Clinico-Biochemical Study of the Safety and Tolerability of Selective Serotonin Reuptake Inhibitors (SSRI) with Special Reference to SSRI Induced Hyponatremia in Humans and Animals

Introduction: Selective Serotonin Reuptake Inhibitors (SSRIs) are recommended as first-line anti-depressants in Major Depressive Disorder (MDD) because of their relatively benign safety profile. Hyponatremia is under reported and notorious adverse effect of SSRIs shown by few Randomised Clinical Trials (RCTs). There are only few published studies of SSRIs on serum sodium level in human and animal model. Aim: To determine SSRI induced hyponatremia in human and its correlation with age. Materials and Methods: The clinical part is a prospective cohort study whereas second part is experimental study involving animals. In clinical part-Patients of either sex, aged above 18 years, attending the Out-Patient Department (OPD) of Psychiatry of a tertiary hospital and diagnosed as MDD Diagnostic and Statistical Manual (DSM) V with the help of a senior psychiatrist, were screened and recruited in the study after satisfying the inclusion and exclusion criteria by consecutive sampling. Patients were prescribed fluoxetine (n=90), sertraline (n=55), paroxetine (n=30) and escitalopram (n=25). Parameters recorded (serum sodium) at baseline, 4th week, 8th week and 12th week. Symptoms due to hyponatremia and Adverse Drug Reactions (ADR) were also checked. Multiple group comparison at different visits for sodium level was done using one-way ANOVA and repeated measures ANOVA test and relationship of blood sodium level with age were estimated with bivariate correlation. Animal experiment was done in Pharmacology Department, animals were randomised into 5 groups control, fluoxetine, sertraline, paroxetine and escitalopram (n=6). Blood sodium checked at baseline, 2nd week and 4th week. Kruskal Wallis test and Friedman’s test done to detect changes in sodium level in follow-up period. Results: Mean age ranged between 40-50 years with equal gender distribution. Both within group and between group analysis revealed significant difference in blood sodium level (p-value< 0.0001). Hyponatremia was strongly correlated with age (correlation coefficient >-0.783). Most participants (184 out of 200) developed asymptomatic hyponatremia. Two among sertraline developed seizure leading to discontinuation to therapy. About 72 (38.09%) ADRs belonged to probable, mostly belonging to fluoxetine and sertraline group, developement of hyponatremia was 9 days (median) from starting SSRI. In animal part within group analysis revealed significant change of sodium from baseline in all drug treated animals (p-value<0.0001). Conclusion: SSRI is associated with hyponatremia and is common in elderly patients. Monitoring of serum sodium is necessary for patients on SSRI.

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Problemi di psicoterapia

RUOLO TERAPEUTICO (IL) ◽

10.3280/rt2009-112006 ◽

2009 ◽

pp. 45-56

Author(s):

Paolo Migone

Keyword(s):

Clinical Trials ◽

Serotonin Reuptake ◽

Selective Serotonin Reuptake Inhibitors ◽

Randomized Clinical Trials ◽

Interpersonal Relationship ◽

Depression Scale ◽

Serotonin Reuptake Inhibitors ◽

Selective Serotonin ◽

Hamilton Depression Scale ◽

Significant Difference

- Kirsch et al. (2002) studied all 47 randomized clinical trials (RCT) submitted by pharmaceutical companies to the U.S. Food and Drug Administration (FDA) for approval of the six most prescribed Selective Serotonin Reuptake Inhibitors (SSRI) antidepressants. The mean difference between drug and placebo was less than 2 points on the 21-item (62- point) Hamilton Depression Scale (which is the version used in many of the these RTCs). This superiority to placebo, although statistically significant, was not clinically significant. Furthermore, 57% of the trials funded by the pharmaceutical industry failed to show a significant difference between drug and placebo. Most of these negative data were not published and were accessible only thanks to the Freedom of Information Act. Also other studies confirming this research (Whittington et al., 2004; Moncrieff & Hardy, 2007; Turner et al., 2008) are presented. These data are discussed in light of the wider problem of the roles of interpersonal relationship in psychiatric practice.KEY WORDS: antidepressants drugs, Selective Serotonin Reuptake Inhibitors (SSRI), placebo, Kirsch, Randomized Clinical Trials (RCT)]

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Therapeutic efficacy of duloxetine versus selective serotonin reuptake inhibitors in irritable bowel syndrome

European Psychiatry ◽

10.1016/s0924-9338(11)72996-0 ◽

2011 ◽

Vol 26 (S2) ◽

pp. 1291-1291

Author(s):

D. Vasile ◽

O. Vasiliu ◽

C. Tudor ◽

V. Bogdan ◽

A.G. Mangalagiu ◽

...

Keyword(s):

Irritable Bowel Syndrome ◽

Serotonin Reuptake ◽

Selective Serotonin Reuptake Inhibitors ◽

Rating Scale ◽

Gastrointestinal Symptoms ◽

Serotonin Reuptake Inhibitors ◽

Selective Serotonin ◽

Affective Symptoms ◽

Significant Difference ◽

Irritable Bowel

IntroductionSelective serotonin reuptake inhibitors (SSRIs) are frequently used for irritable bowel syndrome, while duloxetine was evaluated in other similar psycho-somatic syndromes.ObjectiveThis prospective, single-blind trial intends to compare the efficacy of SSRIs and duloxetine in the treatment of irritable bowel syndrome.MethodsA group of 22 patients, 15 female and 7 male, mean age 50.2, diagnosed with irritable bowel syndrome according to the Rome II Diagnostic Criteria (1992) were treated with either an SSRI (escitalopram 20 mg/day, n = 6 or fluoxetine 40 mg/day, n = 6) or duloxetine (90 mg/day, n = 10). Patients were evaluated initially and every 4 weeks, for 6 months, using Hamilton Anxiety Rating Scale (HAMA), Hamilton Depression Rating Scale 17 items version (HAMD), Clinical Global Impressions -Severity/Improvement (CGI-I/S) and a 7-points Likert scale (LS) for self-evaluated severity.ResultsDuloxetine improved anxiety and depressive symptoms, as reflected by the significant decrease of HAMA (−17.6 points, p < 0.05) and HAMD scores (−18.2 points, p < 0.05) at week 12. SSRIs also reduced the affective symptoms, significantly to baseline (p < 0.05), but less than duloxetine (−14.3, −15.2) at week 12, with no significant difference at week 24 (p = 0.120). The CGI-I results paralleled the decrease of HAMD and HAMA, while the LS evaluation of gastrointestinal symptoms improved similarly in both groups, with no significant difference (p = 0.09).ConclusionDuloxetine is an efficient agent in the treatment of irritable bowel syndrome, because it decreases the mood symptoms more rapidly than SSRIs. The overall efficacy of SSRIs and duloxetine at 6 months is nevertheless similar.

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Trends in the use of antidepressants among older adults: Bambuí Project

Revista de Saúde Pública ◽

10.1590/s0034-8910.2014048005406 ◽

2014 ◽

Vol 48 (6) ◽

pp. 857-865 ◽

Cited By ~ 4

Author(s):

Antônio Ignácio de Loyola Filho ◽

Érico Castro-Costa ◽

Josélia Oliveira Araújo Firmo ◽

Sérgio Viana Peixoto

Keyword(s):

Older Adults ◽

Serotonin Reuptake ◽

Selective Serotonin Reuptake Inhibitors ◽

Family Income ◽

Population Based ◽

Serotonin Reuptake Inhibitors ◽

Selective Serotonin ◽

International Studies ◽

Significant Difference ◽

Antidepressant Use

OBJECTIVE To analyze the trends and factors associated with the antidepressant use among older adults. METHODS This population-based study evaluated older adults in 1997 (n = 351, baseline) and the survivors at the 15th follow-up year (n = 462, in 2012) among the aging cohort of Bambuí. The prevalence of antidepressant use was estimated, and the most commonly used antidepressants each year were identified. Prevalence ratios with 95% confidence intervals were estimated using Poisson regression with robust variance to investigate differences in the prevalence of use between 1997 and 2012. RESULTS The overall consumption of antidepressants (PR = 2.87, 95%CI 1.94;4.25) and of selective serotonin reuptake inhibitors (PR = 7.50, 95%CI 3.74;15.02) was significantly higher in 2012. However, no significant difference was observed in the use of tricyclic antidepressants between the two cohorts (PR = 0.89, 95%CI 0.49;1.62). In the 2012 cohort, antidepressant use was associated with females, increased age, increased income (≥ 4 minimum wages), self-assessment of health as reasonable, and attending ≥ 5 medical consultations in the last 12 months. CONCLUSIONS The increased consumption of antidepressants in the period due to increased use of selective serotonin reuptake inhibitors was consistent with results observed in international studies of different population groups and contexts. The positive correlation observed between antidepressant use and family income may be a warning of possible inequalities in access to mental health services.

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Efficacy of the Addition of Celecoxib to Selective Serotonin Reuptake Inhibitors in Treating Obsessive–Compulsive Disorder: A Double-Blind Clinical Trial Study

Basic and Clinical Neuroscience Journal ◽

10.32598/bcn.2021.1998.1 ◽

2021 ◽

Author(s):

Najmeh Shahini ◽

◽

Ali Talaei ◽

Mohammadreza Shalbafan ◽

Farhad Faridhosseini ◽

...

Keyword(s):

Obsessive Compulsive Disorder ◽

Serotonin Reuptake ◽

Selective Serotonin Reuptake Inhibitors ◽

Serotonin Reuptake Inhibitors ◽

Cyclooxygenase Inhibitors ◽

Selective Serotonin ◽

Control Group ◽

Obsessive Compulsive ◽

Compulsive Disorder ◽

Significant Difference

Purpose of the Study: Inflammatory processes in the brain play an important role in etiopathogenesis of Obsessive-Compulsive Disorder (OCD). Cyclooxygenase inhibitors such as celecoxib reduce the production of proinflammatory cytokines. This triple-blind study aimed to investigate the efficacy of the addition of Celecoxib to selective serotonin reuptake inhibitors in treating Obsessive–Compulsive Disorder (OCD) Ther Methods: Sixty patients who met the diagnostic and statistical manual of mental disorders criteria –fourth edition (DSM-IV) were recruited in the study for OCD screening by two psychiatrists to participate in the trial. The participants included 23 patients who received SSRIs and celecoxib (400 mg twice daily) and 22 patients in the control group that received SSRIs and placebo. At the beginning of the study, in weeks four, eight and 12, the patients were assessed by a psychiatrist using the Yale-Brown Obsessive Compulsive Scale (Y-BCOS). The Results: A significant difference was observed in the change of scores on the Yale–Brown Obsessive–Compulsive Scale (Y-BOCS) in week 12 compared with the onset of the study in two groups (t:-8.976, df:38, P:0.001). There was a significant difference between two groups in obsession (F:49.19, df:1, P≤0.001) and compulsion (F:13.78, df:1, P:0.001), and in obsessive compulsive disorder (F:57.25, df:1, P≤0.001) which was higher in Celecoxib group. The Conclusion: This study showed that adjuvant treatment with celecoxib can treat symptoms of OCD under treatment with SSRIs.

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Addition of benzodiazepines to selective serotonin reuptake inhibitors to optimize treatment of depression: a hospital based study

International Journal of Research in Medical Sciences ◽

10.18203/2320-6012.ijrms20182293 ◽

2018 ◽

Vol 6 (6) ◽

pp. 2081

Author(s):

S. A. Dar ◽

B. A. Bhat ◽

M. M. Jan

Keyword(s):

Depressive Symptoms ◽

Serotonin Reuptake ◽

Sleep Disturbances ◽

Selective Serotonin Reuptake Inhibitors ◽

Group Versus ◽

Serotonin Reuptake Inhibitors ◽

Selective Serotonin ◽

Open Label ◽

Onset Of Action ◽

Significant Difference

Background: Selective serotonin reuptake inhibitors ameliorate depression and anxiety slowly and in fact increase anxiety or insomnia initially. Addition of clonazepam to escitalopram improves response: thereby improving symptoms associated with depression, reducing side-effects and alleviating core depressive symptoms. The aim of study was to assess the benefits of adding benzodiazepines in management of depression.Methods: It was an open label prospective study of 8 weeks of escitalopram group versus escitalopram with benzodiazepine group in moderate to severe depression. 51 subjects who gave written informed consent and were fulfilling the inclusion and exclusion criteria were included in the study and grouped into escitalopram alone or escitalopram with benzodiazepines.Results: In the present study nearly 60% of the patients were prescribed clonazepam. Though combined group with benzodiazepines had faster onset of action in controlling depressive symptoms than escitalopram group alone at 4 weeks of treatment, there was no significant difference in the pattern of reduction of MADRS score in both the groups at 8 weeks of follow up.Conclusions: Augmenting benzodiazepines to antidepressants are more effective in management of depression associated anxiety and sleep disturbances initially till SSRIs start action.

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The role of selective serotonin reuptake inhibitors in preventing relapse of major depressive disorder

Therapeutic Advances in Psychopharmacology ◽

10.1177/2045125317737264 ◽

2017 ◽

Vol 8 (1) ◽

pp. 49-58 ◽

Cited By ~ 15

Author(s):

Steven S. Clevenger ◽

Devvrat Malhotra ◽

Jonathan Dang ◽

Brigitte Vanle ◽

Waguih William IsHak

Keyword(s):

Major Depressive Disorder ◽

Side Effects ◽

Depressive Disorder ◽

Serotonin Reuptake ◽

Selective Serotonin Reuptake Inhibitors ◽

Serotonin Reuptake Inhibitors ◽

Selective Serotonin ◽

Major Depressive ◽

Significant Difference ◽

Atypical Antidepressants

The objective of this review was to evaluate the efficacy of selective serotonin reuptake inhibitors (SSRIs) and SSRIs compared with other treatment modalities in preventing relapse after an episode of major depressive disorder (MDD). An Ovid MEDLINE and PsycINFO search (from 1987 to August 2017) was conducted using the following terms: selective serotonin reuptake inhibitors, antidepressants, depression, prevention, prophylaxis, relapse and MDD. Using predefined criteria, two authors independently selected and reached consensus on the included studies. Sixteen articles met the criteria: 10 compared the relapse rate of selective SSRIs with placebo or other SSRIs; one discussed the effectiveness of SSRIs plus psychotherapy, two compared SSRI versus tricyclic antidepressants (TCAs), two were mainly composed of TCAs plus psychotherapy, and one compared SSRIs and serotonin norepinephrine reuptake inhibitors (SNRIs). According to the included studies, the relapse risk in adults was lower when SSRIs were combined with psychotherapy. Results comparing SSRIs and SNRIs were inconclusive. TCAs may be equally as effective as SSRIs. Atypical antidepressants (mirtazapine and St John’s Wort) had no significant difference in efficacy and remission rates compared with SSRIs. Escitalopram appeared to fare better in efficacy than other SSRIs, owing to a higher prophylactic efficacy and lower side effects; however, according to the current data, this difference was not significant. To conclude, this review provides evidence that continuing SSRIs for 1 year reduces risk of MDD and relapse. Furthermore, the combination of SSRIs and cognitive behavioural therapy may effectively reduce relapse. Escitalopram appeared to yield better results and fewer side effects than did other SSRIs or SNRIs. The effectiveness in reducing relapse of SSRIs was similar to that of TCAs and atypical antidepressants.

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