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The Cochrane Database of Systematic... Jul 2012Recent US and UK clinical practice guidelines recommend that second-generation antidepressants should be considered amongst the best first-line options when drug therapy... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Recent US and UK clinical practice guidelines recommend that second-generation antidepressants should be considered amongst the best first-line options when drug therapy is indicated for a depressive episode. Systematic reviews have already highlighted some differences in efficacy between second-generation antidepressants. Citalopram, one of the first selective serotonin reuptake inhibitors (SSRI) introduced in the market, is one of these antidepressant drugs that clinicians use for routine depression care.
OBJECTIVES
To assess the evidence for the efficacy, acceptability and tolerability of citalopram in comparison with tricyclics, heterocyclics, other SSRIs and other conventional and non-conventional antidepressants in the acute-phase treatment of major depression.
SEARCH METHODS
We searched The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register and the Cochrane Central Register of Controlled Trials up to February 2012. No language restriction was applied. We contacted pharmaceutical companies and experts in this field for supplemental data.
SELECTION CRITERIA
Randomised controlled trials allocating patients with major depression to citalopram versus any other antidepressants.
DATA COLLECTION AND ANALYSIS
Two reviewers independently extracted data. Information extracted included study characteristics, participant characteristics, intervention details and outcome measures in terms of efficacy (the number of patients who responded or remitted), patient acceptability (the number of patients who failed to complete the study) and tolerability (side-effects).
MAIN RESULTS
Thirty-seven trials compared citalopram with other antidepressants (such as tricyclics, heterocyclics, SSRIs and other antidepressants, either conventional ones, such as mirtazapine, venlafaxine and reboxetine, or non-conventional, like hypericum). Citalopram was shown to be significantly less effective than escitalopram in achieving acute response (odds ratio (OR) 1.47, 95% confidence interval (CI) 1.08 to 2.02), but more effective than paroxetine (OR 0.65, 95% CI 0.44 to 0.96) and reboxetine (OR 0.63, 95% CI 0.43 to 0.91). Significantly fewer patients allocated to citalopram withdrew from trials due to adverse events compared with patients allocated to tricyclics (OR 0.54, 95% CI 0.38 to 0.78) and fewer patients allocated to citalopram reported at least one side effect than reboxetine or venlafaxine (OR 0.64, 95% CI 0.42 to 0.97 and OR 0.46, 95% CI 0.24 to 0.88, respectively).
AUTHORS' CONCLUSIONS
Some statistically significant differences between citalopram and other antidepressants for the acute phase treatment of major depression were found in terms of efficacy, tolerability and acceptability. Citalopram was more efficacious than paroxetine and reboxetine and more acceptable than tricyclics, reboxetine and venlafaxine, however, it seemed to be less efficacious than escitalopram. As with most systematic reviews in psychopharmacology, the potential for overestimation of treatment effect due to sponsorship bias and publication bias should be borne in mind when interpreting review findings. Economic analyses were not reported in the included studies, however, cost effectiveness information is needed in the field of antidepressant trials.
Topics: Antidepressive Agents; Antidepressive Agents, Second-Generation; Citalopram; Cyclohexanols; Depression; Humans; Morpholines; Paroxetine; Reboxetine; Selective Serotonin Reuptake Inhibitors; Venlafaxine Hydrochloride
PubMed: 22786497
DOI: 10.1002/14651858.CD006534.pub2 -
Journal of Clinical Sleep Medicine :... Jul 2020Sexsomnia is a parasomnia consisting of sexual behavior during non-rapid eye movement sleep. To date, there have been 116 clinical cases of sexsomnia reported and most...
Sexsomnia is a parasomnia consisting of sexual behavior during non-rapid eye movement sleep. To date, there have been 116 clinical cases of sexsomnia reported and most were treated with clonazepam. We present a case of an adult male with sexsomnia that started during his college days. He presented to us because of problems in his current marriage arising from sexual behavior during sleep. Polysomnography revealed no significant sleep-disordered breathing, electroencephalography abnormality, or abnormal movement during non-rapid eye movement and rapid eye movement (REM) sleep. Alcohol consumption was reported to worsen his sexsomnia. To avoid the neuro-depressant effects of benzodiazepines, paroxetine was administered and resulted in complete resolution of sexsomnia.
Topics: Adult; Humans; Male; Parasomnias; Paroxetine; Polysomnography; Sleep; Sleep Apnea Syndromes
PubMed: 32672534
DOI: 10.5664/jcsm.8478 -
Journal of Neurochemistry Sep 2022Selective serotonin reuptake inhibitor (SSRI) antidepressants are commonly prescribed treatments for depression, but their effects on serotonin reuptake and release are...
Selective serotonin reuptake inhibitor (SSRI) antidepressants are commonly prescribed treatments for depression, but their effects on serotonin reuptake and release are not well understood. Drosophila melanogaster, the fruit fly, expresses the serotonin transporter (dSERT), the major target of SSRIs, but real-time serotonin changes after SSRIs have not been characterized in this model. The goal of this study was to characterize effects of SSRIs on serotonin concentration and reuptake in Drosophila larvae. We applied various doses (0.1-100 μM) of fluoxetine (Prozac), escitalopram (Lexapro), citalopram (Celexa), and paroxetine (Paxil), to ventral nerve cord (VNC) tissue and measured optogenetically-stimulated serotonin release with fast-scan cyclic voltammetry (FSCV). Fluoxetine increased reuptake from 1 to 100 μM, but serotonin concentration only increased at 100 μM. Thus, fluoxetine occupies dSERT and slows clearance but does not affect concentration. Escitalopram and paroxetine increased serotonin concentrations at all doses, but escitalopram increased reuptake more. Citalopram showed lower concentration changes and faster reuptake profiles compared with escitalopram, so the racemic mixture of citalopram does not change reuptake as much as the S-isomer. Dose response curves were constructed to compare dSERT affinities and paroxetine showed the highest affinity and fluoxetine the lowest. These data demonstrate SSRI mechanisms are complex, with separate effects on reuptake or release. Furthermore, dynamic serotonin changes in Drosophila are similar to previous studies in mammals. This work establishes how antidepressants affect serotonin in real-time, which is useful for future studies that will investigate pharmacological effects of SSRIs with different genetic mutations in Drosophila.
Topics: Animals; Antidepressive Agents; Citalopram; Drosophila; Drosophila melanogaster; Fluoxetine; Mammals; Paroxetine; Serotonin; Selective Serotonin Reuptake Inhibitors
PubMed: 35736504
DOI: 10.1111/jnc.15658 -
Biological Psychiatry Mar 1995
Topics: Akathisia, Drug-Induced; Clonazepam; Depressive Disorder; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Humans; Male; Middle Aged; Neurologic Examination; Paroxetine; Propranolol
PubMed: 7748986
DOI: 10.1016/0006-3223(94)00158-Y -
The Cochrane Database of Systematic... Feb 2011Depression is a common problem in patients with multiple sclerosis (MS). It is unclear which pharmacologic treatment is the most effective and the least harmful. (Review)
Review
BACKGROUND
Depression is a common problem in patients with multiple sclerosis (MS). It is unclear which pharmacologic treatment is the most effective and the least harmful.
OBJECTIVES
To investigate the efficacy and tolerability of pharmacologic treatments for depression in patients with MS.
SEARCH STRATEGY
We searched the Cochrane Multiple Sclerosis Group's Trials Register (June 2010), reference lists of relevant articles and conference proceedings. Regulatory agencies were used as additional sources of information on adverse effects.
SELECTION CRITERIA
Adequately and quasi-randomized controlled blinded or unblinded trials in children and adults with MS.
EXPERIMENTAL INTERVENTION
pharmacologic treatments for depression without restrictions regarding dose, route of administration, frequency, or duration. Control intervention: placebo treatment or no treatment.
DATA COLLECTION AND ANALYSIS
Two teams of reviewers independently assessed trial quality and extracted data. We contacted study authors for additional information. We collected adverse effects from the trials.Information about study population, type of intervention, outcome measures, and study design were extracted from the selected studies. Trial quality was evaluated with the criteria: randomization, allocation concealment, blinding, handling of incomplete outcome data, freedom from selective reporting and freedom from other bias.The impact of missing data on the study results was explored with sensitivity analyses comparing the results from the analyses of study completers with those from best- and worst-case scenarios.
MAIN RESULTS
Two trials (70 participants) were included. One trial (28 participants) compared treatment with desipramine for five weeks to placebo. The other trial (42 participants) compared treatment with paroxetine for twelve weeks to placebo. Both trials had a significant number of patients lost to follow-up or with missing outcome measurements.There was a trend towards efficacy of both treatments compared to placebo, but this difference was not statistically significant except for one outcome. Confidence intervals were wide in all analyses and our sensitivity analysis showed that the missing data may have had an important effect in both trials, with large differences between best-case and worst-case scenarios for all assessed outcomes.Both treatments were associated with adverse effects, with significantly more patients treated with paroxetine suffering from nausea or headache. Given the difference in trial duration and type of drug, we decided not to perform a meta-analysis.
AUTHORS' CONCLUSIONS
Both desipramine and paroxetine show a trend towards efficacy in depression in MS the short term, but both treatments were associated with adverse effects, with significantly more patients treated with paroxetine suffering from nausea or headache. Further clinical research on the treatment of depression in MS is clearly needed. Future trials should address the efficacy and tolerability in the long term and compare antidepressant treatments head-to-head.
Topics: Adult; Antidepressive Agents; Depression; Desipramine; Humans; Multiple Sclerosis; Paroxetine; Randomized Controlled Trials as Topic
PubMed: 21328292
DOI: 10.1002/14651858.CD007295.pub2 -
The Journal of Steroid Biochemistry and... Dec 2019Serotonin reuptake inhibitors (SRIs) are currently the main molecules prescribed to pregnant women that suffer from depression. Placental cells are exposed to SRIs via...
Serotonin reuptake inhibitors (SRIs) are currently the main molecules prescribed to pregnant women that suffer from depression. Placental cells are exposed to SRIs via maternal blood, and we have previously shown that SRIs alter feto-placental steroidogenesis in an in vitro co-culture model. More specifically, serotonin (5-HT) regulates the estrogen biosynthetic enzyme aromatase (cytochrome P450 19; CYP19), which is disrupted by fluoxetine and its active metabolite norfluoxetine in BeWo choriocarcinoma cells. Based on molecular simulations, the present study illustrates that the SRIs fluoxetine, norfluoxetine, paroxetine, sertraline, citalopram and venlafaxine exhibit binding affinity for the active-site pocket of CYP19, suggesting potential competitive inhibition. Using BeWo cells and primary villous trophoblast cells isolated from normal term placentas, we compared the effects of the SRIs on CYP19 activity. We observed that paroxetine and sertraline induce aromatase activity in BeWo cells, while venlafaxine, fluoxetine, paroxetine and sertraline decrease aromatase activity in primary villous trophoblast. The effects of paroxetine and sertraline in primary villous trophoblasts were observed at the lower doses tested. We also showed that 5-HT and the 5-HT receptor agonist 2,5-dimethoxy-4-iodoamphetamine (DOI) induced CYP19 activity. An increase in phosphorylation of serine and tyrosine and a decrease in threonine phosphorylation of CYP19 was also associated with DOI treatment. Our results contribute to better understanding how 5-HT and SRIs interact with CYP19 and may affect estrogen production. Moreover, this study suggests that alteration of placental 5-HT levels due to depression and/or SRI treatment during pregnancy may be associated with disruption of placental estrogen production.
Topics: Aromatase; Cells, Cultured; Citalopram; Female; Fluoxetine; Humans; Molecular Docking Simulation; Paroxetine; Placenta; Pregnancy; Serotonin; Selective Serotonin Reuptake Inhibitors; Sertraline; Trophoblasts; Venlafaxine Hydrochloride
PubMed: 31509772
DOI: 10.1016/j.jsbmb.2019.105470 -
ELife Jul 2020Antidepressants target the serotonin transporter (SERT) by inhibiting serotonin reuptake. Structural and biochemical studies aiming to understand binding of...
Antidepressants target the serotonin transporter (SERT) by inhibiting serotonin reuptake. Structural and biochemical studies aiming to understand binding of small-molecules to conformationally dynamic transporters like SERT often require thermostabilizing mutations and antibodies to stabilize a specific conformation, leading to questions about relationships of these structures to the bonafide conformation and inhibitor binding poses of wild-type transporter. To address these concerns, we determined the structures of ∆N72/∆C13 and ts2-inactive SERT bound to paroxetine analogues using single-particle cryo-EM and x-ray crystallography, respectively. We synthesized enantiopure analogues of paroxetine containing either bromine or iodine instead of fluorine. We exploited the anomalous scattering of bromine and iodine to define the pose of these inhibitors and investigated inhibitor binding to Asn177 mutants of ts2-active SERT. These studies provide mutually consistent insights into how paroxetine and its analogues bind to the central substrate-binding site of SERT, stabilize the outward-open conformation, and inhibit serotonin transport.
Topics: Cryoelectron Microscopy; Crystallography, X-Ray; Humans; Molecular Structure; Paroxetine; Protein Structure, Tertiary; Serotonin; Serotonin Plasma Membrane Transport Proteins; Selective Serotonin Reuptake Inhibitors
PubMed: 32618269
DOI: 10.7554/eLife.56427 -
Ugeskrift For Laeger Apr 2022Treatment with SSRI have a high frequency of treatment of emergent sexual dysfunction. The mechanism is thought to be through serotoninergic inhibition of the sexual... (Review)
Review
Treatment with SSRI have a high frequency of treatment of emergent sexual dysfunction. The mechanism is thought to be through serotoninergic inhibition of the sexual response. More than 70% of patients treated with sertraline, citalopram or paroxetine experience sexual side effects, while escitalopram and fluvoxamine yield the lowest degree of sexual dysfunction within the group. This review suggests management strategies including dose reduction, change of medication and add-on treatment. A small group of patients experience post-SSRI dysfunction, in which sexual dysfunction persists after treatment termination.
Topics: Citalopram; Humans; Paroxetine; Selective Serotonin Reuptake Inhibitors; Sertraline; Sexual Dysfunction, Physiological
PubMed: 35410653
DOI: No ID Found -
The International Journal of... Apr 2022Venlafaxine is a dual serotonin (5-HT) and norepinephrine reuptake inhibitor. The specific dose at which it begins to efficiently engage the norepinephrine transporter...
BACKGROUND
Venlafaxine is a dual serotonin (5-HT) and norepinephrine reuptake inhibitor. The specific dose at which it begins to efficiently engage the norepinephrine transporter (NET) remained to be determined. Paroxetine is generally considered as a selective 5-HT reuptake inhibitor but exhibits some affinity for NET. Atomoxetine is a NET inhibitor but also has some affinity for the 5-HT reuptake transporter (SERT).
METHODS
This study examined the effects of forced titration of venlafaxine from 75 to 300 mg/d, paroxetine from 20 to 50 mg/d, or atomoxetine from 25 to 80 mg/d in 32 patients with major depressive disorder. Inhibition of SERT was estimated using the depletion of whole-blood 5-HT. Inhibition of NET was assessed using the attenuation of the systolic blood pressure produced by i.v. injections of tyramine.
RESULTS
All 3 medications significantly reduced 5-HT levels at the initiating regimens: venlafaxine and paroxetine by approximately 60% and atomoxetine by 16%. The 3 subsequent regimens of venlafaxine and paroxetine reduced 5-HT levels by over 90%, but the highest dose of atomoxetine only reached a 40% inhibition. Atomoxetine dose dependently inhibited the tyramine pressor response from the lowest dose, venlafaxine from 225 mg/d, and paroxetine left it unaltered throughout.
CONCLUSION
These results confirm that venlafaxine and paroxetine are potent SERT inhibitors over their usual therapeutic range but that venlafaxine starts inhibiting NET only at 225 mg/d, whereas paroxetine remains selective for SERT up to 50 mg/d. Atomoxetine dose dependently inhibits NET from a low dose but does not inhibit SERT to a clinically relevant degree.
Topics: Antidepressive Agents, Second-Generation; Atomoxetine Hydrochloride; Cyclohexanols; Depressive Disorder, Major; Humans; Norepinephrine; Norepinephrine Plasma Membrane Transport Proteins; Paroxetine; Serotonin; Selective Serotonin Reuptake Inhibitors; Tyramine; Venlafaxine Hydrochloride
PubMed: 34958348
DOI: 10.1093/ijnp/pyab086 -
Frontiers in Immunology 2023Up to 40 per cent of people with active inflammatory bowel disease (IBD) also suffer from mood disorders such as anxiety and depression. Notwithstanding, the fundamental...
BACKGROUND
Up to 40 per cent of people with active inflammatory bowel disease (IBD) also suffer from mood disorders such as anxiety and depression. Notwithstanding, the fundamental biological pathways driving depression in IBD remain unknown.
METHODS
We identified 33 core genes that drive depression in IBD patients and performed consensus molecular subtyping with the NMF algorithm in IBD. The CIBERSORT were employed to quantify the immune cells. Metabolic signature was characterized using the "IOBR" R package. The scoring system (D. score) based on PCA. Pre-clinical models are constructed using DSS.
RESULTS
Using transcriptome data from the GEO database of 630 IBD patients, we performed a thorough analysis of the correlation between IBD and depression in this research. Firstly, the samples were separated into two different molecular subtypes (D. cluster1 and D. cluster2) based on their biological signatures. Moreover, the immunological and metabolic differences between them were evaluated, and we discovered that D. cluster2 most closely resembled IBD patients concomitant with depression. We also developed a scoring system to assess the IBD-related depression and predict clinical response to anti-TNF- therapy, with a higher D. score suggesting more inflammation and worse reaction to biological therapies. Ultimately, we also identified through animal experiments an antidepressant, paroxetine, has the added benefit of lowering intestinal inflammation by controlling microorganisms in the digestive tract.
CONCLUSIONS
This study highlights that IBD patients with or without depression show significant variations and antidepressant paroxetine may help reduce intestinal inflammation.
Topics: Humans; Paroxetine; Depression; Tumor Necrosis Factor Inhibitors; Inflammatory Bowel Diseases; Anti-Inflammatory Agents; Antidepressive Agents; Inflammation
PubMed: 36923403
DOI: 10.3389/fimmu.2023.1145070