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  1. GENDEP Investigators, MARS Investigators, STAR*D Investigators
    Am J Psychiatry, 2013 Feb;170(2):207-17.
    PMID: 23377640 DOI: 10.1176/appi.ajp.2012.12020237
    OBJECTIVE: Indirect evidence suggests that common genetic variation contributes to individual differences in antidepressant efficacy among individuals with major depressive disorder, but previous studies may have been underpowered to detect these effects.

    METHOD: A meta-analysis was performed on data from three genome-wide pharmacogenetic studies (the Genome-Based Therapeutic Drugs for Depression [GENDEP] project, the Munich Antidepressant Response Signature [MARS] project, and the Sequenced Treatment Alternatives to Relieve Depression [STAR*D] study), which included 2,256 individuals of Northern European descent with major depressive disorder, and antidepressant treatment outcomes were prospectively collected. After imputation, 1.2 million single-nucleotide polymorphisms were tested, capturing common variation for association with symptomatic improvement and remission after up to 12 weeks of antidepressant treatment.

    RESULTS: No individual association met a genome-wide threshold for statistical significance in the primary analyses. A polygenic score derived from a meta-analysis of GENDEP and MARS participants accounted for up to approximately 1.2% of the variance in outcomes in STAR*D, suggesting a weakly concordant signal distributed over many polymorphisms. An analysis restricted to 1,354 individuals treated with citalopram (STAR*D) or escitalopram (GENDEP) identified an intergenic region on chromosome 5 associated with early improvement after 2 weeks of treatment.

    CONCLUSIONS: Despite increased statistical power accorded by meta-analysis, the authors identified no reliable predictors of antidepressant treatment outcome, although they did identify modest, direct evidence that common genetic variation contributes to individual differences in antidepressant response.

    Matched MeSH terms: Antidepressive Agents, Second-Generation/administration & dosage; Antidepressive Agents, Second-Generation/pharmacokinetics
  2. Ng CG, Wong SK, Loh HS, Yee A
    Clin Ter, 2014;165(6):e384-90.
    PMID: 25524191 DOI: 10.7417/CT.2014.1778
    BACKGROUND AND AIMS: Escitalopram has widely been recognized as one of the most frequently used antidepressants, with superior tolerability and great efficacy in preventing major depressive disorder (MDD) relapse and recurrence. However, anhedonia, which is a core symptom of MDD, remains difficult to treat. This study investigates the hedonic levels of MDD patients treated with Escitalopram.

    MATERIALS AND METHODS: A total of 108 participants, 26 of whom with MDD on Escitalopram, were recruited in this cross sectional study. They were evaluated using the Snaith-Hamilton Pleasure Scale (SHAPS) and Beck Depression Inventory (BDI) questionnaires to assess their hedonic state, general mental health condition and level of depression.

    RESULTS: Our study shows that most items in the SHAPS scores are significantly different between MDD patients on Escitalopram and the controls.

    CONCLUSIONS: The hedonic capacity remains different between the two groups despite patients with MDD are put on Escitalopram treatment. Escitalopram fails to alleviate the hedonic state of MDD patients. Antidepressants that improve both depressive symptoms and hedonic states should be considered when treating MDD patients in clinical settings.
    Matched MeSH terms: Antidepressive Agents, Second-Generation/therapeutic use*
  3. Hassan Basri M, Khoo CS, Che Hamzah J
    Acta Neurol Belg, 2021 Apr;121(2):573-574.
    PMID: 33068282 DOI: 10.1007/s13760-020-01519-8
    Matched MeSH terms: Antidepressive Agents, Second-Generation/therapeutic use
  4. Emsley R, Ahokas A, Suarez A, Marinescu D, Dóci I, Lehtmets A, et al.
    J Clin Psychiatry, 2018 07 03;79(4).
    PMID: 29995359 DOI: 10.4088/JCP.17m11741
    OBJECTIVE: The present placebo-controlled study evaluated the efficacy and safety of 8 weeks of treatment with tianeptine 25-50 mg/d in elderly patients suffering from major depressive disorder (MDD) according to DSM-IV-TR. Escitalopram 5-10 mg/d was used as an active comparator.

    METHODS: Elderly outpatients aged at least 65 years with a primary diagnosis of moderate to severe episode of recurrent MDD were recruited by psychiatrists in 44 clinical centers in 10 countries from October 2013 to January 2016. Patients were randomly assigned to receive tianeptine (n = 105), placebo (n = 107), or escitalopram (n = 99) for 8 weeks. The primary outcome measure was the 17-item Hamilton Depression Rating Scale (HDRS₁₇) total score.

    RESULTS: Tianeptine improved depressive symptoms, as evaluated by the HDRS₁₇ total score in terms of absolute change from baseline (week 0) to week 8 (placebo-tianeptine difference [SE] of 3.84 [0.85] points, P < .001, using a last-observation-carried-forward approach) and response to treatment (tianeptine: 46.7%; placebo: 34.0%, estimate [SE] = 12.70% [6.70], P = .06). A sensitivity analysis using a mixed model for repeated measures confirmed the main results on HDRS total s​core. The placebo-tianeptine difference (SE) was 0.66 (0.15) for Clinical Global Impressions-Severity of Illness (95% CI, 0.37 to 0.96; P < .001) and 0.57 (0.14) for Clinical Global Impressions- Improvement (95% CI, 0.30 to 0.83; P < .001). Positive results were also obtained with the active control escitalopram (HDRS₁₇ total score placebo-escitalopram difference of 4.09 ± 0.86 points, P < .001), therefore validating the sensitivity of the studied population. Tianeptine was well tolerated, with only minimal differences in tolerability from placebo.

    CONCLUSIONS: The present study provides robust evidence that an 8-week treatment period with tianeptine 25-50 mg is efficacious and well tolerated in depressed patients aged 65 years or older.

    TRIAL REGISTRATION: EudraCT identifier: 2012-005612-26​.

    Matched MeSH terms: Antidepressive Agents, Second-Generation/adverse effects; Antidepressive Agents, Second-Generation/therapeutic use
  5. Soga T, Wong DW, Clarke IJ, Parhar IS
    Neuropharmacology, 2010 Jul-Aug;59(1-2):77-85.
    PMID: 20381503 DOI: 10.1016/j.neuropharm.2010.03.018
    Citalopram is the most potent selective serotonin reuptake inhibitor (SSRI) which is used as an antidepressant but causes sexual dysfunction. Whether citalopram induced sexual dysfunction is a result of gonadotropin-releasing hormone (GnRH), kisspeptin or RF-amide related peptide (RFRP) alteration is unknown. In this study, we tested mice for sexual behavior after vehicle (0.9% NaCl) and citalopram treatment (5 mg/kg) daily for 1 day (acute) and 21 or 28 days (chronic). Effects of acute and chronic treatments on neuronal numbers and mRNA expression of GnRH, kisspeptin and RFRP were measured. In addition, RFRP fiber projections to preoptic (POA)-GnRH neurons were analyzed using double-label immunohistochemistry. The expression of 14 different serotonin receptor types mRNA was examined in immunostained laser dissected single RFRP neurons in the dorsomedial hypothalamus (DMH), however only 11 receptors types were identified. Acute citalopram treatment did not affect sexual behavior, whereas, the total duration of intromission was reduced with chronic treatment. There was no effect in the expression of kisspeptin (neuronal numbers and mRNA) in the anteroventral periventricular nucleus and the arcuate nucleus and expression of GnRH (neuronal numbers and mRNA) in the POA after citalopram treatment. However, RFRP neuronal numbers in the DMH and fiber projections to the POA were significantly increased after chronic citalopram treatment, which suggests citalopram induced inhibition of sexual behavior involves the modulation of RFRP through serotonin receptors in the DMH.
    Matched MeSH terms: Antidepressive Agents, Second-Generation/administration & dosage; Antidepressive Agents, Second-Generation/adverse effects*
  6. Ramli FF, Azizi MH, Syed Hashim SA
    Int J Med Sci, 2021;18(11):2372-2380.
    PMID: 33967614 DOI: 10.7150/ijms.57641
    Sexual dysfunction is a common condition in the opioid substitution therapy (OST) population. We aimed to determine the efficacy and safety of treatment for sexual dysfunction in the OST population. We searched for interventional studies from Medline, PubMed, and Scopus. Three independent authors conducted a risk-of-bias assessment (RoB 2). A total of seven studies (five randomized-controlled trials, two quasi-experimental), including 473 patients with sexual dysfunction, were identified. Among these, three bupropion (n=207), one trazodone (n=75), two rosa Damascena (n=100), and one ginseng (n=91) studies had reported significantly improve various sexual functioning domains in both genders. In a meta-analysis, bupropion significantly increased male sexual function with standardized mean difference of 0.53; 95% confidence interval of 0.19-0.88; P < 0.01; I2=0. The adverse effects were minor for all agents, and no significant difference between treatment and placebo groups in randomized-controlled trials. These agents have a promising future as therapy for sexual dysfunction in the OST population. However, given the limited sample size and number of studies, further studies should be conducted to confirm the use of these agents.
    Matched MeSH terms: Antidepressive Agents, Second-Generation/therapeutic use*
  7. Yee, A., Kanagasundram, S., Gill, J.S., Zainal, N.Z.
    MyJurnal
    Objective: This systematic review is aimed to quantitatively summarise the
    prevalence of sexual dysfunction among non-SSRI second generation
    antidepressants namely agomelatine, bupropion, duloxetine, venlafaxine, and
    mirtazapine.

    Methods: Relevant studies published from inception till
    December 2012 were identified by searching PubMed, OVID and Embase.
    We included all literatures encompassing randomized controlled, cohort,
    case-controlled and cross-sectional studies, which contained quantitative data
    for prevalence on all aspects of sexual dysfunction in depressive patients who
    were older than 18 years of age. Heterogeneity, publication bias and odds
    ratio were assessed thoroughly.

    Results: In the non-SSRI second generation
    antidepressant group which consisted of 17,316 subjects, various studies
    showed the range of sexual dysfunction prevalence between 0% and 67%.
    Sexual dysfunction in patients who took non-SSRI second generation
    antidepressants constituted a meta-analytical pooled prevalence of 15%, and
    36% in those who took SSRIs. The combined relative risk of sexual
    dysfunction in the non-SSRI second generation antidepressant group when
    compared with SSRI was 0.57.

    Conclusions: The pooled prevalence of sexual
    dysfunction in non-SSRI second generation antidepressant is lower than in
    SSRI antidepressants.
    Matched MeSH terms: Antidepressive Agents, Second-Generation
  8. Soga T, Wong DW, Putteeraj M, Song KP, Parhar IS
    Neuroscience, 2012 Dec 6;225:172-84.
    PMID: 22960312 DOI: 10.1016/j.neuroscience.2012.08.061
    Postnatal treatment with selective serotonin reuptake inhibitors (SSRIs) has been found to affect brain development and the regulation of reproduction in rodent models. The normal masculinization process in the brain requires a transient decrease in serotonin (5-HT) levels in the brain during the second postnatal week. Strict regulation of androgen receptor (AR) and gonadotropin-releasing hormone (GnRH) expression is important to control male reproductive activity. Therefore, this study was designed to examine the effects of a potent SSRI (citalopram) on male sexual behavior and expression levels of AR and GnRH in adult male mice receiving either vehicle or citalopram (10mg/kg) daily during postnatal days 8-21. The citalopram-treated male mice showed altered sexual behavior, specifically a significant reduction in the number of intromissions preceding ejaculation compared with the vehicle-treated mice. The citalopram-treated male mice displayed elevated anxiety-like behavior in an open field test and lower locomotor activity in their home cage during the subjective night. Although there was no change in GnRH and AR mRNA levels in the preoptic area (POA), quantified by real-time polymerase chain reaction, immunostained AR cell numbers in the medial POA were decreased in the citalopram-treated male mice. These results suggest that the early-life inhibition of 5-HT transporters alters the regulation of AR expression in the medial POA, likely causing decreased sexual behavior and altered home cage activity in the subjective night.
    Matched MeSH terms: Antidepressive Agents, Second-Generation/toxicity*
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