2014, volume 30, issue 2

Review article

Selective or multimodal? The development of serotonin reuptake inhibitors – the case of vortioxetine

Przemysław Bieńkowski, Łukasz Święcicki
Farmakoterapia w Psychiatrii i Neurologii, 2014, 2, 61–67

The recent approval of vortioxetine in the USA and Europe adds a new medication to a group of multi-modal antidepressant drugs modulating both serotonin transporters and some serotonin receptors. Both in vitro and in vivo studies indicate that vortioxetine is a potent and relatively selective inhibitor of serotonin reuptake with marginal affi nity to norepinephrine and dopamine transporters. In addition, vortioxetine at the concentrations needed to inhibit serotonin transporters antagonize serotonin 5-HT3 (3.7 nM) and 5-HT7 (19 nM) receptors and stimulate serotonin 5-HT1A receptors (15 nM). The affi nity of vortioxetine to other serotonin receptors (5-HT1B, 5-HT1D) is weaker but can contribute to its clinical effects. The antidepressant effects of vortioxetine have been assessed in several clinical studies, in patients with a diagnosis of major depression according to the DSM-IV criteria. The drug exerted dose-dependent antidepressant effects comparable to those produced by the active comparators used in the study, duloxetine and venlafaxine. The authors of clinical reports concluded that the drug was safe and well tolerated. The most common side effects associated with vortioxetine administration were nausea and headache. The risk of sexual dysfunction in patients treated with vortioxetine was relatively low. The aim of this brief review is to familiarize psychiatrists with the most important features of vortioxetine, with special emphasis given to a possible relationship between its pharmacological properties and clinical indications.

Original article

Second generation antipsychotics in the opinions of Internet forum users

Katarzyna Szaulińska, Olga Sikorska, Jerzy Samochowiec
Farmakoterapia w Psychiatrii i Neurologii, 2014, 2, 69–89

Introduction: Patients with schizophrenia use the Internet not only in search of support, but also to share their knowledge about the effects of medication. The aim of the study was a comparative analysis of the side effects of the second generation antipsychotics (SGAs) as described on the forum and those listed in the Summary of Product Characteristics (SPC).
Method: Patients' posts in the section "drugs, therapies" (Polish: "leki, terapie") subsection "antipsychotics" (Polish: "neuroleptyki") were analysed for the period between February 2003 and March 2013. We were looking for information on the tolerance of the following drugs: amisulpride, aripiprazole, clozapine, quetiapine, olanzapine, risperidone, sertindole and ziprasidone. Next, we calculated the frequency of the occurrence of each side effect (in percentages) and presented the data against the frequency of their occurrence as listed in the SPCs.
Results: Users of the forum paid most attention to drowsiness, effects of the drug on body weight, disorders of sexual function and psychiatric symptoms such as anxiety, depression and cognitive disorders. The mention of gastroenterological symptoms and dizziness was lower than their occurrence in the relevant SPCs. Most users did not report any deviations in the results of their laboratory tests or ECG. What has been noted, however, is the aggravation of the symptoms of glaucoma in clozapine users, which was a serious side effect reported on the forum yet absent from the SPC.
Conclusions: The offi cial information released about a pharmaceutical product often varies from the opinions given by its users. However patients' subjective opinions, even if their sources are hard to verify scientifi cally, play an important role in the healing process and should not be ignored.

Review article

Epilepsy: inflammation and blood-brain barrier in the pathogenesis of the disease – new therapeutic targets

Agnieszka M. Cudna, Iwona Kurkowska-Jastrzębska
Farmakoterapia w Psychiatrii i Neurologii, 2014, 2, 91–111

In recent years, the infl ammatory reactions and the associated disturbance of the blood-brain barrier integrity have been found to affect the course of the disease and the response to treatment in both the experimental models as well as in patients with epilepsy. Increased permeability of the blood-brain barrier causes the influx of leukocytes and the accumulation of albumin leading to the activation of glial cells. Glial cells, through secreted chemokines and cytokines (e.g. IL1β, IL6, TNFα) activate the endothelium. Moreover, proinfl ammatory factors are involved in the mechanism of neuronal hyperexcitability, including interactions with the neurotransmitter systems (e.g. glutamate, GABA) and the modifi cation of the external environment of the nerve cells, which consequently leads to the formation of seizures. The interaction between the blood-brain barrier and the glial cells may represent a new therapeutic target for the treatment of refractory epilepsy.

Review article

Neuroprotective and neurotoxic effects of lithium: the role of different brain structures

Adrian Andrzej Chrobak, Maciej Hyla, Anna Tereszko, Szymon Jeziorko, Marcin Siwek, Dominika Dudek
Farmakoterapia w Psychiatrii i Neurologii, 2014, 2, 113–120


Lithium salts are the most commonly used drug in the treatment of bipolar disorder, with proven effectiveness in reducing the risk of relapses. However, the narrow therapeutic range of concentrations and high risk of side effects require a closer look at their mechanisms of action. Lithium exhibits a neuroprotective effect in hippocampus and amygdala as well as the neurotoxic properties which are most evident in the cerebellum. The purpose of this paper is to review the literature on the neuroprotective and neurotoxic properties of lithium salts.
Neuroprotective properties of prolonged lithium treatment result from the inhibition of neuronal excitotoxicity by blocking the NMDA receptors, and anti-apoptotic action in the particular areas of the brain. In vitro studies have also found a positive effect on neurogenesis, which coincides with the morphometric studies in humans, where increased volume of grey matter in the prefrontal cortex and the limbic system was reported. A lot of research indicates, however, the occurrence of serious adverse effects of prolonged lithium therapy, not necessarily resulting from an overdose. Symptoms of chronic intoxication include both cognitive disorders, peripheral neuropathy giving rise to sensomotoric disturbances, and cerebellar dysfunctions. All of these are the aspects of the syndrome of irreversible lithium-effectuated neurotoxicity. Neuropathological studies indicate signifi cant structural changes occurring mainly in the cerebellum, including the disappearance of the granular layer and Purkinje cells, with associated gliosis. These changes, caused by lithium toxicity, might be a signifi cant factor impeding the determination of the aetiology of bipolar disorder, which also includes disturbances in the cerebellum, both at the structural and functional level.

Letter to the Editor

Transparent cooperation between pharmaceutical companies and the medical community and its value for the development of medicine

Paweł Sztwiertnia
Farmakoterapia w Psychiatrii i Neurologii, 2014, 2, 121–123

Cooperation between innovative pharmaceutical companies and the medical community is a natural and necessary part of the health care system. Sharing knowledge and experience is essential in the process of new drugs and therapies development. Today, however, the image of this cooperation is unclear to the public, and therefore it is impossible to properly assess its value.
All around the world, actions are taken to increase the transparency of these relationships. In some countries, such as the United States and France, legal solutions enforcing full transparency are already in force.
The European Federation of Pharmaceutical Industries and Associations (EFPIA), the Polish representative is INFARMA, decided to implement the Code of Transparency to meet the public expectations in this matter. This document is a formal code of conduct that requires all EFPIA member companies and companies which are members of EFPIA member associations to disclose transfers of value to healthcare professionals (HCPs) and healthcare organizations (HCOs). In accordance with the Transparency Code starting from 2016 all INFARMA members, with the knowledge and consent of the medical professionals and health organizations, will publically show the benefits associated with cooperation.
Transparency Code aims to raise standards of this cooperation. INFARMA hopes that by thanks to this process the public opinion will be able to recognize the real value of the health care system. Implementation of the Code is based on a dialogue with the medical community, patients' organizations, trade organizations and independent authorities in the field of ethics.

Scientific conference report

The report from the ECNP School of Child and Adolescent Neuropsychopharmacology (Venice, Italy, 6–11.04.2014)

Marta Gawłowska, Barbara Remberk
Farmakoterapia w Psychiatrii i Neurologii, 2014, 2, 125–130

The participants in the Second ECNP School of Child and Adolescent Neuropsychopharmacology, which took place in Venice (6–11.04.2014), present a summary of the lectures given at the school. Some of the leading experts in the fi eld of child and adolescent psychiatry gave lectures and held workshops with a focus on the application of the latest research results in clinical practice.