Biological and Pharmacogenomics Bases of Gastrointestinal and Some Long-Term Selective Serotonin Reuptake Inhibitors-Induced Adverse Effects

Tryptophan Hydroxylase ◽

Great Promise ◽

Nucleotide Polymorphisms ◽

Base Pair Deletion ◽

Ssri Treatment

Background: Patients being treated with SSRIs who experience intolerable Adverse Effects (AEs) have a penchant for discontinuing treatment, inevitably jeopardizing any probability for treatment response. Aim: This study aims to identify the Single Nucleotide Polymorphisms (SNPs) that are associated with certain AEs of SSRI treatment in Major Depression Disorder (MDD). Results: Patients with the short (SS) genotype (44 base pair deletion) and those with the long along with guanine substitution (LgLg - 44 base pair insertion with rs25531- guanine substitution variant) of the serotonin transporter gene (STG) have substantially been reported with a higher incidence of AEs to SSRI. While variants of glutamate receptor ionotropic genes have been found to be linked with different domains of sexual dysfunction, polymorphisms of 5-HT2A gene - rs6311 (G > A), the long allele (L) of STG, rs6295 (C > G) polymorphism of HTR1A and polymorphism rs1160351 (A > C) of MAM domain-containing glycosyl-phosphatidyl inositol anchor 2 (MDGA2) gene have also been found to be associated with sexual dysfunction. The rs4680 (G>A; Val > Met) polymorphism of catechol-O-methyltransferase (COMT), AA genotype of rs18532 polymorphism of tryptophan hydroxylase, the rs6318 (C > G) polymorphism of the serotonin receptor 2C (HTR2C), and S allele of STG were found to be associated with weight gain following SSRI treatment. The sanctity of these results is limited by the inability of some researchers to replicate these association findings. Conclusion: This review highlights a number of polymorphisms associated with some of the key AEs encountered in SSRI treatments. Standardized study designs in pharmacogenomic evaluations hold great promise for replication of association findings.

Female Sexual Side Effects Associated with Selective Serotonin Reuptake Inhibitors: A Descriptive Clinical Study of 33 Patients

The International Journal of Psychiatry in Medicine ◽

10.2190/n6c0-dwx2-g4ea-7688 ◽

1995 ◽

Vol 25 (3) ◽

pp. 239-248 ◽

Cited By ~ 47

Author(s):

Winston W. Shen ◽

Jeffrey H. Hsu

Keyword(s):

Side Effects ◽

Sexual Dysfunction ◽

Adverse Effects ◽

Serotonin Reuptake ◽

Female Sexual Dysfunction ◽

Spontaneous Remission ◽

Selective Serotonin ◽

Sexual Side Effects

Objective: After the advent of selective serotonin reuptake inhibitors on the U.S. market in 1988, American psychiatrists have been faced with more choices of antidepressants for the treatment of depression. The prescribing of SSRIs has been increasing in popularity because they are easily titrated by the physicians and tolerated by patients. However, the SSRI use is frequently associated with female sexual dysfunction. The aim of this study was to describe these SSRI-associated female sexual side effects. Methods: In a retrospective series, clinic records of 110 female SSRI-treated outpatients were reviewed for loss of or decreased libido, orgasmic disturbances (anorgasmia or delayed orgasm), as well as clinical management patterns to alleviate sexual side effects. Results: Twenty-one fluoxetine-, nine paroxetine-, and five sertraline-treated cases with female sexual inhibition were identified. The fates of SSRI-associated sexual adverse effects and clinical managements of restoring these side effects were described. Conclusions: With some limitations in interpreting the data, the findings of this study suggest that SSRI-associated female sexual dysfunction occurs at a higher rate than we previously thought, equal potentials in implicating female sexual side effects among three SSRIs, and the absence or the low incidence of female sexual adverse effects from bupropion, and that these side effects can be managed by waiting for a spontaneous remission, dosage reduction of SSRIs, substitution with bupropion and other antidepressants, or the use of an antidote.

Sexual adverse effects with new antidepressants

Psychiatric Bulletin ◽

10.1192/pb.22.7.438 ◽

1998 ◽

Vol 22 (7) ◽

pp. 438-441 ◽

Cited By ~ 5

Author(s):

Shameem Mir ◽

David Taylor

Keyword(s):

Adverse Effect ◽

Sexual Dysfunction ◽

Adverse Effects ◽

Monoamine Oxidase ◽

Serotonin Reuptake ◽

Case Reports ◽

Depressive Illness ◽

Psychotropic Agents

Sexual dysfunction is a widely recognised adverse effect of many psychotropic agents. Older antidepressants such as monoamine oxidase inhibitors and tricycles, particularly clomipramine, are known to engender sexual adverse effects. In depression, this problem is exacerbated by the occurrence of impotence and lowered libido as part of depressive illness itself. We examined evidence relating to more recently introduced antidepressants: selective serotonin reuptake inhibitors, moclobemide, venlafaxine, nefazodone, mirtazapine and reboxetine. We reviewed published trials and case reports collated from searches of Medline, PsychLit and Micromedex from 1985 to December 1997, and contacted manufacturers of new antidepressants and requested information from them.

Clinician compliance to recommendations regarding the risk of suicidality with selective serotonin reuptake inhibitors in the treatment of children and adolescents

European Child & Adolescent Psychiatry ◽

10.1007/s00787-019-01435-0 ◽

2019 ◽

Vol 29 (5) ◽

pp. 707-718

Author(s):

Johanne Østerby Sørensen ◽

Annette Rasmussen ◽

Troels Roesbjerg ◽

Anne Katrine Pagsberg

Keyword(s):

Adverse Effects ◽

Children And Adolescents ◽

Serotonin Reuptake ◽

Selective Serotonin ◽

Pharmacological Interventions ◽

Younger Age ◽

Meta Analyses ◽

Ssri Treatment

Abstract Meta-analyses of randomized-controlled trials have established a heightened risk of suicidality for children and adolescents treated with selective serotonin reuptake inhibitors (SSRIs). The present study examined to what extent daily clinical practice complied with specific recommendations regarding the risk of suicidality when treating children and adolescents with SSRIs. All in- and outpatients aged 0–17 years at the Child and Adolescent Mental Health Services, Capital Region of Denmark with a prescription for SSRI on January 1st, 2016 were identified. Data were obtained for n = 365 patients regarding the level of clinician compliance to deliver pre-consent information about adverse effects, monitor for suicidality, and provide non-pharmacological interventions. 81.7% (n = 298) of patients received pre-consent information about adverse effects. 67.7% (n = 247) were monitored for suicidality within 6 weeks after SSRI initiation. Children (0–13 years) were less likely to be monitored for suicidality compared to adolescents (14–17 years) (49.6% vs. 77.5%, p < 0.001). Patients with depression as indication for SSRI treatment were more likely to be monitored for suicidality than patients with other indications (OR = 3.4, p = 0,002) and more likely to receive information specifically about suicidality (34.7% vs. 19.7%, p = 0.002). Respectively, 89.3% (n = 326) and 93.4% (n = 341) of all SSRI-treated patients were treated with non-pharmacological interventions prior to and in parallel with SSRI treatment. For the majority of cases, treatment of children and adolescents with SSRI complied with recommendations from clinical guidelines. However, patients of younger age and/or with indications for SSRIs other than depression were less likely to be managed according to recommendations.

Detection of the Glanzmann's Thrombasthenia Mutations in Arab and Iraqi-Jewish Patients by Polymerase Chain Reaction and Restriction Analysis of Blood or Urine Samples

Thrombosis and Haemostasis ◽

10.1055/s-0038-1646446 ◽

1991 ◽

Vol 66 (04) ◽

pp. 500-504 ◽

Cited By ~ 28

Author(s):

H Peretz ◽

U Seligsohn ◽

E Zwang ◽

B S Coller ◽

P J Newman

Keyword(s):

Polymerase Chain Reaction ◽

Base Pair ◽

Restriction Analysis ◽

Urine Samples ◽

Chain Reaction ◽

Base Pairs ◽

Glanzmann’S Thrombasthenia ◽

Glanzmann's Thrombasthenia ◽

Base Pair Deletion ◽

Polymerase Chain

SummarySevere Glanzmann's thrombasthenia is relatively frequent in Iraqi-Jews and Arabs residing in Israel. We have recently described the mutations responsible for the disease in Iraqi-Jews – an 11 base pair deletion in exon 12 of the glycoprotein IIIa gene, and in Arabs – a 13 base pair deletion at the AG acceptor splice site of exon 4 on the glycoprotein IIb gene. In this communication we show that the Iraqi-Jewish mutation can be identified directly by polymerase chain reaction and gel electrophoresis. With specially designed oligonucleotide primers encompassing the mutation site, an 80 base pair segment amplified in healthy controls was clearly distinguished from the 69 base pair segment produced in patients. Patients from 11 unrelated Iraqi-Jewish families had the same mutation. The Arab mutation was identified by first amplifying a DNA segment consisting of 312 base pairs in controls and of 299 base pairs in patients, and then digestion by a restriction enzyme Stu-1, which recognizes a site that is absent in the mutant gene. In controls the 312 bp segment was digested into 235 and 77 bp fragments, while in patients there was no change in the size of the amplified 299 bp segment. The mutation was found in patients from 3 out of 5 unrelated Arab families. Both Iraqi-Jewish and Arab mutations were detectable in DNA extracted from blood and urine samples. The described simple methods of identifying the mutations should be useful for detection of the numerous potential carriers among the affected kindreds and for prenatal diagnosis using DNA extracted from chorionic villi samples.

Mutation Spectrum in Patients with Wiskott-Aldrich Syndrome and X-linked Thrombocytopenia: Identification of Twelve Different Mutations in the WASP Gene

Thrombosis and Haemostasis ◽

10.1055/s-0038-1650318 ◽

1996 ◽

Vol 75 (04) ◽

pp. 546-550 ◽

Cited By ~ 21

Author(s):

Marianne Schwartz ◽

Albert Békássy ◽

Mikael Donnér ◽

Thomas Hertel ◽

Stefan Hreidarson ◽

...

Keyword(s):

Base Pair ◽

Hot Spot ◽

Missense Mutations ◽

Nucleotide Substitutions ◽

Exon 2 ◽

Wiskott Aldrich Syndrome ◽

Base Pair Deletion ◽

Reliable Diagnosis ◽

Wasp Gene ◽

Detection Of Mutations

SummaryTwelve different mutations in the WASP gene were found in twelve unrelated families with Wiskott-Aldrich syndrome (WAS) or X-linked thrombocytopenia (XLT). Four frameshift, one splice, one nonsense mutation, and one 18-base-pair deletion were detected in seven patients with WAS. Only missense mutations were found in five patients diagnosed as having XLT. One of the nucleotide substitutions in exon 2 (codon 86) results in an Arg to Cys replacement. Two other nucleotide substitutions in this codon, R86L and R86H, have been reported previously, both giving rise to typical WAS symptoms, indicating a mutational hot spot in this codon. The finding of mutations in the WASP gene in both WAS and XLT gives further evidence of these syndromes being allelic. The relatively small size of the WASP gene facilitates the detection of mutations and a reliable diagnosis of both carriers and affected fetuses in families with WAS or XLT.

Selective Serotonin Reuptake Inhibitors: Infrequent Medical Adverse Effects

Archives of Family Medicine ◽

10.1001/archfami.7.1.78 ◽

1998 ◽

Vol 7 (1) ◽

pp. 78-84 ◽

Cited By ~ 40

Author(s):

R. J. Goldberg

Keyword(s):

Adverse Effects ◽

Serotonin Reuptake ◽

Selective Serotonin

Statin-induced adverse effects – facts and genes

Orvosi Hetilap ◽

10.1556/oh.2013.29530 ◽

2013 ◽

Vol 154 (3) ◽

pp. 83-92

Author(s):

Mariann Harangi ◽

Noémi Zsíros ◽

Lilla Juhász ◽

György Paragh

Keyword(s):

Risk Factors ◽

Single Nucleotide Polymorphisms ◽

Adverse Effects ◽

Adverse Events ◽

Statin Therapy ◽

Significant Proportion ◽

Gene Mutations ◽

Nucleotide Polymorphisms ◽

Serious Adverse Events ◽

Single Nucleotide

Statin therapy is considered to be safe and rarely associated with serious adverse events. However, a significant proportion of patients on statin therapy show some degree of intolerance which can lead to decreased adherence to statin therapy. The authors summarize the symptoms, signs and frequencies of the most common statin-induced adverse effects and their most important risk factors including some single nucleotide polymorphisms and gene mutations. Also, they review the available approaches to detect and manage the statin-intolerant patients. Orv. Hetil., 2013, 154, 83–92.