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Pharmacopsychiatry May 1998The selective serotonin reuptake inhibitor paroxetine has been extensively studied and is now an established therapy for the treatment of depressive disorders.... (Review)
Review
The selective serotonin reuptake inhibitor paroxetine has been extensively studied and is now an established therapy for the treatment of depressive disorders. Paroxetine has demonstrated efficacy in major depression in both young and elderly patients, with an improved tolerability profile over conventional antidepressants. Paroxetine is effective across a continuum of anxiety and depressive disorders, including severe depression, depression with anxiety, comorbid depression and obsessive-compulsive disorder. The first agent of its class licensed for use in panic disorder, paroxetine has been shown to be effective in reducing the number of panic attacks and preventing relapse. A worldwide clinical database has established that paroxetine has a benign adverse event profile. Paroxetine therefore offers an effective and well tolerated treatment for a broad spectrum of psychiatric disorders.
Topics: Antidepressive Agents, Second-Generation; Depressive Disorder; Humans; Paroxetine
PubMed: 9657236
DOI: 10.1055/s-2007-979307 -
Drug Design, Development and Therapy 2023Osteoarthritis (OA), a common chronic joint disease, is characterized by cartilage degeneration and subchondral bone reconstruction. NF-κB signaling pathway-activated...
BACKGROUND
Osteoarthritis (OA), a common chronic joint disease, is characterized by cartilage degeneration and subchondral bone reconstruction. NF-κB signaling pathway-activated inflammation and NLRP3-induced pyroptosis play essential roles in the development of OA. In this study, we examine whether paroxetine can inhibit pyroptosis and reduce osteoclast formation, thereby delaying the destruction of knee joints.
METHODS
We employed high-density cultures, along with quantitative polymerase chain reactions and Western blotting techniques, to investigate the effects of paroxetine on extracellular matrix synthesis and degradation. The expression levels of NF-κB and pyroptosis-related signaling pathway proteins were examined by Western blotting and immunofluorescence. Furthermore, the impact of paroxetine on RANKL-induced osteoclast formation was evaluated through TRAP staining and F-actin ring fluorescence detection. To investigate the role of paroxetine in vivo, we constructed a mouse model with destabilization of the medial meniscus (DMM) surgery. Safranin O-Fast Green staining, Hematoxylin-Eosin staining, and immunohistochemistry were conducted to observe the extent of knee joint cartilage deformation. In addition, TRAP staining was used to observe the formation of osteoclasts in the subchondral bone.
RESULTS
In the in vitro experiments with ATDC5, paroxetine treatment attenuated IL-1β-induced activation of the pyroptosis-related pathway and suppressed extracellular matrix catabolism by inhibiting the NF-kB signaling pathway. In addition, paroxetine treatment decreased the expression of RANKL-induced osteoclast marker genes and reduced osteoclast formation. In animal experiments conducted in vivo, mice treated with paroxetine exhibited thicker knee cartilage with a smoother surface compared to the DMM group. Additionally, the formation of osteoclasts in the subchondral bone was reduced in the paroxetine-treated mice. Further analysis revealed that paroxetine treatment played a role in preserving the balance of the extracellular matrix and delaying knee joint degeneration.
CONCLUSION
Paroxetine can inhibit pyroptosis and reduce osteoclast formation via inhibiting the NF-κB signaling pathway, suggesting that it may have therapeutic effects in patients with OA.
Topics: Animals; Mice; NF-kappa B; Chondrocytes; Osteoclasts; Paroxetine; Pyroptosis; Signal Transduction; Osteoarthritis, Knee
PubMed: 37605762
DOI: 10.2147/DDDT.S417598 -
The Annals of Pharmacotherapy Oct 2006To evaluate the literature assessing the neonatal risks of antepartum paroxetine use. (Review)
Review
OBJECTIVE
To evaluate the literature assessing the neonatal risks of antepartum paroxetine use.
DATA SOURCES
MEDLINE (1966-August 2006) and International Pharmaceutical Abstracts (1970-August 2006) searches were performed. Key search terms included paroxetine, SSRI, pregnancy, malformations, neonate, and fetus.
DATA SYNTHESIS
Selective serotonin-reuptake inhibitors (SSRIs) are associated with neonatal withdrawal symptoms such as respiratory distress, irritability, lethargy, and tremors. In a cohort study, 30% of infants exposed to SSRIs had poor neonatal adaptation, compared with 9% of controls (p = 0.018). Some reports indicate that paroxetine is more commonly associated with neonatal withdrawal than other SSRIs. Recently, paroxetine was associated with a 1.82-fold (95% CI 1.17 to 2.82) increased risk of congenital malformations compared with other antidepressants. Other SSRIs were also associated with an increased risk of congenital malformations; however, the results were not statistically significant. Literature supporting these findings includes case reports and case-control or cohort studies. The Food and Drug Administration recommendations regarding paroxetine use during pregnancy have been added to the labeling information.
CONCLUSIONS
Paroxetine may cause adverse outcomes in the neonate when used during pregnancy and should be discontinued in women who are pregnant or trying to become pregnant. The risks and benefits of other antidepressant use should be analyzed on an individual basis.
Topics: Female; Humans; Infant, Newborn; Paroxetine; Pregnancy; Prenatal Exposure Delayed Effects; Risk Factors
PubMed: 16926304
DOI: 10.1345/aph.1H116 -
Drugs Jan 1998Paroxetine is a potent and selective inhibitor of the neuronal reuptake of serotonin (5-hydroxytryptamine; 5-HT), which was previously reviewed as an antidepressant in... (Review)
Review
Paroxetine is a potent and selective inhibitor of the neuronal reuptake of serotonin (5-hydroxytryptamine; 5-HT), which was previously reviewed as an antidepressant in Drugs in 1991. Since then, more comparative trials with other antidepressants have become available, and its use in the elderly and as long term maintenance therapy has been investigated. Paroxetine has also been studied in several other disorders with a presumed serotonergic component, primarily obsessive compulsive disorder (OCD) and panic disorder. In short term clinical trials in patients with depression, paroxetine produced clinical improvements that were significantly greater than those with placebo and similar to those achieved with other agents including tricyclic antidepressants (TCAs), maprotiline, nefazodone and the selective serotonin reuptake inhibitors (SSRIs) fluoxetine, fluvoxamine and sertraline. Long term data suggest that paroxetine is effective in preventing relapse or recurrence of depression in patients treated for up to 1 year. In the elderly, the overall efficacy of paroxetine was at least as good as that of comparator agents. In short term clinical trials involving patients with OCD or panic disorder, paroxetine was significantly more effective than placebo and of similar efficacy to clomipramine. Limited long term data show that paroxetine is effective in maintaining a therapeutic response over periods of 1 year (OCD) and up to 6 months (panic disorder). Preliminary data suggest that paroxetine has potential in the treatment of social phobia, premenstrual dysphoric disorder and chronic headache. Like the other SSRIs, paroxetine is better tolerated than the TCAs, causing few anticholinergic adverse effects. The most commonly reported adverse event associated with paroxetine treatment is nausea, although this is generally mild and subsides with continued use. Fewer withdrawals from treatment due to adverse effects occurred with paroxetine treatment than with TCAs. The adverse events profile of paroxetine appears to be broadly similar to that of other SSRIs, although data from comparative trials are limited. Serious adverse effects associated with paroxetine are very rare. In conclusion, paroxetine is effective and well tolerated, and suitable as first-line therapy for depression. It also appears to be a useful alternative to other available agents for the treatment of patients with OCD or panic disorder.
Topics: Antidepressive Agents, Second-Generation; Depressive Disorder; Humans; Nausea; Obsessive-Compulsive Disorder; Panic Disorder; Paroxetine; Selective Serotonin Reuptake Inhibitors
PubMed: 9463792
DOI: 10.2165/00003495-199855010-00007 -
The Annals of Pharmacotherapy Oct 1993To review the pharmacology, pharmacokinetics, clinical investigations, adverse effects, and dosing strategies of paroxetine as a treatment of major depression. (Comparative Study)
Comparative Study Review
OBJECTIVE
To review the pharmacology, pharmacokinetics, clinical investigations, adverse effects, and dosing strategies of paroxetine as a treatment of major depression.
DATA SOURCES
Specific paroxetine information was selected from a MEDLINE search using paroxetine as the search term. Other sources included manual searches of pertinent journal article references, meeting abstracts, and the manufacturer.
STUDY SELECTION
Clinical investigations with a blind, controlled (placebo and/or active), randomized design were selected. With the exception of treatment-resistant depression, no short-term, open investigations were selected.
DATA EXTRACTION
Clinical investigations were evaluated for design, sample size, diagnosis, duration, definition of response, and outcome. Data from all investigations were selected by one author and reviewed by both authors.
DATA SYNTHESIS
Paroxetine is a selective serotonin reuptake inhibitor (SSRI) recently approved for the treatment of major depression. It is a potent and selective inhibitor of serotonin reuptake and has weak or no activity on the other monoamines; it is also weakly anticholinergic. Although pharmacokinetic parameters are variable, paroxetine is generally well absorbed, highly protein bound, hepatically cleared, and has no active metabolites. Clinical investigations support paroxetine's effectiveness as an antidepressant in an outpatient population with moderately severe depression. Its effectiveness is superior to that of placebo and is comparable to that of active controls. The majority of investigations have been six weeks in duration. Additional data are required to support paroxetine's promise for longer treatment periods (i.e., > or = 1 y), in the elderly, and for treatment-resistant depression. Adverse effects appear to be similar to those caused by the other SSRIs; some of the most common are nausea, diarrhea, insomnia, dry mouth, and nervousness. Significant drug interactions may occur with the monoamine oxidase inhibitors, phenobarbital, and phenytoin.
CONCLUSIONS
Paroxetine is safe and effective for treatment of outpatients with moderately severe depression. Further clinical data and experience are necessary to determine this agent's place in the long-term treatment of major depression.
Topics: Aged; Antidepressive Agents; Depressive Disorder; Drug Interactions; Humans; Paroxetine; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors
PubMed: 8251692
DOI: 10.1177/106002809302701012 -
Fortschritte Der Neurologie-Psychiatrie Sep 1994Paroxetine is a trans-isomeric phenylpiperidine with antidepressant properties induced by selective inhibition of the neuronal high affinity uptake of serotonin. In... (Review)
Review
Paroxetine is a trans-isomeric phenylpiperidine with antidepressant properties induced by selective inhibition of the neuronal high affinity uptake of serotonin. In comparison with other selective serotonin uptake inhibitors paroxetine is 2 to 23 times more potent. With the exception of a low affinity to muscarinic receptors, which is not relevant for therapeutic effects, it does not interact directly with monoamine neurotransmitter receptors. Paroxetine is applied orally at single daily doses of 20 to 50 mg and well absorbed from the gastrointestinal tract. It undergoes a partially saturated first pass metabolism which reduces the bioavailability at therapeutic doses to about 30-60%. Maximal blood levels are reached 2 to 8 hours after oral administration. In the plasma 95% of the drug are bound to protein. Paroxetine is eliminated after transformation in the liver into pharmacologically inactive metabolites. High affinity to the cytochrome P450 isoenzyme CYP2D6 indicates that interferences occur with other drugs which are metabolized via the same isoenzyme. Although clinical practice has not reported problematic drug interactions so far, comedications with tricyclic antidepressants should be avoided. The most frequent side effects of paroxetine concern nausea and somnolescence. Since cardiotoxicity or other toxic side effects are much less frequent than under tricyclic antidepressants paroxetine seems advantageous in elderly patients. The onset of antidepressant effects requires several weeks as known for all currently available antidepressants. The pharmacokinetic and pharmacodynamic properties of paroxetine taken together indicate that this selective serotonin uptake inhibitor seems advantageous to other antidepressant agents because of its high selectivity and poor toxicity.
Topics: Animals; Humans; Paroxetine
PubMed: 7959522
DOI: No ID Found -
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: Administration, Oral; Adult; Aged; Antidepressive Agents, Second-Generation; Clinical Trials as Topic; Comorbidity; Half-Life; Humans; Intestinal Absorption; Mental Disorders; Middle Aged; Paroxetine; Psychomotor Performance; Treatment Outcome
PubMed: 11893234
DOI: 10.2165/00003495-200262040-00010 -
Psychopharmacology Bulletin 2003Generalized anxiety disorder (GAD) is a prevalent and disabling anxiety disorder, conservatively believed to affect at least 5% of the general population. Cardinal... (Review)
Review
Generalized anxiety disorder (GAD) is a prevalent and disabling anxiety disorder, conservatively believed to affect at least 5% of the general population. Cardinal symptoms of GAD include chronic and uncontrollable worry, anxiety, and tension, which result in difficulty fulfilling social, professional, and family roles. Treatment options include benzodiazepines, tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), and the serotonin-norepinephrine reuptake inhibitor (SNRI) venlafaxine XR. Because of the high comorbidity of GAD with other psychiatric disorders, pharmacologic therapy should possess both anxiolytic and antidepressive properties for best outcomes. The SSRIs are a good treatment option, and paroxetine is the best studied SSRI for GAD and the only SSRI to date approved by the US Food and Drug Administration for this indication. Results of randomized, controlled studies of paroxetine have demonstrated its efficacy in the short-term treatment of GAD, in achieving and sustaining full remission, and in preventing relapse. This article provides an overview of GAD and a discussion of studies of paroxetine treatment in this anxiety disorder.
Topics: Agoraphobia; Antidepressive Agents, Second-Generation; Humans; Paroxetine; Secondary Prevention
PubMed: 14566202
DOI: No ID Found -
Expert Opinion on Pharmacotherapy Feb 2010Currently available small case reports clearly propose that existing regulatory procedures to approve generic versions only require essential bioequivalence, have... (Comparative Study)
Comparative Study Review
IMPORTANCE OF THE FIELD
Currently available small case reports clearly propose that existing regulatory procedures to approve generic versions only require essential bioequivalence, have limitations and fail to meet stricter scientific and clinical demands.
AREAS COVERED IN THIS REVIEW
Data indicate that paroxetine mesylate has some potential differences in bio- and clinical equivalence compared with paroxetine hydrochloride, although it has not been fully and sufficiently investigated in well-designed clinical trials. Data available now regarding safety, tolerability, efficacy and practical issues dealing with debates between generic and brand-name products paroxetine mesylate and paroxetine hydrochloride are presented in the review.
WHAT THE READER WILL GAIN
Preclinical and clinical data are reviewed, and clinical issues relating to use of generic version versus original product are comprehensively discussed; tips for the clinician in clinical practice are also provided.
TAKE HOME MESSAGE
Potential differences in efficacy and safety but also reduction in the use of health care and in pharmacy cost should be considered when choosing the generic version or the original product based on the clear benefit-risk ratio in patients.
Topics: Consumer Product Safety; Cost of Illness; Drug Approval; Humans; Paroxetine; Randomized Controlled Trials as Topic
PubMed: 20088740
DOI: 10.1517/14656560903451708 -
Expert Opinion on Pharmacotherapy Aug 2004Paroxetine is a selective serotonin re-uptake inhibitor useful in the treatment of a wide range of psychiatric disorders. Generalised anxiety disorder (GAD) is... (Review)
Review
Paroxetine is a selective serotonin re-uptake inhibitor useful in the treatment of a wide range of psychiatric disorders. Generalised anxiety disorder (GAD) is characterised by excessive persistent anxiety and worry about a number of events and activities occurring on more days than not for at least 6 months. GAD is the most common anxiety disorder in primary care settings. Paroxetine was the second antidepressant to receive an FDA indication for the treatment of GAD. In contrast to benzodiazepines, which had been the mainstay of treatment for anxiety disorders for many years, antidepressants, such as paroxetine, are more effective for the psychic symptoms of anxiety, which include worry, tension, irritability and concentration difficulties, and carry a more tolerable and safe side effect profile.
Topics: Anti-Anxiety Agents; Antidepressive Agents, Second-Generation; Antidepressive Agents, Tricyclic; Anxiety Disorders; Benzodiazepines; Buspirone; Delayed-Action Preparations; Humans; Paroxetine; Selective Serotonin Reuptake Inhibitors
PubMed: 15264994
DOI: 10.1517/14656566.5.8.1799