Serotonin syndrome in a case of depression with various somatic symptoms: The difficulty in differential diagnosis

Terao, Takeshi; Hikichi, Takatoshi

doi:10.1016/j.pnpbp.2006.07.007

Cited by 7 publications

(3 citation statements)

References 5 publications

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“…Our results were corroborated with findings that 5-HT 2A receptors had an excitatory effect on postsynaptic neurons (Aghajanian and Marek, 1999) and activated a neural circuit between dorsal raphe serotonergic and prefrontal cortical glutamatergic neurons, regions crucial in maintaining mood stability and mental health (Martin-Ruiz et al, 2001;Puig et al, 2003). Although the raphe-cortical circuit was proposed to be implicated in schizophrenia and hallucination (Aghajanian and Marek, 2000;Martin-Ruiz et al, 2001), it is most likely that the same pathway was responsible for mental disorientation in patients during the 5-HT toxidrome (Mills, 1995;Terao and Hikichi, 2007). Moreover, our studies suggest that head shakes and hyperthermic responses might be also integrated with the pathway since the NMDA receptor blocker (+)-MK-801 had the same selective effects on the symptoms as the 5-HT 2A receptor antagonist ketanserin.…”

Section: Discussionsupporting

confidence: 88%

Characterization of serotonin-toxicity syndrome (toxidrome) elicited by 5-hydroxy-l-tryptophan in clorgyline-pretreated rats

Ma¹,

Zhang²,

Jenney³

et al. 2008

European Journal of Pharmacology

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Patients are at high risk of developing serotonin-toxicity syndrome (toxidrome) when they take multiple serotonergic drugs, particularly co-administered with monoamine oxidase inhibitors or 5-hydroxytryptamine (5-HT) reuptake blockers. The toxidrome can vary from mild to severe. The primary goal of the present study was to understand the relationship between behavioral signs and degrees of toxidrome induced by 5-hydroxy-L-tryptophan (5-HTP) in clorgylinized rats. The severity was obtained by scoring behavioral signs including head shakes, penile erection, forepaw treading, hind limb abduction, Straub tail and tremor. It was found that 5-HTP produced a dosedependent increase in degrees of the toxidrome. Furthermore, correlation between the toxidrome and changes in body-core temperature (claudqcT cor ) was determined. There was hypothermia in the mild toxidrome (claudqcT cor < −1 °C), high hyperthermia in the severe toxidrome (claudqcT cor > +2 °C) and a small change in T cor in the moderate toxidrome (−1 °C < claudqcT cor < +2 °C). Thus, claudqcT cor in response to drugs can be used to estimate the severity of the toxidrome. The second attempt was to identify the receptors mediating those changes. 5-HT 1A receptors were involved in the hypothermic response while 5-HT 2A and NMDA receptors mediated head shakes, hyperthermia, forepaw treading and Straub tail. Lastly, antidotal effect of cyproheptadine and (+)-MK-801 was examined. Both drugs blocked hyperthermia and death. However, the effects on mortality became poor when the antidotes were injected 60 min after high hyperthermia had been induced. These findings demonstrate the importance of the time frame using antidotes in the treatment of the 5-HT toxidrome.

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Section: Discussionsupporting

confidence: 88%

Characterization of serotonin-toxicity syndrome (toxidrome) elicited by 5-hydroxy-l-tryptophan in clorgyline-pretreated rats

Ma¹,

Zhang²,

Jenney³

et al. 2008

European Journal of Pharmacology

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“…Given that the syndrome in human patients is caused mainly by SSRIs in the course of either monotherapy (Terao and Hikichi, 2007) or combined therapies (Boyer and Shannon, 2005; Gillman, 2005), caution should be taken in use of interpretations obtained in this observational study. For example, although the present data demonstrate that the primary efflux of 5-HT in the pre-synaptic site may be the initial cause of the syndrome in animal models, causal mechanisms in patients remain elusive but likely due to molecular alterations at post-synaptic sites (Zhang and Tao, unpublished observations).…”

Section: Discussionmentioning

confidence: 98%

Assessment of 5-hydroxytryptamine efflux in rat brain during a mild, moderate and severe serotonin-toxicity syndrome

Zhang

Krishnamoorthy

et al. 2009

European Journal of Pharmacology

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Serotonin (5-hydroxytryptamine; 5-HT)-toxicity syndrome, an iatrogenic brain disorder induced by excessive efflux of 5-HT, has received much attention because of increasing incidents of serotonergic antidepressants. However, the neural mechanism by which extracellular 5-HT is elevated to a toxic level for the syndrome remains to be determined. The goal of the present study was to test the hypothesis that extracellular 5-HT is composed of two component effluxes responsible for distinct aspects of the syndrome. The first set of experiments was to characterize the syndrome by measuring changes in neuromuscular signs, body-core temperature and mortality rate. Our results indicate that the syndrome severity can be categorized into mild, moderate and severe levels. The second set of experiments was to determine a threshold of extracellular 5-HT for induction of each level of the syndrome. Our results demonstrate that there were an 11-fold increase in the mild syndrome and an over 55-fold increase in the severe syndrome. In the last series of experiments, the excessive increases in 5-HT were pharmacologically separated into primary and secondary component effluxes with the 5-HT 2A receptor antagonists cyproheptadine and ketanserin and NMDA receptor antagonist (+)-MK-801. Our results suggest primary component efflux was caused by direct drug effects on 5-HT biosynthetic and metabolic pathways and secondary efflux ascribed to indirect drug effect on a positive feedback circuit involving 5-HT 2A and NMDA receptors. In summary, the primary efflux could be an initial cause for the induction of the syndrome while the secondary efflux might involve deterioration of the syndrome.

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“…This case highlights that headache may be a prominent feature in patient with SS. Terao and Hikichi (6) reported a 65-year-old female with SS who had dysarthria, tremor and headache caused by paroxetine. Discontinuation of paroxetine led to the improvement of the symptoms.…”

Section: Discussionmentioning

confidence: 99%

Headache as a presenting feature in patients with serotonin syndrome: A case series

Prakash¹,

Belani²,

Trivedi³

2013

Cephalalgia

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Serotonin syndrome in a case of depression with various somatic symptoms: The difficulty in differential diagnosis

Cited by 7 publications

References 5 publications

Characterization of serotonin-toxicity syndrome (toxidrome) elicited by 5-hydroxy-l-tryptophan in clorgyline-pretreated rats

Characterization of serotonin-toxicity syndrome (toxidrome) elicited by 5-hydroxy-l-tryptophan in clorgyline-pretreated rats

Assessment of 5-hydroxytryptamine efflux in rat brain during a mild, moderate and severe serotonin-toxicity syndrome

Headache as a presenting feature in patients with serotonin syndrome: A case series

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