“Dopamine-Dependent” Side Effects of Selective Serotonin Reuptake Inhibitors

Damsa, Cristian; Bumb, Anja; Bianchi‐Demicheli, Francesco; Vidailhet, Pierre; Sterck, Robert; Andréoli, A.; Beyenburg, Stefan

doi:10.4088/jcp.v65n0806

Cited by 144 publications

(70 citation statements)

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“…Reduced DA signaling following chronic SSRI administration may underlie several SSRI induced side effects and might lower therapeutic response rates (Damsa et al, 2004). Our findings reported here provide substantial support for this hypothesis.…”

Section: Discussionsupporting

confidence: 80%

“…This 5-HT/DA interaction plays a critical role in the action of antidepressant drugs. 5-HTselective reuptake inhibitors (SSRIs) for example, block 5-HT transporter (5-HTT) function to increase 5-HT signaling, but may also induce side effects typically associated with reduced DA signaling, such as anhedonia, apathy, reduced libido, akathisia, and extrapyramidal motor symptoms (EPSs) (Settle, 1998;Cassano and Fava, 2004;Damsa et al, 2004;Preskorn et al, 2004). These side effects can lead to discontinuation even when treatment is efficacious (Kaplan, 1997;Chelben et al, 2001) and reduce response rates (Rush et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

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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: Discussionsupporting

confidence: 80%

Section: Introductionmentioning

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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“…The basal firing of dopamine neuron rising from ventral tegmental area is negatively modulated by SSRIs (Di Mascio et al, 1998). Microdialysis studies in rats and monkeys indicate that SSRI reduce striatal dopamine levels (Dewey et al, 1995;Di Rocco et al, 1998;Smith et al, 2000) and some of SSRIs side effects have been associated with the reduction of striatal dopamine levels induced by their administration (Damsa et al, 2004;Shioda et al, 2004). Thus in the light of these results, the increase in receptors availability observed in this study, may be consequent to the reduction of dopamine concentration induced by fluvoxamine.…”

Section: Discussionsupporting

confidence: 55%

Fluvoxamine Treatment and D2 Receptors: a Pet Study on OCD Drug-Naïve Patients

Moresco

Pietra

Henin

et al. 2006

Neuropsychopharmacol

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Changes in D 2 receptors during antidepressant therapy have been reported in patients with major depressive disorder using PET/SPET. The aim of this study was to evaluate modifications in D 2 receptors that might occur in patients affected by obsessive-compulsive disorder (OCD) during serotonin reuptake sites inhibitors (SSRIs). To this purpose, we measured the in vivo binding of [ 11 C]raclopride ([ 11 C]Rac)in the brain of a group of OCD naïve patients before and after the repeated administration of the inhibitor SSRI fluvoxamine. Eight patients with a Diagnostic and Statistical Manual of Mental Disorders IVth edition diagnosis of OCD completed the study undergoing a PET scan and a complete clinical evaluation before and during treatment with fluvoxamine. Patients have been compared also with a group of nine age-matched normal volunteers. Fluvoxamine treatment significantly improved clinical symptoms and increased [ 11 C]Rac binding potential (BP) in the basal ganglia of OCD patients (7.575.2, 6.976.9, and 9.979.3% in dorsal caudate, dorsal putamen, and ventral basal ganglia, respectively; po0.01) to values closer to those observed in the group of normal subjects. Chronic treatment with fluvoxamine induces a slight but significant increase in striatal [ 11 C]Rac BP of previously drug-naïve OCD patients. The modifications in D 2 receptor availability might be secondary to fluvoxamine effects on serotoninergic activity.

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“…35 Bupropion, which is not an SSRI, does not appear to have the same sexual side effects as other modern antidepressants. [36][37][38] Although bupropion may reverse SSRI-induced sexual dysfunction, it is still unclear whether bupropion is useful in treating sexual dysfunctions caused by other etiologies. [39][40][41] However, the fact that antidepressant-related sexual dysfunction can be managed pharmacologically indicates the importance of CNSacting neurotransmitters in the sexual cycle.…”

Section: Serotoninmentioning

confidence: 99%

Clinical applications of centrally acting agents in male sexual dysfunction

Hellstrom

2008

Int J Impot Res

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Currently available agents for erectile dysfunction (ED) share the same mechanism of action and pharmacologic properties. Therefore, they share the same limitations, including a principal focus on erection as an end-organ process. One of the relatively unexplored areas of research has been the potential for centrally acting agents to improve male sexual response. A variety of neurohormones and neurotransmitter systems are involved in the male sexual response, including testosterone, dopamine, serotonin and the melanocortin systems. Investigations to determine the utility of centrally acting agents as monotherapy or adjunctive therapy in men with ED or other forms of sexual dysfunction are underway. Bremelanotide, a melanocortin agonist, has been tested in men with ED and may prove to be one of the first centrally acting agents to have clinical utility in male sexual dysfunction.

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“Dopamine-Dependent” Side Effects of Selective Serotonin Reuptake Inhibitors

Cited by 144 publications

References 0 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

Fluvoxamine Treatment and D2 Receptors: a Pet Study on OCD Drug-Naïve Patients

Clinical applications of centrally acting agents in male sexual dysfunction

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