The orexin (hypocretin) system plays a central role in regulating the sleep–wake cycle through two neuropeptides, orexin-A and orexin-B, which act on OX1R and OX2R receptors. Emerging evidence links heightened orexin signaling with the pathophysiology of chronic insomnia. This review outlines the neurobiology of the orexinergic system, compares the pharmacological profile of dual orexin receptor antagonists (DORAs) to traditional GABAergic hypnotics, and evaluates the clinical efficacy and safety of Suvorexant, Lemborexant, and Daridorexant. DORAs function by selectively dampening orexin-driven arousal, thereby facilitating sleep onset and maintenance without disrupting natural sleep architecture. Clinical trials have shown that these agents significantly reduce sleep latency and enhance sleep continuity, with a favorable side effect profile. Overall, DORAs represent a distinct and clinically advantageous option for insomnia treatment, with growing interest in their potential utility across mood, anxiety, and neurodegenerative disorders.

Insomnia is a common and complex disorder, rooted in the dysregulation of circadian rhythms, impaired neurotransmitter function, and disturbances in sleep–wake homeostasis. While conventional hypnotics such as benzodiazepines and Z-drugs are effective in the short term, their use is limited by a high potential for dependence, cognitive side effects, and withdrawal symptoms. In contrast, melatonergic receptor agonists—melatonin, ramelteon, tasimelteon, and agomelatine—represent a pharmacologically targeted alternative that modulates MT1 and MT2 receptors, which are pivotal to the regulation of circadian timing and sleep initiation. Clinical evidence supports the efficacy of these agents in reducing sleep onset latency, extending total sleep duration, and re-aligning disrupted circadian rhythms, particularly among older individuals and patients with non-24 h sleep–wake disorders. Notably, agomelatine offers additional antidepressant properties through selective antagonism of the 5-HT_2C receptor in micromolar concentrations. In contrast, its agonistic activity at melatonergic receptors is observed in the low sub-nanomolar range, which illustrates the complexity of this drug’s interactions with the human body. All compounds reviewed demonstrate a generally favorable safety and tolerability profile. Accumulating evidence highlights that selected medicinal plants, such as chamomilla, lemon balm, black cumin, valeriana, passionflower and lavender, may exert relevant hypnotic or anxiolytic effects, thus complementing melatonergic strategies in the management of insomnia. This structured narrative review presents a comprehensive analysis of the molecular pharmacology, receptor affinity, signaling pathways, and clinical outcomes associated with melatonergic agents. It also examines their functional interplay with serotonergic, GABAergic, dopaminergic, and orexinergic systems involved in arousal and sleep regulation. Through comparative synthesis of pharmacokinetics and neurochemical mechanisms, this work aims to inform the development of evidence-based strategies for the treatment of insomnia and circadian rhythm sleep–wake disorders.

Lamotrigine is the drug of choice for the treatment of depressive episodes in bipolar disorder (BD). Despite its generally favorable tolerability profile, lamotrigine use is associated with a risk of Cutaneous Adverse Drug Reactions (cADRs), including Stevens–Johnson Syndrome (SJS) and Lyell’s syndrome, also known as toxic epidermal necrolysis (TEN). Genetic markers HLA and, in particular, HLA-B 15:02 and HLA-A 31:01 are crucial in predicting individuals’ susceptibility to developing the symptoms. The symptoms are triggered by type IV hypersensitivity developing because of CTL and NK cell activation, leading to keratinocyte apoptosis, epidermal necrosis and skin detachment. The exact pharmacotherapy that should be widely utilized in treating affected patients has not yet been established. New therapies including JAK inhibitors or cyclosporine show potential in improving outcomes by reducing mortality and enhancing the period of recovery. Key factors in preventing cADRs may include adequate patient observation, gradual titration of the patient’s dose, and reduction of risk factors through screening for HLA polymorphisms. When the initial symptoms of cADR are identified, it is imperative to make an immediate decision to discontinue treatment, as this can significantly reduce the risk of progression to SJS/TEN and systemic complications. The purpose of this review is to identify a significant correlation between lamotrigine use in BD and the occurrence of SJS by showing the risk factors, neuropharmacological mechanisms, immune response and correctness of pharmacotherapy.

Congenital nasolacrimal duct obstruction (CNLDO) is a prevalent condition in newborns, characterized by lacrimation excess due to anatomic occlusion of the nasolacrimal ducts (NLD). This narrative review provides a comprehensive overview of CNLDO, encompassing its etiology, epidemiology, clinical manifestations, diagnosis and current treatment options. Diagnosis comprises the fluorescein dye disappearance test (FDDT) and imaging studies. In most cases, CNLDO resolves spontaneously within the first year of life. However, if spontaneous resolution does not occur, or if complications arise during observation period, treatment with conservative methods such as massage is introduced earlier, depending on the severity and complexity of the case. If these methods prove unsuccessful, more invasive procedures, including probing, intubation or dacryocystorhinostomy, are employed. While early diagnosis is crucial, its direct impact on treatment outcomes is more related to the prompt identification of cases that may require escalation of care.

Background: Driving is a coordinated psychomotor activity that involves reaction time, attention, and decision-making. Psychoactive substances such as 2-phenylethylamine (PEA) derivatives and opioids may affect these functions and contribute to traffic safety. This systematic review revealed the effects of the selected PEA derivatives and opioids on psychomotor performance among drivers and potential road safety outcomes. Methods: The review followed PRISMA 2020 standards. Using the PICO method, we conducted a systematic search in Embase, PubMed, and Web of Science (2000–2025). Included studies involved adult participants and quantified the effect of PEA derivatives or opioids on driving-related psychomotor function. Thirty-one articles, such as randomized controlled trials, crossover studies, observational studies, and simulator-based studies, were examined. Risk of bias was evaluated using the RoB2 tool. Results: Evidence indicates therapeutic amphetamine and methylphenidate doses can enhance psychomotor function and safety in patients with ADHD. Recreational or high-dose use of methamphetamine and MDMA is associated with impaired coordination, variable speed, and increased impulsivity. Opioid effects are tolerance- and dose-dependent. Small therapeutic doses of fentanyl in chronically treated patients do not notably impair driving. On the other hand, methadone and tramadol commonly cause somnolence, retardation of reaction, and increased accident risk. Conclusions: The impact of opioids and PEA derivatives on psychomotor function is multifactorial, depending on dose, time, route of administration, and patient status. These substances can either improve or impair driving safety. The findings confirm the need for individual-specific pharmacotherapy treatment. They also highlight the importance of further studies to formulate evidence-based clinical and legislative guidelines.

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder generally associated with pediatric patients and in lesser extent with adults. Patients diagnosed with ADHD have a higher likelihood of developing addiction. Consequently, a disorder that frequently co-occurs with ADHD is Substance Use Disorder (SUD). The pharmaceuticals prescribed in the treatment of ADHD are predominantly stimulants, such as methylphenidate and amphetamines, which possess a high addiction potential. The objective of this study is to examine the risk of developing substance dependence during stimulant treatment in individuals with ADHD who have a natural predisposition to addiction, with particular emphasis on adult patients with a history of SUD. Our literature review was conducted using research papers from PubMed, Google Scholar, Embase, ProQuest and ScienceDirect. The main results from our review are as follows: (i) the majority of studies indicate that the administration of stimulants in the treatment of ADHD does not increase the risk of developing Substance Use Disorder; (ii) stimulants may also be used in the treatment of SUD; (iii) while pharmacotherapy is a crucial part of ADHD treatment, a holistic approach comprising pharmacological and non-pharmacological therapy is most effective; (iv) holistic management of ADHD is necessary to improve patients’ quality of life to the greatest extent possible.