2016, volume 32, issue 2

Original article

The metabolic effects of antipsychotic medication in youth

Barbara Remberk, Joanna Brągoszewska, Agnieszka Jarząbek-Cudo, Agnieszka Piróg-Balcerzak, Filip Rybakowski
Farmakoterapia w Psychiatrii i Neurologii 2016, 32 (2), 65–78

Objectives. Metabolic side effects of antipsychotic medi­cations have been observed for years and described in many studies. There is, however, a dearth of research focusing on the Polish adolescent population. The aim of this study was the assessment of metabolic side effects of antipsychotics in adolescent inpatients.

Material and methods. In 2014 and 2015, antipsychotic medication was administered in fifty nine patients hospitalised in Child and Adolescent Psychiatry Department for the first time. In each of the patients at the admission the following were assessed: body weight, body mass index (BMI), waist circumference and blood pressure and in blood samples levels of glucose, lipids, creatinine, transaminases and prolactin were tested. Thirty two patients, who had the second assessment in the course of the treatment were included in this study.

Results. During antipsychotic treatment statistically significant increase in body weight and BMI (mean 0.7 ± 0.9 and 2.1 ± 2.7 kg, respectively) were observed during the mean 4.1 ± 2.2 weeks. The increment of glucose, prolactin and lipids levels did not reach statistical significance. In all the included patients, antipsychotics were used off-label.

Conclusions. Body weight monitoring at least once a fortnight and a periodical assessment of laboratory tests and ECG seem to be crucial during psychotic treatment in children and youth. Moreover, according to current legal regulations, most of the first-line antipsychotics are prescribed off-label to children and youth. In such circumstances, monitoring of adverse effects should be essential.

Original article

The long term administration of haloperidol supports the origin of DCX-expressing cells in the adult rat brain

Artur Pałasz, Michalina Respondek, Ewa Rojczyk, Katarzyna Bogus, Łukasz Filipczyk, Marek Krzystanek, Ryszard Wiaderkiewicz
Farmakoterapia w Psychiatrii i Neurologii 2016, 32 (2), 79–84

Aims. Continuously active neurogenic regions in the adult mammalian brain are located in the subventricular zone (SVZ) of the lateral ventricles and the subgranular zone (SGZ) of the hippocampal dentate gyrus. The neurogenesis process is modulated by many factors e.g. growth factors, neurotransmitters and hormones. Neuropsychiatric drugs, especially antidepressants, mood stabilizers and antipsychotics may also affect the dynamics of the origin of neuronal cells. The purpose of the study was to determine the effects of long-term haloperidol treatment on adult rat neurogenesis at the level of canonical neurogenic sites.

Materials and methods. The studies were carried out on adult male Sprague-Dawley rats. Two groups of animals (5 in each) received, respectively, saline and haloperidol (2 mg/kg/day) by intraperitoneal injection for 28 days. The number of neuroblasts was evaluated using immunohistochemical detection of doublecortin (DCX) expressing cells. The total number of DCX-positive cells in the neurogenic zones was counted for each rat (which was the sum of cells from 10 slices) and the results were divided per length of the studied subependymal area (SGZ) and dentate gyri (SGZ) to obtain density of immunopositive cells per one millimeter of length.

Results. The results indicate that haloperidol has proneurogenic effects on the adult rat brain, especially in the SVZ, as the mean number of DCX-positive cells increased significantly in SVZ and there was a similar tendency in the SGZ.

Conclusions. We found that long-term treatment with haloperidol stimulated DCX-positive cell formation in the SVZ, which supports adult neurogenesis.

Original article

Peripheral blood mRNA expression of neural stem cell markers in bipolar disorder and the effect of long-term lithium treatment

Ewa Ferensztajn-Rochowiak, Maciej Tarnowski, Paweł Mierzejewski, Michał Michalak, Mariusz Z. Ratajczak, Janusz Rybakowski
Farmakoterapia w Psychiatrii i Neurologii 2016, 32 (2), 85–96

Objectives. Research on stem cells indicates their role in the pathogenesis of psychiatric disorders and mechanisms of psychotropic drugs. In this study, we evaluated expression of mRNA markers of neural stem cells (NSCs): nestin, β3-tubulin and vimentin in peripheral blood of patients with bipolar disorder (BD) and assessed the ­effect of long-term lithium treatment.

Material and methods. Thirty patients with BD were included (fifteen during remission, with illness duration minimum 10 years, never treated with lithium, and 15 treated with lithium for 8–40 years, 16 years on average), and 15 control subjects, matched in terms of sex and age. Assessment of the mRNA was performed using the ­real-time quantitative reverse transcription PCR procedure.

Results. In BD patients never treated with lithium, the mRNA expression of nestin and β3-tubulin was signifi­cantly higher, compared to the control group. In ­lithium-treated patients, the expression of β3-tubulin was similar to the control group. The mRNA expression of vimentin was higher in lithium-treated BD patients, compared to non-lithium-treated patients and the control group. In the control group, the mRNA expression of nestin and vimentin correlated negatively with the number of CD133+ VSELs (very small embryonic-like stem cells), which was not observed in BD subjects.

Conclusions. The results show a differential mRNA ­expression of NSCs markers in BD patients and variable effects of long-term lithium treatment on these ­parameters. Increased levels of nestin and β3-tubulin may indicate excessive regenerative processes occurring in the course of BD, and long-term lithium treatment may inhibit overexpression of β3-tubulin. Elevated mRNA levels of vimentin in lithium-treated patients may be related to neuroprotective properties of this ion.

Review article

The therapeutic effects of lithium in the context of the purinergic theory of affective disorders

Magda K. Malewska, Anna Jasińska, Janusz Rybakowski
Farmakoterapia w Psychiatrii i Neurologii 2016, 32 (2), 97–109

Lithium as a chemical element was discovered nearly 200 years ago. Its introduction to the treatment of affective disorders at the end of the nineteenth century by Carl Lange in Denmark and, in the second half of the twentieth century, by John Cade in Australia was linked to studies on uric acid. Carl Georg Lange (1834–1900) is regarded as one of the most prominent Danish scientists of the nineteenth century. His achievements in neurology, psychology and psychiatry are still relevant today. He was a co-founder of a neurophysiological theory of emotions, known as the James–Lange theory. In 1886 he wrote a clinical treatise on periodic depression, in which he presented a biochemical theory that postulated the pathogenic role of an excess of uric acid in the brain. Based on this, he used lithium for the treatment of patients with depression. John Frederic Cade (1912–1980), to whom the introduction of lithium to contemporary psychiatry is owed, used lithium after experimenting with uric acid in guinea pigs. He was the first psychiatrist to give lithium to manic patients, with spectacular therapeutic effects. His paper, published in 1949 in “The Australian Journal of Psychiatry”, is regarded as a harbinger of modern psychopharmacology. In recent years, it has been demonstrated that uric acid and the associated purinergic system may play a role in the pathogenesis and treatment of affective disorders. A purinergic hypothesis of affective disorders is presented in this study, assuming a significant pathogenic role for uric acid, adenosine receptors P1 and nucleotide receptors P2X and P2Y.

Review article

Effective stroke prevention

Michał Karliński, Anna Członkowska
Farmakoterapia w Psychiatrii i Neurologii 2016, 32 (2), 111–128

Objectives. The aim of this paper is to review selected aspects of the primary and secondary prevention of ischaemic stroke with a special emphasis on recent publications, as well as the differences between these two types of prevention.

Literature review. The role of lifestyle and its modification, treatment of blood hypertension and dyslipidaemia, the use of antiplatelet agents and the management of carotid stenosis are reviewed. For each of the elements of stroke prevention, the scientific background and current recommendations are provided.

Conclusions. Stroke is a condition that can be prevented. To achieve this, it is vital to recognize early and properly treat concomitant diseases such as hypertension, carotid atherosclerosis, atrial fibrillation or dyslipidaemia. However, on the population level, it is lifestyle optimization that is even more important. It has been estimated that about 50% of strokes can be avoided by the implementation of five low-risk behaviours, including regular physical activity, healthy diet, moderate alcohol consumption or avoiding excessive drinking, and weight control. This kind of lifestyle improves control of the major vascular risk factors in a way that is directly reflected in lower risk of first-ever stroke. Secondary stroke prevention should additionally involve detailed assessment of extracranial arteries and screening for atrial fibrillation. In the case of a symptomatic carotid stenosis of 70% or more it is recommended that early carotid endarterectomy is performed or, in some cases, stenting. Long-term use of oral anticoagulants is indicated in all individuals suffering from cardio-embolic strokes. Other patients should receive antiplatelets.


The report on the ECNP School of Child and Adolescent Neuropsychopharmacology, 3–8 April 2016, Venice, Italy

Ksymena Urbanek
Farmakoterapia w Psychiatrii i Neurologii 2016, 32 (2), 129–132

ECNP School of Child and Adolescent Neuropsychopharmacology is organized to provide high-level training in child and adolescent neuropsychopharmacology from a faculty of international experts. Its aim is to develop local good practice in teaching and training across European countries through the participants of the School.

The aim of this report is to present topics covered during the School, which took place in Venice (3–8 April 2016).