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Mood Disorders
Published in Vincenzo Berghella, Maternal-Fetal Evidence Based Guidelines, 2022
Madeleine A. Becker, Tal E. Weinberger, Leigh J. Ocker
However, based on currently available data in early pregnancy, avoidance of paroxetine is advised if effective alternative treatment is available, because of the slightly higher, though still small, risk compared with other SSRIs [65]. Given the findings, it is impossible to completely rule out the possibility that SSRIs may lead to a slight increase in risk of congenital malformations. However, the associations from the studies show that the absolute risk of any of these malformations, if present, would still be extremely small.
Drugs Affecting the Central Nervous System
Published in Radhwan Nidal Al-Zidan, Drugs in Pregnancy, 2020
Risk Summary: The use of Paroxetine should be avoided in pregnant women because the pregnancy experience in humans has shown the risk of congenital malformations and cardiac defects associated with the use of this drug.
pushing children into suicide with happy pills
Published in Peter C. Gøtzsche, Richard Smith, Drummond Rennie, Deadly Medicines and Organised Crime, 2019
Peter C. Gøtzsche, Richard Smith, Drummond Rennie
Many suicides are missing in the FDA analysis. In a 1995 meta-analysis, there were five suicides on paroxetine in 2963 patients,32 which is 17 per 10 000 patients. This meta-analysis wrongly reported two suicides on placebo, which had occurred in the washout period. The UK drug regulator was much more careful than the FDA and did not only search for suicide terms in the documents but also read text in case report forms and narratives.33They showed that paroxetine was harmful in adults with major depressive disorder. There were 11 suicide attempts on paroxetine (3455 patients) and only one on placebo (1978 patients), P = 0.058 for the difference. I wonder why no suicides were reported, as we would have expected six on paroxetine.
Fabrication of solid lipid nanoparticles-based patches of paroxetine and their ex-vivo permeation behaviour
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2023
Fahad Pervaiz, Ayesha Saba, Haya Yasin, Manal Buabeid, Sobia Noreen, Abida Kalsoom Khan, Ghulam Murtaza
Paroxetine is one of the most potent clinically available selective serotonin reuptake inhibitors (SSRI) antidepressants [1]. It acts by blocking serotonin reuptake [2], but its action is less selective at the serotonin site than other SSRIs, i.e. fluvoxamine or sertraline [3]. Paroxetine is, clinically available in oral dosage forms (such as tablets, capsules and in oral suspension) [4], readily absorbed from the gastrointestinal tract (GIT) and extensively metabolized in the liver [5]; thus, a much lesser amount of the drug reaches the systemic circulation, resulting in poor bioavailability [6]. The t1/2 varies according to the dosage and administration duration. The half-life of up to 21 h following oral paroxetine dosing of 30 mg per day [2]. The pharmacodynamics of paroxetine is not suitable for its oral administration due to its extensive first-pass metabolism, thus resulting in less bioavailability [7].
Asymmetric organocatalysis in drug discovery and development for active pharmaceutical ingredients
Published in Expert Opinion on Drug Discovery, 2023
(-)-Paroxetine is a selective serotonin reuptake inhibitor that is prescribed for depression and other nervous disorders. In 2019, Kappe and Pericàs reported a multigram-scale flow synthesis of the chiral intermediate 31 of this API starting with the p-fluorocinamaldehyde 29 along with dimethyl malonate 18 and acetic acid using the immobilized Jørgensen-Hayashi diphenylprolinol silyl ether 30 (in a packed bed reactor heated at 60°C) (Figure 4 a) [49]. The reaction was run on the multi-gram scale to produce 17.26 g of intermediate 31 over a 7 h period with a residence time of 20 min and a flow rate of 70 μL/min, with an accumulated TON of 132. This large-scale synthesis had a productivity of 2.47 g/h of pure product, which was considered an outstanding result for organocatalytic reactions under flow conditions. This intermediate was then transformed into an advanced phenylpiperidine 32, which is a key intermediate of (-)-paroxetine, by a tandem reductive amination-lactamization sequence, also conducted under continuous flow conditions.
Contemporary management of unipolar depression in the perinatal period
Published in Expert Review of Neurotherapeutics, 2021
Bhuvaneshwari Sethuraman, Susan Thomas, Krishnamachari Srinivasan
Most protocols recommend the use of sertraline and citalopram as the first line of treatment for antenatal depression [3,10,84]. Paroxetine is to be avoided during pregnancy as its use during pregnancy is associated with an increased risk of cardiac malformations in the newborn [112]. Similarly, it is better to avoid clomipramine during pregnancy as in some studies it has been associated with an increased risk of congenital malformations such as cleft palate, open eyelids, ear defects and neck defects [114]. UK Teratology body recommends the use of amitriptyline and imipramine as the first line options for treatment of depression during pregnancy [10]. Benzodiazepines as a class of drugs should be avoided as some studies have noted its use to be associated with an increased risk for floppy infant syndrome, withdrawal signs in the newborn, congenital malformations such as esophageal atresia, microphthalmia and pulmonary valve stenosis [115] and impaired cognitive development in children [116]. There is limited evidence for safe and efficacious use of other antidepressant medications during pregnancy.