Serotonin Syndrome Induced by Fluvoxamine-Lithium Interaction

Ohman, R; Spigset, Olav

doi:10.1055/s-2007-1014367

Cited by 45 publications

(13 citation statements)

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“…Moreover, studies based on the microdialysis technique have shown that lithium increases 5-HT release in some areas of the brain but not in others (Baptista et al 1990;West et al 1991;Mork 1998;Wegener et al 2000;Muraki et al 2001). The fact that lithium affects the 5-HT system is furthermore supported by the appearance of the serotonin syndrome (Sternbach 1991) after the addition of lithium to the ongoing antidepressant treatment (Öhman and Spigset 1993;Kofman and Patishi 1999). One clinical study has shown success with the citalopram-lithium combination (Baumann et al 1996).…”

Section: Introductionmentioning

confidence: 99%

Increased extracellular serotonin level in rat hippocampus induced by chronic citalopram is augmented by subchronic lithium: neurochemical and behavioural studies in the rat

et al. 2003

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Section: Introductionmentioning

confidence: 99%

Increased extracellular serotonin level in rat hippocampus induced by chronic citalopram is augmented by subchronic lithium: neurochemical and behavioural studies in the rat

et al. 2003

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“…In the case reported by Hadley and Cason [41], the lithium concentration increased from 0.96 to 1.38 mEq/l after fluoxetine augmentation at 20 mg/day. No elevation of lithium concentration after introduction of fluvoxamine at 200 mg/day was found in the case described by Öhman and Spigset [71].…”

Section: Pharmacokineticsmentioning

confidence: 63%

“…Case reports describing a serotonin syndrome have been published after the combination of lithium with fluvoxamine [71], paroxetine [87] or fluoxetine [63]. Hadley and Cason [41] had reported two cases of induced mania under a combination of fluoxetine-lithium in bipolar patients.…”

Section: Adverse Eventsmentioning

confidence: 99%

“…Most reports describing pharmacokinetic features of the SSRIlithium combination measured lithium plasma levels following SSRI-augmentation in mostly bipolar patients with long-term lithium treatment [10,16,41,48,71,79]. In a case report, Salama and Shaffey described a toxic lithium concentration (1.7 mEq/l) after introduction of a fluoxetine treatment in a patient with former normal lithium concentrations [79].…”

Section: Pharmacokineticsmentioning

confidence: 99%

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Lithium Augmentation in Depressive Patients Not Responding to Selective Serotonin Reuptake Inhibitors1

Zullino¹,

Baumann²

2001

Pharmacopsychiatry

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This communication reviews current literature on lithium augmentation in patients not responding to SSRIs, giving some recommendations at the end. A significant proportion of depressive patients do not respond to a first antidepressive treatment independently of the class of drugs used. During the last 10 years, there have been several case reports published about open and controlled studies on the use of lithium augmentation in patients who were non-responders to SSRIs, including citalopram, fluoxetine, paroxetine and sertraline. The main underlying hypothesis is a synergistic effect between SSRIs and lithium, which both act on serotonergic neurotransmission. The available studies vary considerably in methodology. There are insufficient results available to confirm a rapid improvement (within 24-48h) after introduction of lithium, but most studies show substantial effects after 1 - 2 weeks, and some after 6 weeks. There is as yet no more clear evidence for a pharmacokinetic interaction between lithium and SSRIs with pharmacodynamic consequences. In conclusion, present evidence suggests that a lithium augmentation in depressive patients who do not respond to SSRIs may be an efficacious and generally well tolerated treatment, with a response rate of at least 50% after a period lasting 1 - 2 weeks. However, special care is indicated when treating elderly patients, where the risk of adverse effects is higher.

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“…The combination of lithium with serotonin selective reuptake inhibitors (SSRI) must be monitored because drug interactions may induce the serotonin syndrome [9] and increase plasma lithium levels (as observed after fluoxetine, but not with other SSRIs) [5,7]. Therefore, patients treated with lithium-fluvoxamine combination may complain of side effects such as anxiety, agitation, insomnia and tremor [6,8]. Nevertheless, we report a case of severe diurnal somnolence in a patient treated with lithium-fluvoxamine combination.…”

mentioning

confidence: 99%

Severe Diurnal Somnolence Induced by Fluvoxamine-Lithium Combination

Marchesi¹,

Paini²,

Maggini³

2005

Pharmacopsychiatry

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Clinical studies [4] suggest that lithium in combination with antidepressants (AD) can be effective in treatment of bipolar depression, refractory major depression (MD) and relapse of recurrent MD. The efficacy of the combination of lithium and AD has been attributed to a lithium-induced increase of serotonin neurotransmission [1]. The combination of lithium with serotonin selective reuptake inhibitors (SSRI) must be monitored because drug interactions may induce the serotonin syndrome [9] and increase plasma lithium levels (as observed after fluoxetine, but not with other SSRIs) [5,7]. Therefore, patients treated with lithium-fluvoxamine combination may complain of side effects such as anxiety, agitation, insomnia and tremor [6,8]. Nevertheless, we report a case of severe diurnal somnolence in a patient treated with lithium-fluvoxamine combination.A 40-year-old man sought treatment for an episode of major depression, which had been refractory to paroxetine (60 mg/day), mirtazapine (60 mg/day) and venlafaxine (225 mg/day). Clorimipramine was started and progressively titrated to 300 mg/day without a significant clinical improvement. Then lithium was added, leading to a slight reduction in depressive symptom severity, even though plasma levels ranged between 0.58 mEq/L and 0.74 mEq/L. Two months later, clorimipramine was discontinued and fluvoxamine was administered and titrated to 300 mg/day. During the next two months a complete remission of depressive symptoms was observed, but a severe diurnal somnolence occurred: the patient repeatedly fell asleep at work and had to pull over while driving his car because of sleepiness. Somnolence was not due to increased plasma lithium levels (0.61±0.68 mEq/L), insomnia, neurological disorders, or administration of other drugs. Moreover, blood count, renal and liver function tests, and electrolytes were in the normal range. Lithium was decreased (plasma level 0.20 mEq/L), but somnolence persisted even after fluvoxamine reduction to 200 mg/day. Therefore, lithium was discontinued, leading to recovery from somnolence after a few days. Fluvoxamine was well tolerated during the six months of continuation treatment.This case report confirms that somnolence may represent a side effect of the fluvoxamine-lithium combination, as first described by Evans and Marwick [3].It is difficult to establish the mechanism by which this uncommon side effect occurred in our patient when we take into account the following: ± pharmacokinetic interactions were not involved: (1) plasma lithium concentrations were not increased by fluvoxamine and (2) even though plasma fluvoxamine levels were not measured, lithium is known [6] to be unable to increase fluvoxamine concentrations. ± An idiosyncratic effect is unlikely because somnolence occurred after two months of therapy and not during the first days of treatment, as observed by Evans and Marwick [3]. ± Even though the involvement of a serotonergic mechanism may be supposed (probably through a GABAergic pathway), somnolence was not observed during th...

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Serotonin Syndrome Induced by Fluvoxamine-Lithium Interaction

Cited by 45 publications

References 1 publication

Increased extracellular serotonin level in rat hippocampus induced by chronic citalopram is augmented by subchronic lithium: neurochemical and behavioural studies in the rat

Increased extracellular serotonin level in rat hippocampus induced by chronic citalopram is augmented by subchronic lithium: neurochemical and behavioural studies in the rat

Lithium Augmentation in Depressive Patients Not Responding to Selective Serotonin Reuptake Inhibitors1

Severe Diurnal Somnolence Induced by Fluvoxamine-Lithium Combination

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