Bupropion is a novel atypical antidepressant that inhibits dopamine (DA) uptake. The present expe... more Bupropion is a novel atypical antidepressant that inhibits dopamine (DA) uptake. The present experiments investigated the effects of acute (10 mg/kg, twice daily for 2 days) and chronic (10 mg/kg, twice daily for 21 days) bupropion treatment on interstitial DA concentrations using simultaneous in vivo microdialysis in the nucleus accumbens (NAC) and striatum of awake freely moving rats. Compared to animals that had not previously been exposed to the drug, bupropion (25 mg/kg, IP) induced increases in extracellular DA were significantly enhanced in the NAC of the chronic but not the acute bupropion group. This effect was regionally selective, as it was not observed in the striatum. In accordance with previous reports, concurrent behavioral measurements indicated that the locomotor stimulant effects of bupropion were also enhanced in the chronic group. These results demonstrate that bupropion-induced behavioral sensitization is accompanied by a selective potentiation of the effects of this compound on interstitial DA concentrations in the NAC.
Caffeine, the most widely consumed of all psychostimulant drugs, exerts its action by antagonizin... more Caffeine, the most widely consumed of all psychostimulant drugs, exerts its action by antagonizing adenosine receptors. To study the arousing properties of caffeine, we injected rats intraperitoneally with vehicle, caffeine (7.5, 15 or 30 mg/kg), the selective adenosine A 2A receptor ...
Progress in Neuro-psychopharmacology & Biological Psychiatry, Mar 1, 1995
1.1. Effects of acute and chronic electroconvulsive treatment (ECT) and sham-ECT on extracellular... more 1.1. Effects of acute and chronic electroconvulsive treatment (ECT) and sham-ECT on extracellular concentrations of somatostatin-like immunoreactivity (SS-LI) from the hippocampus and striatum of awake rats were studied with in vivo microdialysis in combination with a high-sensitivity radioimmunoassay.2.2. Acute ECT and sham-ECT did not affect hippocampal or striatal SS-LI concentrations during the first 4 hr after the treatment. However, 24 hr later acute ECT significantly decreased SS-LI concentrations from both areas by approximately 40%.3.3. Chronic ECT and sham-ECT did not influence basal hippocampal or striatal SS-LI concentrations.4.4. Administration of a challenge ECT in animals treated chronically with ECT or sham-ECT did not affect hippocampal or striatal SS-LI concentrations during the first 4 hr after the treatment. However, 24 hr later hippocampal and striatal SS-LI levels were decreased by 30–40% in all groups.5.5. The delayed ECT-induced changes in regional, extracellular concentrations of SS-LI may be secondary to increased somatostatin metabolism and are perhaps related to the therapeutic or adverse effects of this antidepressant treatment.
Brain dopaminergic dysfunction in psychotic behaviour: stabilization by 5-HT2A and a1-receptor an... more Brain dopaminergic dysfunction in psychotic behaviour: stabilization by 5-HT2A and a1-receptor antagonistic drugs
ObjectivesThis study aimed to evaluate the risk of suicidal ideation and behavior associated with... more ObjectivesThis study aimed to evaluate the risk of suicidal ideation and behavior associated with vortioxetine treatment in adults with major depressive disorder (MDD).MethodsSuicide-related events were evaluated post hoc using 2 study pools: one short-term pool of 10 randomized, placebo-controlled studies (6–8 weeks) and another long-term pool that included 3 open-label extension studies (52 weeks). Evaluation of suicide-related events was performed using Columbia-Suicide Severity Rating Scale (C-SSRS) scores and treatment-emergent adverse events (TEAEs) data.ResultsAt baseline, the percentage of patients reporting any C-SSRS ideation or behavior events in short-term studies was similar between placebo (14.7%), vortioxetine (19.8%, 13.0%, 11.2%, and 13.7% for 5-, 10-, 15-, and 20-mg groups, respectively), and duloxetine active reference (13.2%) and did not change throughout the 6- to 8-week treatment period for placebo (17.0%), vortioxetine (19.3%, 13.5%, 12.6%, and 15% for 5-, 10-...
Introduction Sexual dysfunction is prevalent among patients with depression, but assessment of tr... more Introduction Sexual dysfunction is prevalent among patients with depression, but assessment of treatment-emergent sexual dysfunction (TESD), a common side effect of antidepressants, can be confounded by the treatment of depressive symptoms in some patients. Aim To evaluate sexual functioning in healthy volunteers administered vortioxetine compared with paroxetine, an antidepressant known to cause sexual dysfunction, and placebo. Methods This phase 4, multicenter, randomized, double-blind, placebo-controlled, 4-arm, fixed-dose, head-to-head study compared sexual functioning in healthy volunteers administered vortioxetine (10 and 20 mg once daily [QD]), paroxetine (20 mg QD), or placebo for 5 weeks. Approximately equal numbers of men and women ages 18–40 years with normal sexual functioning (self-reported Changes in Sexual Functioning Questionnaire Short-Form [CSFQ-14] score > 47 for men; > 41 for women) were enrolled. Two modified full analysis sets adjusting for treatment non-...
Objective:The objective of this work was to describe treatment-emergent sexual dysfunction (TESD)... more Objective:The objective of this work was to describe treatment-emergent sexual dysfunction (TESD) and tolerability following a switch from selective serotonin reuptake inhibitor (SSRI: citalopram, paroxetine, or sertraline) monotherapy to vortioxetine or escitalopram monotherapy in adults with well-treated major depressive disorder (MDD) and SSRI-induced sexual dysfunction.Methods:Data were analyzed from the primary study, an 8-week, randomized, double-blind, head-to-head study in which participants with well-treated depressive symptoms but experiencing TESD with SSRIs were directly switched to flexible doses (10/20 mg) of vortioxetine or escitalopram. Sexual functioning was assessed by the Changes in Sexual Functioning Questionnaire-14 (CSFQ-14), efficacy by the Montgomery–Åsberg Depression Rating Scale scores (MADRS) and Clinicians Global Impression of Severity/Improvement (CGI-S/CGI-I), and tolerability by adverse events. Efficacy and tolerability were assessed by pre-switch SSRI...
Translational Medicine in CNS Drug Development, 2019
Abstract Cognitive dysfunction represents a primary unmet medical need in the treatment of major ... more Abstract Cognitive dysfunction represents a primary unmet medical need in the treatment of major depressive disorder (MDD). Recently, a new antidepressant drug, vortioxetine, was introduced in the clinic that shows a differentiated mechanism of action compared with established antidepressants and exhibits efficacy in the treatment of cognitive impairment associated with MDD. This chapter presents the line of evidence based on translational drug discovery and development approaches in support of vortioxetine's distinct effect on cognitive function in MDD.
Bupropion is a novel atypical antidepressant that inhibits dopamine (DA) uptake. The present expe... more Bupropion is a novel atypical antidepressant that inhibits dopamine (DA) uptake. The present experiments investigated the effects of acute (10 mg/kg, twice daily for 2 days) and chronic (10 mg/kg, twice daily for 21 days) bupropion treatment on interstitial DA concentrations using simultaneous in vivo microdialysis in the nucleus accumbens (NAC) and striatum of awake freely moving rats. Compared to animals that had not previously been exposed to the drug, bupropion (25 mg/kg, IP) induced increases in extracellular DA were significantly enhanced in the NAC of the chronic but not the acute bupropion group. This effect was regionally selective, as it was not observed in the striatum. In accordance with previous reports, concurrent behavioral measurements indicated that the locomotor stimulant effects of bupropion were also enhanced in the chronic group. These results demonstrate that bupropion-induced behavioral sensitization is accompanied by a selective potentiation of the effects of this compound on interstitial DA concentrations in the NAC.
Caffeine, the most widely consumed of all psychostimulant drugs, exerts its action by antagonizin... more Caffeine, the most widely consumed of all psychostimulant drugs, exerts its action by antagonizing adenosine receptors. To study the arousing properties of caffeine, we injected rats intraperitoneally with vehicle, caffeine (7.5, 15 or 30 mg/kg), the selective adenosine A 2A receptor ...
Progress in Neuro-psychopharmacology & Biological Psychiatry, Mar 1, 1995
1.1. Effects of acute and chronic electroconvulsive treatment (ECT) and sham-ECT on extracellular... more 1.1. Effects of acute and chronic electroconvulsive treatment (ECT) and sham-ECT on extracellular concentrations of somatostatin-like immunoreactivity (SS-LI) from the hippocampus and striatum of awake rats were studied with in vivo microdialysis in combination with a high-sensitivity radioimmunoassay.2.2. Acute ECT and sham-ECT did not affect hippocampal or striatal SS-LI concentrations during the first 4 hr after the treatment. However, 24 hr later acute ECT significantly decreased SS-LI concentrations from both areas by approximately 40%.3.3. Chronic ECT and sham-ECT did not influence basal hippocampal or striatal SS-LI concentrations.4.4. Administration of a challenge ECT in animals treated chronically with ECT or sham-ECT did not affect hippocampal or striatal SS-LI concentrations during the first 4 hr after the treatment. However, 24 hr later hippocampal and striatal SS-LI levels were decreased by 30–40% in all groups.5.5. The delayed ECT-induced changes in regional, extracellular concentrations of SS-LI may be secondary to increased somatostatin metabolism and are perhaps related to the therapeutic or adverse effects of this antidepressant treatment.
Brain dopaminergic dysfunction in psychotic behaviour: stabilization by 5-HT2A and a1-receptor an... more Brain dopaminergic dysfunction in psychotic behaviour: stabilization by 5-HT2A and a1-receptor antagonistic drugs
ObjectivesThis study aimed to evaluate the risk of suicidal ideation and behavior associated with... more ObjectivesThis study aimed to evaluate the risk of suicidal ideation and behavior associated with vortioxetine treatment in adults with major depressive disorder (MDD).MethodsSuicide-related events were evaluated post hoc using 2 study pools: one short-term pool of 10 randomized, placebo-controlled studies (6–8 weeks) and another long-term pool that included 3 open-label extension studies (52 weeks). Evaluation of suicide-related events was performed using Columbia-Suicide Severity Rating Scale (C-SSRS) scores and treatment-emergent adverse events (TEAEs) data.ResultsAt baseline, the percentage of patients reporting any C-SSRS ideation or behavior events in short-term studies was similar between placebo (14.7%), vortioxetine (19.8%, 13.0%, 11.2%, and 13.7% for 5-, 10-, 15-, and 20-mg groups, respectively), and duloxetine active reference (13.2%) and did not change throughout the 6- to 8-week treatment period for placebo (17.0%), vortioxetine (19.3%, 13.5%, 12.6%, and 15% for 5-, 10-...
Introduction Sexual dysfunction is prevalent among patients with depression, but assessment of tr... more Introduction Sexual dysfunction is prevalent among patients with depression, but assessment of treatment-emergent sexual dysfunction (TESD), a common side effect of antidepressants, can be confounded by the treatment of depressive symptoms in some patients. Aim To evaluate sexual functioning in healthy volunteers administered vortioxetine compared with paroxetine, an antidepressant known to cause sexual dysfunction, and placebo. Methods This phase 4, multicenter, randomized, double-blind, placebo-controlled, 4-arm, fixed-dose, head-to-head study compared sexual functioning in healthy volunteers administered vortioxetine (10 and 20 mg once daily [QD]), paroxetine (20 mg QD), or placebo for 5 weeks. Approximately equal numbers of men and women ages 18–40 years with normal sexual functioning (self-reported Changes in Sexual Functioning Questionnaire Short-Form [CSFQ-14] score > 47 for men; > 41 for women) were enrolled. Two modified full analysis sets adjusting for treatment non-...
Objective:The objective of this work was to describe treatment-emergent sexual dysfunction (TESD)... more Objective:The objective of this work was to describe treatment-emergent sexual dysfunction (TESD) and tolerability following a switch from selective serotonin reuptake inhibitor (SSRI: citalopram, paroxetine, or sertraline) monotherapy to vortioxetine or escitalopram monotherapy in adults with well-treated major depressive disorder (MDD) and SSRI-induced sexual dysfunction.Methods:Data were analyzed from the primary study, an 8-week, randomized, double-blind, head-to-head study in which participants with well-treated depressive symptoms but experiencing TESD with SSRIs were directly switched to flexible doses (10/20 mg) of vortioxetine or escitalopram. Sexual functioning was assessed by the Changes in Sexual Functioning Questionnaire-14 (CSFQ-14), efficacy by the Montgomery–Åsberg Depression Rating Scale scores (MADRS) and Clinicians Global Impression of Severity/Improvement (CGI-S/CGI-I), and tolerability by adverse events. Efficacy and tolerability were assessed by pre-switch SSRI...
Translational Medicine in CNS Drug Development, 2019
Abstract Cognitive dysfunction represents a primary unmet medical need in the treatment of major ... more Abstract Cognitive dysfunction represents a primary unmet medical need in the treatment of major depressive disorder (MDD). Recently, a new antidepressant drug, vortioxetine, was introduced in the clinic that shows a differentiated mechanism of action compared with established antidepressants and exhibits efficacy in the treatment of cognitive impairment associated with MDD. This chapter presents the line of evidence based on translational drug discovery and development approaches in support of vortioxetine's distinct effect on cognitive function in MDD.
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