Carbamazepine‐Induced Release of Serotonin from Rat Hippocampus In Vitro

Dailey, John W.; Reith, Maarten E. A.; Steidley, Kevin R.; Milbrandt, Joseph C.; Jobe, Phillip C.

doi:10.1111/j.1528-1157.1998.tb01290.x

Cited by 55 publications

(18 citation statements)

References 33 publications

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“…In the rat brain, carbamazepine treatment leads to an increase of serotonin (Dailey et al, 1998). This observation suggests that a combination of carbamazepine and VEN may be advantageous by the combined serotonergic effect, but a risk of a serotonin syndrome cannot be excluded.…”

mentioning

confidence: 81%

Combination therapy with venlafaxine and carbamazepine in depressive patients not responding to venlafaxine: pharmacokinetic and clinical aspects

et al. 2004

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The chiral antidepressant venlafaxine (VEN) is both a serotonin and a norepinephrine uptake inhibitor. CYP2D6 and CYP3A4 contribute to its metabolism, which has been shown to be stereoselective. Ten CYP2D6 genotyped and depressive (F32x and F33x, ICD-10) patients participated in an open study on the pharmacokinetic and pharmacodynamic consequences of a carbamazepine augmentation in VEN non-responders. After an initial 4-week treatment with VEN (195 +/- 52 mg/day), the only poor metabolizer out of 10 depressive patients had the highest plasma concentrations of S-VEN and R-VEN, respectively, whereas those of R-O-demethyl-VEN were lowest. Five non-responders completed the second 4-week study period, during which they were submitted to a combined VEN-carbamazepine treatment. In the only non-responder to this combined treatment, there was a dramatic decrease of both enantiomers of VEN, O-demethylvenlafaxine, N-desmethylvenlafaxine and N, O-didesmethylvenlafaxine in plasma, which suggests non-compliance, although metabolic induction by carbamazepine cannot entirely be excluded. The administration of carbamazepine [mean +/- SD, range: 360 +/- 89 (200-400) mg/day] over 4 weeks did not result in a significant modification of the plasma concentrations of the enantiomers of VEN and its O- and N-demethylated metabolites in the other patients. In conclusion, these preliminary observations suggest that the combination of VEN and carbamazepine represents an interesting augmentation strategy by its efficacy, tolerance and absence of pharmacokinetic modifications. However, these findings should be verified in a more comprehensive study.

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confidence: 81%

Combination therapy with venlafaxine and carbamazepine in depressive patients not responding to venlafaxine: pharmacokinetic and clinical aspects

et al. 2004

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“…The drug binds to voltage-gated sodium channels and stabilizes the sodium inactivation state, thereby reducing neural firing (157–159). Its mode of action, however, may be more complex than this, as some reports indicate that carbamazepine enhances outward, voltage-dependent potassium currents, inhibits L-type calcium channels and enhances the release of 5-HT (160–162). The results for carbamazepine in the treatment of tinnitus have been mixed.…”

Section: Drug Therapy For Tinnitus: Pharmacological Studiesmentioning

confidence: 99%

Pharmacological treatments for tinnitus: New and old

Salvi¹,

Lobariñas²,

Sun³

2009

Drugs Fut

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Subjective tinnitus, the phantom ringing or buzzing sensation that occurs in the absence of sound, affects 12–14% of adults; in some cases the tinnitus is so severe or disabling that patients seek medical treatment. However, although the economic and emotional impact of tinnitus is large, there are currently no FDA-approved drugs to treat this condition. Clinical trials are now underway to evaluate the efficacy of N-methyl-d-aspartate (NMDA) and dopamine D2 antagonists, selective serotonin reuptake inhibitors (SSRIs), γ-aminobutyric acid (GABA) agonists and zinc dietary supplements. Previous off-label clinical studies, while not definitive, suggest that patients with severe depression may experience improvement in their tinnitus after treatment with antidepressants such as nortriptyline or sertraline. A small subpopulation of patients with what has been described as “typewriter tinnitus” have been shown to gain significant relief from the anticonvulsant carbamazepine. Preliminary studies with misoprostol, a synthetic prostaglandin E1 analogue, and sulpiride, a dopamine D2 antagonist, have shown promise. Animal behavioral studies suggest that GABA transaminase inhibitors and potassium channel modulators can suppress tinnitus. Additionally, improvements in tinnitus have also been noted in patients taking melatonin for significant sleep disturbances. Like other complex neurological disorders, one drug is unlikely to resolve tinnitus in all patients; therapies targeting specific subgroups are likely to yield the greatest success.

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“…12 In addition, oxcarbazepine has been shown to increase extracellular hippocampal serotonin in a rat model of epilepsy (as has carbamazepine), which could have also contributed to the development of the syndrome in our patient. 13,14 He would further have been predisposed to developing the syndrome due to his ischemic heart and chronic pulmonary disease; these have been shown to impair monoamine oxidase activity, which is responsible for serotonin metabolism. 15 CONCLUSIONS Serotonin syndrome remains a potentially fatal toxicological emergency.…”

Section: Discussionmentioning

confidence: 98%

Fatal Serotonin Syndrome Precipitated by Oxcarbazepine in a Patient Using an Selective Serotonin Reuptake Inhibitor

Dardis

Omoregie²,

Ly³

2012

The Neurologist

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Oxcarbazepine, a metabolite of carbamazepine, is used as an antiepileptic, analgesic for neuropathic pain and in the treatment of affective disorders. It has been approved by the Food and Drug Administration for partial seizures in adults as both adjunctive and monotherapy, and as adjunctive therapy in children aged from 2 to 16 years (http://www.fda.gov/ohrms/dockets/ac/06/briefing/2006-4254b_07_05_KP%20OxcarbazepineFDAlabel102005.pdf). We present a case of serotonin syndrome, which was precipitated by this medicine in a patient who had been predisposed by long-term treatment with sertraline, a selective serotonin reuptake inhibitor. This is the first reported fatality due to this drug interaction and only the second case of serotonin syndrome reported with oxcarbazepine. Physicians should consider this risk when prescribing the above combination.

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Carbamazepine‐Induced Release of Serotonin from Rat Hippocampus In Vitro

Cited by 55 publications

References 33 publications

Combination therapy with venlafaxine and carbamazepine in depressive patients not responding to venlafaxine: pharmacokinetic and clinical aspects

Combination therapy with venlafaxine and carbamazepine in depressive patients not responding to venlafaxine: pharmacokinetic and clinical aspects

Pharmacological treatments for tinnitus: New and old

Fatal Serotonin Syndrome Precipitated by Oxcarbazepine in a Patient Using an Selective Serotonin Reuptake Inhibitor

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