paliperidone-palmitate and Hyperprolactinemia

The aim of this study was to perform a systematic review of the effects of 1-month paliperidone palmitate (PP1M) for the treatment of schizophrenia and related psychotic disorders in terms of outcomes reported in real-world evidence studies. A systematic review of real-world randomized and nonrandomized studies with PP1M was performed and is reported according to PRISMA guidelines. Comparative effectiveness data with oral antipsychotics indicate that PP1M has a lower likelihood of relapse-related events, including rehospitalization, and these differences are clinically relevant. A randomized, double-blind study showed that PP1M has no advantage over haloperidol decanoate in the time to treatment failure. Although there was a marked variability across studies, PP1M was not superior to other antipsychotics in terms of study completion rates. Pharmacoeconomic data show that, during a follow-up period of 12 months, the mean total healthcare cost was not significantly different in patients treated with PP1M compared with those receiving oral antipsychotics. The mean maximum prolactin levels were significantly higher with PP1M than with haloperidol decanoate; however, neither drug differs in the frequency of prolactin-related adverse events. Results on prolactin-related adverse events were inconsistent in two randomized comparisons with oral antipsychotics and were not reported in a randomized comparison with aripiprazole. There were no significant differences between haloperidol decanoate and PP1M in the severity of abnormal involuntary movements and parkinsonism, or in the incidence of tardive dyskinesia; however, patients treated with haloperidol decanoate showed greater worsening of akathisia and required treatment for parkinsonism and akathisia significantly more frequently than patients who received PP1M. In conclusion, real-world data that originate from both pragmatic randomized clinical trials and observational studies indicate that PP1M is superior to oral antipsychotics in delaying the time to relapse or treatment failure. Furthermore, the pharmacoeconomic data reviewed for this article suggest that the advantages of PP1M compared with oral antipsychotics are not associated with an increased total cost for healthcare providers.

Topics: Antipsychotic Agents; Humans; Hyperprolactinemia; Paliperidone Palmitate; Pragmatic Clinical Trials as Topic; Psychotic Disorders; Randomized Controlled Trials as Topic; Schizophrenia; Statistics as Topic

Paliperidone, the major active metabolite of risperidone, is a second-generation antipsychotic that has been developed as an extended-release (ER) oral formulation and a long-acting injectable paliperidone palmitate (PP) formulation. Paliperidone has demonstrated efficacy in the reduction of acute schizophrenia symptoms and clinical benefits were maintained also in the long-term treatments. Paliperidone ER and PP are generally well tolerated with a predictable adverse event profile. Areas covered: Data from studies evaluating safety and tolerability in the acute and maintenance treatment of schizophrenia with paliperidone are reviewed. The reported treatment-emergent adverse events of these formulations are discussed. Expert opinion: In the treatment of schizophrenia and schizoaffective disorders the safety profile has a central role because it can enhance patient compliance. In fact treatment-emergent adverse events are one of the main causes of discontinuation in these patients. In particular the main limitation in the administration of paliperidone could be represented by the onset of hyperprolactinemia (especially in women) and of mild parkinsonism. Paliperidone has a high impact on current long-term drug strategies, especially given the new 3 month long-acting injectable formulation of PP.

Topics: Antipsychotic Agents; Delayed-Action Preparations; Humans; Hyperprolactinemia; Medication Adherence; Paliperidone Palmitate; Parkinsonian Disorders; Psychotic Disorders; Schizophrenia

The altered profiles of prolactin secretion in the anterior hypophysis, generated by pathological, pharmacological or toxicological causes, have special consequences on multiple functions in both genders.. This selective review presents the main mechanisms controlling prolactin secretion, focusing on the interplay of various neurotransmitters or xenobiotics, but also on the role of psychic or posttraumatic stress. A detailed analysis of several pharmacotherapeutic groups with hyperprolactinemic effects emphasize on the relevance of the pharmacokinetic/pharmacodynamic mechanisms and the clinical significance of the long term administration.. Accurate monitoring and evaluation of the hyperprolactinemia induced by xenobiotics is strongly recommended. The typical antipsychotics and some of the atypical agents (amisulpride, risperidone, paliperidone), as well as some antidepressants, antihypertensives and prokinetics, are the most important groups inducing hyperprolactinemia. The hyperprolactinemic effects are correlated with their affinity for dopamine D2 receptors, their blood-brain barrier penetration and, implicitly, the requested dose for adequate occupancy of cerebral D2 receptors. Consequently, integration of available pharmacokinetic and pharmacodynamic data supports the idea of therapeutic switch to non-hyperprolactinemic agents (especially aripiprazole) or their association, for an optimal management of antipsychotic-induced hyperprolactinemia. Possible alternative strategies for counteracting the xenobiotics-induced hyperprolactinemia are also mentioned.

Topics: Amisulpride; Antipsychotic Agents; Aripiprazole; Blood-Brain Barrier; Humans; Hyperprolactinemia; Isoxazoles; Paliperidone Palmitate; Piperazines; Prolactin; Pyrimidines; Quinolones; Receptors, Dopamine D2; Risperidone; Stress, Psychological; Sulpiride; Xenobiotics

This analysis of the Paliperidone Palmitate Research in Demonstrating Effectiveness (PRIDE) study (NCT01157351) compared outcomes after administration of once-monthly paliperidone palmitate (PP) vs conventional oral antipsychotics (COAs) or atypical oral antipsychotics (AOAs).. PRIDE was a 15-month study of 444 individuals with schizophrenia and a history of incarceration. They were randomly assigned to PP or to 1 of 7 commonly prescribed OAs. Primary endpoint was time to first treatment failure (TF). Event-free probabilities were estimated using the Kaplan-Meier method; treatment group differences (PP vs COAs, PP vs AOAs, and PP vs oral paliperidone/risperidone) were assessed using a log-rank test. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression models. No adjustment was made for multiplicity.. Compared with PP, risk for first TF was 34% higher with COAs (HR: 1.34; 95% CI: 0.80-2.25), 41% higher with AOAs (HR: 1.41; 95% CI: 1.06-1.88), and 39% higher with paliperidone/risperidone (HR: 1.39; 95% CI: 0.97-1.99). Incidences of extrapyramidal symptom-related adverse events (AEs) were 45.7%, 13.7%, and 10.6% in the COA, AOA, and oral paliperidone/risperidone groups vs 23.9% in the PP group. Incidences of prolactin-related AEs were 5.7%, 3.8%, and 3.5% vs 23.5%, and incidences of ≥7% weight increase were 11.4%, 14.9%, and 16.0% vs 32.4%.. Results suggest a lower risk of TF but a higher rate of some AEs after treatment with PP vs COAs, AOAs, and paliperidone/risperidone. Deselection of specific OAs and low patient-compliance rates with OAs likely biased the safety results.

Topics: Administration, Oral; Adult; Antipsychotic Agents; Aripiprazole; Basal Ganglia Diseases; Benzodiazepines; Delayed-Action Preparations; Female; Haloperidol; Humans; Hyperprolactinemia; Injections, Intramuscular; Male; Middle Aged; Olanzapine; Paliperidone Palmitate; Perphenazine; Proportional Hazards Models; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Treatment Failure; Treatment Outcome

Paliperidone palmitate has been associated with serum prolactin elevations in some patients. However, few individuals with elevated prolactin levels (hyperprolactinemia) have symptomatic potentially prolactin-related adverse events (PPR-AEs).. To quantify rates of hyperprolactinemia in subjects treated with the newly marketed paliperidone palmitate long-acting injection (PP-LAI) in randomized clinical trials, summarize rates of PPR-AEs in those trials by sex and dose, and determine how many PPR-AEs required treatment.. Numbers and rates of investigator-reported hyperprolactinemia and PPR-AEs were obtained from the sponsor's clinical trial database and have been included in regulatory filings. Results were tabulated for males, females, and overall, and by dose administered, using descriptive statistics. Those requiring treatment were described as well.. There were 3173 subjects (61.4% males) exposed to PP-LAI in 10 clinical trials; 2831 (89.2%) patients had recorded prolactin levels, including 1759 males (90.3% of exposed males) and 1072 females (87.5% of exposed females). Overall, at any time, prolactin levels were elevated for 38.8% of the subjects (39.5% for males and 37.7% for females; p = 0.354 between sexes). However, there was no significant correlation between monthly dose and proportion of subjects with elevated prolactin levels (p = 0.109). There were 115 PPR-AEs in 107 patients (3.4%); 51 (44.3% of PPR-AEs) cases represented asymptomatic hyperprolactinemia. The remaining 64 symptomatic PPR-AEs affected 2.0% of the total number of subjects. Fifteen events in 13 participants (0.41% of patients or 4.7 events/1000 patients) required treatment.. Clinicians should periodically assess patients on paliperidone palmitate for any PPR-AEs and carefully assess the benefits and risks when managing these effects.

Topics: Adult; Antipsychotic Agents; Female; Humans; Hyperprolactinemia; Isoxazoles; Male; Middle Aged; Paliperidone Palmitate; Palmitates; Prolactin; Young Adult

Topics: Administration, Oral; Adult; Antipsychotic Agents; Female; Humans; Hyperprolactinemia; Injections, Intramuscular; Isoxazoles; Male; Middle Aged; Paliperidone Palmitate; Prolactin; Pyrimidines; Research Design; Risperidone; Schizophrenia; Schizophrenic Psychology

Long-acting injectable (LAI) antipsychotics were developed to improve adherence to schizophrenia treatment. Paliperidone palmitate (PP) has two LAI forms: Monthly (PP1M) and three-monthly (PP3M). PP3M shows less difference in Peak-to-Trough drug concentration levels. This could be related to a lower incidence of hyperprolactinemia, which may negatively affect adherence. We aimed to compare prolactin levels and investigate relationships between prolactin levels, symptomatology and sexual function in patients with schizophrenia after switching from PP1M to PP3M.. Twenty-five patients were enrolled. The sociodemographic data form, the Positive and Negative Syndromes Scale (PANSS) and the Arizona Sexual Experience Scale (ASEX) were used. Morning blood samples were drawn to determine prolactin levels.. Prolactin level (p < 0.001), the total score and arousal sub-score of ASEX (respectively; p = 0.015, p = 0.020) and the total score and positive scale of PANSS (respectively; p = 0.017, p = 0.021) were decreased on the 90th day (±15 days).. After switching to PP3M, the decreases in prolactin levels and potentially related sexual side effects was statistically significant. There may be a difference between two formulations of the same drug in terms of side effects, and there is a need for prospective follow-up studies with larger samples.

Topics: Antipsychotic Agents; Humans; Hyperprolactinemia; Paliperidone Palmitate; Prolactin; Schizophrenia

One strategy to address hyperprolactinemia and associated sexual side effects in patients receiving antipsychotics is switching to an antipsychotic not associated with prolactin elevation (eg, aripiprazole). This post hoc analysis assessed prolactin concentrations and sexual side effects in an open-label prospective study of switching long-acting injectable antipsychotics from paliperidone palmitate (PP) to aripiprazole lauroxil (AL). Serum prolactin was measured throughout the study. Patient-reported sexual and endocrine side effects were assessed on the UKU Side Effect Rating Scale sexual function subscale and analyzed in study completers. Prior to starting AL treatment (screening), 49/50 (98%) patients had prolactin concentrations above the upper limit of normal (ULN; >13.13 ng/mL [males]; >26.72 ng/mL [females]). Six months after beginning AL treatment, prolactin levels were above ULN in 2/32 (6.3%) patients. Among 32 study completers, 81.3% reported sexual dysfunction in ≥1 domain at screening versus 56.3% at 6 months after starting AL treatment. Diminished sexual desire was the most common patient-reported sexual complaint at screening (46.9%); at 6 months, it was reported by 18.8%. In this post hoc analysis, the high levels of prolactin observed at screening decreased during AL treatment, and modest improvements in sexual side effects were evident in patients with schizophrenia.

Topics: Antipsychotic Agents; Aripiprazole; Female; Humans; Hyperprolactinemia; Male; Paliperidone Palmitate; Prolactin; Prospective Studies; Schizophrenia

Several reports have shown that risperidone increases prolactin concentrations, while aripiprazole decreases prolactin concentrations. The frequency of abnormal prolactin concentrations in patients with schizophrenia receiving these drugs is still unknown. Furthermore, although hyperprolactinemia leads to sexual dysfunction, the relationship between hyperprolactinemia and testosterone, which may be directly related to male sexual function, is not well understood.. The subjects were 94 male schizophrenia outpatients receiving risperidone or paliperidone (risperidone group) and 83 male schizophrenia outpatients receiving aripiprazole. We measured the serum prolactin and total and free testosterone concentrations. We compared the prolactin and testosterone levels in patients receiving risperidone or paliperidone and patients receiving aripiprazole.. The average serum prolactin concentration was 27.5 ± 13.1 ng/mL for the risperidone group and 3.9 ± 3.5 ng/mL for the aripiprazole group, and the concentrations were significantly different (P < .001). Hypoprolactinemia was observed in 75% of the aripiprazole group and hyperprolactinemia in 65% of the risperidone group. A positive correlation between prolactin levels and the risperidone daily dose was found, whereas a negative correlation between prolactin levels and the aripiprazole daily dose was observed. In the risperidone group, total testosterone concentrations were correlated with age, while free testosterone concentrations were inversely correlated with age and prolactin levels.. We found very common hyperprolactinemia and hypoprolactinemia in the risperidone or paliperidone group and aripiprazole group, respectively. Testosterone concentrations were associated with elevated prolactin levels in patients receiving risperidone or paliperidone. Further studies are needed to determine the clinical relevance of abnormal prolactin concentrations in male and female patients with schizophrenia.

Topics: Antipsychotic Agents; Aripiprazole; Female; Genetic Diseases, Inborn; Humans; Hyperprolactinemia; Lactation Disorders; Male; Paliperidone Palmitate; Prolactin; Risperidone; Schizophrenia; Testosterone

The aim of this study was to explore the effectiveness and tolerability of long-acting paliperidone palmitate antipsychotic in adolescent first-episode schizophrenia patients while comparing the results with the oral antipsychotic risperidone.. This study is a retrospective, noninterventional study to assess the effectiveness and tolerability of long-acting injectable antipsychotic paliperidone palmitate in first-episode adolescent patients during the first 12 months of treatment compared with the oral antipsychotic risperidone. The data include general sociodemographic characteristics, number of hospitalizations, side effects, and the following clinical scales: Positive and Negative Syndrome Scale (PANSS), Personal and Social Performance Scale (PSP), Clinical Global Impression Improvement and Severity (CGI-I and CGI-S), and Treatment Satisfaction Questionnaire for Medication (TSQM).. During the 12-month study period significant improvement was registered in patients receiving both paliperidone palmitate and risperidone in the following scales: PANSS, PSP, CGI-I, and CGI-S. Patients receiving paliperidone palmitate had significantly greater improvement in PANSS, CGI-S, and PSP compared with the risperidone group. Patients receiving risperidone had significantly higher number of hospitalizations than the patients receiving paliperidone palmitate. The TSQM revealed that the patients who were receiving paliperidone palmitate achieved significantly higher scores on the convenience scale, global satisfaction, and on the overall result, whereas no difference was observed on the effectiveness scale. There were several side effects reported for paliperidone (5.5% hyperprolactinemia, 5.5% weight gain) and risperidone (5.5% hyperprolactinemia, 16.7% weight gain).. In conclusion, paliperidone palmitate seems to be safe and effective in adolescent patients. Furthermore, it compared favorably with risperidone in the clinical response, side effects, and hospitalizations.

Topics: Adolescent; Antipsychotic Agents; Brief Psychiatric Rating Scale; Female; Hospitalization; Humans; Hyperprolactinemia; Male; Paliperidone Palmitate; Retrospective Studies; Risperidone; Schizophrenia; Weight Gain

Elevated prolactin levels (hyperprolactinemia) are a frequent adverse effect of antipsychotic medications, especially in young populations. Prolonged hyperprolactinemia may affect sexual functioning and the onset and progression of puberty.. This study assessed potentially prolactin-related treatment-emergent adverse events (PPRL-TEAEs) and sexual maturation during long-term treatment of adolescents with paliperidone extended-release (ER).. This post hoc analysis of a 2-year open-label multicenter study (NCT00488319) included patients of either sex aged 12-17 years at study enrollment, diagnosed with schizophrenia (Diagnostic and Statistical Manual of Mental Disorders, 4th edition [DSM-IV]) for ≥1 year, who had received one or more adequate antipsychotic treatment prior to enrollment but had not responded sufficiently. Patients were initially treated with 6 mg/day paliperidone ER and further titrated between 1.5 and 12 mg/day based on clinical response and tolerability. The primary objective was to determine the relationship between characteristics (including sex, age at study entry, ethnicity, geographic region, age at diagnosis, duration of illness, number of prior hospitalizations, serum prolactin, and baseline Tanner stages) and onset or risk of PPRL-TEAEs. The secondary objective was to assess sexual maturation during long-term treatment with paliperidone ER.. Female sex appeared to be associated with an increased risk for PPRL-TEAEs. Other potential predictors, such as ethnicity, region, age at diagnosis, and Tanner stage 4 or 5, all seemed to be related to sex. Evidence from this study was insufficient to definitively conclude that prolactin values at baseline and change during treatment were predictive of PPRL-TEAEs, although there is a signal that this may be the case in girls. These results are exploratory in nature, and confirmatory studies are needed to confirm these observations.. ClinicalTrials.gov identifier: NCT00488319.

Topics: Adolescent; Age Factors; Antipsychotic Agents; Child; Delayed-Action Preparations; Female; Humans; Hyperprolactinemia; Male; Paliperidone Palmitate; Prolactin; Risk Factors; Schizophrenia; Sex Factors; Sexual Maturation; Time Factors

We report a case of early onset schizophrenia that responded favourably to paliperidone but experienced hyperprolactinaemia, tremors, and weight gain, with impaired fasting glycaemia. Addition of bromocriptine helped with both hyperprolactinaemia and tremors, but also brought about euglycaemia and, strikingly, ameliorated negative symptoms.

Topics: Adolescent; Antipsychotic Agents; Bromocriptine; Humans; Hyperprolactinemia; Male; Paliperidone Palmitate; Schizophrenia; Treatment Outcome; Tremor; Weight Gain

Although our previous study revealed an association between prolactin level and risperidone dosage, data regarding the plasma concentration of risperidone are lacking. Therefore, this study aimed to investigate the association between plasma drug concentrations of risperidone, 9-hydroxyrisperidone and serum prolactin level in Thai children and adolescents with autism spectrum disorder (ASD). The individuals for this study were 103 children and adolescents with ASD (90 males and 13 females). In the 12th hour after the last risperidone dose, blood samples were collected for analysis. Serum prolactin, plasma risperidone and 9-hydroxyrisperidone levels were measured. Patients' clinical data were collected from medical records - age, weight, height, body mass index, dose of risperidone and duration of treatment. Serum prolactin level was significantly positively correlated with plasma 9-hydroxyrisperidone level (rs = 0.355, p < 0.001). The median concentration of 9-hydroxyrisperidone in individuals with hyperprolactinaemia (7.59 ng/ml; IQR 4.86-15.55) was significantly higher than non-hyperprolactinaemic individuals (5.18 ng/ml; IQR 2.10-8.99) after risperidone treatment (p = 0.006). By multivariate analysis, high prolactin level was correlated to high 9-hydroxyrisperidone level (p = 0.010). The results of this study showed that serum prolactin levels, especially in autistic individuals with hyperprolactinaemia during risperidone treatment, were significantly correlated with the level of 9-hydroxyrisperidone. These results suggest that hyperprolactinaemia may develop during risperidone treatment.

Topics: Adolescent; Autism Spectrum Disorder; Child; Child, Preschool; Cohort Studies; Dose-Response Relationship, Drug; Female; Humans; Hyperprolactinemia; Linear Models; Male; Multivariate Analysis; Paliperidone Palmitate; Prolactin; Risperidone; Thailand; Young Adult

This study investigated the effects of a low-dose aripiprazole adjunctive treatment for risperidone- or paliperidone-induced hyperprolactinemia in Han Chinese women with schizophrenia. After 4 weeks of risperidone or paliperidone treatment, 60 out of 66 patients improved significantly and experienced hyperprolactinemia. They were randomly assigned to the treatment group (aripiprazole adjunctive treatment) (n=30) or control group (non-adjunctive treatment) (n=30). The dosage of risperidone and paliperidone were maintained; and aripiprazole was maintained at 5mg/day during the 8-week study period. The prolactin levels at the end of the 8th week were significantly lower in the treatment group than in the control group. The estradiol level correlated negatively with serum prolactin level both in the treatment group and the control group at the end of the 8th week and the 4th week respectively. The Positive and Negative Syndrome Scale score improved significantly during the 8-week study period in both groups. The incidence of treatment-emergent adverse event was similar in two groups. Low-dose aripiprazole adjunctive treatment is effective in relieving risperidone- and paliperidone-induced hyperprolactinemia in female schizophrenic patients without increasing adverse event.

Topics: Adolescent; Adult; Antipsychotic Agents; Aripiprazole; Drug Therapy, Combination; Estradiol; Female; Humans; Hyperprolactinemia; Middle Aged; Paliperidone Palmitate; Prolactin; Risperidone; Schizophrenia; Treatment Outcome; Young Adult

The aims of this study were to clarify whether atypical antipsychotics can elevate serum levels of both macroprolactin and prolactin, and whether the macroprolactin levels differ according to the type of atypical antipsychotic being taken. In total, 245 subjects were enrolled consecutively in 6 hospitals. Serum prolactin and macroprolactin levels were measured at a single time point during maintenance antipsychotic monotherapy. The mean total serum prolactin levels including macroprolactin were 11.91, 20.73, 16.41, 50.83, 12.84, and 59.1ng/mL for patients taking aripiprazole, blonanserin, olanzapine, paliperidone, quetiapine, and risperidone, respectively, while those for macroprolactin were 1.71, 3.86, 3.73, 7.28, 2.77, and 8.0ng/mL. The total prolactin and macroprolactin levels were significantly higher among those taking paliperidone and risperidone than among those taking any of the other antipsychotics (p<0.01). Moreover, there was a strong positive correlation between serum levels of prolactin and macroprolactin. Sexual dysfunction was reported in 35.5% (87/245) of the total subjects. However, the total prolactin level did not differ significantly between subjects with and without sexual dysfunction except gynecomastia. These findings suggest that treatment with risperidone and paliperidone can induce hyperprolactinemia and macroprolactinemia in psychiatric patients.

Topics: Adult; Antipsychotic Agents; Female; Humans; Hyperprolactinemia; Male; Mental Disorders; Middle Aged; Paliperidone Palmitate; Prolactin; Risperidone

Hyperprolactinemia is a common adverse in vivo effect of antipsychotic medications that are used in the treatment of patients with schizophrenia. Here, we compared the effects of two atypical antipsychotics, paliperidone and aripiprazole, on cAMP/calcium signaling and prolactin release in female rat pituitary lactotrophs in vitro. Dopamine inhibited spontaneous cAMP/calcium signaling and prolactin release. In the presence of dopamine, paliperidone rescued cAMP/calcium signaling and prolactin release in a concentration-dependent manner, whereas aripiprazole was only partially effective. In the absence of dopamine, paliperidone stimulated cAMP/calcium signaling and prolactin release, whereas aripiprazole inhibited signaling and secretion more potently but less effectively than dopamine. Forskolin-stimulated cAMP production was facilitated by paliperidone and inhibited by aripiprazole, although the latter was not as effective as dopamine. None of the compounds affected prolactin transcript activity, intracellular prolactin accumulation, or growth hormone secretion. These data indicate that paliperidone has dual hyperprolactinemic actions in lactotrophs i) by preserving the coupling of spontaneous electrical activity and prolactin secretion in the presence of dopamine and ii) by inhibiting intrinsic dopamine receptor activity in the absence of dopamine, leading to enhanced calcium signaling and secretion. In contrast, aripiprazole acts on prolactin secretion by attenuating, but not abolishing, calcium-secretion coupling.

Topics: Animals; Aripiprazole; Calcium Signaling; Dopamine; Female; Humans; Hyperprolactinemia; Lactotrophs; Paliperidone Palmitate; Prolactin; Rats; Schizophrenia; Signal Transduction

Hyperprolactinaemia, a common side effect of some antipsychotic drugs, is also present in drug-naïve psychotic patients and subjects at risk for psychosis. Recent studies in non-psychiatric populations suggest that increased prolactin may have negative effects on cognition. The aim of our study was to explore whether high plasma prolactin levels are associated with poorer cognitive functioning in subjects with early psychoses. We studied 107 participants: 29 healthy subjects and 78 subjects with an early psychosis (55 psychotic disorders with <3 years of illness, 23 high-risk subjects). Cognitive assessment was performed with the MATRICS Cognitive Consensus Cognitive Battery, and prolactin levels were determined as well as total cortisol levels in plasma. Psychopathological status was assessed and the use of psychopharmacological treatments (antipsychotics, antidepressants, benzodiazepines) recorded. Prolactin levels were negatively associated with cognitive performance in processing speed, in patients with a psychotic disorder and high-risk subjects. In the latter group, increased prolactin levels were also associated with impaired reasoning and problem solving and poorer general cognition. In a multiple linear regression analysis conducted in both high-risk and psychotic patients, controlling for potential confounders, prolactin and benzodiazepines were independently related to poorer cognitive performance in the speed of processing domain. A mediation analysis showed that both prolactin and benzodiazepine treatment act as mediators of the relationship between risperidone/paliperidone treatment and speed of processing. These results suggest that increased prolactin levels are associated with impaired processing speed in early psychosis. If these results are confirmed in future studies, strategies targeting reduction of prolactin levels may improve cognition in this population.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Case-Control Studies; Cognition; Cognition Disorders; Female; Humans; Hyperprolactinemia; Isoxazoles; Male; Paliperidone Palmitate; Prolactin; Psychiatric Status Rating Scales; Psychotic Disorders; Pyrimidines; Young Adult

To investigate the effect of the Taq1A variant in the Dopamine D2 receptor gene (DRD2) and common functional genetic variants in the cytochrome P450 2D6 gene (CYP2D6) on prolactin levels in risperidone-treated boys with autism spectrum disorders and disruptive behavior disorders.. Forty-seven physically healthy 10-year-old to 19-year-old boys with autism spectrum disorders and/or disruptive behavior disorders, chronically treated (mean 52 months, range 16-126 months) with an antipsychotic, were recruited into this observational study. Prolactin levels, hyperprolactinemia, risperidone levels, and 9-hydroxyrisperidone levels were assessed and the participants were genotyped for common CYP2D6 polymorphisms and the Taq1A allele of the dopamine D2 receptor gene. Group differences were tested using Student's t-test, χ², and logistic regression analysis.. Prolactin levels were associated positively and significantly with risperidone levels (P=0.05), 9-hydroxyrisperidone levels (P≤0.0001), and with the oral risperidone dose in milligrams per kilogram (P≤0.0001). Furthermore, multiple regression analysis showed no correlations between prolactin level and the presence of at least one Taq1A A1 allele of the DRD2 gene (P=0.12).. Although CYP2D6 might have an effect, the presence of at least one Taq1A A1 allele of the D2DR gene did not contribute toward susceptibility to risperidone-induced hyperprolactinemia, and as a result, toward prolactin-related adverse events such as amenorrhea, galactorrhea, and sexual dysfunctioning.

Topics: Adolescent; Alleles; Antipsychotic Agents; Attention Deficit and Disruptive Behavior Disorders; Child; Child Development Disorders, Pervasive; Cytochrome P-450 CYP2D6; Drug Administration Schedule; Genetic Variation; Humans; Hyperprolactinemia; Isoxazoles; Male; Paliperidone Palmitate; Polymorphism, Genetic; Prolactin; Pyrimidines; Receptors, Dopamine D2; Risperidone; Young Adult

Hyperprolactinaemia is a significant side effect of antipsychotic medications and may cause sexual dysfunction. The aim of our study was to assess the effect of switching from long-acting injectable (LAI) risperidone to paliperidone palmitate (PP) on sexual function and prolactin levels in patients with psychosis. We carried out a prospective observational study during a 3-month period that involved 11 patients with psychosis treated with risperidone-LAI who suffered from hyperprolactinaemia and who were then switched to PP. Two assessments were completed: the first one before the switch and the second one 3 months after the switch. These assessments measured sexual function using the Arizona Sexual Experience Scale and assessed prolactin levels. Our results showed a significant decrease in serum prolactin levels (P=0.041). We observed a four-fold reduction in clinically significant sexual dysfunction that is suggestive of benefit, although the sample size is too small to be sure. Our study suggests that prolactin levels seem to decrease after switching from risperidone-LAI to PP in patients with a psychotic disorder.

Topics: Adult; Age Factors; Antipsychotic Agents; Biomarkers; Drug Substitution; Female; Humans; Hyperprolactinemia; Injections; Isoxazoles; Male; Paliperidone Palmitate; Palmitates; Prolactin; Prospective Studies; Psychiatric Status Rating Scales; Psychotic Disorders; Recovery of Function; Risperidone; Sexual Behavior; Sexual Dysfunction, Physiological; Surveys and Questionnaires; Time Factors; Treatment Outcome; Young Adult

The aim of this study was to investigate the long-term treatment effects of risperidone on prolactin levels and prolactin-related side effects in pubertal boys with autism spectrum disorders (ASD) and disruptive behavior disorders (DBD).. Physical healthy 10-20-year-old males with ASD (n=89) and/ or DBD (n=9) chronically treated (mean 52 months, range 16-126 months) with risperidone (group 1, n=51) or not treated with any antipsychotic (group 2, n=47) were recruited to this observational study from the child psychiatry outpatient clinic. Morning non-fasting serum prolactin levels were measured and prolactin-related side effects were assessed by means of questionnaires and physical examination. Group differences were tested with Student's t, χ(2), Fisher exact, and Mann-Whitney tests, and logistic regression analysis, according to the type and distribution of data.. Hyperprolactinemia was present in 47% of subjects in group 1 but only in 2% of subjects in group 2 (odds ratio 71.9; 95% CI, 7.7; 676.3). Forty-six percent of subjects in group 1 had asymptomatic hyperprolactinemia. Current risperidone dose and 9-OH risperidone plasma level were significant predictors of hyperprolactinemia (p=0.035 and p=0.03, respectively). Gynecomastia and sexual dysfunction were present in 43% and 14% of the subjects in group 1, respectively, compared with 21% and 0% of subjects in group 2 (p=0.05 and p=0.01). Gynecomastia was not significantly associated with hyperprolactinemia.. Hyperprolactinemia is a common side effect in young males treated over the long term with risperidone. Young males treated with risperidone are more likely to report diminished sexual functioning than are those not treated with antipsychotics.

Topics: Adolescent; Adult; Antipsychotic Agents; Attention Deficit and Disruptive Behavior Disorders; Child; Child Development Disorders, Pervasive; Cross-Sectional Studies; Dose-Response Relationship, Drug; Gynecomastia; Humans; Hyperprolactinemia; Isoxazoles; Logistic Models; Male; Paliperidone Palmitate; Prolactin; Pyrimidines; Risperidone; Sexual Dysfunction, Physiological; Statistics, Nonparametric; Surveys and Questionnaires; Time Factors; Young Adult

The aim of this paper is to highlight the association between antipsychotic medication, in this instance paliperidone, and hyperprolactinaemia, and discuss the impact of this adverse effect on patient management.. Four patients with paliperidone-induced hyperprolactinaemia are described with a brief review of the literature.. Four female patients aged between 20 and 50 years developed hyperprolactinaemia 3 weeks to 4 months after commencement of treatment with paliperidone. The levels were significantly raised above the normal upper limit of 500 mIU/L, ranging between 1500 and 3996 mIU/L, and returned to within the normal range after cessation of the medication (82-381 mIU/L). Two of the patients were asymptomatic despite significant elevation of prolactin; two experienced galactorrhoea, a distressing adverse effect. Subsequent management was significantly affected.. Routine standardized monitoring of prolactin levels may guide treatment choice, avoiding potential disruption to the therapeutic relationship, enhancing compliance with future medication and preventing negative treatment outcomes. Detailed education should accompany the monitoring process and include discussion of the risks of associated adverse effects of antipsychotic medications versus the benefit of significant symptom relief.

Topics: Adult; Antipsychotic Agents; Aripiprazole; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Monitoring; Female; Galactorrhea; Humans; Hyperprolactinemia; Isoxazoles; Middle Aged; Paliperidone Palmitate; Patient Compliance; Piperazines; Prolactin; Psychotic Disorders; Pyrimidines; Quetiapine Fumarate; Quinolones; Recurrence; Schizophrenia, Paranoid; Young Adult

Topics: Adult; Antipsychotic Agents; Aripiprazole; Drug Therapy, Combination; Female; Humans; Hyperprolactinemia; Isoxazoles; Paliperidone Palmitate; Piperazines; Pyrimidines; Quinolones; Schizophrenia, Paranoid; Treatment Outcome

The atypical antipsychotic risperidone significantly raises plasma prolactin levels in patients, but clozapine, olanzapine, and quetiapine do not. The differences in neuroendocrine response may be connected with the metabolism of the medications. The authors examined the contributory role of risperidone's active metabolite 9-hydroxy-risperidone by measuring plasma concentrations of risperidone, 9-hydroxy-risperidone, and prolactin.. Blood samples taken from 25 patients with psychotic disorders following 6 weeks of treatment with risperidone (mean dose=3 mg/day) were examined. Mean plasma concentrations of risperidone, 9-hydroxy-risperidone, and prolactin were 4.6, 19.4, and 49.3 ng/ml, respectively.. The oral dose of risperidone correlated significantly with plasma concentrations of risperidone, 9-hydroxy-risperidone, active moiety, and prolactin. The plasma concentration of 9-hydroxy-risperidone, but not of risperidone, correlated significantly with increases in plasma prolactin.. These data suggest that the 9-hydroxy metabolite plays a predominant role in risperidone's effect on prolactin release.

Topics: Adolescent; Adult; Antipsychotic Agents; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Hyperprolactinemia; Isoxazoles; Male; Middle Aged; Paliperidone Palmitate; Prolactin; Psychotic Disorders; Pyrimidines; Risperidone