Archives

Insomnia is an important medical problem; its treatment requires both nonpharmacological methods (education and psychotherapy) and the use of hypnotic agents. The benzodiazepine derivatives may be used as hypnotic agents but their use is substantially limited. The alter­native treatment includes so-called z-drugs, which means nonbenzodiazepine hypnotic agents. Their mechanism of pharmacological action is a GABA-receptor agonism. In general, these drugs improve the quality of sleep (sleep latency, wake after sleep onset, number and duration of awakenings, total sleep time). Contrary to the benzo­diazepines they do not possess anti-anxiety, myorelaxant, and anti-seizure properties, and are better tolerated.

Eszopiclone for the treatment of insomnia was not available in Poland. It is not only effective in the treatment of insomnia in comparison to placebo but is also well tolerated. It may be used for a longer time than the benzodiazepines – not only a couple of weeks but per several months. Eszopiclone shortens the sleep latency, decreases the number of wakes after sleep onset and increases total sleep time. It improves the subjective evaluation of sleep by the patients, the quality of sleep and functioning during the day. Its efficacy in the treatment of insomnia in the elderly has also been proved. It is quite well-tolerated and the most frequent side-effect of eszopiclone in the unpleasant taste.

Objective. Zolpidem is a non-benzodiazepine agonist of GABA-A receptor indicated for the short-term insomnia treatment. Over the years, there have been reports in literature on zolpidem abuse complications and neuropsychiatric side effects involving headache, dizziness, nightmares, confusion, depression, sleepiness, memory deficits as well as hallucinations, sensory distortions, delirium and sleep-related complex behaviours with anterograde amnesia. The aim of this work is to review and highlight the most serious adverse reactions to zolpidem with emphasis on sleep-related amnestic behaviours. We also focus our attention on common traits, patterns and predisposing factors. This paper refers to zolpidem side effects or complex amnestic behaviours, or sleep related amnestic behaviours presented in literature.

Literature review. A comprehensive search of PubMed and Google Scholar was conducted to find relevant studies, case reports and literature reviews addressing the zolpidem use in insomniac patients.

Conclusions. Zolpidem may pose a risk for serious adverse reactions most common dose-dependent and associated with age, gender, concurrent use of medications and concomitant comorbidities. If severe adverse reactions occur, the drug should be immediately discontinued or switched to another hypnotic. This review indicates an association between psychotic reactions and complex sleep related behavioural abnormalities in patients using zolpidem alone or in combination with other psychotropic medications. Clinicians should adopt a cautious approach prescribing zolpidem and be alert to possible unusual adverse effects of the drug.

Antihistamines are used for the symptomatic treatment of sleep disorders. The rationale for their use is the participation of the histaminergic system in the subcortical network modulating consciousness. This network consists of several subcortical structures that act on the cerebral cortex and thalamus, activating these structures and maintaining wakefulness. The histaminergic system, as one of the activating systems of the brain, contributes to the excitation of the thalamus and the cerebellum, while inhibition of its activity is used to induce drowsiness. There are only a few clinical studies in the medical literature that provide evidence of the hypnotic effects of I generation antihistamines. The article analyses regi­stered indications of the first generation antihistamines and studies of their effectiveness in various indications in the field of psychiatry. These drugs were analyzed by searching in PubMed (www.ncbi.nlm.nih.gov/pubmed) and Web of Science (www.webofknowledge.com) cli­nical studies on people in whom these drugs were studied in primary sleep disorders. The following terms were used: antihistaminergic drugs AND insomnia, diphenhydramine AND insomnia, doxylamine AND insomnia, hydroxyzine AND insomnia, diphenhydramine AND insomnia, promethazine AND insomnia. The same phrases were also entered in the browser www.google.pl. In summary, there are very few studies on the efficacy of 1st generation antihistamines in the treatment of sleep disorders. Of the first-generation antihistamines, doxy­lamine and diphenhydramine have only registered indications for the treatment of accidental insomnia, but there are no studies justifying the use of hydroxyzine in the treatment of insomnia.

Sleep disorders is a common problem that patients report to their doctor. They can accompany many mental and somatic disorders or be primary. There are many types of sleep disorders; most commonly, they are associated with problems with falling asleep and maintaining sleep continuity, or more complex disorders, such as parasomnias, breathing disorders and movement disorders associated with sleep. In the following work, we have focused on sleep problems in patients with multiple sclerosis (MS). These patients more often than healthy people of the same age complain about sleep disorders and these dis­orders increase with the progress of the disease and the appearance of other symptoms. Depressed mood, chronic fatigue, pain and urinary problems significantly affect the quality of sleep in patients with MS. On the other hand, excessive sleepiness and trouble with falling asleep intensify the feeling of fatigue, which is a major problem and impair cognitive functions. However, sleep-related symptoms are often overlooked during medical visits due to other symptoms of multiple sclerosis, especially those causing motor disability. The treatment of sleep disorders in patients with MS is based on basic methods used in the general population. In the treatment of sleep disorders in patients with multiple sclerosis, appropriate disease modifying therapy is also important.

The aim of preventive treatment of episodic and chronic migraine is to reduce the frequency and severity of seizures and thereby improve the quality of patients' lives. It is estimated that 38% of patients with migraine would benefit from preventive treatment. However, in clinical practice only approximately 13% of patients with migraine receive it. Intolerable side effects and lack of efficacy of pharmacological treatment are the main reasons of treatment discontinuation. It is suggested that calcitonin-gene-related-peptide (CGRP) plays a critical role in migraine pathophysiology. One of them is galcanezumab – a humanised monoclonal antibody that selectively binds to the CGRP peptide. Galcanezumab has demonstrated efficacy in EVOLVE-1, EVOLVE-2 and REGAIN trials. It significantly reduces migraine days per month versus placebo. Moreover, the quality of patients' lives treated with galcanezumab also improved. It has a favourable safety profile, similar to placebo groups. The most frequent adverse event in patients treated with galcanezumab was injection site pain. No toxic effects on the liver or negative influences on hemodynamic or laboratory parameters were reported. The discontinuation rates due to adverse events in patients treated with galcanezumab were low. In October 2019, lasmiditan was approved by FDA and EMA in prophylaxis treatment of migraine in adult patients. Currently, this medicine is not accessible in Poland.

Pharmacogenetic research aims to elucidate associations of genetic variants and individual effects of pharmacotherapy. Personalised expected response to medications might be useful in prognosis for polygenetically determined disorders. In bipolar disorder (BP), that is partly hereditary polygenic disorder, a subgroup of patients excellently responding to lithium prophylaxis was described. During the last 20 years molecular technology allowed to investigate genome of patients treated with lithium and candidate association studies characterised them more precisely than clinical features. The role of several neurotransmitters’ pathways, second messengers, neuroprotection involved genes and clock genes associations were discovered. Further laboratory technics development enables us to perform genome-wide association studies (GWAS) and polygenic risk score (PRS) analyses. We aimed to review research on genes involved in lithium treatment efficacy and safety. PubMed for English papers, articles published in Polish and reference lists from full-text available papers were searched. Pharmacogenetic findings for lithium treatment effects might help develop new personalised strategies and consequently better symptom reduction. So far, chronicity and recurrent course of bipolar disorder impair the functioning of numerous patients and strongly increase the risk of suicide.