Treatment Of Antipsychotic-induced Hyperprolactinemia Research Articles

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.

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.

Topiramate in the treatment of antipsychotic-induced hyperprolactinemia

Hyperprolactinemia is a common but neglected adverse effect of antipsychotic agents. Current treatments for antipsychotic-induced hyperprolactinemia exert their action mainly through the mechanism of enhancing the inhibitory effect of dopamine on prolactin secretion; however, patients have to endure the risk of psychotic relapse or exacerbation. Topiramate, a new anticonvulsant, is widely used in the treatment of numerous psychiatric conditions. It can antagonize α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and kainate (KA) glutamate receptors and enhance the inhibitory activity of γ-amino butyric acid (GABA). Inhibition of AMPA and KA receptors and increased GABA activity has been proved to have an inhibitory effect on prolactin release. Thus, topiramate may be an effective agent in the treatment of antipsychotic-induced hyperprolactinemia.

Management of antipsychotic-induced hyperprolactinemia.

Introduction:Antipsychotics represent a large portion of the psychotropics that may induce hyperprolactinemia. Clinical psychiatric pharmacists must be adept in stratifying the relative risk of hyperprolactinemia among psychotropics, identifying patient risk factors, recognizing differential diagnoses, and recommending therapeutic alternatives and treatment strategies. High-potency, typical antipsychotics are more likely to elevate prolactin although exceptions to the rule exist.Methods:A literature search of PubMed and Google Scholar was performed to identify English language articles on the treatment of antipsychotic-induced hyperprolactinemia in humans. Methodological rigor is summarized for compiled studies in addition to feasibility and limitations of application to clinical practice.Results:There is an absence of robust evidence for the management of antipsychotic-induced hyperprolactinemia. Among the pharmacological treatments studied, aripiprazole (switching or augmentation) possessed the strongest evidence. Pharmacological treatments with less evidence encompassed dose reduction, switching to lower potency antipsychotics, and adding dopamine agonists. To date, no head-to-head studies have been published on the above approaches.Discussion:Atypical antipsychotics with low affinity for dopamine (D2) receptors, such as olanzapine, are logical alternatives for the patient experiencing drug-induced hyperprolactinemia. When augmentation is clinically preferred to switching, a viable option is the addition of a full or partial dopamine agonist, such as bromocriptine or aripiprazole, respectively. Patient-specific risk of psychiatric decompensation and the severity of symptomatic hyperprolactinemia should be weighed when formulating treatment strategies.

Efficacy and safety of long-term cabergoline treatment of antipsychotic-induced hyperprolactinemia (naturalistic study)

IntroductionAntipsychotic-induced hyperpolactinemia (AIH) is associated with disturbing clinical symptoms, such as sexual dysfunctions, menstrual disorders and galactorrhea. Long-term studies of dopamine agonists in AIH are scarce.ObjectivesTo assess efficacy and safety of cabergoline use in psychiatric patients with AIH, including impact on sexual function and quality of life(QoL).MethodsIt was an open-labeled non-randomized naturalistic prospective comparison of cabergoline vs nо treatment in 84 chronic psychiatric patients (F/M = 77/7) with AIH. Cabergoline treatment was started in 44 patients, the сontrol group included 40 patients who rejected the treatment with cabergoline. For assessment of QoL, sexual dysfunction and other hyperprolactinemia symptoms, UKU side effects rating scale (UKU) and SF-36 were used.ResultsThe main and control groups were comparable on all main clinical and psychiatric characteristics. The effective cabergoline dose was 0,25-3 (median-0,5) mg weekly; total cabergoline exposure–534 patient-weeks. Normal prolactin levels were achieved after 4-44 (median-14) weeks in 95% of patients. At 3 months after cabergoline discontinuation, prolactin remained normal in 71%, and AIH recurred in 29% of patients. Prolactin normalization was associated with significant reduction of menstrual disorders, galactorrhea, improvement of UKU scores on sexual desire, orgastic dysfunction, total UKU score and SF-36 scores on subscales of social functioning (P = 0,006), role-emotional (P = 0,042), and mental health (P = 0,049). The rate of psychosis exacerbation in control group was higher than in the treatment group (37,5% vs 0%; P < 0,001).ConclusionsCabergoline is effective and safe in majority of AIH patients. Long-term cabergoline treatment is not associated with psychosis exacerbation. Beyond reversal of typical AIH symptoms, treatment with cabergolin improves sexual function and QoL.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Using aripiprazole to reduce antipsychotic-induced hyperprolactinemia: meta-analysis of currently available randomized controlled trials.

BackgroundHyperprolactinemia (HPL) is a common side effect of antipsychotic medications. Recent reports suggest that aripiprazole can ameliorate antipsychotic-induced HPL, but results are inconsistent and the single available systematic review only considered five studies.AimConduct an updated meta-analysis of all randomized controlled trials (RCTs) about the efficacy and safety of aripiprazole as an adjunctive treatment for antipsychotic-induced hyperprolactinemia.MethodsEnglish and Chinese databases were searched for RCTs about the use of aripiprazole in treating antipsychotic-induced HPL published by January 20, 2015. Studies were selected using pre-defined inclusion and exclusion criteria. The Cochrane Risk of Bias tool was used to evaluate risk of biases, the Cochrane GRADE measure was used to assess the quality of evidence, and Review Manager 5.3 software was used for data analysis.ResultsA total of 21 studies, 19 of which were conducted in mainland China, were included in the analysis. Meta-analysis of data from 8 of the studies with a pooled sample of 604 individuals found that compared to the control condition adjunctive aripiprazole significantly increased the proportion of participants who experienced HPL recovery (risk ratio [RR]=19.2, 95%CI=11.0-33.5). The proportion who experienced any adverse effect during follow-up did not differ between the two groups, but the aripiprazole group was more likely to report somnolence (RR=2.76, 95%CI=1.34-5.69) and headaches (RR=2.31, 95%CI=1.08-4.92). High-dose aripiprazole (>5mg/day) was more effective than low-dose (<5mg/day) aripiprazole (RR=30.0, 95%CI=10.2-120.7 v. RR=15.1, 95%CI=8.1-28.1), but this difference was not statistically significant. The risk of bias in the studies was rated as ‘high’ in 6 of the studies and ‘unclear’ in 15 studies, and the quality of evidence was rated as ‘high’ for only 7 of the 57 outcome measures assessed.ConclusionsThis study systematically reviewed and evaluated all relevant RCTs and found that adjunctive aripiprazole is effective and safe to use in the treatment of antipsychotic-induced HPL. However, the low quality of some of the studies, the incomplete methodological information provided for most of the studies, and the relatively short follow-up time of the studies raises question about the validity of the results. Further work that resolves these methodological and reporting issues is needed.

Treatment of Antipsychotic-Induced Hyperprolactinemia: An Update on the Role of the Dopaminergic Receptors D2 Partial Agonist Aripiprazole

Hyperprolactinemia is an unwanted adverse effect present in several typical and atypical antipsychotics. Aripiprazole is a drug with partial agonist activity at the level of dopamine receptors D2, which may be effective for antipsychotic- induced hyperprolactinemia. Therefore, we analyzed the literature concerning the treatment of antipsychoticinduced hyperprolactinemia with aripiprazole by updating a previous paper written on the same topic. More recent studies were reviewed. They showed that there are two options for the treatment of antipsychotic-induced hyperprolactinemia with aripiprazole. The safest strategy may require the addition of aripiprazole to ongoing treatments, in the case patients had previously responded to antipsychotic drugs and then developed hyperprolactinemia. However, it is advisable to monitor the patients in case relapses and/or side effect, although rare, might occur. Switching drugs should be considered when a patient does not appear to be responding to the previous antipsychotic, thus developing hyperprolactinemia. A cross-taper switch should always be considered, but the risk of a relapse in the disorder may occur more frequently and the patients should be closely monitored. However, limitations must be considered and further studies are needed to definitely elucidate this important issue. Some relevant patents are also described in this review.

Treatment of antipsychotic-induced hyperprolactinemia with bromocriptine: A case report

INTRODUCTION Previous literature has highlighted an increase in morbidity and mortality associated with antipsychotic use in persons with severe mental illnesses (SMI), which include schizophrenia and bipolar disorder. Drug-induced hyperprolactinemia is a function of dopamine blockade in the anterior pituitary. Elevated prolactin levels are often accompanied by symptoms of decreased libido and erectile dysfunction (ED) in men, and galactorrhea and amenorrhea in women. However, the extent to which antipsychotic (AP) use is associated with sexual dysfunction has not been extensively reported. Hyperprolactinemia may also increase the risk for osteopenia.

Novel Approaches in the Treatment of Antipsychotic-Induced Hyperprolactinemia:The Role of Partial Agonists of D2 Dopaminergic Receptors

Dopamine is the predominant physiological inhibitory factor of prolactin release. Hyperprolactinemia is associated with potentially serious short and long-term clinical consequences. Several physiological and pathological conditions can cause elevated serum prolactin levels. Of these, in the psychiatric population, antipsychotic drugs are the most common. Because treatment of psychiatric illness often begins during adolescence and involves the long-term administration of these medications, the antipsychotic-induced hyperprolactinemia appears to be a major health concern for these patients. There are many possible management strategies of antipsychotic-induced hyperprolactinemia: estrogen/testosterone replacement, adding a dopamine agonist and introducing an alternative antipsychotic. Aripiprazole, a drug with partial agonist activity at dopamine D2 receptors, may be effective for antipsychotic-induced hyperprolactinemia. This paper reviews recent patents, mechanisms and evidences regarding the clinical action of aripiprazole on antipsychotic-induced hyperprolactinemia. Keywords: Prolactin, hyperprolactinaemia, antipsychotics, aripiprazole, dopamine, partial agonism.