Psychiatric Hospital of The University of Zurich

Attention deficit hyperactivity disorder (ADHD) or syndrome (ADHS) is a symptomatically defined condition that - if untreated - is linked to a significantly increased risk of traffic accidents. In a recent umbrella review, where data from reviews and meta-analyses on 21.142.129 adults was assessed, a pooled prevalence of 3.1% of ADHD in adults was estimated. Considering that globally around 1.35 million people lose their lives and more than 50 million are suffering from injuries or disabilities due to road accidents, the fraction of car accidents caused by ADHD as a risk factor is considerable and needs to be addressed. This risk is largely presumed to be caused by an elevated level of inattentiveness in affected persons.
Compounds of different groups, which can be classified in stimulants - formulations of methylphenidate and amphetamine - and non-stimulants - atomoxetin, guanfacine and clonidine -, have been shown to be effective in alleviating negative effects of ADHD, including inattentiveness. Under well-established but individually managed medication regimes, affected individuals can consequently lead a largely "unirritated" life and are not subject to fundamental restriction with respect to driving anymore.
In children and adolescents, documented negative effects of stimulant medication include loss of appetite and decreased growth rates. It could however be shown that short-term interruptions (weekend, school holidays, and alike), introduced to alleviate aforementioned effects, do not affect the drug's beneficial effects in functional use (e.g., school). Such monitored medication breaks are often called "drug holidays" (D). They have become standard procedure in well-monitored treatment, predominantly including behavioral therapy.
Based on own experience in childhood and or hearsay, also a fraction of affected adults under stimulant medication expresses the desire to take drug holidays and "be themselves" from time to time. With the predominant fraction of medication being fast acting drugs in extended-release formulation and typical patients being not only highly compliant but also extremely informed and adherent, these so-called "drug holidays" are reported an accepted in therapeutically accompanied settings of adults by now.
However, while the overall positive effect of stimulant treatment on driving performance has been confirmed in a row of excellent on road- and/or simulation studies using integrated driving scores (IDS), so far there is no study available addressing the effect of drug holidays in adult drivers on driving performance. This represents a significant gap of evidence for both medical experts and affected.
The proposed study will address this gap by exploring parameters of driving simulation in relation to drug holidays in ADHD patients.

The purpose of this study is:
* To investigate whether the response to antipsychotic treatment can be enhanced by adding cannabidiol (CBD) to the existing treatment, compared to placebo, in participants with a first episode of psychosis, who have had a suboptimal or no response to their first antipsychotic treatment.
* To confirm the safety of CBD in people with psychosis.
The study is a randomized, double-blind, placebo-controlled, multi-centre, clinical trial. Individuals with a diagnosis of first-episode psychosis, who have had a suboptimal or no response to their first antipsychotic treatment will be recruited. These participants are randomised to treatment with CBD oral solution 500mg twice daily, or a matching placebo for 6 weeks, as an adjunct to their existing antipsychotic treatment. By using a battery of clinical outcome assessments, the trial will also assess several biomarkers to determine if they can be used to predict clinical outcomes and response to treatment with CBD. Biomarkers are being assessed as an exploratory outcome measure. Participants will be invited to provide blood and stool samples, and may be asked to complete neuroimaging assessments at certain eligible sites.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to major post-acute sequelae. It is estimated that over 60 million people worldwide are affected by this multisystemic condition, here referred to as post-COVID. Affective symptoms such as fatigue and depressed mood are particularly prevalent in patients with post-COVID and pose significant individual and socioeconomic burdens. This stands in stark contrast to the currently limited number of available therapeutic options. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation modality that has been demonstrated to be both safe and effective in treating various neuropsychiatric disorders, including depression. However, whether rTMS also has an effect on post-COVID associated affective symptoms remains to be elucidated.
The overall objective of this randomized, double-blinded study is twofold: First, the investigators will examine the effect of rTMS on post-COVID associated affective symptoms. 52 individuals with post-COVID will be randomized to either receive 20 sessions of rTMS or sham treatment. A detailed psychopathological assessment of the study participants will be performed before and after the completion of rTMS/sham treatment. Secondly, the investigators will perform detailed characterization of the immune system before and after rTMS/sham treatment.
The individual burden and socioeconomic costs of post-COVID-associated neuropsychiatric symptoms are enormous, however, treatment options are limited. The investigators believe that the current proposal will address this key gap in the literature by testing whether rTMS, which constitutes a novel treatment with little side effects, could alleviate these debilitating symptoms. If proven effective, this study could pave the way for a completely new way in which post-COVID conditions are treated.