 patients (36.6%) had their serum prolactin levels monitored (at baseline and at follow-up, respectively). The prevalence of hyperprolactinemia was observed in 212 patients (32%). Only 76 patients (36%) were symptomatic. Female gender, younger age, and bipolar disorder had a significantly higher risk of developing hyperprolactinemia. 60% of the confirmed cases received treatment, of which 76 (60%) were adherent to treatment guidelines. The most common treatment strategies implemented were dose reduction (42.5%) and aripiprazole augmentation (29.1%). It is imperative to conduct a baseline check of prolactin levels before commencing any antipsychotic therapy. Similarly, routine prolactin level monitoring is recommended regardless of symptoms in patients treated with antipsychotics with a possible prolactin-raising effect. Adherence to evidence-based treatment guidelines can improve patient quality of life and therapeutic compliance.

Treatment of antipsychotic-induced hyperprolactinemia: an umbrella review of systematic reviews and meta-analyses.

Hyperprolactinemia is a common antipsychotic-induced adverse event in psychiatric patients, and the quality of clinical studies investigating the best treatments has varied. Thus, to better summarize the clinical evidence, we performed an umbrella review of overlapping systematic reviews and meta-analyses for the treatment of antipsychotic-induced hyperprolactinemia. The PubMed, Cochrane Library, PsycINFO, Scopus and EMBASE were searched, and reviews and meta-analyses meeting our inclusion criteria were selected. Relevant data were extracted, and an umbrella review was conducted of all included meta-analyses. The quality of included meta-analyses was assessed by using PRISMA scores and AMSTAR 2 quality evaluation. Finally, the clinical evidence for appropriate treatments was summarized and discussed. Five meta-analyses published between 2013 and 2020 met the requirements for inclusion in this umbrella review. The PRISMA scores of the included meta-analyses ranged from 19.5-26. AMSTAR 2 quality evaluation showed that 2 of the 5 included meta-analyses were of low quality and 3 were of very low quality. The included meta-analyses provide clinical evidence that adding aripiprazole or a dopamine agonist can effectively and safely improve antipsychotic-induced hyperprolactinemia. Two meta-analyses also showed that adjunctive metformin can reduce serum prolactin level, but more clinical trials are needed to confirm this finding. Adjunctive dopamine agonists have been proven to be effective and safe for the treatment of antipsychotic-induced hyperprolactinemia. Among the researched treatments, adding aripiprazole may be the most appropriate.

Assessment of prevalence of hyperprolactinemia in patients taking antipsychotic drugs in a tertiary care hospital in eastern India

Background: Researches done over different parts of the world show that hyperprolactinemia in psychotic patients is dependent on many factors such as age, gender, any thyroidal abnormality, drugs such as antipsychotics or antidepressants, psychological stress, and genre of psychosis. In patients taking antipsychotic treatments, prolactin blood levels may rise up to 10 times the normal values. It is very important to differentiate between prolactin-secreting tumor in pituitary and antipsychotic-induced hyperprolactinemia. There has been fewer researches on this topic in Eastern India, so it aims to properly estimate the amount of prolactin rise; a patient has to face after taking anti-psychotic medications and might also help the psychiatrists to adjust the dosage of anti-psychotics or to add some other drugs to lower the prolactin level along with the anti-psychotics in Eastern India. Aim and Objectives: The aims and objectives of the study are to estimate serum prolactin in diagnosed psychiatric patients taking antipsychotic drugs for at least 3 months and to study the difference in serum prolactin between recently diagnosed psychiatric patients taking antipsychotic drugs for at least 3 months and age and gender-matched mentally healthy patients without any psychiatric complication and without any history of in taking antipsychotic drugs. Materials and Methods: The study was conducted over a period of 4 months at Central Laboratory, Dept of Biochemistry, MCK. Before the conduct of the study, informed consent was taken. Patients diagnosed with psychiatric illness and consuming at least one antipsychotic drug for at least 3 months were enrolled after going through inclusion–exclusion criteria. Serum prolactin was measured with help of CLIA (ADVIA CENTAUR). Results: As per our study done in Eastern Indian population, in the female group of psychiatric patients (aged between 18 and 45 years) taking antipsychotics, the prolactin level was 23.6 ± 4.5 ng/ml, and in age-matched control female group, prolactin level was 9.2 ± 3.1 ng/mL, the difference is statistically significant (P < 0.001). Moreover, in male psychiatric patients (aged between 18 and 45 years) taking antipsychotics, the prolactin level was 14.3 ± 1.7 ng/mL, and in age-matched control male group, prolactin level was 8.5 ± 1.5 ng/mL, the difference is statistically significant (P < 0.001). Conclusion: As per our study, psychiatric patients of both gender taking antipsychotic drugs had higher serum prolactin level than age and gender-matched mentally healthy persons not taking antipsychotic drugs. Though the limitation of this study was small sample size and another issue that must be taken into consideration is the fact that prolactin levels can also be dependent of menstrual cycles in women, and in our study, there were 40 (57%) females who were still menstruating.

The effect of antipsychotic medication and the associated hyperprolactinemia as a risk factor for periodontal diseases in schizophrenic patients: a cohort retrospective study

BackgroundPeriodontal disease is a major health problem that results in tooth loss and thus affects oral health, which affects quality of life. In particular, schizophrenic patients are at higher risk for periodontal disease due to several factors, including the effect of antipsychotic medications received by those patients. Accordingly, the aim of the present cohort retrospective study is to explore the effect of antipsychotics on periodontal health and the possible effect of antipsychotic-induced hyperprolactinemia as a risk factor for periodontal disease progression in schizophrenic patients.Methods and outcomesThe study population consisted of three groups: Group A (n = 21): schizophrenic patients that have been taking “prolactin-inducing” antipsychotics for at least 1 year; Group B (n = 21): schizophrenic patients who have been taking “prolactin-sparing” antipsychotics for at least 1 year; and Group C (n = 22): newly diagnosed schizophrenic patients and/or patients who did not receive any psychiatric treatment for at least 1 year. The study groups underwent assessment of periodontal conditions in terms of pocket depth (PD), clinical attachment loss (CAL), gingival recession, tooth mobility, and bleeding on probing (BOP). Also, bone mineral density was evaluated using DEXA scans, and the serum prolactin level was measured by automated immunoassay.ResultsResults revealed a statistically significant difference in PD, CAL, and serum prolactin levels (P ≤ 0.001, P = 0.001, and P ≤ 0.001, respectively) among the 3 study groups. For both PD and CAL measurements, group A has shown significantly higher values than both groups B and C, whereas there was no statistically significant difference between the values of groups C and B. Concerning serum prolactin levels, group A had significantly higher values than groups B and C (P ≤ 0.001 and P ≤ 0.001 respectively). There was a statistically significant difference (P ≤ 0.001) between the 3 study groups in terms of bone mineral density. Moreover, there was a statistically significant direct relation between serum prolactin level and other parameters including clinical attachment loss, pocket depth measurements and bone mineral density.ConclusionAccording to our results, it could be concluded that all antipsychotics contribute to the progression of periodontal disease, with a higher risk for prolactin-inducing antipsychotics. However, further long term, large sampled, interventional and controlled studies are required to reach definitive guidelines to allow clinicians properly manage this group of patients.

SAT620 Dopamine Challenge: Treatment Of Pituitary Macroadenoma/Prolactinoma In Patient On Antipsychotic Medication

Abstract Disclosure: A. Bazhenov: None. I. Alpertunga: None. Background When hyperprolactinemia is a well-known side effect of antipsychotic medications1, the link between prolonged treatment with dopamine antagonist and the development of lactotroph adenomas is still unclear4. Treating a patient with prolactinoma and psychotic disorder may pose a challenge. Antipsychotic agents can cause increases in prolactin levels. Additionally, treatment of prolactinoma with dopamine agonists may worsen psychotic symptoms. Case presentation We present a case of 56 yo male with a PMH of bipolar disorder with psychotic features who was found to have a macroprolactinoma after 18 years of treatment with antipsychotic medications. At age 30, the patient was diagnosed with Bipolar Disorder with psychotic features. The course of the disease was complicated by numerous hospitalizations and frequent changes to the treatment plan, with different combination of second-generation antipsychotic, haloperidol and antiseizure medications. The patient’s prolactin level was 50 ng/ml at the time. 18 years after the diagnosis, the patient developed severe headaches. An MRI revealed a pituitary macroadenoma measuring 1.3 cm, and a repeat prolactin level resulted in 729 ng/ml. He was started on cabergoline 0.5 mg twice a week. As a result, the prolactin level dropped to 32 ng/ml and the macroprolactinoma size decreased to 1.1 cm. Unfortunately, the patient was lost to follow up. Once he re-established his care, he was started on Olanzapine 15 mg daily, Lamotrigine 200 mg daily and cabergoline 0.5 mg twice a week. After reinitiating cabergoline, the patient developed three maniac episodes, two of which required hospitalization. The dose of the cabergoline was decreased to avoid future maniac episodes. Neurosurgery will be consulted for possible surgery treatment. Discussion The treatment of a patient with prolactinoma and a psychotic disorder poses a particular challenge. We believe that care of these patients requires a multidisciplinary approach, and surgical treatment should be considered for those who cannot tolerate dopamine-agonist therapy. Literature 1. Bostwick JR, et al. Antipsychotic-induced hyperprolactinemia. Pharmacotherapy. 2009;29(1):64-73. 2. Lertxundi U et al. Antipsychotics and pituitary tumors. Int Clin Psychopharmacol. 2019;34(2)89. 3. Andrade EH, et al. Insights in the management of antipsychotics. Case Rep Med. 2010;2010. 4. McCarren M,et al. Follow-up study of a pharmacovigilance signal. J Clin Psychopharmacol. 2012;32(6)743. 5. Bakker IC, et al. Successful treatment of a prolactinoma on antipsychotic drug. Endocrinol Diabetes Metab Case Rep. 2016. 6. The challenges in managing prolactinomas SFEBES2009 Accessed April 11 2023. https://endocrine-abstracts.org 7. Howes OD et al. The role of dopamine in schizophrenia. Biol Psychiatry. 2017;81(1)9. 8.Bamarinejad A, et al. Schizophrenia and Macroprolactinoma: Adv Biomed Res. 2020;9(1)38. Presentation: Saturday, June 17, 2023

FRI398 A Case Of Secondary Amenorrhea: Is It Only PCOS To Blame?

Abstract Disclosure: P. Panjawatanan: None. S. Riahi: None. S.S. Chaidarun: None. Background: One of the most common causes of secondary amenorrhea is PCOS (polycystic ovary syndrome) which accounts for 30% of the cases. Though not as common, hyperprolactinemia similarly contributes to the condition. Here we describe a patient who presented with secondary amenorrhea from medication-induced hyperprolactinemia with underlying PCOS. Clinical Case: A 31-year-old female with a past medical history of bipolar disorder, hypothyroidism, and PCOS, presented with secondary amenorrhea. The patient started menarche at 11 years old and was diagnosed with PCOS a year later due to irregular menses and hirsutism. The estrogen-containing pill was prescribed, but she developed a blood clot due to Factor V Leiden thrombophilia. She was taking atomoxetine, lithium, mirtazapine, and olanzapine for her psychiatric issues and recently started on paliperidone last year. She reported no period in the past two years after stopping oral contraception. Pregnancy was ruled out. She tried progesterone challenge test but did not have any flow. Transvaginal ultrasound showed thin endometrium. She had IUD placed for contraception. Laboratory testing four months and one year after starting paliperidone showed prolactin of 79.2 ng/mL and 110 ng/mL consecutively. The patient reported headaches but denied galactorrhea or visual loss. There are no signs or symptoms of Cushing’s disease, acromegaly, or hypothyroidism. Further workup showed TSH 1.52 mcIU/mL, estradiol 16 pg/mL, FSH 5.6 mIU/mL, 17-OH progesterone <40 ng/dL, total testosterone 14 ng/dL, ACTH 11 pg/mL, IGF-1 z-score -0.67 SD. MRI brain was ordered, which ruled out pituitary adenoma. Repeat prolactin level remained elevated at 87.7 ng/mL without treatment. We concluded that the patient has secondary amenorrhea from PCOS and antipsychotic-induced hyperprolactinemia. Patient was referred to a psychiatrist for antipsychotic medication changes. Conclusion: Antipsychotics, typically first-generation, are known to cause hyperprolactinemia due to their dopamine-antagonist effect. Prolactin level ranging from 25-100 ng/mL is seen in medication-induced hyperprolactinemia, while particular medication like risperidone and phenothiazines can raise the level to more than 200 ng/mL. Newer agent paliperidone has been reported to induce hyperprolactinemia similarly to risperidone which explains significant prolactin elevation in this patient. Hyperprolactinemia poses a risk for hypogonadism due to suppressed pituitary-gonadal axis, resulting in anovulation and bone loss. Estrogen therapy is considered an adjunct to help with hypogonadism. However, it is contraindicated in patients with thrombophilia. The guideline recommends switching to a low-risk antipsychotic agent if feasible. Despite having an established diagnosis of PCOS, it is important to consider other secondary causes of amenorrhea which may occur concomitantly. Presentation: Friday, June 16, 2023

Development of a Guideline for Antipsychotic-induced Hyperprolactinemia in Korea Using the ADAPTE Process.

To develop an evidence-based guideline for the diagnosis and treatment of antipsychotic-induced hyperprolactinemia by adapting existing high-quality clinical guidelines with a view to improve the clinical symptoms and long-term quality of life of patients by providing appropriate management. This guideline was developed according to the ADAPTE methodology. The adaptation process included determining key health questions, systematically searching and screening guidelines, evaluating the quality and contents of these guidelines, deriving recommendations for key questions, and performing a peer review. The selection criteria for the guideline search were (1) evidence-based guidelines, (2) published within the last 5 years, and (3) written in English or Korean. After evaluating the quality and content, we finally selected three guidelines for adaptation. The final output of the development process was 25 recommendations for 10 key questions. We adopted the Agency for Health Research Quality methodology and presented the level of evidence from levels I to IV. In addition, we defined the recommendation grades from grade A (strongly recommended) to D (no recommendation) based on the level of evidence and clinical significance of the recommendation. The development and dissemination of the adapted guideline is expected to increase the certainty of medical decision making and improve the quality of medical care. Further studies on the effectiveness and applicability of the developed guideline are necessary.

Study of Associations of the GRM8 Gene with Antipsychoticinduced Hyperprolactinemia

Hyperprolactinemia is one of the common adverse events of antipsychotic therapy. The role of genetic factors in the development of drug-induced side effects is being actively investigated. The present study examined the association of two polymorphisms rs2237748 and rs2299472 in the GRM8 gene encoding the glutamate metabotropic receptor type 8 with antipsychotic-induced hyperprolactinemia in 536 patients with schizophrenia from several regions of Siberia (Russia). The investigated polymorphisms are not associated with drug-induced hyperprolactinemia in patients with schizophrenia. There were no associations of the GRM8 gene polymorphisms with serum prolactin levels in patients taking antipsychotic therapy. Our results did not confirm the involvement of the GRM8 rs2237748 and rs2299472 in the development of antipsychotic-induced hyperprolactinemia.

Pharmacological Features of 18β-Glycyrrhetinic Acid: A Pentacyclic Triterpenoid of Therapeutic Potential.

Glycyrrhiza glabra L. (belonging to the family Leguminosae), commonly known as Licorice, is a popular medicinal plant that has been used in traditional medicine worldwide for its ethnopharmacological efficacy in treating several ailments. Natural herbal substances with strong biological activity have recently received much attention. The main metabolite of glycyrrhizic acid is 18β-glycyrrhetinic acid (18βGA), a pentacyclic triterpene. A major active plant component derived from licorice root, 18βGA has sparked a lot of attention due to its pharmacological properties. The current review thoroughly examines the literature on 18βGA, a major active plant component obtained from Glycyrrhiza glabra L. The current work provides insight into the pharmacological activities of 18βGA and the potential mechanisms of action involved. The plant contains a variety of phytoconstituents such as 18βGA, which has a variety of biological effects including antiasthmatic, hepatoprotective, anticancer, nephroprotective, antidiabetic, antileishmanial, antiviral, antibacterial, antipsoriasis, antiosteoporosis, antiepileptic, antiarrhythmic, and anti-inflammatory, and is also useful in the management of pulmonary arterial hypertension, antipsychotic-induced hyperprolactinemia, and cerebral ischemia. This review examines research on the pharmacological characteristics of 18βGA throughout recent decades to demonstrate its therapeutic potential and any gaps that may exist, presenting possibilities for future drug research and development.

Hyperprolactinemia in patients taking antipsychotics: the importance of a shared approach between psychiatry and endocrinology

IntroductionHyperprolactinemia is a commonly encountered adverse effect of antipsychotic medication. Short and long-term repercussions of high prolactin, such as amenorrhea, sexual dysfunction, osteopenia and increased cardiovascular risk carry significant burden and may compromise therapeutic adherence. Despite its serious practical implications, hyperprolactinemia is still underscreened and its management neglected.ObjectivesTo review current clinical guidelines regarding the management of hyperprolactinemia associated with the use of antipsychotics, reflecting upon the importance and need to share the management of this risk with an endocrinology expert.MethodsWe performed a literature review to identify clinical guidelines containing specific recommendations for antipsychotic-induced hyperprolactinemia (British Association of Psychopharmacology [BAP], NICE, Maudsley Prescribing Guidelines, Royal Australian and New Zealand College of Psychiatrists), published over the last ten years, with a particular focus on its physical risks.ResultsMost guidelines do not recommend routine monitoring of prolactin levels in asymptomatic patients. NICE and BAP guidelines have suggested measuring the baseline prolactin level, but have not specified follow-up monitoring, while Maudsley guidelines have. Management strategies depend on factors such as sex, age, as well as the clinical manifestations that ensue. Different treatment strategies have been described, such as decreasing the dose of the antipsychotic, switching antipsychotics, adding aripiprazole or adding dopaminergic agonists. Referral to an endocrinology specialist should be made if the aetiology is unclear, prolactin levels continue to rise despite some intervention, the hyperprolactinaemia is severe (>3000 mIU/L) or there is suspected/confirmed pituitary adenoma. Further physical implications of having hyperprolactin are to be dressed by the endocrinology expert, namely those on bone metabolism, gonodal function and cancer risk.ConclusionsGiven the widespread use of antipsychotics and the need to have psychotic patients stabilized (sometimes with a lack of effective alternative), early detection and shared management of hyperprolactinemia are instrumental towards assisting both clinician’s and patients’ decision-making, be it towards lowering prolactin levels or managing its risk without compromising the antipsychotic’s efficacy.Disclosure of InterestNone Declared

Characteristics and Management of Granulomatous Lobular Mastitis Associated with Antipsychotics-Induced Hyperprolactinemia.

Background: Granulomatous lobular mastitis (GM) is a rare inflammatory breast disease. Reports focusing on GM caused by antipsychotic-induced hyperprolactinemia (HPRL) are very rare. Aim: To report a study of GM associated with antipsychotic-induced HPRL and discuss the mechanism and management. Materials and Methods: A retrospective review of patients with GM and psychiatric disorders were carried out. The clinical characteristics, management and outcome were collected and analyzed. The relationship between antipsychotics and GM was evaluated using the Naranjo Adverse Drug Reaction Probability Scale (Naranjo scale). Results: Nineteen female GM patients with psychiatric diseases, aged 21-39 years, who had received antipsychotics for 0.5-10.2 years were included. Most patients took multiple antipsychotics, and 10 (52.6%) took risperidone-containing regimens. Increased prolactin (PRL) was detected in all patients (range 35.15-200 ng/mL). The scores of Naranjo scale were 7-8, indicated the antipsychotics probably induced GM. All patients received systemic therapy, and were prescribed bromocriptine. Seven patients (36.8%) decreased the dose of antipsychotics, six (31.6%) switched antipsychotics, three (15.8%) continued the primary antipsychotics, and three (15.8%) discontinued antipsychotics. In addition, 14 patients (73.7%) received corticosteroid, 4 (21.1%) received antimycobacterials. PRL decreased to normal in 1 month. Seven patients (36.8%) received excisional surgery. After 12 months' follow-up (range 9-56 months), only three patients (15.8%) had a recurrence. Conclusion: Long-term use of antipsychotics may increase PRL levels, and lead to GM. It is vital to assess PRL level and reduce PRL to normal in patients with GM.

Efficacy and Safety of Adjunctive Aripiprazole, Metformin, and Paeoniae-Glycyrrhiza Decoction for Antipsychotic-Induced Hyperprolactinemia: A Network Meta-Analysis of Randomized Controlled Trials.

Aripiprazole, metformin, and paeoniae–glycyrrhiza decoction (PGD) have been widely used as adjunctive treatments to reduce antipsychotic (AP)-induced hyperprolactinemia in patients with schizophrenia. However, the comparative efficacy and safety of these medications have not been previously studied. A network meta-analysis of randomized controlled trials (RCTs) was conducted to compare the efficacy and safety between aripiprazole, metformin, and PGD as adjunctive medications in reducing AP-induced hyperprolactinemia in schizophrenia. Both international (PubMed, PsycINFO, EMBASE, and Cochrane Library databases) and Chinese (WanFang, Chinese Biomedical, and Chinese National Knowledge infrastructure) databases were searched from their inception until January 3, 2019. Data were analyzed using the Bayesian Markov Chain Monte Carlo simulations with the WinBUGS software. A total of 62 RCTs with 5,550 participants were included in the meta-analysis. Of the nine groups of treatments included, adjunctive aripiprazole (<5 mg/day) was associated with the most significant reduction in prolactin levels compared to placebo (posterior MD = −65.52, 95% CI = −104.91, −24.08) and the other eight treatment groups. Moreover, adjunctive PGD (>1:1) was associated with the lowest rate of all-cause discontinuation compared to placebo (posterior odds ratio = 0.45, 95% CI = 0.10, 3.13) and adjunctive aripiprazole (>10 mg/day) was associated with fewer total adverse drug events than placebo (posterior OR = 0.93, 95% CI = 0.65, 1.77) and other eight treatment groups. In addition, when risperidone, amisulpride, and olanzapine were the primary AP medications, adjunctive paeoniae/glycyrrhiza = 1:1, aripiprazole <5 mg/day, and aripiprazole >10 mg/day were the most effective treatments in reducing the prolactin levels, respectively. Adjunctive aripiprazole, metformin, and PGD showed beneficial effects in reducing AP-induced hyperprolactinemia in schizophrenia, with aripiprazole (<5 mg/day) being the most effective one.

Safety and Efficacy of High-Dose Vitamin B6 as an Adjunctive Treatment for Antipsychotic-Induced Hyperprolactinemia in Male Patients With Treatment-Resistant Schizophrenia.

This study aimed to investigate the safety and efficacy of high-dose vitamin B6 (vB6) as an adjunct treatment for antipsychotic-induced hyperprolactinemia (AIHP) in male patients with treatment-resistant schizophrenia (TRS). In this randomized double-blinded controlled study, patients were randomized (1:1) into a control group given aripiprazole (ARI; 10 mg/day; n = 100) or an intervention group given vB6 (300 mg/12 h for 16 weeks; n = 100). Prolactin levels, psychotic symptoms [Positive and Negative Syndrome Scale (PANSS)], cognitive function [MATRICS Consensus Cognitive Battery (MCCB)], liver function, kidney function, growth hormone level, micronutrient levels, blood lipids, and adverse secondary effects (ASEs)[Treatment Emergent Symptom Scale (TESS) and Barnes-Akathisia scale] were monitored. After a 16-week treatment period, the vB6 group showed a 68.1% reduction in serum prolactin levels (from 95.52 ± 6.30 μg/L to 30.43 ± 18.65 μg/L) while the ARI group showed only a 37.4% reduction (from 89.07 ± 3.59 μg/L to 55.78 ± 7.39 μg/L). During weeks 1–4, both treatments reduced prolactin similarly. Subsequently, the ARI effect plateaued, while the vB6 effect remained robust. The vB6 group showed better alleviation of psychotic symptoms and cognitive impairment. No serious ASEs were observed; ASEs were more frequent in the ARI group. AIHP reduction efficacy of vB6 was associated with baseline prolactin and triglyceride levels, total vB6 dosage, and education level. In conclusion, compared with the ARI group, TRS patients given vB6 showed better attenuation of AIHP, lower ASE scores, and greater improvements in clinical symptoms and cognitive impairments. These results support further consideration of vB6 as a putative treatment for AIHP.Trial Registration: ChiCTR1800014755

Guidance on the treatment of antipsychotic-induced hyperprolactinemia when switching the antipsychotic is not an option.

DisclaimerIn an effort to expedite the publication of articles related to the COVID-19 pandemic, AJHP is posting these manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.PurposeThis article aims to evaluate management options for antipsychotic-induced hyperprolactinemia and associated treatment considerations such as efficacy, tolerability, drug interactions, contraindications, and dosing regimens.SummaryHyperprolactinemia is a common adverse effect of antipsychotics. First-line management includes reducing the dose of the offending antipsychotic, discontinuing the antipsychotic, or switching to another antipsychotic associated with a lower risk of hyperprolactinemia. However, these options are not always practical and are associated with a risk of relapse of the psychiatric illness. Other management options include adjunctive aripiprazole, dopamine agonists (cabergoline and bromocriptine), metformin, and herbal supplements. A search of Embase, PubMed, and Google Scholar using key terms such as hyperprolactinemia, prolactin, antipsychotic, treatment guidelines, aripiprazole, dopamine agonist, cabergoline, bromocriptine, metformin, herbals, supplements, and medications was conducted for literature retrieval. Upon evaluation of the available literature we found the following: (1) aripiprazole is safe and effective in lowering prolactin levels within normal limits; (2) adjunctive cabergoline and bromocriptine decrease elevated prolactin levels, while cabergoline may be more effective in reducing prolactin but can also be associated with a more serious adverse effect of cardiac valvular abnormalities; (3) metformin causes a mild reduction of prolactin levels; and (4) there are limited data to support use of herbal medications (chamomile, Peony-Glycyrrhiza decoction, and shakuyaku-kanzo-to) in antipsychotic-induced hyperprolactinemiaConclusionThere are treatments available for antipsychotic-induced hyperprolactinemia in patients who are unable to alter their current antipsychotic regimen. However, there remains a need for additional short- and long-term studies to determine the efficacy and safety of these treatment strategies, given that patients taking antipsychotics typically require chronic, life-long treatment for their illnesses.

Abnormally low prolactin levels in schizophrenia patients after switching to aripiprazole in a randomized trial: a biomarker for rebound in psychotic symptoms?

BackgroundSwitching to aripiprazole from other antipsychotics can avoid antipsychotic-induced hyperprolactinemia but may result in an abnormally low prolactin level. This study aimed to assess whether the aripiprazole-induced abnormally low prolactin level was a biomarker for subsequent rebound of positive symptoms in schizophrenia patients.MethodsParticipants were 63 patients in an 8-week trial of switching to aripiprazole, in which preswitching antipsychotics were maintained for the first 2 weeks and aripiprazole was fixed at 15 mg orally throughout the trial. A prolactin level of < 3.7 ng/ml was defined as abnormally low, and an increase of two or more points in the positive subscore of the Positive and Negative Syndrome Scale at two adjacent ratings was defined as a psychotic rebound.ResultsAmong 63 patients, 25 (39.7%) had an abnormally low prolactin level and 21 (33.3%) had a psychotic rebound after switching to aripiprazole. In patients with abnormally low prolactin levels, 48.0% of them had a rebound in psychotic symptoms, whereas in those without abnormally low prolactin levels 23.7% did so. Multivariable logistic regression analysis with adjustment for sex, early age at onset, and preswitching medications revealed that abnormally low prolactin levels were associated with psychotic rebound (adjusted odds ratio = 3.55, 95% confidence interval = 1.02, 12.5). Furthermore, there was concurrency between the trend of the cumulative proportion of patients having an abnormally low prolactin level and that of the cumulative proportion of patients having a rebound in psychotic symptoms.ConclusionsAn abnormally low prolactin level after switching to aripiprazole in schizophrenia patients was a potential warning sign of a psychotic rebound. Hence, monitoring of prolactin levels after switching to aripiprazole may help avoid such rebound in schizophrenia.Trial registrationNCT00545467; Date of registration: 17/10/2007.

P.583 Polymorphisms in BDNF, AKT1, GSK3B genes: possible association with antipsychotic-induced hyperprolactinemia in schizophrenia patients

This study presents new developments for the performance-based assessment of seismically-induced slope displacements (D). Performance-based procedures enable a hazard-consistent and rational seismic design of slope systems; hence, their use in practice is appealing. However, they are not the standard in engineering practice because their use is considered too complex to be used for non-critical projects. The developments presented in this study allow the straightforward estimation of displacement hazard curves (DHC) for a wide range of slope systems subjected to earthquakes in different tectonic settings (i.e., shallow crustal, and subduction), considering a rigorous quantification of the existing uncertainties.The new developments include 1) full integration of probabilistic seismic hazard assessments (PSHA), and the estimation of DHCs, 2) automatic estimation of DHC for D models with multiple intensity measures through vector PSHA, 3) estimation of DHC for systems with contributions from multiple tectonic settings, 4) uncertainty treatment (i.e., epistemic and aleatory) on DHCs, through a logic tree scheme, 5) deaggregation of earthquake scenarios from DHCs, and 6) uncertainty quantification on DHCs through the polynomial chaos theory. The new developments are implemented in a MATLAB graphical user interface (GUI) to facilitate its use by engineers and researchers. We discuss illustrative examples and guidelines for the application of the GUI to evaluate the seismic performance of different slope systems that are affected by earthquakes from multiple tectonic settings.

Overview of The Incidence of Hyperprolactinemia Side Effects in Schizophrenia Patients With Antipsychotic Therapy

Antipsychotic-induced hyperprolactinemia disorder affects the morbidity and quality of life of the patient, and can lower the patient's adherence to taking antipsychotics, thereby lowering the therapeutic success rate. This study aims to figure out the incidence of hyperprolactinemia side effects in schizophrenia patients receiving antipsychotic therapy. This descriptive research was conducted at HB Saanin Psychiatric Hospital Padang in January-June 2018. The population in this study is all schizophrenia patients in the HB. Saanin Psychiatric Hospital Padang Year 2018 and involved participants as many as 100 people recruited in consecutive sampling. Data were analyzed using a descriptive statistical method. The results showed that more than half of the patients were 59 people (59.0%) hyperprolactinemia. Patients with gynecomastia amounted to 16 people (16%). Patients with galactorrhea amounted to 3 people (3%). Patients with sexual dysfunction amounted to 19 people (19%). Male patients amounted to 60 people, 21 people (35%) The sexual dysfunction of female patients amounted to 40 people, 26 people (65%) Menstrual cycle changes. More than half of the Schizophrenia patients receiving antipsychotic therapy in this study suffer symptoms of hyperprolactinemia in the manifestation of galactorrhea, gynecomastia, menstrual disorders, and sexual dysfunction.

Association of ANKK1 polymorphism with antipsychotic-induced hyperprolactinemia.

ObjectiveSchizophrenia is a severe highly heritable mental disorder. Genetic polymorphisms of dopaminergic pathways are related to pathogenesis of drug response. Hyperprolactinemia (HPRL), a common adverse effect of antipsychotics, is attributed to blockade of dopamine D2 receptors. Ankyrin Repeat and Kinase Domain containing 1 (ANKK1) gene is closely related to Dopamine Receptor D2 type (DRD2) gene functioning. We examined whether the functional polymorphism rs2734849 in the ANKK1 gene is associated with antipsychotic‐induced HPRL.MethodsWe recruited 446 patients with schizophrenia from among the Russian population of the Siberian region. The polymorphism rs2734849 in the ANKK1 gene was genotyped with The MassARRAY® Analyzer 4 by Agena Bioscience™, using the kit SEQUENOM Consumables iPLEXGold 384. Genotype and allele frequencies were compared between groups of schizophrenia patients with and without HPRL using the χ2 test.ResultsA comparison between schizophrenia patients with and without HPRL revealed significantly higher frequency of the C allele of the polymorphic variant rs2734849 in the ANKK1 gene in patients with HPRL as compared to the patients without it (χ2 = 3.70; p = .05; odds ratio [OR] = 1.30 [0.99–1.69]).ConclusionThe functional polymorphism rs2734849 in the ANKK1 gene was associated with HPRL in patients with schizophrenia.

Paeoniflorin ameliorates antipsychotic-induced hyperprolactinemia in rats by attenuating impairment of the dopamine D2 receptor and TGF-β1 signaling pathways in the hypothalamus and pituitary

Ethnopharmacological relevancePaeoniflorin, a prominent component in some Chinese formulas for hyperprolactinemia-associated disorders, has been found to inhibit prolactin secretion in prolactinoma cells. AimTo examine the efficacy of paeoniflorin on hyperprolactinemia and the underlying mechanisms of action. Materials and methodsHyperprolactinemia in female rats was generated by administration of olanzapine (5 mg/kg, by a gavage method, once daily, × 13 weeks). The rats were co-treated with paeoniflorin (10 and 50 mg/kg). Prolactin and TGF-β1 concentrations were detected by ELISA. Protein expression was determined by Western blot. The effect in MMQ cells was also examined. ResultsPaeoniflorin inhibited olanzapine-induced increases in plasma prolactin concentration and prolactin protein overexpression in the pituitary and hypothalamus of rats. Further, paeoniflorin restored olanzapine-induced downregulation of pituitary and hypothalamic dopamine D2 receptor (D2R) protein expression. More importantly, paeoniflorin attenuated olanzapine-suppressed protein expression of transforming growth factor (TGF)-β1 and its downstream genes, type II TGF-β receptor, type I TGF-β receptor and phosphorylated SMAD3 in the tissues. However, paeoniflorin did not affect plasma TGF-β1 concentration and hepatic TGF-β1 protein expression. In accord, olanzapine-induced increase in prolactin concentration, upregulation of prolactin protein expression, and downregulation of protein expression of the D2R and TGF-β1 signals in MMQ cells were attenuated. ConclusionsThis study demonstrates that paeoniflorin ameliorates olanzapine-induced hyperprolactinemia in rats by attenuating impairment of the D2R and TGF-β1 signaling pathways in the hypothalamus and pituitary. Our findings may provide evidence to support the use of paeoniflorin-contained Chinese herbs and formulas for hyperprolactinemia and its associated disorders.

Association between 8 P-glycoprotein (MDR1/ABCB1) gene polymorphisms and antipsychotic drug-induced hyperprolactinaemia.

IntroductionHyperprolactinaemia, a common adverse effect of antipsychotic drugs, is primarily linked to blockade of dopamine D2 receptors in the pituitary gland. Certain antipsychotic drugs, such as, for example risperidone and paliperidone, are more likely to induce hyperprolactinaemia compared to others. This effect is probably caused by a relatively high blood/brain concentration ratio, a consequence of being a substrate of P‐glycoprotein. Genetic variants of P‐glycoprotein with changed functional activity might influence the potential of risperidone and paliperidone to cause hyperprolactinaemia as the altered blood/brain concentration ratio would lead to a reduced therapeutic drug level within essential brain areas making dose adaptations necessary. This increases exposure of dopamine D2 receptors within the pituitary gland.AimsTo investigate possible associations between MDR1/ABCB1 gene polymorphisms and antipsychotic drug‐induced hyperprolactinaemia in Russian patients with schizophrenia and to determine possible differences between risperidone/paliperidone and other antipsychotics.MethodsIn total, 446 patients with schizophrenia were included from 3 psychiatric hospitals in Siberia. Blood samples were obtained in a cross‐sectional study design for DNA extraction and prolactin measurement. Associations between hyperprolactinaemia and 8 MDR1/ABCB1 gene‐polymorphisms were assessed using logistic regression analysis accounting for covariates. The analysis was repeated in a patient subgroup using risperidone or paliperidone.ResultsWe did not observe an association between any of the 8 single nucleotide polymorphisms and the prevalence of antipsychotic‐induced hyperprolactinaemia in the total patient population. However, in the risperidone/paliperidone subgroup, the single nucleotide polymorphism rs2032582 (G2677T) was found to be negatively associated with risperidone/paliperidone‐induced hyperprolactinaemia.ConclusionThis study revealed a significant association between the ABCB1 gene polymorphism rs2032582 (G2677T) and risperidone/paliperidone‐induced hyperprolactinaemia.