Nitrous oxide (N2O) has been known since the late 18th century and is widely used in medical contexts for its analgesic and anaesthetic properties, particularly in dentistry, surgery, gynaecology, and obstetrics. Recently, its substantial potential in treating psychiatric disorders – especially severe and treatment-resistant depression – has gained scientific attention, with promising results already observed in off-label use at various university centres. The antidepressant effects are thought to arise mainly through inhibition of the NMDA receptor and additional opioid-related mechanisms. To make nitrous oxide more widely accessible as a fast-acting antidepressant, large-scale, preferably multicentre clinical trials are urgently required. Key questions include optimal dosage, duration, and frequency of administration. Risks related to repeated use – especially outside medical supervision – primarily concern vitamin B12 deficiency, which may result in serious neurological, haematological, and dermatological complications.

Therapeutic drug monitoring (TDM) as part of pharmacotherapy allows for treatment personalization based on estimation of pharmacogenetic and pharmacokinetic variation. Specifically, TDM refers to the process starting from the TDM request ending to the interpretation of the blood concentrations of the drug and the related consequences for the clinical decision process. The clinical utility of TDM may be challenged due to lack of systematic recommendations, when it comes to the therapeutic reference ranges of medications and the way these are defined. Here we describe a step-by-step method of how to determine a therapeutic reference range (TRRs) in psychiatry based various data types and sources including clinical trials and positron emission tomography studies. The lower limits of the TRR ideally derive from studies assessing associations between blood drug concentrations and clinical effectiveness, whereas the upper limits of the TRRs depend on the concentrations associated with adverse reactions or maximal clinical response. Ultimately, this proposed method describes a procedure that allows for a standardized and evidence-based determination of TRRs. The applicability of the procedure has been previously demonstrated with escitalopram and other antidepressant drugs, as well as with antipsychotic drugs. In the upcoming update of the AGNP TDM consensus guidelines this method will be widely applied for the first time.

Driving mobility is important for daily life functioning affecting mental, physical, social and economic well-being. Psychoactive drugs are prescribed frequently according to the frequency of psychiatric disorders. Empirical data impact of psychopharmacological treatment on driving performance in patients is rare. Experimental data have been analysed in detail in various reviews, with particularly sedating CNS effects in the acute phase of treatment being of major concern. When validating treatment with respect to driving performance stabilizing effects of pharmacological treatment have to be weighted against possible detrimental cognitive, vegetative-somatic and psychomotor effects within the treatment phase. Most patients benefit from treatment with psychotropic medicines over time with respect to driving performance, when given on clinical considerations; i. e. adjustment of dosing regimen according to clinical response or nocturnal administration, especially in the case of sedating medications. Major depressions treated adequately with antidepressants show better results than patients without treatment with antidepressants. Remitted patients under SSRIs and SNRIs have no reduction of driving ability. Schizophrenic patients show impairment in skills relevant for driving, data point to an advantage of SGA compared to FGA, considerable interindividual variance makes individual judgement necessary. (Benzodiazepine) tranquilizers and hypnotics worse driving in the first weeks after treatment initiation. Psychostimulans like methylphenidate can improve the restricted driving ability in ADHD patients. Effects of cannabis use are negative but varying. Neuropsychological testing is recommended if concise decision criteria are necessary. Psychopharmacologic medicines improve or at least stabilize driving performance of patients under long-term treatment when given on clinical considerations. Clinicians should be aware of possible detrimental effects of psychotropic medicines on driving performance and should patients individually counsel and advise to monitor for side effects.

Drug interactions represent a significant risk in clinical practice, particularly for psychiatric patients, who are often affected by polypharmacy. In this study, twelve drug interaction databases were systematically evaluated and compared using a newly developed 11-point quality scoring system. The analysis included both paid and freely accessible systems. Data from 104 patients with depressive disorders were analyzed, resulting in the identification of 1619 potential drug interactions across 506 drug pairs. The results revealed substantial differences in the quality and sensitivity of the evaluated databases. Paid systems such as ifap and PGXperts performed best, achieving 8.5 out of 11 points. Freely available databases scored significantly lower, with an average of 1.5 points compared to 6.4 points for paid systems (p = 0.009). The highest number of identified interactions involved combinations of two psychotropic drugs. However, agreement among databases in classifying severe interactions was extremely low (5 %). The substances most frequently involved in serious interactions exclusively were psychotropic drugs – led by mirtazapine, quetiapine, lithium and SSRI/SSNRIs. The study highlights the urgent need for better integration of pharmacogenetic factors, standardization of severity ratings, and interprofessional medication reviews as well as interdisciplinary collaboration with clinical pharmacists. Sole reliance on a single drug interaction database is not sufficient; rather, a combined use of multiple tools and expert judgment is recommended to improve medication safety.