Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Paroxetine in the treatment of post-traumatic stress disorder: pooled analysis of placebo-controlled studies. 1452 92

Paroxetine is a potent and selective serotonin reuptake inhibitor (SSRI) with some neuropharmacologic properties unique among this class of compounds. The findings of early in vitro studies demonstrated the potency of paroxetine at inhibiting 5-HT uptake in rat synaptosomes. Paroxetine also has been shown to be a potent and selective inhibitor of the human serotonin transporter (SERT) and has recently been demonstrated to have moderate affinity for the norepinephrine transporter (NET). Because of the affinity and in vitro selectivity of this SSRI, tritiated paroxetine is now widely used as a marker for SERT in laboratory settings, and its use has advanced our understanding of neurotransmitter function in the brain and periphery. The in vivo pharmacologic properties of paroxetine are well characterized, especially following acute administration. However, the pharmacologic effects of chronically administered paroxetine remain an active area of study. Paroxetine administration in laboratory animals has been shown to be associated with decreased SERT density and function, maintenance of normal firing rates and release of 5-HT, and increased activation of postsynaptic 5-HT receptors. Using a novel ex vivo assay, we have demonstrated that paroxetine exhibits dose-related inhibition of the NET in patients treated for depression. At usual clinical doses (ie, 20 mg/d), paroxetine is a potent and selective inhibitor of the SERT; however, at higher doses (ie, 40 mg/d), paroxetine can exhibit marked NET inhibition. The application of these findings of in vivo NET inhibition by paroxetine in the treatment of mood and anxiety disorders will be informed by further clinical studies.
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PMID:Neuropharmacology of paroxetine. 1456 96

Paroxetine controlled-release (CR) was developed with the objective of minimizing the occurrence and severity of selective serotonin reuptake inhibitor (SSRI)-associated adverse events, thereby improving clinical outcomes. Paroxetine CR delays the onset and controls the rate of absorption of medication. Multicenter controlled clinical trials have found lower rates of early-onset, treatment-associated nausea and lower dropout rates from adverse events in depressed patients treated with paroxetine CR compared with those treated with the conventional, immediate-release formulation. At the same time, clinical response and remission rates are favorable. Other studies have demonstrated the efficacy and tolerability of paroxetine CR in geriatric depression, panic disorder, and social anxiety disorder. The CR formulation of paroxetine appears to represent an effective pharmacokinetic approach to minimizing SSRI adverse events and thereby enhancing clinical outcomes.
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PMID:Efficacy and tolerability of controlled-release paroxetine. 1456 10

Tricyclic antidepressants have notable cardiac side effects, and this issue has become important due to the recent reports of increased cardiovascular mortality in patients with depression and anxiety. Several previous studies indicate that serotonin reuptake inhibitors (SRIs) do not appear to have such adverse effects. Apart from the effects of these drugs on routine 12-lead ECG, the effects on beat-to-beat heart rate (HR) and QT interval time series provide more information on the side effects related to cardiac autonomic function. In this study, we evaluated the effects of two antidepressants, nortriptyline (n=13), a tricyclic, and paroxetine (n=16), an SRI inhibitor, on HR variability in patients with panic disorder, using a measure of chaos, the largest Lyapunov exponent (LLE) using pre- and posttreatment HR time series. Our results show that nortriptyline is associated with a decrease in LLE of high frequency (HF: 0.15-0.5 Hz) filtered series, which is most likely due to its anticholinergic effect, while paroxetine had no such effect. Paroxetine significantly decreased sympathovagal ratios as measured by a decrease in LLE of LF/HF. These results suggest that paroxetine appears to be safer in regards to cardiovascular effects compared to nortriptyline in this group of patients.
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PMID:Effect of nortriptyline and paroxetine on measures of chaos of heart rate time series in patients with panic disorder. 1464 80

Paroxetine, a selective serotonin reuptake inhibitor (SSRI) may be given in severe cases of maternal depression and panic disorders during pregnancy. However, it may lead to severe withdrawal symptoms: respiratory distress, jitteriness, convulsions, hypoglycaemia, an impaired muscle tone and necrotising enterocolitis. These symptoms, also called neonatal withdrawal syndrome, may last up to one month. We report a girl born at 37 weeks of gestation presenting 12 hours after birth with hypopnea, bradycardia and a decreased muscular tone of unknown origin. The child was transferred to the NICU and was intubated and ventilated mechanically. Within the first days the patient also developed cerebral seizures. The EEG showed severe abnormalities. Later we learned that the patient's mother had been treated with Paroxetine during pregnancy. The patient recovered after two days of ventilation and anticonvulsive medication with phenobarbital. The EEG result showed a siginificant improvement. At day 10 she was discharged in good condition. Recognition and treatment of the presented neonatal problems could have been more effective and faster, if the attending pediatricians had been informed earlier about the maternal medication with SSRIs. Neonates of mothers who were treated with SSRIs during pregnancy should be monitored. Paroxetine withdrawal syndrome should be considered as one of the differential diagnosis of neonatal encephalopathy.
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PMID:[Paroxetine withdrawal syndrome as differential diagnosis of acute neonatal encephalopathy?]. 1511 41

We report a case of serotonin syndrome in a patient being treated with paroxetine for depression. Despite prompt discontinuation of medication, his serotonin syndrome continued for 10 days before full consciousness was restored. The patient was a 48-year-old male with chief complaints of hypobulia and suicidal thoughts. He consulted as a psychiatric outpatient, and oral paroxetine 20 mg/day, etizolam 1.0 mg/day, and brotizolam 0.25 mg/day were immediately started. Upsurge of feeling and disinhibition state were noted the following day, then on treatment day 6 his condition deteriorated to substupor state and he was admitted for further treatment. On admission, change of mental condition (consciousness disturbance), perspiration, hyperreflexia, myoclonus and tremor were seen, and serotonin syndrome caused by paroxetine was suspected. Paroxetine was thus discontinued, and under intravenous drip his condition gradually improved. However, it was not until the 10th hospital day that he became fully alert. In examinations, no infectious, metabolic or organic diseases were detected. The patient's condition often improves with in 24 hours of discontinuation of the causative medication in serotonin syndrome. Symptoms continued for 10 days in this patient, however, perhaps because paroxetine was administered for 6 days before discontinuation. In addition, interaction with other medications may have occurred. Therefore, when serotonin syndrome is suspected, prompt discontinuation of the suspected causative medication, followed by close monitoring of the pharmacokinetics is warranted.
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PMID:[Case of prolonged recovery from serotonin syndrome caused by paroxetine]. 1502 11

Depressive and anxiety disorders appear during the transplant process due to psychological stressors, medications and physiological disturbances. Treatment is necessary to prevent impact on patient compliance, morbidity and mortality. Psychotropic medications provide an effective option, although most are only available as oral formulations. Because of this, they are more susceptible to alterations in pharmacokinetic behaviour arising from organ dysfunction in the pretransplant period. Kinetics are also an issue when considering potential drug-drug interactions before and after transplantation. Prior to transplant, organ dysfunction can change the pharmacokinetic behaviour of some psychotropic agents, requiring adjustment of dosage and schedules. Thoracic or abdominal organ failure may reduce drug absorption through disturbances in intestinal motility, perfusion and function. Cirrhotic patients experience increased drug bioavailability due to portosystemic shunting, and thus dosage is adjusted downward. In contrast, dosage needs to be raised when peripheral oedema expands the drug distribution volume for hydrophilic and protein-bound agents. Drug clearance for most psychotropic medications is dependent upon hepatic metabolism, which is often disrupted by endstage organ disease. Selection of drugs or their dosage may need to be adjusted to lower the risk of drug accumulation. Further adjustments in dosage may be called for when renal failure accompanies thoracic or abdominal organ failure, resulting in further impairment of clearance. Studies regarding the treatment of anxiety and depressive disorders in the medically ill are limited in number, but recommendations are possible by review of clinical and pharmacokinetic data. Selective serotonin reuptake inhibitors are well tolerated and efficacious for depression, panic disorder and post-traumatic stress disorder. Adjustments in dosage are required when renal or hepatic impairment is present. Among them, citalopram and escitalopram appear to have the least risk of drug-drug interactions. Paroxetine has demonstrated evidence supporting its use with generalised anxiety disorder. Venlafaxine is an alternative option, beneficial in depression, post-traumatic stress and generalised anxiety disorders. Nefazodone may also be considered, but there is some risk of hepatotoxicity and interactions with immunosuppressant drugs. Mirtazapine still needs to be studied further in anxiety disorders, but can be helpful for depression accompanied by anorexia and insomnia. Bupropion is effective in the treatment of depression, but data are sparse about its use in anxiety disorders. Psychostimulants are a unique approach if rapid onset of antidepressant action is desired. Acute or short-term anxiolysis is obtained with benzodiazepines, and selection of particular agents entails consideration of distribution rate, half-life and metabolic route.
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PMID:Treatment of anxiety and depression in transplant patients: pharmacokinetic considerations. 1508 75

A controlled-release (CR) formulation of the SSRI paroxetine has been developed. This CR formulation delays the release of paroxetine until the tablet has passed through the stomach; the drug is then released over 4-5 hours. In well designed placebo-controlled trials in patients with major depressive disorder (including a study in the elderly), social anxiety disorder or premenstrual dysphoric disorder (PMDD), paroxetine CR was consistently superior to placebo with regards to primary endpoints (i.e. mean Hamilton Rating Scale for Depression total score [major depressive disorder], Liebowitz social anxiety scale total score and Clinical Global Impressions-Global Improvement score [social anxiety disorder] and Visual Analogue Scale-Mood score [PMDD]). The duration of treatment was 12 weeks or, in PMDD, over three menstrual cycles (intermittent or continuous administration). Paroxetine CR also demonstrated efficacy in three well designed studies in patients with panic disorder with or without agoraphobia. Paroxetine CR was generally well tolerated in clinical trials, with an adverse-event profile typical of SSRIs, although recipients of paroxetine CR experienced significantly less nausea than recipients of immediate-release paroxetine in the first week of treatment.
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PMID:Paroxetine controlled release. 1508 3

Paroxetine hydrochloride hemihydrate (the active ingredient in Paxil) is a pharmaceutical compound used for the treatment of depression, social anxiety disorder, obsessive compulsive disorder, panic disorder, and generalized anxiety disorder. Paroxetine (PA) is extensively metabolized in humans, with about 97% of the parent compound being excreted as metabolites through the urine and feces of patients. Therefore PA and metabolites have the potential to be discharged into wastewater treatment systems after therapeutic use. PA and its major human metabolite (PM) were investigated using studies designed to describe physical/chemical characteristics and determine their fate and effects in the aquatic environment. A significant portion of the PM entering a wastewater treatment plant would be expected to biodegrade given the higher activated sludge solids concentrations present in a typical wastewater treatment plant. The potential for direct photolysis of PM is also possible based on photolysis results for PA itself. These results provide strong support for expecting that PA and PM residuals will not persist in the aquatic environment after discharge from a wastewater treatment facility. This conclusion is also supported by the results of a USGS monitoring study, where no PM was detected in any of the samples at the 260 ng/L reporting limit. The results presented here also demonstrate the importance of understanding the human metabolism of a pharmaceutical so that the appropriate molecule(s) is used for fate and effects studies. In addition to the PA fate studies, PM was investigated using studies designed to determine potential environmental effects and a predicted no effect level (PNEC). The average measured activated sludge respiration inhibition value (EC50) for PM was 82 mg/L. The measured Microtox EC50 value was 33.0 mg/L, while the Daphnia magna EC50 value was 35.0 mg/L. The PNEC for PM was calculated to be 35.0 microg/L. Fate data were then used in a new watershed-based environmental risk assessment model, PhATE, to predict environmental concentrations (PECs). Comparison of the calculated PECs with the PNEC allows an assessment of potential environmental risk. Within the 1-99% of stream segments in the PhATE model, PEC values ranged from 0.003 to 100 ng/L. The risk assessment PEC/PNEC ratios ranged from approximately 3 x 10(-8) to approximately 3 x 10(-3), indicating a wide margin of safety, since a PEC/PNEC ratio <1 is generally considered to represent a low risk to the environment. In addition, Microtox studies carried out on PM biodegradation byproducts indicated no detectable residual toxicity. Any compounds in the environment as a result of the biodegradation of PM should be innocuous polar byproducts that should not exert any toxic effects.
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PMID:Environmental risk assessment of paroxetine. 1526 Mar 35

The present study aimed to compare the effects of two currently used selective serotonin reuptake inhibitors (SSRIs) in Japan taking the individual background in 5-HTT gene-linked polymorphic region (5HTTLPR) genotype into account. Clinical responses to paroxetine and fluvoxamine were evaluated by total and cluster depressive symptoms for 81 Japanese patients who were diagnosed with major depression. Patients with the l allele had a greater percentage reduction on the total score (P=0.059) and somatic anxiety items (P=0.026) of the 21-item Hamilton Depression Rating Scale (HAM-D) score compared to s/s genotype carriers. Paroxetine was significantly more effective than fluvoxamine in the s/s carriers, as evaluated on the percentage reduction in total score (P=0.012) and core (P=0.049) HAM-D after 4 weeks of medication, but not in the l/s carriers. These findings suggest that the genetic test may be useful in investigating the efficacy of the two SSRIs, and that normalization by the 5HTTLPR genotypes may lead to improvement of the precision of comparative analysis.
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PMID:Controlled clinical comparison of paroxetine and fluvoxamine considering the serotonin transporter promoter polymorphism. 1581 65


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