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)

Paroxetine is a selective serotonin reuptake inhibitor (SSRI) with proven efficacy in the treatment of depression, panic disorder and obsessive-compulsive disorder. Evidence that paroxetine may be effective in social anxiety disorder (social phobia) first arose from open-label studies. More recently, three multicentre, randomized, placebo-controlled trials have been performed, each lasting 12 weeks, to assess the efficacy and tolerability of paroxetine in the treatment of social anxiety disorder, and these studies are reviewed here. The data from all three studies consistently demonstrated that paroxetine was effective in reducing both the symptoms of anxiety and the disability and impairment of social anxiety disorder. Paroxetine performed significantly better than placebo on all primary (Liebowitz Social Anxiety Scale, Clinical Global Impression) and secondary (Social Avoidance and Distress Scale, Sheehan Disability Scale) outcome measures. Adverse events were restricted to those already known to be associated with SSRIs, no serious adverse events associated with medication were experienced, and the numbers withdrawing from the studies were not significantly different in the paroxetine and control groups. Taken together, these studies confirm that paroxetine is an effective and well tolerated treatment for patients with social anxiety disorder.
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PMID:Clinical experience with paroxetine in social anxiety disorder. 1099 79

Depression is a common finding in patients with Parkinson's disease (PD). Traditionally, depression has been treated with tricyclic antidepressants, which are often associated with undesirable side effects that may limit their use in PD. Few studies have been performed with selective serotonin reuptake inhibitors (SSRIs) in these patients. We assessed the tolerability of the SSRI antidepressant paroxetine (10-20 mg once per day) in 65 outpatients with PD and depression for a period of at least 3 months. Treatment was continued for 125.3+/-89.6 days (mean +/- standard deviation) in 52 patients. In these subjects the Hamilton Disease Rating Scale improved from 21.7+/-6.4 to 13.8+/-5.8 (p <0.001). Overall, 13 patients stopped paroxetine after 9.6+/-10.6 days because of adverse reactions. Two patients reported increased "off" time and tremor that reversed after treatment was stopped. No risk factors for intolerance were identified. Paroxetine is a safe and effective drug to treat depression in PD.
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PMID:Tolerability of paroxetine in Parkinson's disease: a prospective study. 1100 10

The abrupt discontinuation of antidepressants can result in a syndrome of adverse events, including somatic, mood and psychomotor reactions. This study examined the effects of discontinuing and resuming antidepressant treatment with four selective serotonin reuptake inhibitors (SSRIs) on cognitive and psychomotor function. Eighty-seven patients receiving maintenance therapy with fluoxetine, sertraline, paroxetine or citalopram had their treatment interrupted for 4-7 days using double-blind placebo. Assessments of aspects of cognitive and psychomotor performance, mood and symptoms were carried out at each visit. Following interruption of treatment, significant differences between the groups emerged. Paroxetine treated patients experienced significantly more cognitive failures (P = 0.007), poorer quality of sleep (P = 0.016), and an increase in depressive symptoms, as rated both subjectively, using the Zung scale (P = 0.006) and by the clinician, using the Montgomery-Asberg Depression Rating Scale (P = 0.0003) and Clinical Global Impression (P = 0.0003), compared to some or all of the other drugs. All changes were reversed on reinstatement of treatment. Abrupt discontinuation of treatment with paroxetine leads to deterioration in various aspects of health and functioning, which may be related to the antidepressant discontinuation syndrome. These effects are not evident in patients receiving fluoxetine, sertraline and citalopram, suggesting they are not an SSRI class phenomenon.
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PMID:Abrupt and brief discontinuation of antidepressant treatment: effects on cognitive function and psychomotor performance. 1111 6

Previous studies have shown a positive association between pain and depression, though evidence supporting a direct link between these two variables is less robust. Using a placebo-controlled trial, the authors examined the analgesic and antidepressant efficacy of paroxetine (20 mg) in chronic low back pain sufferers. The authors examined the associations among pain, depression, disability, and illness attitudes. Paroxetine showed no effects on pain or depression compared with placebo; however, subjects randomized to paroxetine were more likely to reduce concomitant analgesic medication. The cross-sectional association of depression and pain at baseline (r = 0.2, P = 0.02) was weaker than the association between depression and disability (r = 0.3, P = 0.004). Similarly, the association of change in depression scores with change in pain (r = 0.25, P = 0.016) was weaker than change between depression and disability (r = 0.49, P<0.0005). Whereas the relationship between pain and depression became nonsignificant when disability and illness attitudes were controlled, the relationship between depression and disability remained highly significant when pain and illness attitudes were controlled. These data are consistent with the association between pain and depression being wholly modulated by disability and illness attitudes, with no direct relationship between pain and depression.
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PMID:The relationship between pain and depression in a trial using paroxetine in sufferers of chronic low back pain. 1218 67

Numerous studies have reported gender differences in the rates of depression in humans, but few behavioural observations of antidepressant drug effects have been investigated in female mice. The forced swimming test (FST) is widely used as a predictor of antidepressant activity in rodents, as is the tail suspension test (TST), where immobility is objectively measured and in this last test, no hypothermia is induced by immersion in cold water. The present study investigated gender differences in the temperature profile of mice after acute antidepressant administration (imipramine and paroxetine) and exposure to two animal models of depression. Imipramine and paroxetine were active at 32 mg/kg in male mice in the FST, whereas they were active at 8, 16 and 32 mg/kg in female mice. In the TST, for both antidepressants immobility duration was reduced at a dose of 16 and 32 mg/kg in male mice and at 32 mg/kg in female mice. No significant difference was observed between male and female mice for immobility duration. Imipramine administration, but not paroxetine, decreased the temperature at the higher dose (32 mg/kg) in male and female mice in the FST. The body temperature was reduced in male and female mice for all treatment groups after FST challenge. Imipramine (16 and 32 mg/kg in male and 32 mg/kg in female mice), paroxetine (4, 16 and 32 mg/kg in male and 4 to 32 mg/kg in female mice) attenuated the reduction in temperature due to the FST. In the TST, imipramine tends to decrease the temperature in male and female mice, even though only imipramine at a dose of 32 mg/kg in female mice significantly decreases the temperature. Paroxetine had no effect on temperature. The TST enhanced the body temperature in male and female mice. In mice, there was no difference between the sexes after imipramine or paroxetine administration in the FST and TST. Both tests can be used to predict the activity of antidepressants as the decrease or enhancement of temperature is not correlated with a reduction in immobility duration.
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PMID:Are there gender differences in the temperature profile of mice after acute antidepressant administration and exposure to two animal models of depression? 1116 36

Elderly depressed patients are vulnerable to recurrence of depression and benefit from long-term antidepressant therapy. Physicians increasingly use selective serotonin re-uptake inhibitors (SSRIs) as maintenance therapy, although in the absence of data showing that SSRIs are as efficacious as tricyclic antidepressants (TCAs) in the prevention of depression relapse and recurrence. Our objective was to evaluate, in an open trial, the efficacy of paroxetine versus nortriptyline for preventing recurrence of depression in the elderly. Elderly patients with major depression were randomly assigned in a double-blinded fashion to receive either paroxetine or nortriptyline for the acute treatment of depression. Patients who did not respond or tolerate their assigned medications were crossed over openly to the comparator agent. Patients whose depression remitted continued antidepressant medication (paroxetine n = 38; nortriptyline n = 21) during an open 18-month follow-up study. We examined the rates of and times to relapse and to termination of treatment for any reason. Paroxetine (PX) and nortriptyline (NT) patients had similar rates of relapse (16% vs. 10%, respectively) and time to relapse (60.3 weeks vs. 58.8 weeks, respectively) over 18 months. A lower burden of residual depressive symptoms and side effects during continuation and maintenance treatment was evident in nortriptyline-treated patients. Paroxetine and nortriptyline demonstrated similar efficacy in relapse and recurrence prevention in elderly depressed patients over an 18-month period.
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PMID:Paroxetine versus nortriptyline in the continuation and maintenance treatment of depression in the elderly. 1123 59

This meta-analysis examined efficacy and tolerability data from 39 randomized, double-blind, parallel-group studies comparing paroxetine (n = 1924) with clomipramine (n = 141) or other tricyclic antidepressants (TCAs; n = 1693) in the treatment of major depression. Paroxetine had comparable antidepressant efficacy to TCAs, including clomipramine, as assessed by response rates based on a < or = 50% reduction in Hamilton Rating Scale for Depression (HAMD) total score (58-66%) and a HAMD total score < or = 8 (38-48%) at endpoint, and absolute improvements in HAMD total score (mean change 12.3-14.5). Absolute improvements in HAMD anxiety factor scores were similar between paroxetine and clomipramine (mean change 2.3 versus 2.4, P = 0.566), but paroxetine was statistically significantly more effective on this measure than other TCAs (mean change 2.3 versus 2.1, P = 0.028). The proportion of patients who experienced adverse events with > 1% incidence was statistically significantly lower with paroxetine than with clomipramine (64% versus 77%, P = 0.02) or other TCAs (64% versus 71%, P < 0.001). The incidence of patient withdrawals due to adverse events was also statistically significantly lower with paroxetine than with clomipramine (17% versus 27%, P = 0.014), but an advantage seen for paroxetine over other TCAs (17% versus 20%, P = 0.130) did not reach statistical significance. These findings demonstrate that paroxetine has comparable efficacy to and better tolerability than TCAs, including clomipramine, and is therefore an appropriate treatment strategy for depression, particularly in the common clinical situation where concomitant anxiety symptoms are present.
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PMID:A meta-analysis of the efficacy and tolerability of paroxetine versus tricyclic antidepressants in the treatment of major depression. 1135 39

Paroxetine is a potent and selective serotonin reuptake inhibitor (SSRI) with currently approved indications for the treatment of depression, obsessive-compulsive disorder, panic disorder and social phobia. It is also used in the treatment of generalized anxiety disorder, post traumatic stress disorder, premenstrual dysphoric disorder and chronic headache. Paroxetine, a phenylpiperidine derivative, is the most potent inhibitor of the reuptake of serotonin (5-hydroxytryptamine, 5-HT) of all the currently available antidepressants including the class of SSRIs. It is a very weak inhibitor of norepinephrine (NE) uptake but it is still more potent at this site than the other SSRIs. The selectivity of paroxetine, i.e., the ratio of inhibition of uptake of norepinephrine to serotonin (NE/5-HT) is amongst the highest of the SSRIs. Paroxetine has little affinity for catecholaminergic, dopaminergic or histaminergic systems and by comparison with tricyclic antidepressants (TCAs) has, therefore, a reduced propensity to cause central and autonomic side effects. Paroxetine exhibits some affinity for the muscarinic cholinergic receptor but much less than the TCAs. In addition, the adaptive changes of somatodendritic (5-HT(1A)) and terminal (5-HT(1B/1D)) autoreceptors observed with paroxetine are different to those observed with TCAs; it also inhibits nitric oxide synthase. It is both a substrate and an inhibitor of cytochrome isoenzyme P450 2D6. Paroxetine is well absorbed orally and undergoes extensive first pass metabolism that is partially saturable. Its metabolites are pharmacologically inactive in vivo. Steady state levels are achieved after 4-14 days and an elimination half-life of 21 h is consistent with once-daily dosing. There is wide inter-individual variation in the pharmacokinetics of paroxetine in adults as well as in the young and the elderly with higher plasma concentrations and slower elimination noted in the latter. Elimination is also reduced in severe renal and hepatic impairment. Serious adverse events are, however, extremely rare even in overdose. In summary, paroxetine is well tolerated and effective in the treatment of both depressive and anxiety disorders across the age range.
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PMID:Paroxetine: a review. 1142 May 71

Three new antidepressants were used in treating posttraumatic stress disorder (PTSD) and symptoms of depression in Bosnian refugees. Thirty-two Bosnian refugees seeking treatment at a mental health clinic participated in a case series study. All received open trials of Sertraline (n = 15), Paroxetine (n = 12), or Venlafaxine (n = 5), with standard clinical doses. Overall, Sertraline and Paroxetine produced statistically significant improvement at 6 weeks in PTSD symptom severity in depression, and in Global Assessment of Functioning. Venlafaxine produced improvement in PTSD symptom severity and in Global Assessment of Functioning, did not yield improvement in symptoms of major depressive disorder; and had a high rate of side effects. Notwithstanding improvement of symptoms, all 32 refugees remained PTSD positive at the diagnostic level at the 6-week follow-up.
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PMID:Sertraline, paroxetine, and venlafaxine in refugee posttraumatic stress disorder with depression symptoms. 1153 76

The authors describe the use of three new antidepressants: Sertralilne, Paroxetine and Venlafaxine in treating Posttraumatic Stress Disorder and symptoms of Depression in adult Bosnian refugees victims of ethnic cleansing. 32 Bosnian refugees with PTSD and symptoms of Depression presenting for treatment of the mental health consequences of surviving ethnic cleansing, participated in a case series study. All subjects completed open trials of Sertraline (15), Paroxetine (12) or Venlafaxine (5), with standard clinical doses. Overall, Sertraline and Paroxetine yielded statistically significant improvement at 6 weeks in the total PTSD symptom severity, in each symptom cluster, in Beck Depression Inventory and in Global Assessment of Functioning. Venlafaxine produced statistically significant improvement at 6 weeks in the total PTSD symptom severity, in each symptom cluster and in Global Assessment of Functioning but did not yield significant improvement in symptoms of depression and had a high rate of side effects.
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PMID:Sertralilne, paroxetine and venlafaxine in refugee post traumatic stress disorder with depression symptoms. 1179 92


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