-
Pharmacotherapy Jun 2022Antipsychotic medications demonstrate a variable range of efficacy and side effects in patients with mental illness. Research has attempted to identify biomarkers... (Meta-Analysis)
Meta-Analysis Review
Antipsychotic medications demonstrate a variable range of efficacy and side effects in patients with mental illness. Research has attempted to identify biomarkers associated with antipsychotic effects in various populations. Research designs utilizing healthy volunteers may have the added benefit of measuring the effect of antipsychotics on a given biomarker (s) independent of the varied environmental and clinical factors that often accompany patient populations. The aim of this systematic review and meta-analysis was to synthesize the current evidence of hormonal, inflammatory, and metabolic biomarker studies of antipsychotic treatment in study designs using healthy volunteers. The systematic review was performed according to established guidelines and a random effects meta-analysis of biomarkers appearing in at least three studies was performed while biomarkers in two or less studies were qualitatively summarized. A total of 28 studies including 28 biomarkers were identified. Meta-analyses were carried out for 14 biomarkers, showing significant effects within six biomarkers (cortisol, C-peptide, free fatty acids, leptin, thyroid-stimulating hormone, and prolactin). Many of these effects were associated with olanzapine, the most used antipsychotic amongst the trials, observed on sub-analyses. When combining biomarkers into categories, some additional effects were observed, for example, when grouping inflammatory biomarkers. These findings suggest that antipsychotics exert potentially strong effects on several biomarkers of interest independent of psychiatric disease which could be used to spur future investigations, however, replication work is needed for many biomarkers included in this review.
Topics: Antipsychotic Agents; Humans; Olanzapine
PubMed: 35508603
DOI: 10.1002/phar.2689 -
Annals of Internal Medicine Nov 2009Erectile dysfunction (ED) is a common male sexual disorder. The relative benefits and harms of pharmacologic therapies for ED, as well as the value of hormonal testing... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Erectile dysfunction (ED) is a common male sexual disorder. The relative benefits and harms of pharmacologic therapies for ED, as well as the value of hormonal testing in men with ED, are uncertain.
PURPOSE
To evaluate the efficacy and harms of oral phosphodiesterase-5 (PDE-5) inhibitors and hormonal treatments for ED and assess the effect of measuring serum hormone levels on treatment outcomes for ED.
DATA SOURCES
English-language studies from MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, PsycINFO, AMED, and SCOPUS through April 2009. Trial reference lists also were scanned.
STUDY SELECTION
Randomized, controlled trials (RCTs) of oral PDE-5 inhibitors and hormonal treatment for ED, and observational studies reporting measurement of serum hormone levels, prevalence of hormonal abnormalities, or both in men with ED.
DATA EXTRACTION
Two independent reviewers abstracted data on study, participant, and treatment characteristics; efficacy and harms outcomes; and prevalence of hormonal abnormalities.
DATA SYNTHESIS
Data, primarily from short-term trials (
LIMITATIONS
Many RCTs were of low methodological and reporting quality, particularly those involving hormonal treatments or directly comparing different PDE-5 inhibitors. Most RCTs provided only short-term efficacy and harms data.
CONCLUSION
Oral PDE-5 inhibitors improved erectile functioning and had similar efficacy and safety profiles. Results on the efficacy of hormonal treatments and the value of hormone testing in men with ED were inconclusive.
PRIMARY FUNDING SOURCE
Agency for Healthcare Research and Quality.
Topics: Contraindications; Cyclic Nucleotide Phosphodiesterases, Type 5; Erectile Dysfunction; Hormone Replacement Therapy; Humans; Hyperprolactinemia; Hypogonadism; Male; Penile Erection; Prolactin; Testosterone
PubMed: 19884626
DOI: 10.7326/0003-4819-151-9-200911030-00150 -
Journal of Neurotrauma May 2015The aim of this study was to systematically review clinical studies examining biofluid biomarkers of brain injury for concussion in athletes. Data sources included... (Review)
Review
The aim of this study was to systematically review clinical studies examining biofluid biomarkers of brain injury for concussion in athletes. Data sources included PubMed, MEDLINE, and the Cochrane Database from 1966 to October 2013. Studies were included if they recruited athletes participating in organized sports who experienced concussion or head injury during a sports-related activity and had brain injury biomarkers measured. Acceptable research designs included experimental, observational, and case-control studies. Review articles, opinion papers, and editorials were excluded. After title and abstract screening of potential articles, full texts were independently reviewed to identify articles that met inclusion criteria. A composite evidentiary table was then constructed and documented the study title, design, population, methods, sample size, outcome measures, and results. The search identified 52 publications, of which 13 were selected and critically reviewed. All of the included studies were prospective and were published either in or after the year 2000. Sports included boxing (six studies), soccer (five studies), running/jogging (two studies), hockey (one study), basketball (one study), cycling (one study), and swimming (one study). The majority of studies (92%) had fewer than 100 patients. Three studies (23%) evaluated biomarkers in cerebrospinal fluid (CSF), one in both serum and CSF, and 10 (77%) in serum exclusively. There were 11 different biomarkers assessed, including S100β, glial fibrillary acidic protein, neuron-specific enolase, tau, neurofilament light protein, amyloid beta, brain-derived neurotrophic factor, creatine kinase and heart-type fatty acid binding protein, prolactin, cortisol, and albumin. A handful of biomarkers showed a correlation with number of hits to the head (soccer), acceleration/deceleration forces (jumps, collisions, and falls), postconcussive symptoms, trauma to the body versus the head, and dynamics of different sports. Although there are no validated biomarkers for concussion as yet, there is potential for biomarkers to provide diagnostic, prognostic, and monitoring information postinjury. They could also be combined with neuroimaging to assess injury evolution and recovery.
Topics: Athletic Injuries; Biomarkers; Brain Concussion; Humans
PubMed: 25254425
DOI: 10.1089/neu.2014.3655 -
Psychoneuroendocrinology Dec 2023The role of anterior pituitary hormones - i.e., adrenocorticotropic hormone (ACTH), luteinizing and follicle stimulating hormones (LH and FSH), growth hormone (GH),... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
The role of anterior pituitary hormones - i.e., adrenocorticotropic hormone (ACTH), luteinizing and follicle stimulating hormones (LH and FSH), growth hormone (GH), prolactin (PRL), and thyroid-stimulating hormone (TSH) - in early schizophrenia and psychoses unclear. We thus performed a systematic review and meta-analysis on the blood concentrations of ACTH, LH and FSH, GH, PRL, and TSH in drug-naïve people with first-episode psychosis (FEP) as compared with healthy controls.
METHODS
We searched Embase, MEDLINE, and PsycInfo for articles indexed until September 2022. Data quality was appraised. Random-effects meta-analyses were carried out, generating pooled standardized mean differences (SMDs). Between-study heterogeneity was estimated using the I statistic. Sensitivity and meta-regression analyses were performed.
RESULTS
Twenty-six studies were included. Drug-naïve people with FEP, compared to healthy subjects, had higher blood concentrations of ACTH (k = 7; N = 548; SMD = 0.62; 95%CI: 0.29 to 0.94; p < 0.001; I = 60.9%) and PRL (k = 17; N = 1757; SMD = 0.85; 95%CI: 0.56 to 1.14; p < 0.001; I = 85.5%) as well as lower levels of TSH (k = 6; N = 677; SMD = -0.34; 95%CI: -0.54 to -0.14; p = 0.001; I = 29.1%). Meta-regressions did not show any moderating effect of age (p = 0.78), sex (p = 0.21), or symptom severity (p = 0.87) on PRL concentrations in drug-naïve FEP. Available data were not sufficient to perform meta-analyses on FSH, LH, and GH.
CONCLUSIONS
Drug-naïve people with FEP have altered ACTH, PRL, and TSH blood concentrations, supporting the hypothesis that an abnormal anterior pituitary hormone secretion may be involved in the onset of schizophrenia and psychoses. Further research is needed to elucidate the role of pituitary hormones in FEP.
Topics: Humans; Prolactin; Growth Hormone; Follicle Stimulating Hormone; Thyrotropin; Adrenocorticotropic Hormone; Human Growth Hormone; Psychotic Disorders; Pituitary Hormones
PubMed: 37778198
DOI: 10.1016/j.psyneuen.2023.106392 -
Translational Psychiatry Dec 2022Is paliperidone palmitate (PP) a useful treatment option for adults with acute symptoms of schizophrenia? We conducted a systematic review and a random-effects pairwise... (Meta-Analysis)
Meta-Analysis
Is paliperidone palmitate (PP) a useful treatment option for adults with acute symptoms of schizophrenia? We conducted a systematic review and a random-effects pairwise and network meta-analysis that compared PP (25-150 mg equivalent) with paliperidone extended-release (PAL-ER, 3-12 mg/d) regarding their efficacy and safety in adults with acute symptoms of schizophrenia. The outcomes were the total score of the Positive and Negative Syndrome Scale (PANSS-T) at week 6 (the primary outcome for efficacy) and all-cause discontinuation(the primary outcome for acceptability), discontinuation due to inefficacy, discontinuation due to adverse events, discontinuation due to the withdrawal of consent, and the incidence of individual adverse events. Five studies on PP and seven studies on PAL-ER, which involved 4970 individuals in total, were included in this study. For the primary outcomes, we only included data from the treatment arms that used 100 or 150 mg equivalent as an initial dose of PP and data from the treatment arms that used 6, 9, or 12 mg as an initial dose of PAL-ER. The pairwise meta-analyses showed that both PP and PAL-ER outperformed placebo regarding PANSS-T at week 6 and all-cause discontinuation. However, there were no statistically significant differences in these outcomes between the effect sizes of PP and that of PAL-ER. Both PP and PAL-ER increased blood prolactin levels in both females and males compared with placebo. PAL-ER significantly increased blood prolactin in both females and males compared with PP. There were no statistically significant differences in other outcomes between the effect sizes of PP and that of PAL-ER. Similar results in all outcomes were observed in the network meta-analyses. In conclusion, PP might be a useful treatment option for adults with acute symptoms of schizophrenia. A noninferiority study that directly compares PP with PAL-ER for acute schizophrenia, conducted according to the recommended regimen, is required to provide solid evidence.
Topics: Male; Female; Adult; Humans; Paliperidone Palmitate; Schizophrenia; Network Meta-Analysis; Antipsychotic Agents; Prolactin; Isoxazoles; Pyrimidines; Delayed-Action Preparations; Treatment Outcome
PubMed: 36535950
DOI: 10.1038/s41398-022-02286-1 -
International Journal of Endocrinology 2019IgG4-related hypophysitis (IgG4-RH) is a rare disease, and its prevalence remains unclear. In recent years, an increasing number of cases have been reported because of... (Review)
Review
BACKGROUND
IgG4-related hypophysitis (IgG4-RH) is a rare disease, and its prevalence remains unclear. In recent years, an increasing number of cases have been reported because of the increasing recognition of this disease. We aimed to summarize case reports of IgG4-RH and outline the clinical features and outcomes.
METHODS
We performed PubMed search of articles using the search terms "hypophysitis [AND] IgG4." Consequently, only 54 English articles (76 cases) met Leporati's diagnostic criteria.
RESULTS
Of the 76 cases, the ratio of men to women was 1.5 : 1, and the age at diagnosis was 54.1 ± 17.8 years. The median IgG4 concentration was 405.0 mg/dl. Anterior hypopituitarism, isolated central diabetes insipidus, and panhypopituitarism were observed in 14 (18.4%), 12 (15.8%), and 44 (57.9%) cases, respectively. The sequence of anterior hormone deficiency was as follows: gonadotropin (68.4%), ACTH (63.2%), TSH (59.2%), GH (48.7%), and prolactin (42.1%). The median number of involved organs was 1.5, and the lung (18.4%), retroperitoneum (17.1%), kidney (15.8%), submandibular glands (14.5%), and pancreas (13.2%) were the common involved organs. Elevated IgG4 concentration and normal IgG4 level were in 42 (76.4%) and 13 (23.6%) cases, respectively. Patients with elevated serum IgG4 concentration were older (60.9 ± 14.3 vs 45.6 ± 17.4, =0.001) and male-prone (78.6% vs 40.4%, =0.003) and had a susceptibility of multiple organ involvement (78.6% vs 35.0%, =0.001) compared to those with normal serum IgG4 levels. Males were older at disease onset (61.5 ± 12.6 vs 42.9 ± 18.8, < 0.001) and had a higher IgG4 concentration (425.0 vs 152.5, =0.029) and a greater number of involved organs (2.0 vs 0.0, =0.001), while isolated hypophysitis was more prominent in female (63.3% vs 26.1%, =0.001).
CONCLUSION
In this review, we found that there were different characteristics between different genders. Patients with elevated serum IgG4 level in terms of some clinical features were also different from those with normal serum IgG4 level. However, the data in this review were limited by bias and confounding. Further clinical studies with larger sample sizes are warranted.
PubMed: 31929792
DOI: 10.1155/2019/5382640 -
PloS One 2020Oxytocin is a key hormone in breastfeeding. No recent review on plasma levels of oxytocin in response to breastfeeding is available.
INTRODUCTION
Oxytocin is a key hormone in breastfeeding. No recent review on plasma levels of oxytocin in response to breastfeeding is available.
MATERIALS AND METHODS
Systematic literature searches on breastfeeding induced oxytocin levels were conducted 2017 and 2019 in PubMed, Scopus, CINAHL, and PsycINFO. Data on oxytocin linked effects and effects of medical interventions were included if available.
RESULTS
We found 29 articles that met the inclusion criteria. All studies had an exploratory design and included 601 women. Data were extracted from the articles and summarised in tables. Breastfeeding induced an immediate and short lasting (20 minutes) release of oxytocin. The release was pulsatile early postpartum (5 pulses/10 minutes) and coalesced into a more protracted rise as lactation proceeded. Oxytocin levels were higher in multiparous versus primiparous women. The number of oxytocin pulses during early breastfeeding was associated with greater milk yield and longer duration of lactation and was reduced by stress. Breastfeeding-induced oxytocin release was associated with elevated prolactin levels; lowered ACTH and cortisol (stress hormones) and somatostatin (a gastrointestinal hormone) levels; enhanced sociability; and reduced anxiety, suggesting that oxytocin induces physiological and psychological adaptations in the mother. Mechanical breast pumping, but not bottle-feeding was associated with oxytocin and prolactin release and decreased stress levels. Emergency caesarean section reduced oxytocin and prolactin release in response to breastfeeding and also maternal mental adaptations. Epidural analgesia reduced prolactin and mental adaptation, whereas infusions of synthetic oxytocin increased prolactin and mental adaptation. Oxytocin infusion also restored negative effects induced by caesarean section and epidural analgesia.
CONCLUSIONS
Oxytocin is released in response to breastfeeding to cause milk ejection, and to induce physiological changes to promote milk production and psychological adaptations to facilitate motherhood. Stress and medical interventions during birth may influence these effects and thereby adversely affect the initiation of breastfeeding.
Topics: Adrenocorticotropic Hormone; Anxiety; Breast Feeding; Female; Humans; Hydrocortisone; Lactation; Oxytocin; Pregnancy; Prolactin; Stress, Physiological
PubMed: 32756565
DOI: 10.1371/journal.pone.0235806 -
Cureus Feb 2023The management of dopamine agonist (DA)-resistant prolactinomas unresponsive to second and third-line treatment is challenging and requires alternative medical therapy.... (Review)
Review
The management of dopamine agonist (DA)-resistant prolactinomas unresponsive to second and third-line treatment is challenging and requires alternative medical therapy. The presence of estrogen receptors on pituitary tumors, and the variable behavior of pituitary tumors in the presence of estrogen, prompted investigation of the role of anti-estrogen in the treatment of DA-resistant prolactinomas. The goal of this paper is to perform a systematic review of the role of tamoxifen in the treatment of DA-resistant prolactinomas. A systematic review was conducted. Inclusion criteria were case reports, case series, and experimental studies using tamoxifen in DA-resistant prolactinomas. Exclusion criteria included review articles, DA-sensitive prolactinomas, and those that were not previously treated with DA. Data were analyzed using descriptive statistics. For continuous data, the mean was used. For dichotomous data, frequencies and percentages were used. Data on 22 patients were extracted from the seven included studies. Twenty patients (90.9%) responded positively to the use of tamoxifen with a mean reduction in prolactin levels of 57.4%. Ten patients (45.5%) showed normalization of prolactin post-tamoxifen administration. Regression of tumor size and stability of tumor growth were reported in four out of 22 cases (18.2%). Combination therapy with DA and tamoxifen increased DA sensitivity and had a clinically significant inhibitory effect on prolactin secretion. Furthermore, tamoxifen may be considered an effective adjuvant for tumor size control. Therefore, further studies are needed to draw more clinically and statistically robust conclusions.
PubMed: 36950000
DOI: 10.7759/cureus.35171 -
International Journal of Clinical... Sep 2015To describe the efficacy, tolerability and safety of brexpiprazole for the treatment of schizophrenia and as adjunct for major depressive disorder (MDD). (Review)
Review
Brexpiprazole for schizophrenia and as adjunct for major depressive disorder: a systematic review of the efficacy and safety profile for this newly approved antipsychotic - what is the number needed to treat, number needed to harm and likelihood to be helped or harmed?
OBJECTIVE
To describe the efficacy, tolerability and safety of brexpiprazole for the treatment of schizophrenia and as adjunct for major depressive disorder (MDD).
DATA SOURCES
The pivotal registration trials were accessed by querying http://www.ncbi.nlm.nih.gov/pubmed/ and http://www.clinicaltrials.gov, for the search terms 'brexpiprazole' OR 'OPC-34712', and by also querying the EMBASE (Elsevier) commercial database for clinical poster abstracts, and by asking the manufacturer for copies of posters presented at congresses. Product labelling provided additional information.
STUDY SELECTION
All available clinical reports of studies were identified.
DATA EXTRACTION
Descriptions of the principal results and calculation of number needed to treat (NNT) and number needed to harm (NNH) for relevant dichotomous outcomes were extracted from the available study reports and other sources of information.
DATA SYNTHESIS
Brexpiprazole is a new dopamine D2 receptor partial agonist that received approval for the treatment of schizophrenia and for adjunctive use for the treatment of MDD based on a clinical trial development programme that included two pivotal Phase III trials of brexpiprazole monotherapy in acute schizophrenia, and two pivotal Phase III trials of adjunctive brexpiprazole in acute MDD in patients who demonstrated inadequate response to standard antidepressant therapy. In addition, results from a 52-week relapse prevention/maintenance randomised placebo-controlled withdrawal study in patients with schizophrenia are available. In these trials, brexpiprazole was administered once daily and titrated to target doses. The recommended dose for the treatment of schizophrenia is 2-4 mg/day and that for MDD, 2 mg/day. Pooling together all the available data for the recommended target dose of brexpiprazole for acute schizophrenia from the above studies, the percentage of responders is 45.5% vs. 31.0% for placebo, yielding a NNT of 7 (95% CI 5-12). In the relapse prevention/maintenance trial, significantly fewer patients relapsed in the brexpiprazole group compared with placebo (13.5% vs. 38.5%), resulting in a NNT of 4 (95% CI 3-8). When the results for brexpiprazole 1, 2 and 3 mg from the two Phase III MDD trials are pooled together, 23.2% of the patients receiving brexpiprazole were responders, vs. 14.5% for placebo, yielding a NNT of 12 (95% CI 8-26). Brexpiprazole was well tolerated - for schizophrenia, discontinuation rates because of an adverse event (AE) were overall lower for patients receiving brexpiprazole vs. placebo, and for MDD a total of 3% of brexpiprazole-treated patients and 1% of placebo-treated patients discontinued because of AEs, resulting in a NNH of 53 (95% CI 30-235). Although the most commonly encountered AE noted in product labelling was akathisia (5.5% in the acute schizophrenia trials and 8.6% in the MDD trials), differences from placebo were small, generating a non-significant NNH of 112 for patients with schizophrenia and a modest NNH of 15 (95% CI 11-23) for patients with MDD. Short-term weight gain appears modest; however, more outliers with an increase of ≥ 7% of body weight were evident in open-label 52-week safety studies. Effects on glucose and lipids were small. Minimal effects on prolactin were observed, and no clinically relevant effects on the ECG QT interval were evident.
CONCLUSIONS
Clinical trials of brexpiprazole support its efficacy at the recommended target dose of 2-4 mg/day for the treatment of schizophrenia, and at the recommended target dose of 2 mg/day as adjunct to antidepressant medication for the treatment of MDD. Head-to-head comparisons with other available agents among patients with schizophrenia and MDD in the 'real world' are needed.
Topics: Antidepressive Agents; Antipsychotic Agents; Chemotherapy, Adjuvant; Clinical Trials as Topic; Depressive Disorder, Major; Dopamine Agonists; Humans; Quinolones; Schizophrenia; Thiophenes
PubMed: 26250067
DOI: 10.1111/ijcp.12714 -
Frontiers in Endocrinology 2020Previous studies were controversial in the effects of metabolic syndrome (MetS) on semen quality and circulating sex hormones, and thus we conducted a systematic review... (Meta-Analysis)
Meta-Analysis
Previous studies were controversial in the effects of metabolic syndrome (MetS) on semen quality and circulating sex hormones, and thus we conducted a systematic review and meta-analysis to clarify the association. A systematic search was conducted in public databases to identify all relevant studies, and study-specific standardized mean differences (SMD) and 95% confidence intervals (CI) were pooled using a random-effects model. Finally, 11 studies were identified with a total of 1,731 MetS cases and 11,740 controls. Compared with the controls, MetS cases had a statistically significant decrease of sperm total count (SMD: -0.96, 95% CI: -1.58 to -0.31), sperm concentration (SMD: -1.13, 95% CI: -1.85 to -0.41), sperm normal morphology (SMD: -0.61, 95% CI: -1.01 to -0.21), sperm progressive motility (SMD: -0.58, 95% CI: -1.00 to -0.17), sperm vitality (SMD: -0.83, 95% CI: -1.11 to -0.54), circulating follicle-stimulating hormone (SMD: -0.87, 95% CI: -1.53 to -0.21), testosterone (SMD: -5.61, 95% CI: -10.90 to -0.31), and inhibin B (SMD: -2.42, 95% CI: -4.52 to -0.32), and a statistically significant increase of sperm DNA fragmentation (SMD: 0.76, 95% CI: 0.45 to 1.06) and mitochondrial membrane potential (SMD: 0.89, 95% CI: 0.49 to 1.28). No significant difference was found in semen volume, sperm total motility, circulating luteinizing hormone (LH), estradiol, prolactin and anti-Müllerian hormone (AMH) ( > 0.05). In conclusion, this meta-analysis demonstrated the effects of MetS on almost all the semen parameters and part of the circulating sex hormones, and MetS tended to be a risk factor for male infertility. Further larger-scale prospective designed studies were needed to confirm our findings.
Topics: Gonadal Steroid Hormones; Humans; Male; Metabolic Syndrome; Semen; Sperm Motility; Spermatozoa
PubMed: 32849258
DOI: 10.3389/fendo.2020.00428