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Drugs & Aging 1993Paroxetine is a selective serotonin reuptake inhibitor effective in a once-daily administration regimen in the treatment of depression. In elderly patients (aged > or =... (Comparative Study)
Comparative Study Review
Paroxetine is a selective serotonin reuptake inhibitor effective in a once-daily administration regimen in the treatment of depression. In elderly patients (aged > or = 60 years) with major depression, short term (6 weeks) treatment with paroxetine produces clinical improvements significantly superior to those seen with placebo and similar to those with tricyclic antidepressant agents, mianserin and fluoxetine. There is evidence that paroxetine has positive effects on co-existing anxiety and does not precipitate agitation. Paroxetine has also shown potential in the symptomatic treatment of diabetic neuropathy; however, further clinical experience is needed to confirm this preliminary result. Short term paroxetine therapy is associated with fewer anticholinergic and CNS adverse effects, but generally more gastrointestinal disturbances, than tricyclic antidepressants and mianserin. Unlike the tricyclic agents, paroxetine does not significantly affect cardiovascular function or impair psychomotor performance. This tolerability profile should be particularly beneficial in elderly patients, who are generally more susceptible than younger patients to the anticholinergic and CNS adverse events associated with tricyclic antidepressant drugs, and in whom there is a higher prevalence of pre-existing cardiovascular disease. It also suggests an important potential advantage over tricyclic antidepressants in the setting of overdosage. Thus, primarily because of its better tolerability profile and potentially lower toxicity in overdosage and in patients with cardiovascular disease, paroxetine appears to be a more attractive option than tricyclic antidepressants for the treatment of depression in late life. Future research should attempt to define more fully the efficacy of paroxetine as long term prophylactic therapy for recurrent depression and to assess how its overall therapeutic profile compares with other selective serotonin reuptake inhibitors in the elderly.
Topics: Adult; Aged; Aging; Animals; Depression; Diabetic Neuropathies; Humans; Middle Aged; Paroxetine
PubMed: 8324301
DOI: 10.2165/00002512-199303030-00008 -
Journal of Clinical Psychopharmacology Dec 1993Paroxetine is a novel phenylpiperidine compound that is a potent and selective serotonin reuptake inhibitor. It has little affinity for alpha-adrenergic, dopamine,... (Comparative Study)
Comparative Study Review
Paroxetine is a novel phenylpiperidine compound that is a potent and selective serotonin reuptake inhibitor. It has little affinity for alpha-adrenergic, dopamine, histamine, and cholinergic receptors. The pharmacokinetic properties of paroxetine are well suited to clinical use. Its bioavailability is not affected by food or antacids; its mean half-life of about 24 hours is consistent with once-a-day dosing; also, it has no pharmacologically active metabolites. In clinical studies involving over 6,700 patients worldwide, the efficacy of paroxetine has been shown consistently to be superior to placebo and comparable to tricyclic antidepressant agents in the treatment of depression. During these trials, paroxetine was used in a broad range of depressed patients, including the moderately to severely depressed, the elderly, and patients whose depressions were accompanied by symptoms of anxiety. In addition, it has been shown to be effective for the prevention of depressive relapse during long-term treatment. Side effects associated with paroxetine tend to be relatively mild, transient, and easily managed. As with other selective serotonin reuptake inhibitors, the most common side effect associated with paroxetine treatment is nausea, although this effect rarely leads to dose reduction or drug discontinuation. Paroxetine should not be coadministered with monoamine oxidase inhibitors or L-tryptophan. Animal data and limited clinical experience suggest that paroxetine is considerably safer in overdose than are tricyclic antidepressant drugs.
Topics: Adolescent; Adult; Aged; Animals; Antidepressive Agents, Tricyclic; Clinical Trials as Topic; Depressive Disorder; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Paroxetine; Recurrence
PubMed: 8106649
DOI: No ID Found -
Expert Opinion on Pharmacotherapy Oct 2003Post-traumatic stress disorder (PTSD) is increasingly understood to be a medical disorder characterised by particular psychobiological dysfunctions that respond to... (Review)
Review
Post-traumatic stress disorder (PTSD) is increasingly understood to be a medical disorder characterised by particular psychobiological dysfunctions that respond to specific treatments. Paroxetine is a selective serotonin re-uptake inhibitor that has been found effective in the treatment of major depression as well as a range of anxiety disorders. This paper reviews data on the use of paroxetine for the treatment of adult PTSD. There have been three 12-week, placebo-controlled studies of paroxetine in PTSD. As these followed a partly similar design, a pooled analysis of the studies is possible and is reported here. Paroxetine is effective in the short-term treatment of PTSD, resulting in significantly better response and remission rates than placebo, improving sleep disturbance and reducing each of the symptom clusters of PTSD, as well as the disability associated with this condition. The medication is effective in both male and female PTSD patients and whether or not there are comorbid disorders such as depression.
Topics: Administration, Oral; Humans; Paroxetine; Placebos; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors; Stress Disorders, Post-Traumatic; Treatment Outcome
PubMed: 14521492
DOI: 10.1517/14656566.4.10.1829 -
Profiles of Drug Substances,... 2013The polymorphic (crystal systems for which a substance can exist in structures defined by different unit cells, and where each of the forms has the same elemental... (Review)
Review
The polymorphic (crystal systems for which a substance can exist in structures defined by different unit cells, and where each of the forms has the same elemental composition) and solvatomorphic (systems where the crystal structures of the substance are defined by different unit cells, but where these unit cells differ in their elemental composition through the inclusion of one or molecules of solvent) landscape of paroxetine hydrochloride have been critically evaluated in order to learn how many authentic crystal forms have actually been discovered. After a survey of the patent and open literature, it was determined that paroxetine hydrochloride has been crystallized in four genuine nonsolvated polymorphic forms and in four fully characterized solvatomorphic forms.
Topics: Crystallization; Paroxetine; Selective Serotonin Reuptake Inhibitors; Solvents; X-Ray Diffraction
PubMed: 23668409
DOI: 10.1016/B978-0-12-407691-4.00009-5 -
CNS Drugs 2002Paroxetine is a selective serotonin reuptake inhibitor (SSRI), with antidepressant and anxiolytic activity. In 6- to 24-week well designed trials, oral paroxetine 10 to... (Review)
Review
Paroxetine is a selective serotonin reuptake inhibitor (SSRI), with antidepressant and anxiolytic activity. In 6- to 24-week well designed trials, oral paroxetine 10 to 50 mg/day was significantly more effective than placebo, at least as effective as tricyclic antidepressants (TCAs) and as effective as other SSRIs and other antidepressants in the treatment of major depressive disorder. Relapse or recurrence over 1 year after the initial response was significantly lower with paroxetine 10 to 50 mg/day than with placebo and similar to that with imipramine 50 to 275 mg/day. The efficacy of paroxetine 10 to 40 mg/day was similar to that of TCAs and fluoxetine 20 to 60 mg/day in 6- to 12-week trials in patients aged > or = 60 years with major depression. Paroxetine 10 to 40 mg/day improved depressive symptoms to an extent similar to that of TCAs in patients with comorbid illness, and was more effective than placebo in the treatment of dysthymia and minor depression. Paroxetine 20 to 60 mg/day was more effective than placebo after 8 to 12 weeks' treatment of obsessive-compulsive disorder (OCD), panic disorder, social anxiety disorder (social phobia), generalised anxiety disorder (GAD) and post-traumatic stress disorder (PTSD). Improvement was maintained or relapse was prevented for 24 weeks to 1 year in patients with OCD, panic disorder, social anxiety disorder or GAD. The efficacy of paroxetine was similar to that of other SSRIs in patients with OCD and panic disorder and similar to that of imipramine but greater than that of 2'chlordesmethyldiazepam in patients with GAD. Paroxetine is generally well tolerated in adults, elderly individuals and patients with comorbid illness, with a tolerability profile similar to that of other SSRIs. The most common adverse events with paroxetine were nausea, sexual dysfunction, somnolence, asthenia, headache, constipation, dizziness, sweating, tremor and decreased appetite. In conclusion, paroxetine, in common with other SSRIs, is generally better tolerated than TCAs and is a first-line treatment option for major depressive disorder, dysthymia or minor depression. Like other SSRIs, paroxetine is also an appropriate first-line therapy for OCD, panic disorder, social anxiety disorder, GAD and PTSD. Notably, paroxetine is the only SSRI currently approved for the treatment of social anxiety disorder and GAD, which makes it the only drug of its class indicated for all five anxiety disorders in addition to major depressive disorder. Thus, given the high degree of psychiatric comorbidity of depression and anxiety, paroxetine is an important first-line option for the treatment of major depressive disorder, OCD, panic disorder, social anxiety disorder, GAD and PTSD.
Topics: Adult; Anti-Anxiety Agents; Antidepressive Agents, Second-Generation; Anxiety Disorders; Depressive Disorder; Humans; Paroxetine; Selective Serotonin Reuptake Inhibitors
PubMed: 12027788
DOI: 10.2165/00023210-200216060-00006 -
Archives of Internal Medicine Mar 1995
Topics: Humans; Male; Middle Aged; Paroxetine; Priapism
PubMed: 7887764
DOI: No ID Found -
PharmacoEconomics Jul 1995There has been intense debate about whether the use of paroxetine or other selective serotonin reuptake inhibitors (SSRIs) as alternatives to tricyclic antidepressants... (Review)
Review
There has been intense debate about whether the use of paroxetine or other selective serotonin reuptake inhibitors (SSRIs) as alternatives to tricyclic antidepressants for first-line treatment of depression can be justified, considering their higher acquisition costs. The rationale for using paroxetine in the treatment of depression lies in its more favourable tolerability profile than tricyclic antidepressants and its lower risk of death on overdosage. Depression is one of the most common psychiatric disorders and is associated with substantial direct, indirect and intangible costs. Indirect costs account for the majority of costs associated with depression, while drug costs account for only 9 to 25% of direct costs. Therefore, increased recognition and treatment of depression has the potential to greatly reduce the overall cost of this disease. Pharmacoeconomic data on paroxetine and other SSRIs in the treatment of depression are scarce. Available studies are limited to considerations of direct costs alone and are primarily based on retrospective data from clinical trials. Nevertheless, in terms of costs per successfully-treated patient, available data suggest that the treatment costs associated with paroxetine are similar to those of amitriptyline and possibly less than those of imipramine. Paroxetine treatment costs also appear to be similar to those of amitriptyline and imipramine in terms of expected costs per patient. While one group of investigators suggested that the overall cost of administering paroxetine may also be less than that for fluoxetine and sertraline when drug costs and labour costs associated with dosage adjustment are taken into account, more data are required before conclusions on the relative pharmacoeconomic merits of SSRIs can be made. Despite the lower risk of death from overdosage with SSRIs, switching from an established tricyclic antidepressant to a newer tricyclic or related antidepressant in an attempt to avoid suicide appears to be more cost effective than switching to an SSRI. Thus, evidence available to date indicate that despite higher acquisition costs paroxetine and other SSRIs are no more costly than tricyclic antidepressants when total costs per successfully treated patient or expected costs per patient are considered. With its favourable tolerability profile and low risk of death on overdosage, paroxetine should therefore be considered as an effective alternative to tricyclic antidepressant agents as a first-line treatment of depression.(ABSTRACT TRUNCATED AT 400 WORDS)
Topics: Antidepressive Agents, Second-Generation; Cost of Illness; Depressive Disorder; Humans; Paroxetine
PubMed: 10155603
DOI: 10.2165/00019053-199508010-00008 -
International Clinical... Jun 1992Paroxetine is a new selective serotonin reuptake inhibitor which has been extensively evaluated as an antidepressant in clinical trials and a large computerized safety... (Review)
Review
Paroxetine is a new selective serotonin reuptake inhibitor which has been extensively evaluated as an antidepressant in clinical trials and a large computerized safety database has been accumulated. A comprehensive review of data on dosage supports the recommendation that 20 mg paroxetine daily is the optimal therapeutic dose for most patients. When compared to active controls--mainly tricyclic antidepressants--paroxetine was found to have a different adverse-event profile with fewer anticholinergic, cardiovascular and nervous system events but more gastrointestinal events, particularly nausea. However, these events were not severe and did not usually lead to discontinuation of treatment. The adverse events reported with paroxetine were most likely to occur early in the course of treatment and there was no evidence of any increase in events in the elderly or with longer-term treatment. Paroxetine was not associated with excess of death from any cause, suicides, suicide attempts or serious life-threatening events. No clinically significant drug-related abnormalities were reported in laboratory monitoring, including liver function tests, in short- or long-term use. Finally, and importantly for an antidepressant, paroxetine appears relatively safe in overdose.
Topics: Adult; Aged; Depressive Disorder; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Paroxetine
PubMed: 1431015
DOI: No ID Found -
Science Translational Medicine Feb 2021Osteoarthritis (OA) is a debilitating joint disease characterized by progressive cartilage degeneration, with no available disease-modifying therapy. OA is driven by...
Osteoarthritis (OA) is a debilitating joint disease characterized by progressive cartilage degeneration, with no available disease-modifying therapy. OA is driven by pathological chondrocyte hypertrophy (CH), the cellular regulators of which are unknown. We have recently reported the therapeutic efficacy of G protein-coupled receptor kinase 2 (GRK2) inhibition in other diseases by recovering protective G protein-coupled receptor (GPCR) signaling. However, the role of GPCR-GRK2 pathway in OA is unknown. Thus, in a surgical OA mouse model, we performed genetic GRK2 deletion in chondrocytes or pharmacological inhibition with the repurposed U.S. Food and Drug Administration (FDA)-approved antidepressant paroxetine. Both GRK2 deletion and inhibition prevented CH, abated OA progression, and promoted cartilage regeneration. Supporting experiments with cultured human OA cartilage confirmed the ability of paroxetine to mitigate CH and cartilage degradation. Our findings present elevated GRK2 signaling in chondrocytes as a driver of CH in OA and identify paroxetine as a disease-modifying drug for OA treatment.
Topics: Animals; Cartilage; Cartilage, Articular; Chondrocytes; G-Protein-Coupled Receptor Kinase 2; Mice; Osteoarthritis; Paroxetine
PubMed: 33568523
DOI: 10.1126/scitranslmed.aau8491 -
Naunyn-Schmiedeberg's Archives of... Nov 2023Paroxetine is extensively utilized in the management of depressive and anxious conditions. Paroxetine works by increasing serotonin levels in nerve cells in the brain....
Paroxetine is extensively utilized in the management of depressive and anxious conditions. Paroxetine works by increasing serotonin levels in nerve cells in the brain. However, limited information is available regarding the direct effects of paroxetine on macrophage cells. Macrophages are a type of leukocytes involved in the body's immune response, playing a crucial role in combating infections. The impact of paroxetine on macrophages has been explored in research, although a comprehensive understanding is still pending. This study aimed to research the potential of administering paroxetine to J774.2 macrophage cells to stimulate the release of GM-CSF, TNF-α, IL-12p40, and IL-6 cytokines. Additionally, we examined the mechanisms of action of paroxetine on the p38 signaling pathway, which is involved in cytokine production, and the PI3K pathway, which is an important mechanism in intracellular signaling. Our findings revealed that paroxetine induced an inflammatory response in macrophages by promoting cytokine synthesis in a non-lipopolysaccharide (LPS) environment. We observed that paroxetine triggered the inflammatory response through the PI3K signaling pathway while suppressing the p38 signaling pathway.
Topics: Cytokines; Paroxetine; Phosphatidylinositol 3-Kinases; Signal Transduction; Tumor Necrosis Factor-alpha; Lipopolysaccharides
PubMed: 37589738
DOI: 10.1007/s00210-023-02669-1