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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pharmacology and pharmacokinetics, adverse effects, drug interactions, efficacy, and dosage and administration of the new selective serotonin reuptake inhibitors paroxetine, sertraline, and fluvoxamine are reviewed. Paroxetine, sertraline, and fluvoxamine all have large volumes of distribution and are highly bound to plasma proteins. In contrast to fluoxetine, these three drugs possess shorter elimination half-lives of approximately one day and are metabolized to clinically inactive compounds. Nausea was the most commonly reported adverse effect for all three agents. Other reported adverse effects are headache, sedation, dry mouth, insomnia, sexual dysfunction, and constipation. Because of their favorable pharmacokinetic profiles, paroxetine, sertraline, and fluvoxaetine are less likely than fluoxamine to interact with other drugs. Paroxetine has been found to be superior to placebo and equivalent to amitriptyline, imipramine, clomipramine, and doxepin in treatment of depression. Sertraline has been found to be superior to placebo and equivalent to amitriptyline in treatment of depression. Fluvoxamine has been found to be superior to placebo and equivalent to imipramine, clomipramine, desipramine, mianserin, and maprotiline in the treatment of depression. Fluvoxamine and sertraline have been shown to be superior to placebo in the treatment of obsessive-compulsive disorder. Clinical experience has demonstrated all three drugs to be effective in treatment of depression. They may be especially useful in elderly patients, in those who cannot tolerate alternative treatments, and in those who do not respond to adequate trials of other antidepressant therapies.
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PMID:Paroxetine, sertraline, and fluvoxamine: new selective serotonin reuptake inhibitors. 146 19

Depressive illness among the elderly is an important public health concern. However, treatment of the elderly may be complicated by age-related changes in physiology, general medical status, and susceptibility to side effects. There is therefore a need for improved treatment modalities for depressed elderly patients. Paroxetine is an antidepressant that acts through selective inhibition of serotonin reuptake. It lacks the anticholinergic and cardiovascular side effects of most first- and second-generation antidepressants. The authors present the combined data from two similarly designed comparisons of paroxetine and doxepin in outpatients over 60 years of age with major depression. The results show that paroxetine was an effective as doxepin in alleviating depression as measured on the Hamilton Rating Scale for Depression (HAM-D) total score, the Montgomery and Asberg Depression Rating Scale (MADRS), and the Hopkins Symptom Checklist (SCL) depression factor score. Paroxetine was significantly superior to doxepin on the Clinical Global Impressions (CGI) scale for severity of illness, the HAM-D retardation factor, and the HAM-D depressed mood item. Doxepin produced significantly more anticholinergic effects, sedation, and confusion. Paroxetine was associated with more reports of nausea and headache. These results suggest that paroxetine may be a valuable tool for the treatment of major depression in the elderly.
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PMID:Two combined, multicenter double-blind studies of paroxetine and doxepin in geriatric patients with major depression. 153 27

Paroxetine is a potent and selective inhibitor of the neuronal reuptake of serotonin, thereby facilitating serotoninergic transmission; this action appears to account for the antidepressant activity observed with this drug. A mean terminal elimination half-life of approximately 24 hours permits once daily administration. Results of short term clinical trials have shown paroxetine to be significantly superior to placebo, and comparable to amitriptyline, clomipramine, imipramine, dothiepin and mianserin in relieving symptoms associated with major depressive disorders. Paroxetine has shown some preliminary promise in the treatment of depressive illness resistant to tricyclic antidepressant therapy but further studies are required before any conclusions can be drawn. Paroxetine in therapeutic doses has been very well tolerated, and the favourable tolerability profile of this agent appears to be its primary advantage over traditional antidepressant agents. Paroxetine causes minimal anticholinergic-type adverse effects, and unlike tricyclic antidepressants, it does not precipitate cardiovascular effects or provoke cardiac conduction disturbances. Nausea has been the most frequently reported adverse event during short term use of paroxetine, but it is generally mild and transient and subsides with continued use. With longer term use headache, sweating and constipation were the most frequently reported side effects but the incidence rate was not significantly different from that noted for comparator antidepressants. Furthermore, the frequency of withdrawal due to adverse effects is less with paroxetine than with tricyclic antidepressant agents. Overall, available data appear to indicate that while the efficacy of paroxetine is similar to that of traditional antidepressant drugs, the newer agent possesses much improved tolerability. In addition, the wide therapeutic index of paroxetine may be beneficial when treating patients with an increased risk of suicide. Thus, paroxetine clearly looks to become a valuable addition to the range of drugs currently available to treat depressive illness. Future research may help to further define the relative place of this newer agent in antidepressant therapy and determine how its overall therapeutic efficacy compares with that of other related antidepressant agents such as fluoxetine.
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PMID:Paroxetine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in depressive illness. 170 52

Paroxetine is a new antidepressant drug. It is a potent and selective 5-HT re-uptake inhibitor with only weak anticholinergic properties and less effect on the cardiovascular system than the classical tricyclics. In this double-blind multicenter study the antidepressant effect of paroxetine was compared with mianserin in 70 patients with unipolar or bipolar depression. Each drug was administered for 6 weeks after a 1 week run-in period at a daily dosage of 30 mg for paroxetine or 60 mg for mianserin. The 21-item Hamilton Depression Rating Scale (HAM-D) and the physician's global assessment were used to assess efficacy. Both treatment groups showed statistically significant improvement of the HAM-D at Weeks 1 (base-line values: paroxetine mean 28.5; mianserin mean 30.8) through to Week 6 (paroxetine mean 11.5; mianserin mean 17.8) (P less than 0.06). The endpoint differences between treatments however were not statistically different (P = 0.11). The Cleary and Guy factor analysis showed a significant difference (P less than 0.03) at Weeks 2 and 4 for cognitive disturbance and at Weeks 4 and 6 for retardation in favour of paroxetine compared with mianserin. Both drugs were well tolerated with nausea and headache in four patients and somnolence in six patients being reported as the most common side-effect for paroxetine and mianserin respectively.
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PMID:Paroxetine in the treatment of depression. A double-blind multicenter study versus mianserin. 297 Feb 3

Paroxetine, a new, potent and selective serotonin (5-HT) uptake inhibitor has been evaluated in an open study for its clinical effect as well as its effect on the 5-HT concentration in whole blood in 19 patients with depressive illness. Paroxetine was administered in daily doses of 20 to 60 mg. The global evaluation after six to eight weeks showed a marked improvement in 11 patients, a moderate improvement in four and no change in four patients. Assessment with the Hamilton Rating Scale for Depression in ten patients showed a reduction from a mean score of 22.7 to 6.6 in six weeks. Maximal reduction was, however, first seen in three of the patients after 8 to 12 weeks. No correlation between the antidepressant effect and plasma concentrations of paroxetine was found. The only side effects noted with paroxetine were that two patients complained of dry mouth in the beginning of the treatment and a further patient experienced a burning sensation together with periodical light headache. Generally laboratory examinations did not show any trend towards pathological values except in one patient, where a moderate leucopenia was observed. Crista puncture/biopsy showed, however, no specific bone marrow reaction. The 5-HT concentration in whole blood was reduced to about 0.02 micrograms/ml indicating a total depletion of 5-HT from the thrombocytes. The present study indicates that paroxetine possesses a good antidepressive effect in combination with a very low frequency of side effects.
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PMID:An early clinical phase II evaluation of paroxetine, a new potent and selective 5HT-uptake inhibitor in patients with depressive illness. 621 7

Forty-eight patients with chronic daily headache, unresponsive to several combinations of pharmacological treatments, were selected for an open-label study using paroxetine. Patients were given 10 mg to 50 mg of paroxetine for a period of 3 to 9 months. Ninety-two percent of the patients improved significantly, based on the patients' percent of the reduction in number of headache days per month. The common side effects were fatigue, insomnia, and urogenital disturbances. The possible mechanism of action of paroxetine in the treatment of chronic daily headache is discussed. Paroxetine appears to be effective in the treatment of chronic daily headache; however, double blind studies are needed to confirm these preliminary findings.
Headache
PMID:Paroxetine in the treatment of chronic daily headache. 784 54

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.
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PMID:Paroxetine. An update of its pharmacology and therapeutic use in depression and a review of its use in other disorders. 946 92

During the past 4 years, several case reports have been published on the withdrawal syndrome which may be observed after acute interruption of a treatment with selective serotonin reuptake inhibiting antidepressants (SSRI). Paroxetine is the most frequently cited antidepressant in the literature, whereas fluoxetine is the less frequently cited of this type of drugs. The withdrawal symptoms appear a few days after stopping treatment or after a decrease of the dose. The typical symptoms are of the gastro-intestinal type, such as loss of appetite, nausea, vomiting, diarrhea and abdominal cramps. Other symptoms are sensation of instability, vertigo, dizziness, headache, malaise, muscular pains, asthenia, as well as a syndrome of pseudo-influenza. Brief electric shocks throughout the body, which last one or two seconds, have also been reported. A case is reported in detail by the authors, who observed some of these symptoms in a patient after stopping his treatment with paroxetine. This withdrawal syndrome may be due to a rebound phenomenon of the serotonergic systems after interruption of the treatment with SSRIs. It is, therefore, recommended that treatment with SSRIs is progressively stopped over a period of several weeks.
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PMID:[Withdrawal syndrome caused by selective serotonin reuptake inhibitors: apropos of a case]. 954 42

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

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.
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PMID:Paroxetine: an update of its use in psychiatric disorders in adults. 1189 34


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