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Current issue

2018, volume 34, issue 2

Original article

Comparison of the influence of selected psychotropic drugs on the level of tumour necrosis factor in experimentally induced depression

Katarzyna Manikowska, Agnieszka Plebańska, Przemysław Ł. Mikołajczak
Farmakoterapia w Psychiatrii i Neurologii 2018, 34 (2), 95–108

Objectives. Our knowledge of the role of cytokines in the pathogenesis of mental disorders is still insufficient. The aim of this study was to evaluate the effect of antidepressants such as venlafaxine or paroxetine, as well as that of an atypical antipsychotic, i.e. aripiprazole, on the level of TNFα in the peripheral blood of rats.

Material and methods. The study was carried out in three separate experiments on male Wistar rats, each time dividing them into two groups. The first group was subjected for 6 weeks to chronic mild stress (CMS) and the second was a control group (of unstressed animals). Following the development of induced anhedonia, some of the stressed and control rats were treated with venlafaxine (20 mg/kg, p.o. daily), paroxetine (12.5 mg/kg, p.o. daily) or aripiprazole (2,5 mg/kg, p.o. daily) for 3 weeks. On the last day of the experiment a lipopolysaccharide (LPS, 100 µg/kg b.m., i.p.) was injected into 25% of the rats and levels of TNF-α were assayed with ELISA.

Results. The results indicated an increase of TNF-α level in the stressed animals administered LPS. The paroxetine treatment resulted in a significant decrease in TNF-α level in the stressed animals that were also administered LPS. Venlafaxine did not have a significant effect on TNF-α level, whereas aripiprazole significantly increased the level of TNF-α in animals which were administered LPS.

Conclusions. The paroxetine-induced normalisation of the TNF-α level, increased by CMS and LPS, confirms the hypothesis of the influence of some antidepressants on the immunological system. Some atypical antipsychotics, on the other hand, such as aripiprazole can have a stimulatory effect on the immunological factors in the case of acute stress.

Original article

The use of lithium in Poland in 2004–2017

Katarzyna Chęcińska, Janusz Rybakowski
Farmakoterapia w Psychiatrii i Neurologii 2018, 34 (2), 85–94

Objectives. Lithium is the first choice drug for the prophylaxis of recurrences in bipolar disorder (BPD). Besides mood-stabilising activity, it exerts antisuicidal, immunomodulatory and neuroprotective effects. However, the drug is greatly underutilised, due to a promotion of other mood-stabilising drugs, both 1st and 2nd generation, and to exaggerated concerns about lithium toxicity. This has been reflected in many countries by a decrease of lithium prescriptions at the expense of other mood-stabilising drugs. In this paper, the range of lithium use in Poland in recent years, in the context of other mood-stabilising drugs, was assessed.

Material and methods. Lithium use in years 2004–2007 was estimated by the data of the Intercontinental Marketing Statistics, expressed as Days of Treatment (DOT) values. Current lithium use in the context of other mood-stabilising drugs (valproates, carbamazepine, lamotrigine, olanzapine, quetiapine, aripiprazole) was assessed by comparing the prescriptions for a given drug for BPD patients in the second half of 2017.

Results. In seven-year period 2004–2010, a minimal increase of lithium use (4%) occurred, while in 2011–2017, this increase amounted to 16%. In the second half of 2017, the use of valproates was nearly three-times higher than lithium while that of quetiapine, olanzapine and lamotrigine about twice as high.

Conclusions. In recent years, a slight increase of lithium use in Poland has occurred. However, compared with other mood-stabilising drugs, lithium has been underutilised. The authors advise more extensive use of lithium for the prophylaxis of recurrences in BPD, both as monotherapy and in combination with other mood-stabilisers.

Review article

Oxcarbazepine in bipolar affective disorder

Janusz Rybakowski
Farmakoterapia w Psychiatrii i Neurologii 2018, 34 (2), 131–138

Oxcarbazepine (OXC) has a chemical structure similar to that of carbamazepine (CBZ), an anticonvulsant and the first-generation mood stabiliser. The efficacy of CBZ in the treatment and prophylaxis of bipolar disorder (BPD) has been validated in the last four decades. OXC’s metabolism is different from that of CBZ. Carbamazepine is oxidised mainly by the enzyme CYP3A4 of cytochrome P-450, resulting in 10, 11-epoxide of CBZ. On the other hand, OXC is metabolised in the liver by the enzyme CYP2C19 of cytochrome P-450 into pharmacologically active 10-mono-hydroxy-carbazepine (MHD). OXC causes less pharmacokinetic interactions and probably has less adverse effects than CBZ. However, the therapeutic efficacy of OXC in BPD has not been such well confirmed as that of CBZ.

In this work, the pharmacokinetic properties of OXC as compared with CBZ are presented. A review of the studies on the efficacy of OXC in BPD was performed, also considering comparative studies with CBZ efficacy. They show that OXC can be used in the treatment of manic episodes and in the prevention of recurrences in BPD. The analysis of adverse effects of OXC, also in comparison with CBZ, was performed based on data of its application in BD, in epilepsy and trigeminal neuralgia. In summary, it is concluded that given pharmacokinetic and clinical profile and the evidence for its efficacy, OXC can make an important alternative to CBZ in the treatment and prophylaxis of BPD in adults. A possibility of its use in BPD in children and teenagers requires further studies.

Review article

Internet as an addiction. Definition and a literature review of pharmacological interventions

Anna R. Szczegielniak, Marek Krzystanek
Farmakoterapia w Psychiatrii i Neurologii 2018, 34 (2), 119–129

In the last two decades the number of Internet users increased from 1 to 51% of the global population. The figure increased tenfold between 1999 and 2013, and doubled in the past five years. Nowadays 830 million young people aged 15–24 are online, representing almost 25% of the total number of Internet users globally. In 1996 Kimberley Young was the first researcher to bring attention to the negative consequences of Internet use, by demonstrating the presence of the clinical symptoms of addiction and indicating a severe impulse control disorder among some Internet users. Various aspects of the Internet-related disorder have been analysed, initially focusing on defining the phenomenon and examining specific addictive patterns of behaviour, and now primarily investigating the etiological factors and major trends in the development of the disorder. Controversy has quickly grown around the various related issues. There have been discussions about whether Internet Addiction represents a manifestation of an underlying disorder, or constitutes a separate disease. At present, there are no protocols endorsed for pharmacological treatment; the majority of reports describe the empirical treatment of individual cases, and the available studies are lacking consistency in the definitions used, randomization of groups studied, appropriate control groups or information about treatment effects. It seems that at present our knowledge of the neurobiological processes related to Internet Addiction is too basic to formulate any pharmacological recommendations. The presence of disorders in the reward system is suggested and the implementation of therapeutic procedures advised accordingly. The aim of this publication is to review the scientific reports available to lay the foundations for further discussion.

Review article

Pharmacotherapy of circadian rhythm sleep-wake disorders

Adam Wichniak, Michał Dermanowski, Julita Kuczyńska, Alicja Zakrzewska, Paweł Mierzejewski
Farmakoterapia w Psychiatrii i Neurologii 2018, 34 (2), 109–118

Circadian rhythm sleep-wake disorders are characterized by an incorrect regulation of sleep and wakefulness, and a lack of synchronization with the 24-hours rhythm. Circadian rhythm sleep-wake disorders are an increasing civilizational problem related to both the aging of the population, as old people suffer from the deregulation of homeostatic processes, as well as exposure to artificial environmental conditions such as night lighting, reduced exposure to sunlight, and limited physical activity.

The increasing knowledge about the mechanisms regulating the circadian rhythm allows for individualized diagnostics and therapy for people with sleep problems. Our centre specializes in this field by offering innovative diagnostic and therapeutic methods based on objective biological markers, including polysomnography, actigraphy, and the monitoring of melatonin concentrations in saliva.

The aim of this article is to discuss the mechanisms of circadian rhythm regulation, as well as the diagnostic possibilities, and review the drugs available for use in the treatment of circadian rhythm sleep-wake disorders.

Particular attention is paid to the discussion of chronobiotics: this involves melatonin, which is a natural synchronizer of sleep and wakefulness, as well as synthetic drugs such as Ramelteon, Tasimelteon, Agomelatine, which are agonists of melatonin receptors. Symptomatic treatment also includes sleep-promoting drugs, such as benzodiazepines and non-benzodiazepines (“Z-drugs”), antihistamines and, recently introduced to treatment but not available in Poland, suvorexant, an OX1 and OX2 orexin receptor antagonist.

Case report

Rebound effect after S1P receptor modulator treatment in a patient with relapsing-remitting multiple sclerosis

Małgorzata Szymańska, Magdalena Targosz-Gajniak, Maciej Świat, Olga Rezner
Farmakoterapia w Psychiatrii i Neurologii 2018, 34 (2), 139–142

We present a case report of severe steroid-refractory rebound disease activity after cessation of MT-1303 (amiselimod) treatment in a patient with relapsing-remitting multiple sclerosis (RRMS), which has not been described in the literature previously. MT-1303 is a novel selective sphingosine-phosphate receptor (S1P1) modulator that was discovered by the chemical modification of fingolimod with the aim of avoiding its heart rate-reducing effect.