Antidepressants: pharmacological profile and clinical consequences

Rahola, Juan Gibert

doi:10.1080/13651500152048414

Cited by 4 publications

(7 citation statements)

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“…Despite controversy regarding the serotonergic potential of mirtazapine [19], it is listed in Micromedex® as a major drug interaction when combined with fluoxetine and venlafaxine due to the increased risk of serotonin toxicity. Considering the potent serotonergic activity of sertraline even when compared with fluoxetine, and the proserotonergic activity of mirtazapine with fluoxetine or venlafaxine, this drug combination was listed as a moderate drug interaction [20]. Similarly, the combination of methadone with selective serotonin reuptake inhibitors (SSRI) can increase methadone concentrations as a result of the CYP450 enzyme inhibitory action of these antidepressants, in particular fluoxetine and paroxetine [21,22].…”

Section: Cohort Selectionmentioning

confidence: 99%

“…However, the involvement of these particular drugs was not reported. For example, detection of tramadol alongside an antidepressive agent acting upon serotonin (such as an SSRI, mirtazapine or tricyclic antidepressant [TCA]) was reported as a death by multiple drug toxicity in cases 1 through to 4, but not amongst cases involving detection of this same combination (cases 13 through to 20). Similarly, cases 6 through to 12 reported drug toxicity with the combination of a SRI with methadone, along with incidental concentrations of other drugs, but drug toxicity was not reported with cases concerning the same drug combination (cases 27 through to 30).…”

Section: Cases Of Most Interestmentioning

confidence: 99%

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Deaths involving contraindicated and inappropriate combinations of serotonergic drugs

2010

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In the Australian state of Victoria, all fatalities that were recorded from 2002 through to 2008 involving the use of certain serotonin active drugs (tramadol, venlafaxine, fluoxetine, sertraline, citalopram and paroxetine), were reviewed to assess the incidence of contraindicated or ill advised drug combinations. More than 1,000 were identified of which 326 cases formed the basis of this study. These cases involved contraindicated or inappropriate drug combinations that can lead to adverse drug reactions (ADRs) and subsequent fatal toxicity. Of these, 46% were drug-related, 35% were a result of natural disease and 13% were classified as external injury cases. The remaining cases were those where the cause of death (COD) was unascertained. Tramadol was the most common drug, usually detected alongside a serotonergic antidepressant (in 20% of cases). Twenty-five (8%) cases involved contraindicated drug combinations while the remainder (301 cases, 92%) involved drug combinations that are associated with adverse interactions ranging from minor to major severity. Of these 326 cases, the Coroner determined 166 cases (51%) to be acts of intentional self-harm or drug misuse, with the remainder unascertained or attributed to natural disease. Very few post-mortem reports and Coroners' findings made mention of possible ADRs when such combinations were actually present. The majority of cases comprising contraindicated drug combinations involved the combined use of five drugs (24%) at the time of death. A combination of three to five drugs was most common in cases involving inadvisable drug combinations. Combined drug toxicity was the most common COD, with heart disease the most common co-morbidity.

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Section: Cohort Selectionmentioning

confidence: 99%

Section: Cases Of Most Interestmentioning

confidence: 99%

Deaths involving contraindicated and inappropriate combinations of serotonergic drugs

2010

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“…3). Although the mechanism of TCA action is not well understood, it is thought that they block reuptake of both serotonin and noradrenaline and to a lesser extent, dopamine [75]. TCAs have a narrow therapeutic index which consequently results in an increased risk of adverse effects, such as arrhythmias in users who are CYP2D6 PMs [101].…”

Section: Selegilinementioning

confidence: 99%

“…Sertraline is one of the most potent serotonin reuptake inhibitors available, with an inhibitory potential of about 36 times more than fluoxetine and over 200 times that of amitriptyline [75]. Sertraline possesses two chiral centres but the marketed formulation contains only the active S,S-enantiomer, which reduces the chance of drug reactions and interference which may occur in the presence of the racemic mixture [74].…”

Section: Sertralinementioning

confidence: 99%

“…Citalopram possesses one of the highest selectivities for serotonin reuptake inhibition over noradrenaline reuptake of all the SSRIs, inhibiting serotonin reuptake 3,000 times more than noradrenaline and 22,000 times more than dopamine uptake [74,75]. This selectivity in addition to its weaker CYP450 inhibitory activity makes citalopram one of the safest SSRIs with respect to pharmacokinetic drug interactions [76,77].…”

Section: Citaloprammentioning

confidence: 99%

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Review: Pharmacogenetic aspects of the effect of cytochrome P450 polymorphisms on serotonergic drug metabolism, response, interactions, and adverse effects

Pilgrim

Gerostamoulos

Drummer

2010

Forensic Sci Med Pathol

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The field of pharmacogenetics contains a wealth of potential for the enhancement of clinical practice by providing a more effective match between patient and drug, consequently reducing the probability of an adverse drug reaction. Although a relatively novel concept in the forensic context, pharmacogenetics has the capability to assist in the interpretation of drug related deaths, particularly in unintentional drug poisonings where the cause of death remains unclear. However, the complex pharmacology of the drugs when subjected to genetic variations in metabolism makes interpretation of the expected response and adverse events difficult. Many possess multiple metabolic pathways, narrow therapeutic indices and active metabolites or enantiomers which may be eliminated via different pathways to the parent drug. A number of these drugs, which are metabolised primarily by the CYP450 system, are also associated with serotonin syndrome, or serotonin toxicity, especially when used concomitantly with other serotonin active drugs which rely on the same metabolic pathways for drug elimination. A comprehensive understanding of polymorphic drug metabolism and its expected outcomes is therefore essential when interpreting the involvement of drugs in adverse reactions. This review examines the genetically variable CYP450-mediated metabolism of a number of serotonin-active drugs that are often implicated in cases of serotonin toxicity, to assess the impact of pharmacogenetics on drug metabolism, response, interactions and adverse effects.

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Tianeptine and fluoxetine in major depression: a 6‐week randomised double‐blind study

Faltus

2002

Human Psychopharmacology

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In a 6-week, multicentre, randomised, double-blind controlled study, tianeptine (37.5 mg/day) and fluoxetine (20 mg/day) were compared for efficacy and safety in 178 patients with major depression. No significant difference was shown between the two drugs, either in terms of efficacy (MADRS, CGI, COVI) or in terms of safety, except for the CGI 'severity of illness' which was lower at the end point with tianeptine than with fluoxetine. The percentages of responders (as defined by a 50% decrease of the MADRS score from baseline to end point) were 75% with tianeptine and 67% with fluoxetine, showing the efficacy of both drugs. In conclusion, both tianeptine and fluoxetine are effective and well-tolerated treatments for major depression.

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Antidepressants: pharmacological profile and clinical consequences

Cited by 4 publications

References 0 publications

Deaths involving contraindicated and inappropriate combinations of serotonergic drugs

Deaths involving contraindicated and inappropriate combinations of serotonergic drugs

Review: Pharmacogenetic aspects of the effect of cytochrome P450 polymorphisms on serotonergic drug metabolism, response, interactions, and adverse effects

Tianeptine and fluoxetine in major depression: a 6‐week randomised double‐blind study

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