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

Paroxetine is commonly used as a selective serotonin reuptake inhibitor for the treatment of depression and other psychiatric disorders. However, the molecular mechanisms of the paroxetine effects have not yet been sufficiently clarified. Using Xenopus oocyte expression assays, we investigated the effects of paroxetine on G protein-activated inwardly rectifying K+ (GIRK) channels, which play an important role in reducing neuronal excitability in most brain regions and the heart rate. In oocytes injected with mRNAs for GIRK1/GIRK2, GIRK2, or GIRK1/GIRK4 subunits, paroxetine reversibly reduced inward currents through the expressed GIRK channels. The inhibition was concentration-dependent, but voltage-independent and time-independent during each voltage pulse. However, two structurally different antidepressants: milnacipran and trazodone, caused only a small inhibition of basal GIRK currents. Additionally, Kir1.1 and Kir2.1 channels were insensitive to all of the antidepressants. Furthermore, the GIRK currents induced by activation of A1 adenosine receptors or by ethanol were inhibited by extracellularly applied paroxetine in a concentration-dependent manner, but not affected by intracellularly applied paroxetine. Our results suggest that inhibition of GIRK channels by paroxetine may contribute partly to some of its therapeutic effects and adverse side effects.
 ...
PMID:Inhibition of G protein-activated inwardly rectifying K+ channels by the antidepressant paroxetine. 1707 3

The aim of this study was to determine whether treating concomitant depression improves quality of life and exercise tolerance in COPD patients. Out-patients with moderate to severe, stable COPD completed Hospital Anxiety-Depression (HAD) and General Health questionnaires. A psychiatrist interviewed those with high scores. In a randomised, double-blind fashion, 28 depressed COPD patients took a selective serotonin re-uptake inhibitor, Paroxetine 20 mg daily, or matched placebo for 6 weeks. Subsequently, all patients took un-blinded Paroxetine for 3 months. From these questionnaires, 35% of 135 patients had significant depression, but this was confirmed by psychiatric interview in only 21%. Throughout the study, there were no changes in laboratory lung function nor in home peak flow. Six weeks' treatment produced no significant differences between placebo and treatment group in either depression, quality of life scores or 6-minute walking distances, although overall improvements in depression, correlated with increases in walking distance. Three months of un-blinded treatment, significantly improved depression scores (self-complete HAD, Beck's Depression and psychiatrist-completed Montgomery-Asberg scores), walking distances (369 to 427 m, p = 0.0003) and St. George's Respiratory Questionnaire Total Scores (65 to 58, p = 0.033). Although self-complete questionnaires over-diagnose depression, the condition is nevertheless common in patients with moderately severe COPD. Six weeks of antidepressants is insufficient to improve either depression, quality of life or exercise tolerance. However, our study suggests that a longer course of treatment may be effective and that improvements in depression are associated with improvements in exercise tolerance. A larger, double blind study with a longer treatment period is indicated.
 ...
PMID:Effect of treating depression on quality-of-life and exercise tolerance in severe COPD. 1713 45

We present a first case of Parkinson's disease with neuroleptic malignant syndrome by Paroxetine, one of the selective serotonin reuptake inhibitor (SSRI). The patient was a 73-year-old woman who had been diagnosed as Parkinson's disease for one and half year. The severity of her disease was categorized as Hoehn & Yahr 2nd degree and she had taken 0.25 mg/day of Pramipexole. Four days after the addition of 10 mg/day of Paroxetine for the treatment of her depression, she developed consciousness disturbance, severe muscular rigidity, tremor, fever, hyperhidrosis, incontinence and elevated serum creatine kinase level. According to diagnostic criteria, she was diagnosed as neuroleptic malignant syndrome probably induced by Paroxetine. Her clinical symptoms and laboratory data were improved seven days after intravenous drip infusion. We should recognize that SSRI could induce neuroleptic malignant syndrome in patients with Parkinson's disease.
 ...
PMID:[A case of Parkinson's disease with neuroleptic malignant syndrome induced by paroxetine]. 1715 40

Paroxetine is a selective serotonin reuptake inhibitor (SSRI) with antidepressant and anxiolytic properties. It is commercially available in both an immediate-release (paroxetine) and a controlled-release formulation (paroxetine CR). The latter product was developed to improve gastrointestinal tolerability. Paroxetine is the most potent inhibitor of the reuptake of serotonin among the available SSRIs. It has approved indications for the treatment of major depression, obsessive-compulsive disorder, panic disorder, generalized anxiety disorder, post-traumatic stress disorder and social phobia in adults. Paroxetine CR is approved for the treatment of major depression, social anxiety disorder, panic disorder and premenstrual dysphoric disorder in adults. While the overall efficacy of paroxetine appears to be comparable with other SSRIs in the treatment of major depression, it is approved for use in a wider variety of anxiety disorders than any other antidepressant. Long-term data suggest that paroxetine is effective in preventing relapse or recurrence of depression for up to 1 year. Limited data show that paroxetine maintains a therapeutic response over 1 year in obsessive-compulsive disorder and up to 6 months in panic disorder. The side-effect profile of paroxetine is largely similar to that of the other SSRIs, although paroxetine tends to be more sedating and constipating in some patients, perhaps due to its anticholinergic activity. The potential for discontinuation syndrome and weight gain appears to be slightly higher with paroxetine than with other SSRIs. This review focuses on the immediate release and controlled-release formulations of paroxetine. It summarizes the efficacy and tolerability data for both formulations, with a particular emphasis on paroxetine CR which was introduced in 2002. It also discusses emerging evidence in other clinical areas and recent data that have led to modifications in the safety profile of paroxetine.
 ...
PMID:Paroxetine: current status in psychiatry. 1728 45

A history of depression is a risk factor for Alzheimer's disease (AD), suggesting the possibility that antidepressants administered prophylactically might retard the disease process and preserve cognitive function. Here we report that pre-symptomatic treatment with the antidepressant paroxetine attenuates the disease process and improves cognitive performance in the 3xTgAD mouse model of AD. Five-month-old male and female 3xTgAD and non-transgenic mice were administered either paroxetine or saline daily for 5 months. Open-field activity was tested in 7-month-old mice and performance in passive avoidance and Morris swim tasks were evaluated at 10 months. 3xTgAD mice exhibited reduced exploratory activity, increased transfer latency in the passive avoidance test and impaired performance in the Morris spatial navigation task compared to nontransgenic control mice. Paroxetine treatment ameliorated the spatial navigation deficit in 3xTgAD male and female mice, without affecting swim speed or distance traveled, suggesting a preservation of cognitive function. Levels of amyloid beta-peptide (Abeta) and numbers of Abeta immunoreactive neurons were significantly reduced in the hippocampus of male and female paroxetine-treated 3xTgAD mice compared to saline-treated 3xTgAD mice. Female 3xTgAD mice exhibited significantly less tau pathology in the hippocampus and amygdala compared to male 3xTgAD mice, and paroxetine lessened tau pathology in male 3xTgAD mice. The ability of a safe and effective antidepressant to suppress neuropathological changes and improve cognitive performance in a mouse model suggests that such drugs administered prophylactically might retard the development of AD in humans.
 ...
PMID:Prophylactic treatment with paroxetine ameliorates behavioral deficits and retards the development of amyloid and tau pathologies in 3xTgAD mice. 1766 78

A rapid and sensitive high-performance liquid chromatographic method was validated and described for determination of paroxetine in human saliva. Following liquid-liquid extraction of the drug and an internal standard (dibucaine), chromatographic separation was accomplished using a C18 analytical column with a mobile phase consisting of 0.05 mol/L sodium phosphate buffer, pH 5.0, and acetonitrile (A 30:70, v/v; B 60:40, v/v). Paroxetine and the internal standard were detected by ultraviolet absorbance at 205 nm. The average recoveries of the drug and internal standard were 92.5% and 89%, respectively. The lower limits of detection and quantification were 1 and 4 ng/ml, respectively, and the calibration curve was linear over a concentration range of 4 ng/ml. The saliva level of paroxetine in patients with depression taking 10 to 40 mg/day of the drug was significantly correlated with the plasma level of paroxetine in each patient (r = 0.617, P < 0.004, n = 19). These data indicate that the saliva level of paroxetine could be a useful marker to predict the plasma level of the drug.
 ...
PMID:Determination of paroxetine in human saliva by reversed-phase high-performance liquid chromatography with UV detection. 1739 74

The present study was designed to assess the effect of dexamethasone, a synthetic glucocorticoid receptor agonist, in the sucrose preference test in rats. Rats treated acutely with dexamethasone (5-10 mg/kg) showed a significant decrease in sucrose preference (anhedonia) in comparison to vehicle treated rats, although 1 mg/kg dexamethasone did not alter the sucrose preference. Daily paroxetine treatment (10 g/kg, i.p., 14 days) reversed the anhedonic effect of acute dexamethasone (5 mg/kg), while causing no increased sucrose preference in rats that received dexamethasone vehicle. The paroxetine vehicle treated rats showed anhedonia even 14 days after acute dexamethasone administration. Paroxetine (10 mk/kg, i.p. for 28 days) also reversed anhedonia induced by chronic mild stress (8 weeks). In conclusion, acute dexamethasone induced an enduring anhedonic state that was reversed by repeated paroxetine treatment. Thus, the present study adds new data to the evidence supporting an important role for glucocorticoid in depression.
 ...
PMID:Repeated paroxetine treatment reverses anhedonia induced in rats by chronic mild stress or dexamethasone. 1746 66

Tetrahydrobiopterin (BH(4)) is a coenzyme of tyrosine hydroxylase (TH) and tryptophan hydroxylase (TPH), which are rate-limiting enzymes of monoamine biosynthesis. According to the monoamine hypothesis of depression, antidepressants will restore the function of the brain monoaminergic system and the BH(4) concentration. In the present study, we investigated the effect of paroxetine, a selective serotonin reuptake inhibitor (SSRI), on the BH(4) levels and dopamine (DA) and serotonin (5-HT) turnover in the mesoprefrontal system, incorporating two risk factors of depression, social isolation and acute environmental change. Male ddY mice (8W) were divided into two housing groups, i.e., group-housing (eight animals per cage; 28 days), and isolation-housing (one per cage; 28 days), being p.o.-administered paroxetine (5 or 10 mg/kg; days 15-28), and exposed to a 20-min novelty stress (day 28). The levels of BH(4), DA, homovanilic acid (HVA), 5-HT, and 5-hydroxyindoleacetic acid (5-HIAA) were measured in the prefrontal cortex and midbrain. In both the regions, novelty stress significantly increased BH(4) levels under the isolation-housing condition, whereas these levels were decreased under the group-housing condition. Thus, social isolation altered the neurochemical response to novelty stress. Paroxetine significantly decreased BH(4) levels under the isolation-housing condition, whereas decreased HVA/DA and 5-HIAA/5-HT ratios were observed under the group-housing condition. Thus, social isolation may have influenced the suppressive effects of paroxetine on BH(4) levels as well as exerted an influence on DA and 5-HT turnover. We replicated our recent findings that SSRI, fluvoxamine, suppressed BH(4) levels, as well as DA and 5-HT turnover in the mouse mesoprefrontal system.
 ...
PMID:Suppressive effect of paroxetine, a selective serotonin uptake inhibitor, on tetrahydrobiopterin levels and dopamine as well as serotonin turnover in the mesoprefrontal system of mice. 1755 97

Fatigue is a common and highly distressing symptom of cancer associated with reduced quality of life and considerable psychological and functional morbidity. The reported prevalence of cancer-related fatigue ranges from 4% to 91%, depending on the specific cancer population studied and the methods of assessment. Cancer-related fatigue has typically been underreported, underdiagnosed, and undertreated. Fatigue and depression may coexist in cancer patients, and considerable overlap of symptoms occurs. This is partly the reason for the interest in examining the role of psychotropic medications in treating fatigue. Clarifying the relationship between depression and fatigue is necessary to effectively evaluate and treat cancer-related fatigue. Even with International Classification of Diseases criteria, differentiating cancer-related fatigue is difficult. Psychotropic drugs that have been studied for cancer-related fatigue include psychostimulants, wakefulness-promoting agents, and antidepressants. Methylphenidate has been studied most and seems to be effective and well tolerated despite common side effects. Some preliminary data support using modafinil in cancer-related fatigue with less concern about tolerance or dependence. Antidepressant studies have shown mixed results. Paroxetine seems to show benefit for fatigue primarily when it is a symptom of clinical depression. Bupropion, a norepinephrine/dopamine reuptake inhibitor, may have psychostimulant-like effects, and therefore may be more beneficial for treating fatigue. However, studies are currently limited. Randomized, placebo-controlled trials with specific agents are needed to further assess the efficacy and tolerability of psychotropic medications in the treatment of cancer-related fatigue.
 ...
PMID:Update on psychotropic medications for cancer-related fatigue. 1805 30

We report an 82-year old man prescribed paroxetine who had hyponatremia and in whom the syndrome of inappropriate secretion of antidiuretic hormone was diagnosed. He had taken sulpiride for depressed mental status. However, he showed parkinsonism, which was an adverse effect from the treatment of sulpiride. Therefore sulpiride was changed to selective serotonin reuptake inhibitor, paroxetine 10mg daily. His depressed mental status deteriorated after paroxetine treatment started. His depression had not lessened after 12 days, and the dosage was increased to 20mg daily. On the 15th day after starting paroxetine, routine laboratory tests showed that his serum sodium level was 126 mEq/l. We recognized that his confusion and loss of appetite were symptoms of hyponatremia, rather than of worsening depression. Laboratory data revealed hyponatremia, low serum osmolarity (242 mOsm/kg) with a relatively high level of serum antidiuretic hormone, and concentrated urine (439 mOsm/kg). We diagnosed the syndrome of inappropriate secretion of antidiuretic hormone (SIADH), associated with paroxetine. The dosage of paroxetine was reduced gradually and the serum sodium level returned to normal on day 2 after medication ceased completely. Paroxetine produces fewer adverse effects than other types of antidepressants. However, its use can be associated with inappropriate secretion of antidiuretic hormone in the body and may lead to SIADH, which is characterized by hyponatremia, a potentially fatal condition that is typically asymptomatic until it becomes severe. SIADH is more likely in some populations, including the elderly. Serum sodium levels should be monitored closely, especially in elderly patients.
 ...
PMID:[Paroxetine-induced hyponatremia in an elderly man due to the syndrome of inappropriate secretion of antidiuretic hormone]. 1833 78


<< Previous 1 2 3 4 5 6 7 8 9 10