A Double-Blind Comparison of Paroxetine With Imipramine in the Long-Term Treatment of Depression

Claghorn, James L.; Feighner, John P.

doi:10.1097/00004714-199312002-00004

Cited by 37 publications

(19 citation statements)

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“…Such therapy may be important for elderly patients, espe cially if there is a history of earlier depressive illness. In a 1-year study of recovered patients, paroxetine was found to be superior to place bo in preventing both relapse and recurrence of depression [7], In another 1-year study [15]. paroxetine-treated patients were less likely to drop out due to AEs compared with imipramine treatment.…”

Section: Discussionmentioning

confidence: 97%

Paroxetine in the Elderly: A Comparative Meta-Analysis against Standard Antidepressant Pharmacotherapy

Dunbar¹

1995

Pharmacology

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In a meta-analysis often studies in elderly patients, paroxetine (n = 387) was as effective an antidepressant as active controls (amitriptyline n= 110; clomipramine n= 109; doxepin n = 102; mianserin n = 28). The change over 5-6 weeks of therapy, on the Hamilton Depression Rating Scale, was significantly better with paroxetine compared with active controls. A similar advantage was seen when the responder rate was considered. Adverse events were less frequent and less severe with paroxetine treatment, especially anticholinergic adverse events. Paroxetine was effective in treating anxiety symptoms associated with depression, yet caused significantly less sedation compared with active controls. There was little difference in the overall safety profiles seen between the paroxetine and active control groups. However, data are available indicating reduced cardiotoxicity for paroxetine and a beneficial effect on suicidal thoughts. Overall, the results indicate paroxetine is an alternative first-line therapy to these older antidepressants and should be considered when treating elderly patients.

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Section: Discussionmentioning

confidence: 97%

Paroxetine in the Elderly: A Comparative Meta-Analysis against Standard Antidepressant Pharmacotherapy

Dunbar¹

1995

Pharmacology

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“…Relapse studies compared paroxetine to placebo (74) and to imipramine (24). The incidence of relapse in patients on paroxetine was significantly lower than in patients on placebo (15 vs. 25%), but higher than in patients on imipramine (15 vs. 4%).…”

Section: Clinical Studies Depressionmentioning

confidence: 99%

Paroxetine: A Review

Bourin

Chue

Guillon³

2001

CNS Drug Reviews

362

122

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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, has 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. Elimi- 25

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“…[18][19][20][21][22] The length of the acute phase of treatment preceding the continuation phase ranged from 6 to 16 weeks, with 13 of the 16 studies having an acute phase of 6 to 8 weeks ( Table 1). The duration of the continuation phase ranged from 4 to 52 weeks.…”

Section: Resultsmentioning

confidence: 99%

“…9 The length of the continuation phase was 5 to 6 months in 6 studies 5,13,14,20-22 and 9 to 12 months in 9 studies. 8,9,11,12,[15][16][17][18][19] The mean duration of the continuation phase was nearly identical in the extension (34.8 weeks) and placebo substitution studies (34.3 weeks).…”

Section: Resultsmentioning

confidence: 99%

Impact of Study Design on the Results of Continuation Studies of Antidepressants

Zimmerman¹,

Posternak²,

Ruggero³

2007

Journal of Clinical Psychopharmacology

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Antidepressant continuation studies have used 2 different designs. In the placebo substitution design, all patients are initially treated with active medication in an open-label fashion, and then treatment responders are randomized to continue with medication or switch to placebo in a double-blind manner. In the extension design, patients are randomized to a double-blind placebo-controlled acute study at the outset, and responders to active treatment and placebo are continued on the treatment to which they initially responded. We hypothesized that the design of antidepressant continuation studies would impact on the likelihood of relapse. In the extension design, there is no change in treatment. Whether patients responded to placebo or medication, the treatment that produced the response is continued. In contrast, in the placebo substitution design, there is an obvious change in treatment protocol upon initiation of the continuation phase. Patients are aware that they initially received active medication, and there is now a chance that they will be switched to placebo. We speculated that the expectation of a continued positive response is lower in patients treated using the placebo substitution design than the extension design and therefore predicted that relapse rates would be higher. We conducted a meta-analysis of antidepressant continuation studies and compared the relapse rates in continuation studies using these 2 different designs. As predicted, for both the active medication and placebo groups, the frequency of relapse was lower in studies using an extension design. We also found that the difference in relapse risk between antidepressants and placebo was greater with the extension design. Thus, the design of continuation studies of antidepressants was associated with the absolute percentage of patients who relapse on both active medication and placebo, as well as estimates of differential relapse risk between antidepressants and placebo.

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A Double-Blind Comparison of Paroxetine With Imipramine in the Long-Term Treatment of Depression

Cited by 37 publications

References 0 publications

Paroxetine in the Elderly: A Comparative Meta-Analysis against Standard Antidepressant Pharmacotherapy

Paroxetine in the Elderly: A Comparative Meta-Analysis against Standard Antidepressant Pharmacotherapy

Paroxetine: A Review

Impact of Study Design on the Results of Continuation Studies of Antidepressants

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