Risk Factors for Extrapyramidal Symptoms During Treatment With Selective Serotonin Reuptake Inhibitors, Including Cytochrome P-450 Enzyme, and Serotonin and Dopamine Transporter and Receptor Polymorphisms

Hedenmalm, Karin; Güzey, Cüneyt; Yue, Qun‐Ying; Spigset, Olav

doi:10.1097/01.jcp.0000203200.96205.34

Cited by 75 publications

(56 citation statements)

References 40 publications

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“…Our findings reported here provide substantial support for this hypothesis. The impaired BG-dependent motor function after chronic 5-HTT blockade that we observed directly models EPSs elicited by 5-HTT-blocking drugs in humans (Arya, 1994;Leo, 1996;Caley, 1997;Gill et al, 1997;Lane, 1998;Hedenmalm et al, 2006;Madhusoodanan et al, 2010). Our data suggest that concurrent treatment with drugs augmenting nigrostriatal DA signaling might ameliorate EPSs.…”

Section: Discussionmentioning

confidence: 99%

Chronic 5-HT Transporter Blockade Reduces DA Signaling to Elicit Basal Ganglia Dysfunction

Morelli

Moore²,

Rebello³

et al. 2011

J. Neurosci.

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Serotonin (5-HT)-selective reuptake inhibitors (SSRIs) are widely administered for the treatment of depression, anxiety, and other neuropsychiatric disorders, but response rates are low, and side effects often lead to discontinuation. Side effect profiles suggest that SSRIs inhibit dopaminergic activity, but mechanistic insight remains scarce. Here we show that in mice, chronic 5-HT transporter (5-HTT) blockade during adulthood but not during development impairs basal ganglia-dependent behaviors in a dose-dependent and reversible fashion. Furthermore, chronic 5-HTT blockade reduces striatal dopamine (DA) content and metabolism. A causal relationship between reduced DA signaling and impaired basal ganglia-dependent behavior is indicated by the reversal of behavioral deficits through L-DOPA administration. Our data suggest that augmentation of DA signaling would reduce side effects and increase efficacies of SSRIbased therapy.

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Section: Discussionmentioning

confidence: 99%

Chronic 5-HT Transporter Blockade Reduces DA Signaling to Elicit Basal Ganglia Dysfunction

Morelli

Moore²,

Rebello³

et al. 2011

J. Neurosci.

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“…A1+ subjects who were treated with serotonin specific reuptake inhibitors are also reported to have an increased risk for EPS (Hedenmalm, et al, 2006), which demonstrates that A1+ patients are at risk for akathisia across different drug groups. Furthermore, A1+ patients are at an increased risk for tardive dyskinesia (Chen, 1997).…”

Section: Discussionmentioning

confidence: 99%

DRD2/ANKK1 Taq1A (rs 1800497 C>T) genotypes are associated with susceptibility to second generation antipsychotic-induced akathisia

et al. 2012

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Young, R. M. (2013). DRD2/ANKK1 Taq1A (rs 1800497 C>T) genotypes are associated with susceptibility to second generation antipsychotic-induced akathisia. Journal of Psychopharmacology, 27(4), 343-348. doi: 10.1177 Although the advent of atypical, second-generation antipsychotics (SGAs) has resulted in reduced likelihood of akathisia, this adverse effect remains a problem. It is known that extrapyramidal adverse effects are associated with increased drug occupancy of the dopamine 2 receptors (DRD2). The A1 allele of the DRD2/ANKK1, rs1800497, is associated with decreased striatal DRD2 density. The aim of this study was to identify whether the A1(T) allele of DRD2/ANKK1 was associated with akathisia (as measured by Barnes Akathisia Rating Scale) in a clinical sample of 234 patients who were treated with antipsychotic drugs.Definite akathisia (a score ≥ 2 in the global clinical assessment of akathisia) was significantly less common in subjects who were prescribed SGAs (16.8%) than those prescribed FGAs (47.6%), p < 0.0001. Overall, 24.1% of A1+ patients (A1A2/A1A1) who were treated with SGAs had akathisia, compared to 10.8% of A1(thus, A2A2) patients. A1+ patients who were administered SGAs also had higher global clinical assessment of akathisia scores than the A1subjects (p = 0.01). SGAs maintained their advantage over FGAs regarding akathisia, even in A1+ patients who were treated with SGAs. These results strongly suggested that A1+ variants of the DRD2/ANKK1 Taq1A allele do confer an associated risk for akathisia in patients who were treated with SGAs, and these variants may explain inconsistencies found across prior studies, when comparing FGAs and SGAs.

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“…Hedenmalm et al claim that the observation of EPS related side effects in the process of SSRI treatment might depend on the Taq1A polymorphism of the DRD2 gene associated with the existence of the A1 allel within D2 receptor, in addition to CYP enzyme changes in these patients. 15 This situation might also explain why every patient who uses antipsychotic medication and paroxetine does not develop similar EPS related side effects. Paroxetine is an agent often associated with the CYP2D6 inhibition, and in _____________________________________________________________________________________________________ our case, the dyskinesia appeared to slow down after the termination of the paroxetine treatment.…”

Section: Discussionmentioning

confidence: 99%

Paroxetine induced reversible dyskinesia: a case report

Ölmez¹,

Özçetin²,

Ataoğlu³

2017

Anadolu Psikiyatri Derg

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Risk Factors for Extrapyramidal Symptoms During Treatment With Selective Serotonin Reuptake Inhibitors, Including Cytochrome P-450 Enzyme, and Serotonin and Dopamine Transporter and Receptor Polymorphisms

Cited by 75 publications

References 40 publications

Chronic 5-HT Transporter Blockade Reduces DA Signaling to Elicit Basal Ganglia Dysfunction

Chronic 5-HT Transporter Blockade Reduces DA Signaling to Elicit Basal Ganglia Dysfunction

DRD2/ANKK1 Taq1A (rs 1800497 C>T) genotypes are associated with susceptibility to second generation antipsychotic-induced akathisia

Paroxetine induced reversible dyskinesia: a case report

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