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, iloperidone and lurasidone on PRL levels. The objective of this review is to describe PRL physiology; PRL measurement; diagnosis, causes, consequences and mechanisms of HPRL; incidence figures of (new-onset) HPRL with SGAs and newly approved antipsychotics in adolescent and adult patients; and revisit lingering questions regarding this hormone. A literature search, using the MEDLINE database (1966–December 2013), was conducted to identify relevant publications to report on the state of the art of HPRL and to summarize the available evidence with respect to the propensity of the SGAs and the newly approved antipsychotics to elevate PRL levels. Our review shows that although HPRL usually is defined as a sustained level of PRL 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 PRL. Although the highest rates of HPRL 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 SGAs can induce PRL elevations, especially at the beginning of treatment, and have the potential to cause new-onset HPRL. Considering the PRL-elevating propensity of the newly approved antipsychotics, evidence seems to indicate these agents have a PRL profile comparable to that of clozapine (asenapine and iloperidone), ziprasidone and olanzapine (lurasidone). PRL elevations with antipsychotic medication generally are dose dependant. However, antipsychotics having a high potential for PRL elevation (amisulpride, risperidone and paliperidone) can have a profound impact on PRL levels even at relatively low doses, while PRL levels with antipsychotics having a minimal effect on PRL, in most cases, can remain unchanged (quetiapine) or reduce (aripiprazole) over all dosages. Although tolerance and decreases in PRL values after long-term administration of PRL-elevating antipsychotics can occur, the elevations, in most cases, remain above the upper limit of normal. PRL 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 HPRL, recent research has shown that HPRL can be pre-existing in a substantial portion of antipsychotic-naive patients with first-episode psychosis or at-risk mental state.

/pdf/the-effects-of-novel-and-newly-approved-antipsychotics-on-1vhtefoskm.pdf

The Effects of Novel and Newly Approved Antipsychotics on Serum Prolactin Levels: A Comprehensive Review

BackgroundAnorexia nervosa is a potentially deadly psychiatric illness that develops predominantly in females around puberty but is increasingly being recognized as also affecting boys and men and women across the lifespan. The aim of this environmental scan is to provide an overview of best practices in anorexia nervosa treatment across the age spectrum.MethodA triangulation approach was used. First, a detailed review of randomized controlled trials (RCTs) for anorexia nervosa published between 1980 and 2011 was conducted; second, clinical practice guidelines were consulted and reviewed; third, information about RCTs currently underway was sourced. This approach facilitated a comprehensive overview, which addressed the extant evidence base, recent advances in evidence and improvements in treatment, and future directions.ResultsThe evidence base for the treatment of anorexia nervosa is advancing, albeit unevenly. Evidence points to the benefit of family-based treatment for youth. For adults no specific approach has shown superiority and, presently, a combination of renourishment and psychotherapy such as specialist supportive clinical management, cognitive behavioral therapy, or interpersonal psychotherapy is recommended. RCTs have neither sufficiently addressed the more complex treatment approaches seen in routine practice settings, such as multidisciplinary treatment or level of care, nor specifically investigated treatment in ethnically diverse populations. Methodological challenges that hinder progress in controlled research for anorexia nervosa are explained.ConclusionsThe review highlights evidence-based and promising treatment modalities for anorexia nervosa and presents a triangulated analysis including controlled research, practice guidelines, and emerging treatments to inform and support clinical decision making.

Update on the treatment of anorexia nervosa; review of clinical trials, practice guidelines and emerging interventions

https://onlinelibrary.wiley.com/doi/pdf/10.1002/wps.20765

Safety of 80 antidepressants, antipsychotics, anti-attention-deficit/hyperactivity medications and mood stabilizers in children and adolescents with psychiatric disorders: a large scale systematic meta-review of 78 adverse effects

BackgroundTo determine the impact of specialized treatments, relative to comparator treatments, upon the weight and psychological symptoms of anorexia nervosa (AN) at end-of-treatment (EOT) and follow-up.MethodsRandomized controlled trials (RCTs) between January 1980 and December 2017 that reported the effects of at least two treatments on AN were screened. Weight and psychological symptoms were analyzed separately for each study. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were followed, and studies were assessed using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) criteria and Cochrane risk of bias tool.ResultsWe identified 35 eligible RCTs, comprising data from 2524 patients. Meta-analyses revealed a significant treatment effect on weight outcomes at EOT [g = 0.16, 95% CI (0.05–0.28), p = 0.006], but not at follow-up [g = 0.11, 95% CI (−0.04 to 0.27), p = 0.15]. There was no significant treatment effect on psychological outcomes at either EOT [g = −0.03, 95% CI (−0.14 to 0.08), p = 0.63], or follow-up [g = −0.001, 95% CI (−0.11 to 0.11), p = 0.98]. There was no strong evidence of publication bias or significant moderator effects for illness duration, mean age, year of publication, comparator group category, or risk of bias (all p values > 0.05).ConclusionsCurrent specialized treatments are more adept than comparator interventions at imparting change in weight-based AN symptoms at EOT, but not at follow-up. Specialized treatments confer no advantage over comparator interventions in terms of psychological symptoms. Future precision treatment efforts require a specific focus on the psychological symptoms of AN.

https://www.cambridge.org/core/services/aop-cambridge-core/content/view/AB05A8856C66EA5AD99AD9B2DF1C1F80/S0033291718002088a.pdf/div-class-title-treatment-outcomes-for-anorexia-nervosa-a-systematic-review-and-meta-analysis-of-randomized-controlled-trials-div.pdf

Treatment outcomes for anorexia nervosa: a systematic review and meta-analysis of randomized controlled trials.

Eating disorders are serious, potentially life-threatening illnesses afflicting individuals through the life span, with a particular impact on both the physical and psychological development of children and adolescents. Because care for children and adolescents with eating disorders can be complex and resources for the treatment of eating disorders are often limited, pediatricians may be called on to not only provide medical supervision for their patients with diagnosed eating disorders but also coordinate care and advocate for appropriate services. This clinical report includes a review of common eating disorders diagnosed in children and adolescents, outlines the medical evaluation of patients suspected of having an eating disorder, presents an overview of treatment strategies, and highlights opportunities for advocacy.

/pdf/identification-and-management-of-eating-disorders-in-nh91dtl4ef.pdf

Identification and Management of Eating Disorders in Children and Adolescents.

Objective The purpose of this double-blind, placebo-controlled exploratory pilot study was to evaluate the safety and efficacy of risperidone for the treatment of anorexia nervosa. Method Forty female subjects 12 to 21 years of age (mean, 16 years) with primary anorexia nervosa in an eating disorders program were randomized to receive risperidone (n = 18) or placebo (n = 22). Subjects completed the Eating Disorder Inventory 2, Color-A-Person Test, Body Image Software, and Multidimensional Anxiety Scale for Children at baseline and regular intervals. Weight, laboratory values, and electrocardiograms were monitored. Study medication was started at 0.5 mg daily and titrated upward weekly in 0.5-mg increments to a maximum dose of 4 mg until the subject reached a study endpoint. Results The mean dose for the risperidone group was 2.5 mg and for the placebo group was 3 mg for a mean duration of 9 weeks. Subjects taking risperidone had a significant decrease on the Eating Disorder Inventory 2 Drive for Thinness subscale over the first 7 weeks (effect size, 0.88; p = .002), but this difference was not sustained to the end of the study ( p = .13). The Eating Disorder Inventory 2 Interpersonal Distrust subscale decreased significantly more in subjects taking risperidone (effect size, 0.60; p = .03). Subjects taking risperidone had increased prolactin levels (week 7; p = .001). There were no significant differences between groups at baseline or the end of the study for the other rating scales, change in weight, or laboratory measurements. Conclusions This study does not demonstrate a benefit for the addition of risperidone in adolescents with anorexia nervosa during the weight-restoration phase of care. Clinical trial registration information—A Double-Blind, Placebo-Controlled Study of Risperidone for the Treatment of Anorexia Nervosa, http://www.clinicaltrials.gov, NCT00140426.

A double-blind, placebo-controlled study of risperidone for the treatment of adolescents and young adults with anorexia nervosa: a pilot study

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A double-blind, placebo-controlled study of risperidone for the treatment of adolescents and young adults with anorexia nervosa: a pilot study