[Wakefulness-promoting agents for severe fatigue: to use or not to use?] / Medicatie tegen ernstige aanhoudende vermoeidheid.

About 20% of adults experience excessive daytime sleepiness or severe fatigue. Causes include somatic conditions, psychiatric disorders, and medication or drug use. Treatment depends on the underlying cause. If sleepiness persists despite optimal treatment of the underlying condition, exclusion of other causes, and behavioral interventions, wakefulness-promoting agents may be considered. However, no established pharmacological strategy exists for symptomatic treatment. Modafinil and stimulants like methylphenidate may offer some benefit based on experiences with narcolepsy or idiopathic hypersomnia. Studies in specific patient groups (e.g., multiple sclerosis, Parkinson's disease, traumatic brain injury, cancer-related fatigue) show variable results. The use of wakefulness-promoting agents is discouraged for addressing unexplained fatigue, as seen in the context of chronic fatigue syndrome.

Discontinuation of psychotropic medication: a synthesis of evidence across medication classes.

Pharmacotherapy is an effective treatment modality across psychiatric disorders. Nevertheless, many patients discontinue their medication at some point. Evidence-based guidance for patients, clinicians, and policymakers on rational discontinuation strategies is vital to enable the best, personalized treatment for any given patient. Nonetheless, there is a scarcity of guidelines on discontinuation strategies. In this perspective, we therefore summarize and critically appraise the evidence on discontinuation of six major psychotropic medication classes: antidepressants, antipsychotics, benzodiazepines, mood stabilizers, opioids, and stimulants. For each medication class, a wide range of topics pertaining to each of the following questions are discussed: (1) Who can discontinue (e.g., what are risk factors for relapse?); (2) When to discontinue (e.g., after 1 year or several years of antidepressant use?); and (3) How to discontinue (e.g., what's the efficacy of dose reduction compared to full cessation and interventions to mitigate relapse risk?). We thus highlight how comparing the evidence across medication classes can identify knowledge gaps, which may pave the way for more integrated research on discontinuation.

[Insomnia: a persistent problem without optimal pharmacological approach]. / Slapeloosheid: een hardnekkig probleem zonder optimale medicamenteuze strategie.

Insomnia is a highly prevalent disorder in the Netherlands, with an estimated prevalence of 7-22%. The use of pharmacological interventions should be restricted, nevertheless, medications for insomnia are often prescribed. The use of off-label pharmacological interventions is increasing, although supporting evidence for these strategies is limited. In order to understand the use of certain on- and off-label strategies, we describe the pathophysiology of insomnia and the clinical pharmacology of various on- and off-label drugs.

Impulse control disorders associated with dopaminergic drugs: A disproportionality analysis using vigibase.

BACKGROUND: Dopamine receptor agonist drugs, which are used, for example, to treat Parkinson's disease (PD), increase the risk for impulse control disorders (ICDs), potentially resulting in devastating psychosocial consequences. It is unknown whether other drugs with dopaminergic properties also increase the risk for ICDs. This study assesses the disproportionality of reporting ICDs between drugs with dopaminergic properties and selected non-dopaminergic drugs. METHODS: A case/non-case disproportionality analysis was performed, using data from VigiBase (1968-2020). Reports on ICDs as suspected adverse drug reactions (ADRs) were cases (n=852), and those with ADRs other than ICDs were non-cases (n=281,720). Relative reporting frequencies were expressed as adjusted reporting odds ratios (aRORs). Within the dopamine receptor agonists, the relationship between reporting odds ratios and dopamine receptor occupancy was explored. RESULTS: A high disproportionality was found for reporting ICDs for all dopaminergic drugs (aROR 20.4 [95% CI 17.4-24.1]) compared to non-dopaminergic drugs. In pharmacotherapeutic subgroups, a high disproportionality was found for primary dopaminergic agents used in PD (aROR 52.1 [95% CI 44.1-61.5]), and to a lesser extent for ADHD psychostimulants and antidepressants (aROR 5.8 [95% 4.1-8.3] and aROR 3.9 [95% CI 2.9-5.6], respectively). There was no difference in reporting by consumers and healthcare professionals. The highest disproportionality was found for the dopamine receptor agonists pramipexole and ropinirole. CONCLUSIONS: A signal of disproportion in ICD occurrence was found among all investigated drugs with dopaminergic properties, highlighting the importance of counselling and monitoring for ICDs when prescribing dopaminergic drugs.

[Rational prescription of antidepressants for depression]. / Antidepressiva bij depressie: rationeel voorschrijven.

Antidepressants are the subject of lively public debate. Over one million Dutch people are prescribed an antidepressant each year for a variety of reasons. The number of long-term antidepressant users is smaller, estimated to be around 150,000 patients for over a year for depression. Clinicians and patients together must carefully weigh the pros and cons of antidepressants. In this article, we discuss the latest scientific insights how antidepressants can be used rationally.

[Psychotropic drugs and QTc prolongation]. / Psychofarmaca en het QTc-interval.

Assessment of the risk for arrhythmias requires knowledge of QTc interval prolonging drugs and baseline clinical risk factors for QTc prolongation. The combination of both determines whether ECG-monitoring is necessary at the start of a psychotropic drug. In this article, we summarize current literature regarding appropriate methods of calculating the QTc interval, risk factors for QTc prolongation and QTc-prolonging psychotropic drugs. The frequency of cardiac monitoring for patients receiving psychotropic drugs should be individually determined, based on the prescribed agent(s) and additional risk factors for TdP. In patients without baseline clinical risk factors for QTc prolongation or cardiac arrhythmias, starting a single psychotropic drug with a low risk profile, ECG-monitoring might not be necessary.