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The Cochrane Database of Systematic... May 2017Approximately 20% of stroke patients experience clinically significant levels of anxiety at some point after stroke. Physicians can treat these patients with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Approximately 20% of stroke patients experience clinically significant levels of anxiety at some point after stroke. Physicians can treat these patients with antidepressants or other anxiety-reducing drugs, or both, or they can provide psychological therapy. This review looks at available evidence for these interventions. This is an update of the review first published in October 2011.
OBJECTIVES
The primary objective was to assess the effectiveness of pharmaceutical, psychological, complementary, or alternative therapeutic interventions in treating stroke patients with anxiety disorders or symptoms. The secondary objective was to identify whether any of these interventions for anxiety had an effect on quality of life, disability, depression, social participation, caregiver burden, or risk of death.
SEARCH METHODS
We searched the trials register of the Cochrane Stroke Group (January 2017). We also searched the Cochrane Central Register of Controlled Trials (CENTRAL; the Cochrane Library; 2017, Issue 1: searched January 2017); MEDLINE (1966 to January 2017) in Ovid; Embase (1980 to January 2017) in Ovid; the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1937 to January 2017) in EBSCO; and PsycINFO (1800 to January 2017) in Ovid. We conducted backward citation searches of reviews identified through database searches and forward citation searches of included studies. We contacted researchers known to be involved in related trials, and we searched clinical trials registers for ongoing studies.
SELECTION CRITERIA
We included randomised trials including participants with a diagnosis of both stroke and anxiety for which treatment was intended to reduce anxiety. Two review authors independently screened and selected titles and abstracts for inclusion.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data and assessed risk of bias. We performed a narrative review. We planned to do a meta-analysis but were unable to do so as included studies were not sufficiently comparable.
MAIN RESULTS
We included three trials (four interventions) involving 196 participants with stroke and co-morbid anxiety. One trial (described as a 'pilot study') randomised 21 community-dwelling stroke survivors to four-week use of a relaxation CD or to wait list control. This trial assessed anxiety using the Hospital Anxiety and Depression Scale and reported a reduction in anxiety at three months among participants who had used the relaxation CD (mean (standard deviation (SD) 6.9 (± 4.9) and 11.0 (± 3.9)), Cohen's d = 0.926, P value = 0.001; 19 participants analysed).The second trial randomised 81 participants with co-morbid anxiety and depression to paroxetine, paroxetine plus psychotherapy, or standard care. Mean levels of anxiety severity scores based on the Hamilton Anxiety Scale (HAM-A) at follow-up were 5.4 (SD ± 1.7), 3.8 (SD ± 1.8), and 12.8 (SD ± 1.9), respectively (P value < 0.01).The third trial randomised 94 stroke patients, also with co-morbid anxiety and depression, to receive buspirone hydrochloride or standard care. At follow-up, the mean levels of anxiety based on the HAM-A were 6.5 (SD ± 3.1) and 12.6 (SD ± 3.4) in the two groups, respectively, which represents a significant difference (P value < 0.01). Half of the participants receiving paroxetine experienced adverse events that included nausea, vomiting, or dizziness; however, only 14% of those receiving buspirone experienced nausea or palpitations. Trial authors provided no information about the duration of symptoms associated with adverse events. The trial of relaxation therapy reported no adverse events.The quality of the evidence was very low. Each study included a small number of participants, particularly the study of relaxation therapy. Studies of pharmacological agents presented details too limited to allow judgement of selection, performance, and detection bias and lack of placebo treatment in control groups. Although the study of relaxation therapy had allocated participants to treatment using an adequate method of randomisation, study recruitment methods might have introduced bias, and drop-outs in the intervention group may have influenced results.
AUTHORS' CONCLUSIONS
Evidence is insufficient to guide the treatment of anxiety after stroke. Further well-conducted randomised controlled trials (using placebo or attention controls) are required to assess pharmacological agents and psychological therapies.
Topics: Anti-Anxiety Agents; Antidepressive Agents; Anxiety; Buspirone; Depression; Humans; Middle Aged; Paroxetine; Pilot Projects; Psychotherapy; Randomized Controlled Trials as Topic; Relaxation Therapy; Stroke
PubMed: 28535332
DOI: 10.1002/14651858.CD008860.pub3 -
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 -
Psychopharmacology Nov 2023Non-invasive home cage monitoring is emerging as a valuable tool to assess the effects of experimental interventions on mouse behaviour. A field in which these...
RATIONALE
Non-invasive home cage monitoring is emerging as a valuable tool to assess the effects of experimental interventions on mouse behaviour. A field in which these techniques may prove useful is the study of repeated selective serotonin reuptake inhibitor (SSRI) treatment and discontinuation. SSRI discontinuation syndrome is an under-researched condition that includes the emergence of sleep disturbances following treatment cessation.
OBJECTIVES
We used passive infrared (PIR) monitoring to investigate changes in activity, sleep, and circadian rhythms during repeated treatment with the SSRI paroxetine and its discontinuation in mice.
METHODS
Male mice received paroxetine (10 mg/kg/day, s.c.) for 12 days, then were swapped to saline injections for a 13 day discontinuation period and compared to mice that received saline injections throughout. Mice were continuously tracked using the Continuous Open Mouse Phenotyping of Activity and Sleep Status (COMPASS) system.
RESULTS
Repeated paroxetine treatment reduced activity and increased behaviourally-defined sleep in the dark phase. These effects recovered to saline-control levels within 24 h of paroxetine cessation, yet there was also evidence of a lengthening of sleep bouts in the dark phase for up to a week following discontinuation.
CONCLUSIONS
This study provides the first example of how continuous non-invasive home cage monitoring can be used to detect objective behavioural changes in activity and sleep during and after drug treatment in mice. These data suggest that effects of paroxetine administration reversed soon after its discontinuation but identified an emergent change in sleep bout duration, which could be used as a biomarker in future preclinical studies to prevent or minimise SSRI discontinuation symptoms.
Topics: Male; Animals; Mice; Paroxetine; Selective Serotonin Reuptake Inhibitors; Sleep; Circadian Rhythm
PubMed: 37584734
DOI: 10.1007/s00213-023-06442-3 -
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 -
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 -
International Journal of Molecular... Dec 2023Pathological cardiac remodeling is associated with cardiovascular disease and can lead to heart failure. Nuclear factor-kappa B (NF-κB) is upregulated in the...
Cardioprotective Effects of the GRK2 Inhibitor Paroxetine on Isoproterenol-Induced Cardiac Remodeling by Modulating NF-κB Mediated Prohypertrophic and Profibrotic Gene Expression.
Pathological cardiac remodeling is associated with cardiovascular disease and can lead to heart failure. Nuclear factor-kappa B (NF-κB) is upregulated in the hypertrophic heart. Moreover, the expression of the G-protein-coupled receptor kinase 2 (GRK2) is increased and linked to the progression of heart failure. The inhibitory effects of paroxetine on GRK2 have been established. However, its protective effect on IκBα/NFκB signaling has not been elucidated. This study investigated the cardioprotective effect of paroxetine in an animal model of cardiac hypertrophy (CH), focusing on its effect on GRK2-mediated NF-κB-regulated expression of prohypertrophic and profibrotic genes. Wistar albino rats were administered normal saline, paroxetine, or fluoxetine, followed by isoproterenol to induce CH. The cardioprotective effects of the treatments were determined by assessing cardiac injury, inflammatory biomarker levels, histopathological changes, and hypertrophic and fibrotic genes in cardiomyocytes. Paroxetine pre-treatment significantly decreased the HW/BW ratio ( < 0.001), and the expression of prohypertrophic and profibrotic genes Troponin-I ( < 0.001), BNP ( < 0.01), ( < 0.001), hydroxyproline ( < 0.05), ( < 0.05), and ( < 0.01) as well as inflammatory markers. It also markedly decreased pIκBα, NFκB(p105) subunit expression ( < 0.05) and phosphorylation. The findings suggest that paroxetine prevents pathological cardiac remodeling by inhibiting the GRK2-mediated IκBα/NF-κB signaling pathway.
Topics: Rats; Animals; NF-kappa B; Paroxetine; NF-KappaB Inhibitor alpha; Isoproterenol; G-Protein-Coupled Receptor Kinase 2; Ventricular Remodeling; Myocytes, Cardiac; Cardiomegaly; Heart Failure; Rats, Wistar; Gene Expression
PubMed: 38139099
DOI: 10.3390/ijms242417270 -
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 -
British Journal of Clinical Pharmacology Aug 1999The primary aims of the study were to estimate the exposure of infants to paroxetine via breast milk and to determine the maternal milk:plasma ratio (M/P) of paroxetine.... (Clinical Trial)
Clinical Trial
AIMS
The primary aims of the study were to estimate the exposure of infants to paroxetine via breast milk and to determine the maternal milk:plasma ratio (M/P) of paroxetine. Secondary aims were to compare single point and area under the curve (AUC) estimates of M/P, to assess variability of M/P in fore and hind milk, and to compare the observed M/P with that predicted by a model.
METHODS
Two studies were performed. In one study, six nursing mothers who were being treated with paroxetine were studied over a 24 h dose interval at steady-state. The total amount of paroxetine in the milk was measured, which represented the 'dose' to the infant. The M/PAUC was calculated and compared with a predicted value. In the second study, four nursing mothers who were being treated with paroxetine, were studied at steady-state, around a normal infant feeding time. A single plasma sample and a prefeed milk sample were taken approximately 3 h after the morning dose of paroxetine, and a postfeed milk sample taken around 1 h later. The dose received by the infant was estimated from the average milk concentrations of the pre and postfeed samples using standard assumptions, and M/P calculated directly. Plasma concentrations of paroxetine were measured in 8 of the 10 infants in the two studies.
RESULTS
The mean dose of paroxetine received by the infants in the first study was 1.13% (range 0.5-1.7) of the weight adjusted maternal dose. The mean M/PAUC was 0.39 (range 0.32-0.51). The predicted M/P was 0.22. The mean dose of paroxetine received by the infants in the second study was 1.25% (range 0.38-2.24) of the weight adjusted maternal dose. The mean M/P was 0.96 (range 0.31-3.33) and did not differ between fore and hind milk. The drug was not detected in the plasma of seven of the infants studied and was detected but not quantifiable (<4 microg l-1 ) in one infant. No adverse effects were observed in any of the infants.
CONCLUSIONS
Measured M/P and estimated infant dose were similar in the two studies, although the range was wider for the single point study. Paroxetine can be considered 'safe' during breast feeding because the dose transferred to the infant is well below the recommended safety limit of 10% of the weight adjusted maternal dose, concentrations in the infants were generally undetectable, and no adverse effects were reported.
Topics: Adult; Antidepressive Agents, Second-Generation; Area Under Curve; Chromatography, High Pressure Liquid; Female; Humans; Infant; Infant, Newborn; Milk, Human; Models, Biological; Paroxetine
PubMed: 10417489
DOI: 10.1046/j.1365-2125.1999.00992.x -
Cellular Signalling Oct 2017β-adrenergic receptors (βAR) regulate numerous functions throughout the body, however G protein-coupled receptor kinase (GRK)-dependent desensitization of βAR has...
β-adrenergic receptors (βAR) regulate numerous functions throughout the body, however G protein-coupled receptor kinase (GRK)-dependent desensitization of βAR has long been recognized as a maladaptive process in the progression of various disease states. Thus, the development of small molecule inhibitors of GRKs for the study of these processes and as potential therapeutics has been at the forefront of recent research efforts. Via structural and biochemical analyses, the selective serotonin reuptake inhibitor (SSRI) paroxetine was identified as a GRK2 inhibitor that enhances βAR-dependent cardiomyocyte and cardiac contractility and reverses cardiac dysfunction and myocardial βAR expression in mouse models of heart failure. Despite these functional outcomes, consistent with diminished βAR desensitization, the proximal βAR signaling mechanisms sensitive to paroxetine have not been reported. In this study, we aimed to determine whether paroxetine prevents classic βAR desensitization-related signaling mechanisms at a molecular level. Therefore, via immunoblotting, radioligand binding, fluorescence resonance energy transfer (FRET) and microscopy assays, we have performed an assessment of the effect of paroxetine on proximal βAR signaling responses. Indeed, paroxetine treatment inhibited ligand-induced β2AR phosphorylation in a concentration-dependent manner. Additionally, for both β1AR and β2AR, paroxetine decreased ligand-induced βarrestin2 recruitment and subsequent receptor internalization. Thus, paroxetine inhibits βAR desensitization mechanisms consistent with GRK2 inhibition and provides a useful pharmacological tool for studying these proximal GPCR signaling responses.
Topics: Adrenergic beta-Agonists; Cell Line; Endocytosis; Humans; Paroxetine; Phosphorylation; Receptors, Adrenergic, beta; Signal Transduction; beta-Arrestin 2
PubMed: 28711716
DOI: 10.1016/j.cellsig.2017.07.006 -
International Journal of Environmental... Nov 2022Paroxetine is a common pharmaceutical to treat depression and has been found to pose threats to aquatic organisms. However, little is known about the effects of...
Paroxetine is a common pharmaceutical to treat depression and has been found to pose threats to aquatic organisms. However, little is known about the effects of paroxetine on the nutrient cycle in aquatic environments. Therefore, DNA metabarcoding is used in this study to analyze the effects of paroxetine on multi-trophic microorganisms and nitrogen transformation in river sediments. Although paroxetine has no significant effect on the diversity of microbenthos, changes in benthic nitrogen-converting bacteria are consistent with the change in the various forms of nitrogen in the sediment, indicating that paroxetine affects the nitrogen conversion process by affecting nitrogen-converting bacteria. In addition, it is found that paroxetine has the ability to influence nitrogen transformation in an indirect way by affecting the trophic transfer efficiency of higher trophic levels (meiofauna and protozoa, protozoa and protozoa), subsequently affecting the growth of nitrogen-converting bacteria through a top-down mechanism (i.e., predation).The results show that paroxetine affects nitrogen transformation directly by affecting nitrogen-converting bacteria and indirectly through top-down effects, emphasizing that the assessment of paroxetine's ecological risks should consider species within different trophic levels.
Topics: Food Chain; Rivers; Nitrogen; Paroxetine; Aquatic Organisms; Bacteria; Geologic Sediments; Ecosystem
PubMed: 36361481
DOI: 10.3390/ijerph192114602