Selective Serotonin Reuptake Inhibitors In Depression Research Articles

A Study of Sexual Dysfunction and Quality of Life in Female Patients on Selective Serotonin Reuptake Inhibitor (SSRI)

Context: Sexual dysfunction is one of the most common and disconcerting side effect during treatment with Selective serotonin reuptake inhibitors (SSRIs). Sexual side effects from these medications have significant impact on self esteem, quality of life and can lead to non compliance and relapse in long term treatment. Aims: To study prevalence, severity of sexual dysfunction and its possible association with quality of life in female patients on treatment with SSRI for depression and anxiety. Materials and Methods: This was an observational, cross sectional, single-centre study. Hundred consecutive female patients who were sexually active, on SSRIs for six weeks or more were recruited. Diagnosis of Major depressive disorder (MDD), Anxiety disorders and female sexual dysfunction was done by clinician administered interview as per Diagnostic and Statistical Manual of mental disorders (DSM 5). The patients were further assessed for demographic details, CSFQ-F-C, HAM-D, HAM-A and WHOQOL-BREF scales for sexual dysfunction, depression, anxiety and quality of life respectively. p value of <0.05 was considered to be statistically significant. Results: Prevalence of sexual dysfunction was 84%. Patients with sexual dysfunction scored significantly lower value in social relationships (p= 0.0002) and environment (p= 0.033) domains of quality of life. Frequency of sexual dysfunction among patients on fluoxetine was 86.20%, on escitalopram was 86.76% and on sertraline was 66.6%. Frequency of sexual dysfunction was more with higher dose of SSRIs. Conclusions: Patients on various SSRIs experienced sexual dysfunction and had poor quality of life. Frequency of sexual dysfunction was more with higher doses of SSRIs. Keywords: Sexual dysfunction, Selective serotonin reuptake inhibitors, Depression, Anxiety, quality of life.

FRI477 The Effect Of Gestational Selective Serotonin Reuptake Inhibitor (SSRI) Treatment On Newborn Thyroid Screen

Abstract Disclosure: A. Brener: None. O. Raviv: None. E. Cohen-Sela: None. M. Yackobovitch-Gavan: None. S. Almashanu: None. R. Marom: None. L. Hiersch: None. Y. Lebenthal: None. Background: Clinical depression treated by selective serotonin reuptake inhibitors (SSRIs) has become relatively common in women of childbearing age. The effect of gestational exposure to SSRIs on the newborn’s hypothalamic-pituitary-thyroid postnatal adaptation has not yet been determined. We aimed to investigate the characteristics of the mother–infant dyad of term infants of mothers treated with SSRIs for depression during pregnancy. Methods: This observational study included mother-infant dyads of infants delivered at term in a single tertiary medical center between 2011 and 2021. Data on maternal, pregnancy, delivery, and perinatal characteristics of the mother-infant dyads were retrieved from the hospital’s electronic database. The clinical data were linked with the newborn thyroid screening results of total thyroxin (TT4) obtained at 48-72 hours since delivery. Excluded from analysis were mothers with other chronic medical conditions and newborns with genetic syndromes. Primary outcome measures were newborn TT4 levels and fetal growth as expressed by neonatal birthweight z-scores (WHO charts). Results: SSRI anti-depression treatment during gestation was reported in 2577 (2.4%) out of 106,173 infant-mother dyads. Mothers treated with SSRIs were older (35.0±4.8 vs 32.6±4.8 years, p<0.001), had a higher pre-pregnancy body mass index (23.4±4.5 vs 22.7±4.1, p<0.001) and a similar mean weight gain of 13 kg during pregnancy. Elective and emergent cesarean deliveries were more common among SSRI-treated mothers (14.8% vs 11.1% and 16.5% vs 8.6%, respectively, p<0.001). Infants of those mothers were born earlier (gestational age [GA] 38.7±1.9 vs 39.5±11.5 weeks, p<0.001), had lower birthweight z-scores (-0.48±1.24 vs -0.04±0.92, p<0.001) and lower TT4 levels (14.7±3.9 vs 15.0±3.7, p=0.001). A multivariate linear regression model revealed that sex, GA and birthweight z-score were highly significant contributors to TT4 levels (p<0.001 for all), while SSRI treatment during pregnancy was not (p=0.497). Conclusions: Our findings suggest that anti-depressant use of SSRIs during pregnancy does not have a direct effect on the postnatal adaptation of the hypothalamic-pituitary-thyroidal axis. However, differences in fetal growth and in characteristics of delivery may determine newborn thyroid function. Presentation: Friday, June 16, 2023

Serotonin-2B receptor antagonism increases the activity of dopamine and glutamate neurons in the presence of selective serotonin reuptake inhibition.

Previous research has implicated the serotonin-2B (5-HT2B) receptor as a possible contributor to the antidepressant-like response. Aripiprazole has been successfully used in combination with selective serotonin reuptake inhibitors (SSRIs) in treatment-resistant depression and it, among all receptors, exhibits the highest affinity for the 5-HT2B receptor. However, the potential contribution of such an antagonistic action on 5-HT2B receptors in the context of adjunct therapy is not known. In vivo electrophysiological recordings of ventral tegmental area (VTA) dopamine (DA) neurons, dorsal raphe nucleus (DRN) 5-HT neurons and pyramidal neurons in the medial prefrontal cortex (mPFC), and the hippocampus were conducted in anaesthetized Sprague-Dawley rats after the administration of 5-HT2B receptor ligands alone or in combination with the SSRI escitalopram. An escitalopram-induced decrease in DA, but not 5-HT firing activity, was rescued by 2-day co-administration of the selective 5-HT2B receptor antagonist LY266097. In the mPFC, 14-day escitalopram administration alone had no effect on pyramidal neuron firing and burst activity, whereas, aripiprazole administered alone or in combination with escitalopram for 14 days increased pyramidal neuron firing and burst activity. Likewise, the administration of LY266097 alone or its addition on the last 3 days of a 14-day escitalopram regimen increased pyramidal neuron firing and burst activity. These results indicated that 5-HT2B receptors play, at least in part, a role in this enhancement. In the hippocampus, 5-HT2B receptor activation by BW723c86 decreased escitalopram-induced inhibition of 5-HT reuptake, which was reversed by a 5-HT2B receptor antagonist. Altogether, these results put into evidence the possibility that 5-HT2B receptor blockade contributes to the therapeutic effect of aripiprazole addition to SSRIs in depression.

Randomised controlled trial of escitalopram for cervical dystonia with dystonic jerks/tremor

ObjectiveTrials for additional or alternative treatments for cervical dystonia (CD) are scarce since the introduction of botulinum neurotoxin (BoNT). We performed the first trial to investigate whether dystonic jerks/tremor in...

What is the Risk of Suicidality in Depressive Adult Patients Using SSRIs? A Meta-Analysis of RCTs

Introduction: Selective Serotonin Reuptake Inhibitors (SSRIs) are among the most commonly prescribed medications particularly for patients with depressive disorders. Concerns related to increase risk of suicidality associated with the use of SSRIs were raised since early 1990s. Recent studies show inconclusive and conflicting results about this association. Meta-analysis based on Randomized Controlled Trials (RCTs) in depressive disorders has not been done recently.Objective: To establish whether there is increased risk of suicidality with the use of SSRIs compared to placebo in the treatment of depressive disorders in adults.Method and design: Meta-analysis of Randomized Controlled Trials (RCTs).Data sources: I searched for relevant systematic reviews and RCTs in Medline and Cochrane library database. I checked reference lists of included trials. I included trials from Jan 2000 to September 2016.Selection criteria: Published systematic reviews of randomised controlled trials comparing SSRIs with placebo in adults diagnosed with a depressive disorder were eligible for inclusion.Data collection and analysis: One review author selected the trials, assessed their quality. I use random effect meta-analysis. I used Odds Ratio (OR) to summarize dichotomous outcomes.Results: In the 5 studies identified, 556 suicidal events were detected in 71628 patients treated with SSRI for depressive or other disorders. Pooled OR=0.97(95%CI 0.85-1.1).Conclusion: These findings support that there is no increased risk of suicidality in adult patients treated with SSRI for depression.

A meta-analysis on the efficacy and safety of St John's wort extract in depression therapy in comparison with selective serotonin reuptake inhibitors in adults.

ObjectiveThe aim of the study was to investigate the efficacy and safety of St John’s wort extract and selective serotonin reuptake inhibitors (SSRIs) in the treatment of depression.MethodsDatabases were searched for studies comparing efficacy and/or safety of St John’s wort extract with SSRIs in depression from 1966 to April 2015. Stata software was used for statistical analysis.ResultsTwenty-seven studies met the study entry criteria. A total of 3,126 patients with depression were included. St John’s wort extract did not differ from SSRIs in clinical response, remission, and mean reduction in Hamilton Rating Scale for Depression score. St John’s wort extract had a significantly lower rate of adverse events compared to SSRIs (summary relative risk: 0.77; 95% confidence interval: 0.70, 0.84, P=0.00) and had fewer withdrawals due to adverse events. St John’s wort extract had superior safety in the management of patients with depression.ConclusionBoth St John’s wort extract and SSRIs are effective in treating mild-to-moderate depression. St John’s wort extract is safer than SSRIs.

Kleptomania: Beyond serotonin

Sir, Kleptomania has been described as an inability to refrain from the urge to steal things for reasons other than personal use or financial gain. Decades of research show that both dopamine and serotonin are the primary neurotransmitters involved in the pathogenesis and management of kleptomania, respectively. Selective serotonin reuptake inhibitors (SSRIs) have been used as first-line agents for treating kleptomania. On the contrary, cases of kleptomania had been paradoxically induced in three adults who were started on SSRIs for depression.[1] A recent Indian paper also reports a similar manifestation while on fluvoxamine treatment for obsessive compulsive disorder.[2] Restlessness and impulsivity have been recognized as symptoms of behavioral activation during initiation of treatment with SSRIs. Emergence of kleptomania post SSRI treatment may be partly explained by the same phenomenon in which there could be effective depletion of synaptic serotonin post acute administration of SSRIs through serotonin-mediated action on its auto-receptor. While the role of serotonin is murky, the role of dopamine is increasingly getting clearer especially in neurological disorders. Kleptomania is seen as an emergent side effect of the use of dopamine agonists in Parkinson's disease (PD). Other impulse control disorders (ICDs) like pathological gambling, compulsive shopping, compulsive eating and hypersexuality have also been reported with the use of dopamine agonists. This phenomenon is explained by the overdose theory.[3] In PD, ventral striatal dopamine is preserved relative to dorsal striatal activity; thus, dopaminergic treatment titrated to alleviate motor dorsal striatal deficiencies may result in an “over-dosing” in ventral cortico-striatal cognitive and limbic pathways. And as such there is preliminary evidence for the benefit of atypical antipsychotics for treating impulse regulation disorders.[4] At the same time, serotonergic and dopaminergic systems are not mutually exclusive. Could an alteration in dopamine levels post SSRI initiation explain the emergence of kleptomania in rare cases? SSRIs are known to sensitize dopamine (D2) receptors.[5] On the other hand, could the apparent effectiveness of SSRIs in kleptomania be because of their dopaminergic modulation rather than their primary effect on the serotonergic system? Kleptomania shares certain distinct features with substance use disorders, unlike other impulse control disorders like intermittent explosive disorder. This possible association between the two has resulted in naltrexone being tried as a treatment strategy for kleptomania with favorable results.[6] Further supportive evidence can be obtained from the rare finding of new onset alcohol dependence linked to treatment with SSRI.[7] This intriguing phenomenon can be considered similar to the earlier mentioned reports of emergence of kleptomania after taking SSRIs. Probably the mechanism, although still speculative, may be similar in both phenomena. So along with the erstwhile serotonin and dopamine, treatment of kleptomania is further complicated with the involvement of opioid and glutamatergic system.[8] Kleptomania is often been found comorbid with other psychiatric disorders including depression, addiction and personality disorders. Various structural brain lesions have been associated with kleptomania including head trauma.[9] Decreased white matter microstructural integrity in the inferior frontal brain region has also been identified in patients with kleptomania.[10] Functional anatomy of impulse control disorders including kleptomania has recently been reviewed.[11] While medications that affect the serotonergic system have been most widely studied for the treatment of kleptomania, their clinical effects have been modest or inconsistent or even paradoxical. Medications that affect dopaminergic neurotransmission have received less research attention. Kleptomania is the final common manifestation of various underlying pathogenic mechanisms which calls for rationalization of treatment based on co-morbid symptoms and personality traits rather than blanket use of one agent. Extension of this suggestion to other impulse control disorders requires renewed research interest and further elaboration. Developments in neurobiology and pharmaco-genetics, coupled with newer pharmacological models involving the opioid and glutamate systems will surely further our understanding of the pathophysiology and pharmacotherapy of kleptomania.

The association of serotonin transporter genotypes and selective serotonin reuptake inhibitor (SSRI)‐associated sexual side effects: possible relationship to oral contraceptives

To study the relationship between functional variants in the serotonin transporter gene (SLC6A4) and selective serotonin reuptake inhibitor (SSRI)-associated sexual dysfunction. One hundred fifteen subjects aged 18-40 years and currently being treated with an SSRI for depression were assessed for clinical variables known to affect sexual well-being. SSRI-associated sexual difficulties were assessed with the Changes in Sexual Functioning Questionnaire (CSFQ). Subjects were subsequently genotyped for the SLC6A4 promoter region (5HTTLPR) insertion/deletion variant and a variable number of tandem repeats (VNTR) in the second intron. The 5HTTLPR insertion/deletion variant was associated with sexual dysfunction in this study sample [odds ratio (OR) = 2.7; 95% confidence interval (CI) 1.2, 6.4; p = 0.02]. The relationship between promoter genotypes and sexual well-being differed in males and females and was related to whether females were taking an oral contraceptive (OC) medication. Females with the ll genotype were nearly eight times more likely to be categorized as having sexual dysfunction if they were taking OCs, while no relationship was observed in those not taking OCs. These results suggest that a functional variant in the serotonin transporter gene is associated with sexual difficulties in persons taking an SSRI for depression. This relationship may differ by sex and be dependent on OC status in females.

The Effect of Modafinil on Self-Esteem in Spinal Cord Injury Patients: A Report of 2 Cases and Review of the Literature

Mukai A, Costa JL. The effect of modafinil on self-esteem in spinal cord injury patients: a report of 2 cases and review of the literature. We report on 2 cases of the effect of modafinil on the self-esteem of patients with spinal cord injury (SCI). The first patient was a 33-year-old man with history of polysubstance abuse and a C6 American Spinal Injury Association (ASIA) grade A injury, who presented for follow-up to the outpatient rehabilitation clinic for depression, decreased motivation, and lowered self-esteem. The patient had tried a selective serotonin reuptake inhibitor (SSRI) without success, and reported increasing social and legal stressors. Within 1 month of starting on modafinil, he reported increased self-esteem and motivation, as well as decreased self-consciousness. The second patient was a 36-year-old woman with history of depression and a T11 ASIA grade A injury. She tried various SSRIs for depression and adjustment issues before she was started on modafinil. She lost weight and became more assertive and less self-conscious within 1 month after starting on modafinil. These 2 cases suggest that modafinil should be studied as a therapeutic option for treating lowered self-esteem in patients with SCI.

Poster 223: The Effect of Modafinil on Self-Esteem in Patients With Spinal Cord Injury: A Report of 2 Cases

Setting: Outpatient rehabilitation clinic. Patients: A 33-year-old man with history of polysubstance abuse and a C6 American Spinal Injury Association (ASIA) grade A injury and a 36-year-old woman with history of depression and a T11 ASIA grade A injury. Case Descriptions: The first patient presented for follow-up to the outpatient rehabilitation clinic for depression, decreased motivation, and lowered self-esteem. The patient had tried a selective serotonin reuptake inhibitor (SSRI) without success and reported increasing social and legal stressors. His mood also negatively affected his rehabilitation efforts, and he began neglecting his self-catheterization regimen. The second patient had tried various SSRIs for depression and adjustment issues with only modest success. She was frustrated by the pace of her rehabilitation and complained of being a burden to her family. She also complained of weight gain and decreased self-esteem. Assessment/Results: The patients were started on modafinil, a medication used to treat narcolepsy, which has been shown to increase self-esteem in other patient populations. Within 1 month of starting on modafinil, the first patient reported increased self-esteem and motivation, as well as decreased self-consciousness. He was motivated enough to date and ask his employer for a raise. The second patient lost weight and became more assertive and less self-conscious within 1 month after starting on modafinil. Discussion: These are the first reported cases, to our knowledge, of successful use of modafinil in patients with spinal cord injury (SCI) and lowered self-esteem. Conclusions: These 2 cases suggest that modafinil should be studied as a therapeutic option for treating lowered self-esteem in patients with SCI.

Time course of the effects of the serotonin-selective reuptake inhibitor sertraline on central and peripheral serotonin neurochemistry in the rhesus monkey.

Fundamental questions remain regarding the actions of the selective serotonin reuptake inhibitors (SSRIs). To examine the time course of central and peripheral neurochemical effects of sertraline (SER) in non-human primates. SER (20 mg/kg, p.o.) or placebo were administered daily for 4 weeks to two groups of six young adult male rhesus monkeys. Both groups received placebo during a 3-week baseline lead-in period and for 6 weeks after discontinuation. Blood and cisternal cerebrospinal fluid (cCSF) samples were obtained on days -21, -14, -7, 0, +3, +7, +14, +21, +28, +35 and +70. In animals receiving SER, mean (+/-SD) levels of cCSF serotonin (5-HT) increased from 38.6+/-9.0 pg/ml at baseline to 128+/-46.4 pg/ml during treatment (paired t=4.17, P=0.014). Concentrations of cCSF 5-HT were 290% of baseline on day 0 (+3 h), ranged from 260% to 436% of baseline during treatment, and returned to baseline 7 days after discontinuation. Levels of cCSF 5-hydroxyindoleacetic acid declined to 51+/-2.0% of baseline by day +3 and remained at similarly reduced levels during treatment. Plasma drug levels and decrements in platelet 5-HT were similar to those seen in patients. SER rapidly and substantially increases cCSF levels of 5-HT in primates, the extent of elevation is relatively constant during prolonged administration, and values return to baseline shortly after discontinuation. The results suggest that response latency for SSRIs in depression is not due to gradually increasing brain extracellular fluid 5-HT levels and tend not to support theories that posit SSRI response latency as being due to autoreceptor desensitization, transporter downregulation, or drug accumulation.

Effectiveness of pindolol plus serotonin uptake inhibitors in depression: a meta-analysis of early and late outcomes from randomised controlled trials

Background: Contradictory results on the efficacy of pindolol associated with selective serotonin reuptake inhibitors (SSRIs) in depressive illness have been published and no former review has produced an overall figure of its efficacy.This study aims to review the efficacy and tolerability of pindolol plus SSRIs in depressive illness. Methods: A meta-analysis of randomised controlled trials (RCTs) comparing pindolol plus SSRIs with placebo plus SSRIs. Results: Nine RCTs met inclusion criteria. Outcome favoured pindolol at 2 weeks time (N=5; OR=2.8; 95% CI 1.4–5.7), but not at four to 6 weeks (N=7; OR=1.4; 95% CI 0.8–2.7). Results for early outcome studies were robust to sensitivity analysis. Nineteen more studies, averaging null results, would be needed to change the overall probability ( P=0.0001) to a non-significant figure. Conclusions: Pindolol seems to hasten the response to SSRIs in depression with a timing window circumscribed to the first weeks of treatment.

Review: venlafaxine is more effective than selective serotoninreuptake inhibitors for depression

Source Citation Smith D, Dempster C, Glanville J, Freemantle N, Anderson I. Efficacy and tolerability of venlafaxine compared with selective serotonin reuptake inhibitors and other antidepressants:...

Review: Venlafaxine is more effective than selective serotonin-reuptake inhibitors for depression

Review: Venlafaxine is more effective than selective serotonin-reuptake inhibitors for depression