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[PMID]: 29427324
[Au] Autor:Reichl B; Himmelsbach M; Emhofer L; Klampfl CW; Buchberger W
[Ad] Address:Institute of Analytical Chemistry, Johannes Kepler University, Linz, Austria.
[Ti] Title:Uptake and metabolism of the antidepressants sertraline, clomipramine, and trazodone in a garden cress (Lepidium sativum) model.
[So] Source:Electrophoresis;, 2018 Feb 10.
[Is] ISSN:1522-2683
[Cp] Country of publication:Germany
[La] Language:eng
[Ab] Abstract:Environmental contamination with pharmaceuticals has received growing attention in recent years. Several studies describe the presence of traces of drugs in water bodies and soils and their impacts on nontarget organisms including plants. Due to these facts investigations of the uptake and metabolism of pharmaceuticals in organisms is an emerging research area. The present study demonstrates the analysis of three selected antidepressants (sertraline, clomipramine, and trazodone) as well as metabolites and transformation products in a cress model (Lepidium sativum). Cress was treated with tap water containing 10 mg/L of the parent drugs. Employing an analytical approach based on high performance liquid chromatography coupled with quadrupole time of flight or Orbitrap mass spectrometry in MS and MS² modes, in total 14 substances were identified in the cress extracts. All three parent drugs were taken up by the cress and translocated from the roots to the leaves in specific patterns. In addition to this, eleven metabolite species were identified. They were generated by hydroxylation, demethylation, conjugation with amino acids, or combinations of these mechanisms. Finally, the inclusion of control cultures in the experimental setup allowed for a differentiation of "true" metabolites generated by the cress and transformation products generated by plant-independent mechanisms.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1802
[Cu] Class update date: 180308
[Lr] Last revision date:180308
[St] Status:Publisher
[do] DOI:10.1002/elps.201700482

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[PMID]: 29502389
[Au] Autor:Ripoli C; Pinna AP; Podda F; Zanni R; Tronci MG; Nurchi AM
[Ad] Address:Unit of Diabetology-I Pediatric Section, Department of Surgical Sciences, University of Cagliari. annapaola_pinna@yahoo.it.
[Ti] Title:Second-generation antipsychotic and diabetes mellitus in children and adolescents.
[So] Source:Pediatr Med Chir;39(4):149, 2017 Dec 13.
[Is] ISSN:2420-7748
[Cp] Country of publication:Italy
[La] Language:eng
[Ab] Abstract:Second generation antipsychotics (SGA) are used in children for the treatment of various psychiatric diseases, including pervasive developmental disorders. These drugs can cause metabolic effects as hyperglycemia and diabetes. A 16-year-old young-boy, diagnosed with autism, developed diabetes mellitus type 1 whilst he was on treatment with olanzapine (started 4 months before), clomipramine, valproic acid and lithium. The hypothesis of druginduced diabetes imposed olanzapine interruption and clozapine initiation. Insulin therapy was practiced, with progressive dosage reduction, until complete cessation of treatment after 13 months. Blood sugar and HbA1c levels remained stable for about a year and then increased again, requiring the introduction of metformin that improved glycemia. In children and adolescents assuming SGA serum glucose and lipid profile should always be assessed before therapy and then frequently monitored. Drug selection must consider family history and the individual risk. Molecule final choice remains equilibrium between efficacy and safety.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180305
[Lr] Last revision date:180305
[St] Status:In-Process
[do] DOI:10.4081/pmc.2017.149

  3 / 3865 MEDLINE  
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[PMID]: 29477251
[Au] Autor:Cipriani A; Furukawa TA; Salanti G; Chaimani A; Atkinson LZ; Ogawa Y; Leucht S; Ruhe HG; Turner EH; Higgins JPT; Egger M; Takeshima N; Hayasaka Y; Imai H; Shinohara K; Tajika A; Ioannidis JPA; Geddes JR
[Ad] Address:Department of Psychiatry, University of Oxford, Oxford, UK; Oxford Health NHS Foundation Trust, Warneford Hospital, Oxford, UK. Electronic address: andrea.cipriani@psych.ox.ac.uk.
[Ti] Title:Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis.
[So] Source:Lancet;, 2018 Feb 20.
[Is] ISSN:1474-547X
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:BACKGROUND: Major depressive disorder is one of the most common, burdensome, and costly psychiatric disorders worldwide in adults. Pharmacological and non-pharmacological treatments are available; however, because of inadequate resources, antidepressants are used more frequently than psychological interventions. Prescription of these agents should be informed by the best available evidence. Therefore, we aimed to update and expand our previous work to compare and rank antidepressants for the acute treatment of adults with unipolar major depressive disorder. METHODS: We did a systematic review and network meta-analysis. We searched Cochrane Central Register of Controlled Trials, CINAHL, Embase, LILACS database, MEDLINE, MEDLINE In-Process, PsycINFO, the websites of regulatory agencies, and international registers for published and unpublished, double-blind, randomised controlled trials from their inception to Jan 8, 2016. We included placebo-controlled and head-to-head trials of 21 antidepressants used for the acute treatment of adults (≥18 years old and of both sexes) with major depressive disorder diagnosed according to standard operationalised criteria. We excluded quasi-randomised trials and trials that were incomplete or included 20% or more of participants with bipolar disorder, psychotic depression, or treatment-resistant depression; or patients with a serious concomitant medical illness. We extracted data following a predefined hierarchy. In network meta-analysis, we used group-level data. We assessed the studies' risk of bias in accordance to the Cochrane Handbook for Systematic Reviews of Interventions, and certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation framework. Primary outcomes were efficacy (response rate) and acceptability (treatment discontinuations due to any cause). We estimated summary odds ratios (ORs) using pairwise and network meta-analysis with random effects. This study is registered with PROSPERO, number CRD42012002291. FINDINGS: We identified 28 552 citations and of these included 522 trials comprising 116 477 participants. In terms of efficacy, all antidepressants were more effective than placebo, with ORs ranging between 2·13 (95% credible interval [CrI] 1·89-2·41) for amitriptyline and 1·37 (1·16-1·63) for reboxetine. For acceptability, only agomelatine (OR 0·84, 95% CrI 0·72-0·97) and fluoxetine (0·88, 0·80-0·96) were associated with fewer dropouts than placebo, whereas clomipramine was worse than placebo (1·30, 1·01-1·68). When all trials were considered, differences in ORs between antidepressants ranged from 1·15 to 1·55 for efficacy and from 0·64 to 0·83 for acceptability, with wide CrIs on most of the comparative analyses. In head-to-head studies, agomelatine, amitriptyline, escitalopram, mirtazapine, paroxetine, venlafaxine, and vortioxetine were more effective than other antidepressants (range of ORs 1·19-1·96), whereas fluoxetine, fluvoxamine, reboxetine, and trazodone were the least efficacious drugs (0·51-0·84). For acceptability, agomelatine, citalopram, escitalopram, fluoxetine, sertraline, and vortioxetine were more tolerable than other antidepressants (range of ORs 0·43-0·77), whereas amitriptyline, clomipramine, duloxetine, fluvoxamine, reboxetine, trazodone, and venlafaxine had the highest dropout rates (1·30-2·32). 46 (9%) of 522 trials were rated as high risk of bias, 380 (73%) trials as moderate, and 96 (18%) as low; and the certainty of evidence was moderate to very low. INTERPRETATION: All antidepressants were more efficacious than placebo in adults with major depressive disorder. Smaller differences between active drugs were found when placebo-controlled trials were included in the analysis, whereas there was more variability in efficacy and acceptability in head-to-head trials. These results should serve evidence-based practice and inform patients, physicians, guideline developers, and policy makers on the relative merits of the different antidepressants. FUNDING: National Institute for Health Research Oxford Health Biomedical Research Centre and the Japan Society for the Promotion of Science.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1802
[Cu] Class update date: 180225
[Lr] Last revision date:180225
[St] Status:Publisher

  4 / 3865 MEDLINE  
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[PMID]: 29407872
[Au] Autor:Molina-Jiménez T; Limón-Morales O; Bonilla-Jaime H
[Ad] Address:Posgrado en Biología Experimental, Universidad Autónoma Metropolitana-Iztapalapa, Apartado, Postal 55 535, C.P. 09340 Ciudad de México, Mexico.
[Ti] Title:Early postnatal treatment with clomipramine induces female sexual behavior and estrous cycle impairment.
[So] Source:Pharmacol Biochem Behav;166:27-34, 2018 Mar.
[Is] ISSN:1873-5177
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Administration of clomipramine (CMI), a tricyclic antidepressant, in early stages of development in rats, is considered an animal model for the study of depression. This pharmacological manipulation has induced behavioral and physiological alterations, i.e., less pleasure-seeking behaviors, despair, hyperactivity, cognitive dysfunction, alterations in neurotransmitter systems and in HPA axis. These abnormalities in adult male rats are similar to the symptoms observed in major depressive disorders. One of the main pleasure-seeking behaviors affected in male rats treated with CMI is sexual behavior. However, to date, no effects of early postnatal CMI treatment have been reported on female reproductive cyclicity and sexual behavior. Therefore, we explored CMI administration in early life (8-21 PN) on the estrous cycle and sexual behavior of adult female rats. Compared to the rats in the early postnatal saline treatment (CTRL group), the CMI rats had fewer estrous cycles, fewer days in the estrous stage, and longer cycles during a 20-day period of vaginal cytology analysis. On the behavioral test, the CMI rats displayed fewer proceptive behaviors (hopping, darting) and had lower lordosis quotients. Also, they usually failed to display lordosis and only rarely manifested marginal or normal lordosis. In contrast, the CTRL rats tended to display normal lordosis. These results suggest that early postnatal CMI treatment caused long-term disruptions of the estrous cycle and female sexual behavior, perhaps by alteration in the hypothalamic-pituitary-gonadal (HPG) axes and in neuronal circuits involved in the regulation of the performance and motivational of sexual behavior as the noradrenergic and serotonergic systems.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1802
[Cu] Class update date: 180220
[Lr] Last revision date:180220
[St] Status:In-Data-Review

  5 / 3865 MEDLINE  
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[PMID]: 29367071
[Au] Autor:Minguez L; Bureau R; Halm-Lemeille MP
[Ad] Address:CERMN, UFR des Sciences Pharmaceutiques, UPRES EA4258 - FR CNRS INC3 M - SF 4206 ICORE, Université de Caen Basse-Normandie, Bd Becquerel, Caen cedex 14032, France; Université de Lorraine, CNRS UMR 7360, Laboratoire Interdisciplinaire des Environnements Continentaux (LIEC), Campus Bridoux, Rue du Général Delestraint, Metz 57070, France. Electronic address: laetitia.minguez@univ-lorraine.fr.
[Ti] Title:Joint effects of nine antidepressants on Raphidocelis subcapitata and Skeletonema marinoi: A matter of amine functional groups.
[So] Source:Aquat Toxicol;196:117-123, 2018 Mar.
[Is] ISSN:1879-1514
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:Antidepressants are among the most prescribed pharmaceuticals throughout the world. Their presence has already been detected in several aquatic ecosystems worldwide and their effects on non-target organisms justify the growing concern of both the public and regulatory authorities. These emerging pollutants do not occur as isolated compounds but rather as multi-component mixtures, which may lead to increased adverse effects compared to individual compounds. Freshwater and marine algae seem particularly sensitive to pharmaceuticals, including antidepressants. Studies assessing the toxicity of antidepressant mixture to algae focused mainly on binary mixtures of selective serotonin reuptake inhibitors. In the present experiment, the freshwater algae Raphidocelis subcapitata (formerly known as Pseudokirchneriella subcapitata) and the marine diatom Skeletonema marinoi were exposed to equitoxic mixtures of 9 antidepressants (fluvoxamine, fluoxetine, sertraline, duloxetine, venlafaxine, clomipramine, amitriptyline, and citalopram) at different concentrations. The growth inhibition was measured. Results showed that the toxicity of this mixture was higher than the effects of each individual component, highlighting simple additivity or synergistic effects, whereas tested concentrations were below the 10% inhibition concentration (IC ) of each compound. Moreover, the QSAR analysis highlighted that antidepressants would act through narcosis (non-specific mode of action) towards the two species of algae. However, more specific effects can be observed by differentiating compounds with a primary/secondary amine from those with a tertiary amine. These mixture effects on algal species have to be assessed, especially since any impacts on phytoplankton could ultimately impact higher trophic levels (less food, secondary poisoning).
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1801
[Cu] Class update date: 180213
[Lr] Last revision date:180213
[St] Status:In-Process

  6 / 3865 MEDLINE  
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[PMID]: 29332813
[Au] Autor:De Boeck M; Dubrulle L; Dehaen W; Tytgat J; Cuypers E
[Ad] Address:Toxicology and Pharmacology, Department of Pharmaceutical and Pharmacological Sciences, University of Leuven (KU Leuven), Campus Gasthuisberg, O&N II, P.O. Box 922, Herestraat 49, 3000 Leuven, Belgium.
[Ti] Title:Fast and easy extraction of antidepressants from whole blood using ionic liquids as extraction solvent.
[So] Source:Talanta;180:292-299, 2018 Apr 01.
[Is] ISSN:1873-3573
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:This study aims to prove that ionic liquids (ILs) can be used as extraction solvents in a liquid-liquid microextraction, coupled to LC-MS/MS, for the quantification of a large group of antidepressants in whole blood samples. The sample preparation procedure consisted of adding 1.0mL aqueous buffer pH 3.0 and 60µL of IL (1-butyl-3-methylimidazolium hexafluorophosphate) to 1.0mL whole blood. Subsequently, a 5-min rotary mixing step was performed followed by centrifugation. The lower IL phase was collected, diluted 1:10 in methanol and 10µL was injected into the LC-MS/MS. The following analytes were included in the full-quantitative method: agomelatine, amitriptyline, bupropion, clomipramine, dosulepin, doxepin, duloxetine, escitalopram, fluoxetine, imipramine, maprotiline, mianserin, mirtazapine, nortriptyline, paroxetine, reboxetine, trazodone and venlafaxine. Selectivity was checked for 10 different whole blood matrices. Additionally, possible interferences of deuterated standards or other antidepressants were evaluated. Overall, no interferences were found. For each analyte a matrix-matched calibration curve was constructed (7 levels, n = 6), covering therapeutic and low toxic concentrations. Accuracy and precision were evaluated over eight days, at three concentration levels (n = 2). Bias, repeatability and intermediate precision results met with the proposed validation criteria, except for fluvoxamine, which was therefore only included in the semi-quantitative method. LOQs were set at the lowest calibrator concentration and LOD values were - for most analytes - within a range of 1-2ng/mL. Recoveries (RE) and matrix effects (ME) were evaluated for five types of donor whole blood, at two concentration levels. RE values were within a range of 53.11-132.98%. ME values were within a range of 61.92-123.24%. In conclusion, this study proves the applicability of ILs as extraction solvents for a large group of antidepressants in complex whole blood matrices.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1801
[Cu] Class update date: 180115
[Lr] Last revision date:180115
[St] Status:In-Process

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[PMID]: 28470111
[Au] Autor:Brown JT; Schneiderhan M; Eum S; Bishop JR
[Ad] Address:Department of Pharmacy Practice & Pharmaceutical Sciences, College of Pharmacy, University of Minnesota, Duluth, MN 55812, USA.
[Ti] Title:Serum clomipramine and desmethylclomipramine levels in a CYP2C19 and CYP2D6 intermediate metabolizer.
[So] Source:Pharmacogenomics;18(7):601-605, 2017 May.
[Is] ISSN:1744-8042
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Pharmacogenetics within psychiatry has the potential to aid in the dose and selection of medications. A substantial number of psychiatric medications are metabolized through either of the highly polymorphic drug-metabolizing enzymes CYP2D6 and CYP2C19. Of these, clomipramine is subject to metabolism by both CYP2C19 and CYP2D6, leaving individuals with deficiencies of these drug-metabolizing enzymes at risk of higher concentrations of the parent molecule. Herein, we present the case of a 29-year-old male with diagnoses of depression and obsessive compulsive disorder who had trialed and failed a dozen psychiatric medications, many of which are subject to metabolism by CYP2D6 and/or CYP2C19, and had most recently been taking clomipramine for approximately 2.5 years. Pharmacogenetic testing revealed this patient to be an intermediate metabolizer for both CYP2C19 (*1/*2) and CYP2D6 (*4/*41), which resulted in considerably elevated serum trough concentrations of clomipramine and its active metabolite desmethylclomipramine. This case provides a retrospective view of how the knowledge of an individual's pharmacogenetic test results can aid in their clinical care.
[Mh] MeSH terms primary: Clomipramine/analogs & derivatives
Clomipramine/blood
Cytochrome P-450 CYP2C19/metabolism
Cytochrome P-450 CYP2D6/metabolism
[Mh] MeSH terms secundary: Adult
Antidepressive Agents, Tricyclic/blood
Antidepressive Agents, Tricyclic/therapeutic use
Clomipramine/therapeutic use
Cytochrome P-450 CYP2C19/genetics
Cytochrome P-450 CYP2D6/genetics
Depressive Disorder/blood
Depressive Disorder/drug therapy
Depressive Disorder/genetics
Humans
Male
Obsessive-Compulsive Disorder/blood
Obsessive-Compulsive Disorder/drug therapy
Obsessive-Compulsive Disorder/genetics
Retrospective Studies
[Pt] Publication type:CASE REPORTS; JOURNAL ARTICLE; REVIEW
[Nm] Name of substance:0 (Antidepressive Agents, Tricyclic); 01DN47PPQG (desmethylclomipramine); EC 1.14.14.1 (CYP2C19 protein, human); EC 1.14.14.1 (Cytochrome P-450 CYP2C19); EC 1.14.14.1 (Cytochrome P-450 CYP2D6); NUV44L116D (Clomipramine)
[Em] Entry month:1801
[Cu] Class update date: 180112
[Lr] Last revision date:180112
[Js] Journal subset:IM
[Da] Date of entry for processing:170505
[St] Status:MEDLINE
[do] DOI:10.2217/pgs-2017-0015

  8 / 3865 MEDLINE  
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[PMID]: 29278206
[Au] Autor:Albert U; Marazziti D; Di Salvo G; Solia F; Rosso G; Maina G
[Ad] Address:Rita Levi Montalcini Department of Neuroscience, University of Turin. Italy.
[Ti] Title:A systematic review of evidence-based treatment strategies for obsessive-compulsive disorder resistant to first-line pharmacotherapy.
[So] Source:Curr Med Chem;, 2017 Dec 22.
[Is] ISSN:1875-533X
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:BACKGROUND: Serotonin reuptake inhibitors (SRIs) and cognitive-behavioral psychotherapy (CBT) are first-line treatments for obsessive-compulsive disorder (OCD). However, a significant proportion of patients do not respond satisfactorily to first-choice treatments. Several options have been investigated for the management of resistant patients. OBJECTIVE: The aim of the present paper is to systematically review the available literature concerning the strategies for the treatment of resistant adult patients with OCD. METHOD: We first reviewed studies concerning the definition of treatment-resistant OCD; we then analyzed results of studies evaluating several different strategies in resistant patients. We limited our review to double-blind, placebo-controlled studies performed in adult patients with OCD whose resistance to a first adequate (in terms of duration and dosage) SRI trial was documented and where outcome was clearly defined in terms of decrease in Yale-Brown Obsessive-Compulsive Scale (YBOCS) scores and/or response/remission rates (according to the YBOCS). RESULTS: We identified five strategies supported by positive results in placebo-controlled randomized studies: 1) antipsychotic addition to SRIs (16 RCTs, of them 10 positive; 4 head-to-head RCTs); among antipsychotics, available RCTs examined the addition of haloperidol (butyrophenone), pimozide (diphenyl-butylpiperidine), risperidone (SDA: serotonin-dopamine antagonist), paliperidone (SDA), olanzapine (MARTA: multi-acting receptor targeted antipsychotic), quetiapine (MARTA) and aripiprazole (partial dopamine agonist); 2) CBT addition to medication (2 positive RCTs); 3) switch to intravenous clomipramine (SRI) administration (2 positive RCTs); 4) switch to paroxetine (SSRI: selective serotonin reuptake inhibitor) or venlafaxine (SNRI: serotonin-norepinephrine reuptake inhibitor) when the first trial was negative (1 positive RCT); and 5) the addition of medications other than an antipsychotic to SRIs (18 RCTs performed with several different compounds, with only 4 positive studies). CONCLUSION: Treatment-resistant OCD remains a significant challenge to psychiatrists. To date, the most effective strategy is the addition of antipsychotics (aripiprazole and risperidone) to SRIs; another effective strategy is CBT addition to medications. Other strategies, such as the switch to another first-line treatment or the switch to intravenous administration are promising but need further confirmation in double-blind studies. The addition of medications other than antipsychotics remains to be studied, as several negative studies exist and positive ones need confirmation (only 1 positive study).
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1712
[Cu] Class update date: 171226
[Lr] Last revision date:171226
[St] Status:Publisher
[do] DOI:10.2174/0929867325666171222163645

  9 / 3865 MEDLINE  
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[PMID]: 29259169
[Au] Autor:Faissner S; Mishra M; Kaushik DK; Wang J; Fan Y; Silva C; Rauw G; Metz L; Koch M; Yong VW
[Ad] Address:Department of Clinical Neurosciences, Hotchkiss Brain Institute, University of Calgary, Calgary, AB, T2N 4N1, Canada.
[Ti] Title:Systematic screening of generic drugs for progressive multiple sclerosis identifies clomipramine as a promising therapeutic.
[So] Source:Nat Commun;8(1):1990, 2017 Dec 19.
[Is] ISSN:2041-1723
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:The treatment of progressive multiple sclerosis (MS) is unsatisfactory. One reason is that the drivers of disease, which include iron-mediated neurotoxicity, lymphocyte activity, and oxidative stress, are not simultaneously targeted. Here we present a systematic screen to identify generic, orally available medications that target features of progressive MS. Of 249 medications that cross the blood-brain barrier, 35 prevent iron-mediated neurotoxicity in culture. Of these, several antipsychotics and antidepressants strongly reduce T-cell proliferation and oxidative stress. We focus on the antidepressant clomipramine and found that it additionally inhibits B-lymphocyte activity. In mice with experimental autoimmune encephalomyelitis, a model of MS, clomipramine ameliorates clinical signs of acute and chronic phases. Histologically, clomipramine reduces inflammation and microglial activation, and preserves axonal integrity. In summary, we present a systematic approach to identify generic medications for progressive multiple sclerosis with the potential to advance rapidly into clinical trials, and we highlight clomipramine for further development.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1712
[Cu] Class update date: 171222
[Lr] Last revision date:171222
[St] Status:In-Data-Review
[do] DOI:10.1038/s41467-017-02119-6

  10 / 3865 MEDLINE  
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[PMID]: 29256128
[Au] Autor:Drobnis EZ; Nangia AK
[Ad] Address:Obstetrics, Gynecology and Women's Health, University of Missouri School of Medicine, Columbia, MO, USA.
[Ti] Title:Psychotropics and Male Reproduction.
[So] Source:Adv Exp Med Biol;1034:63-101, 2017.
[Is] ISSN:0065-2598
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Psychotropic drugs, including antidepressants, antipsychotics, and anticonvulsants, all have negative effects on sexual function and semen quality. These adverse events vary among men and are less pronounced for some medications, allowing their effects to be managed to some extent. Use of specific serotonin reuptake inhibitors (SSRIs) is prevalent in men of reproductive age; and application to treat premature ejaculation increases the number of young men on SSRI therapy. Oxidative damage to sperm can result from prolonged residence in the male reproductive tract. The increase in ejaculatory latency seen with SSRIs likely underlies some of their negative effects on semen quality, including higher sperm DNA fragmentation, seen in all SSRIs evaluated thus far. These medications increase prolactin (PRL) levels in some men, and this is often credited with inhibitory effects on male reproduction; however, testosterone levels are generally normal, reducing the likelihood of direct HPG axis inhibition by PRL. The tricyclic antidepressants have also been shown to increase PRL levels in some studies but not in others. The exception is the tricyclic antidepressant clomipramine, which profoundly increases PRL levels and may depress semen quality. Other antidepressants modulating synaptic levels of serotonin, norepinephrine, and/or dopamine may have toxicity similar to SSRIs, but most have not been evaluated. In limited studies, norepinephrine-dopamine reuptake inhibitors (NDRIs) and serotonin agonist/reuptake inhibitors (SARIs) have had minimal effects on PRL levels and on sexual side effects. Antipsychotic medications increase PRL, decrease testosterone, and increase sexual side effects, including ejaculatory dysfunction. The greatest evidence is for chlorpromazine, haloperidol, reserpine, risperidone, and thioridazine, with less effects seen with aripiprazole and clozapine. Remarkably few studies have looked at antipsychotic effects on semen quality, and this is an important knowledge gap in reproductive pharmacology. Lithium increases PRL and LH levels and decreases testosterone although this is informed by few studies. The anticonvulsants, many used for other indications, generally decrease free or bioavailable testosterone with variable effects on the other reproductive hormones. Valproate, carbamazepine, oxcarbazepine, and levetiracetam decrease semen quality; other anticonvulsants have not been investigated for this adverse reaction. Studies are required evaluating endpoints of pregnancy and offspring health for psychotropic medications.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1712
[Cu] Class update date: 171219
[Lr] Last revision date:171219
[St] Status:In-Data-Review
[do] DOI:10.1007/978-3-319-69535-8_8


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