Cardiovascular effects of paroxetine, a newly developed antidepressant, in anesthetized dogs in comparison with those of imipramine, amitriptyline and clomipramine.

Yokota, Syunji; Ishikura, Yoshiyuki; Ono, Hiroshi

doi:10.1254/jjp.45.335

Cited by 19 publications

(12 citation statements)

References 21 publications

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“…At an infusion rate of 8.7 -8.9 mg/kg/h, slight increases in QTc were found in two of four rabbits and no cats. In dogs, a dose of up to 10 mg/kg caused increases of QTc, PR and QRS of < 10%, lasting only 1 -2 min, although higher nonphysiological doses caused significant changes [87]. A study in four healthy males of single doses of 45 mg and slow intravenous infusion of 23 -28 mg produced reductions in HR [88].…”

Section: The Ssrismentioning

confidence: 96%

Psychotropic drugs and the ECG: focus on the QTc interval

Goodnick

Jerry²,

Parra³

2002

Expert Opinion on Pharmacotherapy

100

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The QT interval measuring depolarisation and repolarisation has, when lengthened, been implicated as a risk factor for the development of torsades de pointes and sudden death, particularly in patients predisposed to these complications due to cardiovascular impairment. Since some of the medications used in psychiatry have been implicated, an extensive review of available literature was made of the major classes, including antipsychotics, antidepressants, lithium, anticonvulsants and benzodiazepines. Further, where no publications were found on a particular medication, the pharmaceutical firms responsible for these items were contacted concerning possibly unpublished data. Results of the survey indicate that there may be difficulty in one of three situations: immediate (in the first minutes to hours after oral or parenteral administration), short-term use of 4 - 12 weeks or long-term use of 6 months. Based on this approach, the greatest concern is directed at the immediate application of haloperidol, droperidol, pimozide and trazodone, the short-term use of thioridazine, pimozide, sertindole, nortriptyline, clomipramine, doxepin and the long-term use of clozapine, olanzapine and carbamazepine. It is of interest that a reduction in QTc is reported with aripiprazole. Among the antidepressants, the tertiary tricyclic antidepressants (imipramine, amitriptyline and doxepin) appear to have a more general impact, while the secondary tricyclic antidepressants (nortriptyline, desipramine) may impact more on children and the elderly. Among other antidepressants, the only reports of torsades de pointes appeared to occur with mirtazapine. It was also of interest to find data showing no effect or reductions in QTc produced by sertraline, citalopram, paroxetine and bupropion in multiple studies. Effects of medications on other heart parameters are also briefly reviewed. In particular, the safety of sertraline in post-MI patients and of bupropion in heart disease patients is highlighted. Little information was available on other classes of medications used in psychiatric disorders. What is available concerning lithium, the anticonvulsants and the benzodiazepines indicates little effect on the QTc, although there may be effects on other cardiovascular parameters.

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Section: The Ssrismentioning

confidence: 96%

Psychotropic drugs and the ECG: focus on the QTc interval

Goodnick

Jerry²,

Parra³

2002

Expert Opinion on Pharmacotherapy

100

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“…At doses sufficient to produce 5-HT blockade paroxetine has only weak quinidine-like effects. Hypotension, tachycardia, bradycardia and slight prolongation of PQ interval have been reported in dogs (112).…”

Section: Cardiovascular Effectsmentioning

confidence: 98%

Paroxetine: A Review

Bourin

Chue

Guillon³

2001

CNS Drug Reviews

364

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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“…These studies show a favourable cardiovascular profile [103][104][105][106]. In the current primary care setting, SSRIs are considered to be more suitable for depressed patients with a recent history of heart disease than any other group of antidepressants.…”

Section: Ssris and Cvdsmentioning

confidence: 99%

Serotonin reuptake inhibitors and cardiovascular diseases: a platelet connection

Maurer‐Spurej

2005

CMLS, Cell. Mol. Life Sci.

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Selective serotonin reuptake inhibitors (SSRIs) are a heterogeneous group of new antidepressants that cause a well documented acquired but reversible serotonin deficiency in blood platelets. Platelets are small, anucleate cells and are the only blood cells specialized in storing peripheral serotonin. Platelets are also an integral part of the hemostatic process that is initiated during pathologic thrombus formation in cardiovascular diseases. Serotonin release from platelets is important for functional hemostasis as indicated by congenital diseases with serotonin-deficient platelets that can lead to life-threatening bleeding problems. The postulate that SSRIs should have an impact on cardiovascular diseases is therefore well founded. Cardiovascular effects of SSRIs have indeed been shown in a number of studies investigating the effect of SSRIs in patients with psychosomatic comorbidity. SSRIs reduce the incidence of recurrent myocardial infarction (MI) in patients suffering from post-MI depression. In addition, SSRIs inhibit tight clot formation of platelets in vitro, which points to a direct anti-thrombotic or pro-fibrinolytic effect of SSRIs.

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Cardiovascular effects of paroxetine, a newly developed antidepressant, in anesthetized dogs in comparison with those of imipramine, amitriptyline and clomipramine.

Cited by 19 publications

References 21 publications

Psychotropic drugs and the ECG: focus on the QTc interval

Psychotropic drugs and the ECG: focus on the QTc interval

Paroxetine: A Review

Serotonin reuptake inhibitors and cardiovascular diseases: a platelet connection

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