A. Florakis - Academia.edu (original) (raw)

Papers by A. Florakis

Progress in Neuro Psychopharmacology and Biological Psychiatry, Sep 1, 2008

Data Revues 09249338 V25ss1 S0924933810708166, Aug 6, 2010

Objectives: Patients with psychotic or mood disorders often undergo electroconvulsive therapy (EC... more Objectives: Patients with psychotic or mood disorders often undergo electroconvulsive therapy (ECT) while receiving antipsychotic and/or other pharmacological agents. Paliperidone (PLP)-a benzisoxazole derivative and the principal active metabolite of risperidone-is a second-generation antipsychotic which has been developed in an osmotic controlled-release oral-delivery system. Thus the peak-through fluctuations of its concentration in plasma are minimized, with consequently decreased incidence of sideeffects. To the best of our knowledge, there are, as yet, no reports on the safety of ECT-PLP coadministration. Methods: Nine female inpatients suffering from affective disorders (N=7) or schizophrenia (N=2) underwent ECT while receiving PLP (3-12 mg/d). Patients' regimen included other psychotropic medications as well (mainly antidepressants and/or antipsychotics). All patients were monitored closely for recovery time, post-ictal delirium, cardiological and EEG status for at least one hour after each ECT session. In addition to their clinical evaluation, patients' cognitive-especially memory-functioning was regularly assessed by the Mini Mental State Examination. Overall, patients underwent 83 sessions of bilateral ECT. Results: ECT-PLP combination was well tolerated and even in cases where cognitive side-effects were of moderate severity (three cases; all were also receiving venlafaxine), they were transient. Conclusions: Although anecdotal and thus in need of replication in well-designed large studies, our preliminary findings suggest that ECT and PLP can be safely combined whenever both indicated.

Data Revues 09249338 V25ss1 S0924933810710683, 2010

Objectives Both tricyclic antidepressants and some atypical antipsychotics, such as ziprasidone a... more Objectives Both tricyclic antidepressants and some atypical antipsychotics, such as ziprasidone and quetiapine, used as augmentation agents in severe major depression, are known to increase QTc interval to a moderate extent (10-20 msec). Moreover, electroconvulsive therapy (ECT) also increases patients’ propensity to arrhythmias. Finally, females are more prone than males to both drug-induced QTc prolongation and torsades-de-pointes. Thus, the combination of all the above treatments raises serious safety concerns. We investigated the safety of the co-administration of ECT with a tricyclic-ziprasidone-quetiapine combination with respect to QTc interval in six female patients with severe major depression resistant to pharmacotherapy. Methods Each patient underwent a series of 10-11 sessions of bilateral ECT. QTc intervals were calculated at baseline and several times up to 10 min after seizures cessation in a total of 63 patients/ECT sessions. Results A small initial decrease of QTc after the administration of pre-ECT medications was followed by its steady statistically non-significant increase during the first 20 sec after seizure cessation. Thereafter, a steady larger and statistically significant decrease of QTc emerged during the ensuing 21-50 sec interval. Finally, this decrease was gradually reversed within the following 2 min approximately with return of QTc interval to stable baseline levels. Conclusions Overall, QTc interval changes remained within normal limits (fixed at 470 msec in women), without the occurrence of any cardiac adverse events, especially severe arrhythmias such as torsades-de-pointes. Our findings suggest that the co-administration of these treatments might be safe, at least with respect to QTc interval changes.

Clinical Neuropharmacology, 2009

intechopen.com

The PKC family of serine/threonine protein kinases consists of at least ten isoforms that are cla... more The PKC family of serine/threonine protein kinases consists of at least ten isoforms that are classified into three subgroups based on their structure and specific cofactor requirements. Conventional PKCs (cPKCs: α, βI, βII and γ) are activated by the second messengers Ca 2+ and DAG, while novel PKCs (nPKCs: δ, ε, η and θ) are activated only by DAG. In contrast to conventional and novel, atypical PKCs (aPKCs: ζ and λ/ι) are insensitive to both Ca 2+ and DAG, but responsive to the Par6-Cdc42 complex (Parker & Murray-Rust, 2004; Rosse et al., 2010). PKCs are considered hubs for the transduction of signals from G protein-coupled and tyrosine kinase receptors (Parker & Murray-Rust, 2004; Griner and Kazanietz 2007), having long been recognized as a link between receptor-dependent generation of DAG by phospholipases C and D, and the key event for enganging the ERK pathway, the activation of Ras and Raf (Mangoura and Dawson, 1993; Marais et al., 1998). Attesting to the widespread effects of PKC activation, numerous studies have investigated the involvement of all PKC isoforms in oncogenesis and cellular differentiation, proliferation, polarity, migration, apoptosis, and survival (Bosco et al., 2011; Rosse et al., 2010; Larsson, 2006). PKCs are founding members of the AGC kinase group and share a common structure consisting of a conserved C-terminal kinase catalytic domain and a more divergent Nterminal regulatory region. The regulatory region contains C1 and C2-domains (cPKC and nPKCs) that recognize the second messengers DAG/phospholipids or Ca 2+ /phospholipids, respectively, and a pseudosubstrate sequence that serves in autoinhibition by interacting with the substrate-binding pocket of the catalytic domain. Binding of second messengers or allosteric effectors on the C1/C2-domains of the regulatory region results in stabilized interaction with the plasma membrane and activation (Parker & Murray-Rust, 2004; Griner and Kazanietz 2007). PKCs are additionally regulated by specific phosphorylation events that "prime" the kinase for activation. As for all AGC kinases, PDK1 phosphorylates threonines (Thr) in the activation loop (Thr566 in PKCε). Residues in the turn motif (Thr710 in PKCε) and the C-terminal hydrophobic motif of c/nPKCs (Ser729 in PKCε) are often phosphorylated by the mTORC2 complex (Freeley et al., 2011). These phosphorylations critically depend on the occupation of the catalytic site by ATP, stabilize the active conformation of PKCs, and result in a fully primed kinase (Cameron et al., 2009). Additional auto-or in-trans phosphorylation events by other PKC isoforms may have more subtle effects, such as modulation of catalytic activity, protein stability, or binding to other proteins (Freeley et al., 2011). Specifically for PKCε, phosphorylation on Ser368 in the regulatory region by cPKCs suggests a high level of functional crosstalk within members of the PKC family (Durgan et al., 2008). By the acute and reversible post-translational modification of phosphorylation, PKCs regulate the activity and subcellular localization of several of their protein substrates. PKCs phosphorylate an array of substrates that include transcription factors, receptors, ion channels, and cytoskeletal proteins (

It has been suggested that the efficacy of electroconvulsive therapy (ECT) in the treatment of ma... more It has been suggested that the efficacy of electroconvulsive therapy (ECT) in the treatment of major depressive episodes may be enhanced by concurrent administration of antidepressant medication. Therefore, the issue of how safe the combination of these 2 treatment modalities is warrants investigation. Escitalopram (ESC) is a novel selective serotonin reuptake inhibitor that seems to have a favorable side effect profile. To the best of our knowledge, there is no report on the safety of the ECT-ESC combination. We report the cases of 3 female inpatients with major depressive episode--two in the context of major depressive disorder and one in the context of bipolar disorder I--who underwent ECT while concurrently receiving ESC (20 mg/d) as part of their regimen. In all cases, the combination was well tolerated, and only minimal side effects were reported.

Both old and newer antidepressants and some atypical antipsychotics, such as ziprasidone and quet... more Both old and newer antidepressants and some atypical antipsychotics, such as ziprasidone and quetiapine, used as augmentation agents in severe major depression, are known to increase corrected QT (QTc) interval. We investigated the safety of the coadministration of electroconvulsive therapy with an antidepressant-ziprasidone-quetiapine combination with respect to QTc interval in 6 female patients with severe major depression resistant to pharmacotherapy alone. Each patient underwent a series of 10 to 11 sessions of bilateral electroconvulsive therapy. Corrected QT intervals were calculated at baseline and several times up to 10 minutes after seizure cessation. Overall, QTc interval changes remained within normal limits, without the occurrence of any cardiac adverse events. Our findings suggest that the coadministration of these treatments might be safe, at least with respect to QTc interval changes.

The Journal of ECT, 2010

In clinical practice, a nonnegligible proportion of patients with mood or psychotic disorders und... more In clinical practice, a nonnegligible proportion of patients with mood or psychotic disorders undergo electroconvulsive therapy (ECT) concomitantly with pharmacotherapy. Ziprasidone, a combined serotonin and dopamine receptor antagonist, is a second-generation antipsychotic agent with a lower incidence of extrapyramidal motor symptoms and prolactin elevation and a safer profile of adverse effects on plasma lipids, glucose levels, and body weight than other antipsychotics. To the best of our knowledge, there are as yet no available reports on the safety of the ECT-ziprasidone combination. We report here on a series of 8 female inpatients who underwent ECT while receiving ziprasidone (20-80 mg/d) as part of their regimen. Seven patients were treated for major depressive episode in the context of unipolar major depressive disorder (n = 5) or of bipolar disorder I (n = 2), whereas 1 patient was treated for exacerbation of schizophrenic symptoms. In all cases, the combination was well tolerated with only minimal adverse effects and unremarkable changes in corrected QT interval.

Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2008

European Psychiatry, 2010

Clinical Neuropharmacology, 2009

Clinical Neuropharmacology, 2009

European Psychiatry, 2010

Progress in Neuro Psychopharmacology and Biological Psychiatry, Sep 1, 2008

Data Revues 09249338 V25ss1 S0924933810708166, Aug 6, 2010

Objectives: Patients with psychotic or mood disorders often undergo electroconvulsive therapy (EC... more Objectives: Patients with psychotic or mood disorders often undergo electroconvulsive therapy (ECT) while receiving antipsychotic and/or other pharmacological agents. Paliperidone (PLP)-a benzisoxazole derivative and the principal active metabolite of risperidone-is a second-generation antipsychotic which has been developed in an osmotic controlled-release oral-delivery system. Thus the peak-through fluctuations of its concentration in plasma are minimized, with consequently decreased incidence of sideeffects. To the best of our knowledge, there are, as yet, no reports on the safety of ECT-PLP coadministration. Methods: Nine female inpatients suffering from affective disorders (N=7) or schizophrenia (N=2) underwent ECT while receiving PLP (3-12 mg/d). Patients' regimen included other psychotropic medications as well (mainly antidepressants and/or antipsychotics). All patients were monitored closely for recovery time, post-ictal delirium, cardiological and EEG status for at least one hour after each ECT session. In addition to their clinical evaluation, patients' cognitive-especially memory-functioning was regularly assessed by the Mini Mental State Examination. Overall, patients underwent 83 sessions of bilateral ECT. Results: ECT-PLP combination was well tolerated and even in cases where cognitive side-effects were of moderate severity (three cases; all were also receiving venlafaxine), they were transient. Conclusions: Although anecdotal and thus in need of replication in well-designed large studies, our preliminary findings suggest that ECT and PLP can be safely combined whenever both indicated.

Data Revues 09249338 V25ss1 S0924933810710683, 2010

Objectives Both tricyclic antidepressants and some atypical antipsychotics, such as ziprasidone a... more Objectives Both tricyclic antidepressants and some atypical antipsychotics, such as ziprasidone and quetiapine, used as augmentation agents in severe major depression, are known to increase QTc interval to a moderate extent (10-20 msec). Moreover, electroconvulsive therapy (ECT) also increases patients’ propensity to arrhythmias. Finally, females are more prone than males to both drug-induced QTc prolongation and torsades-de-pointes. Thus, the combination of all the above treatments raises serious safety concerns. We investigated the safety of the co-administration of ECT with a tricyclic-ziprasidone-quetiapine combination with respect to QTc interval in six female patients with severe major depression resistant to pharmacotherapy. Methods Each patient underwent a series of 10-11 sessions of bilateral ECT. QTc intervals were calculated at baseline and several times up to 10 min after seizures cessation in a total of 63 patients/ECT sessions. Results A small initial decrease of QTc after the administration of pre-ECT medications was followed by its steady statistically non-significant increase during the first 20 sec after seizure cessation. Thereafter, a steady larger and statistically significant decrease of QTc emerged during the ensuing 21-50 sec interval. Finally, this decrease was gradually reversed within the following 2 min approximately with return of QTc interval to stable baseline levels. Conclusions Overall, QTc interval changes remained within normal limits (fixed at 470 msec in women), without the occurrence of any cardiac adverse events, especially severe arrhythmias such as torsades-de-pointes. Our findings suggest that the co-administration of these treatments might be safe, at least with respect to QTc interval changes.

Clinical Neuropharmacology, 2009

intechopen.com

The PKC family of serine/threonine protein kinases consists of at least ten isoforms that are cla... more The PKC family of serine/threonine protein kinases consists of at least ten isoforms that are classified into three subgroups based on their structure and specific cofactor requirements. Conventional PKCs (cPKCs: α, βI, βII and γ) are activated by the second messengers Ca 2+ and DAG, while novel PKCs (nPKCs: δ, ε, η and θ) are activated only by DAG. In contrast to conventional and novel, atypical PKCs (aPKCs: ζ and λ/ι) are insensitive to both Ca 2+ and DAG, but responsive to the Par6-Cdc42 complex (Parker & Murray-Rust, 2004; Rosse et al., 2010). PKCs are considered hubs for the transduction of signals from G protein-coupled and tyrosine kinase receptors (Parker & Murray-Rust, 2004; Griner and Kazanietz 2007), having long been recognized as a link between receptor-dependent generation of DAG by phospholipases C and D, and the key event for enganging the ERK pathway, the activation of Ras and Raf (Mangoura and Dawson, 1993; Marais et al., 1998). Attesting to the widespread effects of PKC activation, numerous studies have investigated the involvement of all PKC isoforms in oncogenesis and cellular differentiation, proliferation, polarity, migration, apoptosis, and survival (Bosco et al., 2011; Rosse et al., 2010; Larsson, 2006). PKCs are founding members of the AGC kinase group and share a common structure consisting of a conserved C-terminal kinase catalytic domain and a more divergent Nterminal regulatory region. The regulatory region contains C1 and C2-domains (cPKC and nPKCs) that recognize the second messengers DAG/phospholipids or Ca 2+ /phospholipids, respectively, and a pseudosubstrate sequence that serves in autoinhibition by interacting with the substrate-binding pocket of the catalytic domain. Binding of second messengers or allosteric effectors on the C1/C2-domains of the regulatory region results in stabilized interaction with the plasma membrane and activation (Parker & Murray-Rust, 2004; Griner and Kazanietz 2007). PKCs are additionally regulated by specific phosphorylation events that "prime" the kinase for activation. As for all AGC kinases, PDK1 phosphorylates threonines (Thr) in the activation loop (Thr566 in PKCε). Residues in the turn motif (Thr710 in PKCε) and the C-terminal hydrophobic motif of c/nPKCs (Ser729 in PKCε) are often phosphorylated by the mTORC2 complex (Freeley et al., 2011). These phosphorylations critically depend on the occupation of the catalytic site by ATP, stabilize the active conformation of PKCs, and result in a fully primed kinase (Cameron et al., 2009). Additional auto-or in-trans phosphorylation events by other PKC isoforms may have more subtle effects, such as modulation of catalytic activity, protein stability, or binding to other proteins (Freeley et al., 2011). Specifically for PKCε, phosphorylation on Ser368 in the regulatory region by cPKCs suggests a high level of functional crosstalk within members of the PKC family (Durgan et al., 2008). By the acute and reversible post-translational modification of phosphorylation, PKCs regulate the activity and subcellular localization of several of their protein substrates. PKCs phosphorylate an array of substrates that include transcription factors, receptors, ion channels, and cytoskeletal proteins (

It has been suggested that the efficacy of electroconvulsive therapy (ECT) in the treatment of ma... more It has been suggested that the efficacy of electroconvulsive therapy (ECT) in the treatment of major depressive episodes may be enhanced by concurrent administration of antidepressant medication. Therefore, the issue of how safe the combination of these 2 treatment modalities is warrants investigation. Escitalopram (ESC) is a novel selective serotonin reuptake inhibitor that seems to have a favorable side effect profile. To the best of our knowledge, there is no report on the safety of the ECT-ESC combination. We report the cases of 3 female inpatients with major depressive episode--two in the context of major depressive disorder and one in the context of bipolar disorder I--who underwent ECT while concurrently receiving ESC (20 mg/d) as part of their regimen. In all cases, the combination was well tolerated, and only minimal side effects were reported.

Both old and newer antidepressants and some atypical antipsychotics, such as ziprasidone and quet... more Both old and newer antidepressants and some atypical antipsychotics, such as ziprasidone and quetiapine, used as augmentation agents in severe major depression, are known to increase corrected QT (QTc) interval. We investigated the safety of the coadministration of electroconvulsive therapy with an antidepressant-ziprasidone-quetiapine combination with respect to QTc interval in 6 female patients with severe major depression resistant to pharmacotherapy alone. Each patient underwent a series of 10 to 11 sessions of bilateral electroconvulsive therapy. Corrected QT intervals were calculated at baseline and several times up to 10 minutes after seizure cessation. Overall, QTc interval changes remained within normal limits, without the occurrence of any cardiac adverse events. Our findings suggest that the coadministration of these treatments might be safe, at least with respect to QTc interval changes.

The Journal of ECT, 2010

In clinical practice, a nonnegligible proportion of patients with mood or psychotic disorders und... more In clinical practice, a nonnegligible proportion of patients with mood or psychotic disorders undergo electroconvulsive therapy (ECT) concomitantly with pharmacotherapy. Ziprasidone, a combined serotonin and dopamine receptor antagonist, is a second-generation antipsychotic agent with a lower incidence of extrapyramidal motor symptoms and prolactin elevation and a safer profile of adverse effects on plasma lipids, glucose levels, and body weight than other antipsychotics. To the best of our knowledge, there are as yet no available reports on the safety of the ECT-ziprasidone combination. We report here on a series of 8 female inpatients who underwent ECT while receiving ziprasidone (20-80 mg/d) as part of their regimen. Seven patients were treated for major depressive episode in the context of unipolar major depressive disorder (n = 5) or of bipolar disorder I (n = 2), whereas 1 patient was treated for exacerbation of schizophrenic symptoms. In all cases, the combination was well tolerated with only minimal adverse effects and unremarkable changes in corrected QT interval.

Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2008

European Psychiatry, 2010

Clinical Neuropharmacology, 2009

Clinical Neuropharmacology, 2009

European Psychiatry, 2010