Granisetron as an add-on to risperidone for treatment of negative symptoms in patients with stable schizophrenia: Randomized double-blind placebo-controlled study

Khodaie‐Ardakani, Mohammad‐Reza; Seddighi, Sahar; Modabbernia, Amirhossein; Rezaei, Farzin; Salehi, Bahman; Ashrafi, Mandana; Shams-Alizadeh, Narges; Mohammad-karimi, Maryam; Esfandiari, Gholam-Reza; Hajiaghaee, Reza; Akhondzadeh, Shahin

doi:10.1016/j.jpsychires.2013.01.011

Cited by 23 publications

(13 citation statements)

References 40 publications

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“…Other treatments with some evidence of benefit include transcranial magnetic stimulation (Dlabac‐de Lange, Knegtering, & Aleman, ), B12/folate supplementation (Roffman et al, ), 5HT3 antagonists (Khodaie‐Ardakani et al, ) and glutamatergic agents, such as d ‐cycloserine (Goff, ). Antiinflammatory and neuroprotective agents, such as minocycline (Chaudhry et al, ; Jhamnani, Shivakumar, Kalmady, Rao, & Venkatasubramanian, ) and omega 3 fatty acids (Berger et al, ), have also shown some promise.…”

Section: Methodsmentioning

confidence: 99%

Negative symptoms of psychosis: A life course approach and implications for prevention and treatment

Lyne

O’Donoghue

Roche

et al. 2017

Early Intervention Psych

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Section: Methodsmentioning

confidence: 99%

Negative symptoms of psychosis: A life course approach and implications for prevention and treatment

Lyne

O’Donoghue

Roche

et al. 2017

Early Intervention Psych

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“…While several RCTs involving ritanserin offered support for this line of investigation [ 68 , 69 ], the more recent focus has turned to selective 5-HT 3 antagonists (e.g., ondansetron, tropisetron, granisetron). Several trials specifically focused on negative symptoms have supported their efficacy [ 70 , 71 ], as does a recent meta-analysis although it evaluated their effects on schizophrenia in general [ 72 ].…”

Section: Serotoninmentioning

confidence: 99%

Treating Negative Symptoms in Schizophrenia: an Update

Remington

Foussias

Fervaha

et al. 2016

Curr Treat Options Psych

140

101

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Opinion StatementInterest in the negative symptoms of schizophrenia has increased rapidly over the last several decades, paralleling a growing interest in functional, in addition to clinical, recovery, and evidence underscoring the importance negative symptoms play in the former. Efforts continue to better define and measure negative symptoms, distinguish their impact from that of other symptom domains, and establish effective treatments as well as trials to assess these. Multiple interventions have been the subject of investigation, to date, including numerous pharmacological strategies, brain stimulation, and non-somatic approaches. Level and quality of evidence vary considerably, but to this point, no specific treatment can be recommended. This is particularly problematic for individuals burdened with negative symptoms in the face of mild or absent positive symptoms. Presently, clinicians will sometimes turn to interventions that are seen as more “benign” and in line with routine clinical practice. Strategies include use of atypical antipsychotics, ensuring the lowest possible antipsychotic dose that maintains control of positive symptoms (this can involve a shift from antipsychotic polypharmacy to monotherapy), possibly an antidepressant trial (given diagnostic uncertainty and the frequent use of these drugs in schizophrenia), and non-somatic interventions (e.g., cognitive behavioral therapy, CBT). The array and diversity of strategies currently under investigation highlight the lack of evidence-based treatments and our limited understanding regarding negative symptoms underlying etiology and pathophysiology. Their onset, which can precede the first psychotic break, also means that treatments are delayed. From this perspective, identification of biomarkers and/or endophenotypes permitting earlier diagnosis and intervention may serve to improve treatment efficacy as well as outcomes.

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“…Previous data suggested beneficial effects of 5-HT3 receptor antagonists on memory function in preclinical studies (Brambilla et al, 1993;Fontana et al, 1995;Pitsikas and Borsini, 1996;Arnsten et al, 1997;Roychoudhury and Kulkarni, 1997). In clinical settings, ondansetron has shown promise in treating cognitive impairment in schizophrenia (Zhang et al, 2006;Akhondzadeh et al, 2009;Khodaie-Ardakani et al, 2013). Previous preclinical studies also dem-onstrate the memory-enhancing effects of 5-HT7 receptor antagonists, probably through modulation of the glutamatergic or GABAergic systems (Meneses, 2004;McLean et al, 2009;Horiguchi et al, 2011;Horisawa et al, 2011;Nolan and Roman, 2012;Dale et al, 2013).…”

Section: Figurementioning

confidence: 99%

Multimodal antidepressant vortioxetine increases frontal cortical oscillations unlike escitalopram and duloxetine – a quantitative EEG study in rats

Leiser

Pehrson

Robichaud

et al. 2014

British J Pharmacology

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BACKGROUND AND PURPOSEEEG studies show that 5-HT is involved in regulation of sleep–wake state and modulates cortical oscillations. Vortioxetine is a 5-HT3, 5-HT7, and 5-HT1D receptor antagonist, 5-HT1B partial agonist, 5-HT1A agonist, and 5-HT transporter inhibitor. Preclinical (animal) and clinical studies with vortioxetine show positive impact on cognitive metrics involving cortical function. Here we assess vortioxetine's effect on cortical neuronal oscillations in actively awake rats.EXPERIMENTAL APPROACHTelemetric EEG recordings were obtained with the following treatments (mg·kg−1, s.c.): vehicle, vortioxetine (0.1, 1.0, 3.0, 10), 5-HT1A agonist flesinoxan (2.5), 5-HT3 antagonist ondansetron (0.30), 5-HT7 antagonist SB-269970-A (10), escitalopram (2.0), duloxetine (10) and vortioxetine plus flesinoxan. Target occupancies were determined by ex vivo autoradiography.KEY RESULTSVortioxetine dose-dependently increased wakefulness. Flesinoxan, duloxetine, ondansetron, but not escitalopram or SB-269970-A increased wakefulness. Quantitative spectral analyses showed vortioxetine alone and with flesinoxan increased θ (4–8 Hz), α (8–12 Hz) and γ (30–50 Hz) power. Duloxetine had no effect on θ and γ, but decreased α power, while escitalopram produced no changes. Ondansetron and SB-269970 (≈31–35% occupancy) increased θ power. Flesinoxan (≈41% occupancy) increased θ and γ power.CONCLUSIONS AND IMPLICATIONSVortioxetine increased wakefulness and increased frontal cortical activity, most likely because of its 5-HT7 and 5-HT3 antagonism and 5-HT1A agonism. Vortioxetine differs from escitalopram and duloxetine by increasing cortical θ, α and γ oscillations. These preclinical findings suggest a role of vortioxetine in modulating cortical circuits known to be recruited during cognitive behaviours and warrant further investigation as to their clinical impact.

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Granisetron as an add-on to risperidone for treatment of negative symptoms in patients with stable schizophrenia: Randomized double-blind placebo-controlled study

Cited by 23 publications

References 40 publications

Negative symptoms of psychosis: A life course approach and implications for prevention and treatment

Negative symptoms of psychosis: A life course approach and implications for prevention and treatment

Treating Negative Symptoms in Schizophrenia: an Update

Multimodal antidepressant vortioxetine increases frontal cortical oscillations unlike escitalopram and duloxetine – a quantitative EEG study in rats

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