Psychiatric manifestations of post-COVID-19 syndrome: the potential benefit of Silexan

Abstract

Objective: Psychiatric symptoms are common and bothersome in individuals with post-COVID-19 syndrome. Because they are often mixed and subthreshold, established treatment regimens cannot be applied. There is an urgent need to identify therapeutics for affected patients. Silexan, a proprietary essential oil from Lavandula angustifolia, has demonstrated efficacy against anxiety, comorbid symptoms, and subthreshold and mixed syndromes. The aim of the current narrative review is to examine the therapeutic potential of Silexan for psychiatric manifestations in patients with post-COVID-19 syndrome.

Methods: We reviewed clinical evidence regarding the efficacy of Silexan and first clinical experience in patients with psychiatric symptoms attributable to the post-COVID-19 syndrome. Furthermore, we discussed potential modes of action based on nonclinical data.

Results: Silexan has demonstrated therapeutic efficacy for the treatment of generalised anxiety disorder; subsyndromal anxiety disorders; comorbid depressive, somatic, and sleep disturbance symptoms; and mixed anxiety and depression. Emerging clinical experience also suggests the effectiveness and tolerability of Silexan for patients with post-COVID-19 syndrome. This can be explained by the fact that the therapeutic profile of Silexan overlaps with the spectrum of psychiatric symptoms in such patients.

Conclusion: Preliminary findings indicate a promising potential of Silexan for the treatment of psychiatric manifestations in patients with post-COVID-19 syndrome.

Key points

• Anxiety and mixed neuropsychiatric manifestations are commonly observed in patients with post-COVID-19 syndrome.

• Silexan has anxiolytic properties and can alleviate comorbid depressive, somatic, and sleep impairment symptoms.

• Silexan exhibits several biological mechanisms, such as neurotrophic and anti-inflammatory properties, which have the potential to positively impact post-COVID-19 disease.

• Silexan has a favourable safety profile and high acceptance among patients.

• Emerging data suggest that Silexan can alleviate neuropsychiatric symptoms in patients with post-COVID-19 syndrome.

• Silexan should be considered as a therapeutic in patients with psychiatric manifestations of post-COVID-19 syndrome.

Keywords:

• Silexan
• post-COVID-19 syndrome
• psychiatric symptoms
• anxiety
• depressive symptoms
• mixed psychiatric manifestations

Introduction

Post-COVID-19 syndrome’s prevalence, disease course, and public health burden

The coronavirus-19 disease (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has profoundly affected global public health (Stein, 2022). Notably, a number of symptoms may appear or persist in patients with COVID-19 long after the acute infection has subsided. This condition has been designated as post-COVID-19 syndrome, long COVID, or post-COVID conditions. Post-COVID-19 syndrome may affect various organs and organ systems, including the respiratory, cardiovascular, musculoskeletal, and gastrointestinal systems, as well as the central nervous system (CNS) (Crook et al., 2021). Notably, it may develop not only after a severe infection but even after a mild case of COVID-19 (Damiano et al., 2022).

Symptom clusters in patients with post-COVID-19 syndrome

There is marked heterogeneity in the clinical presentations among individuals with post-COVID-19 syndrome. In a large cohort study that followed over 70,000 adults throughout the COVID-19 pandemic, it was observed that there are clusters of symptoms after an infection, and thus long COVID is not just one syndrome (Caspersen et al., 2022). In another large cohort study including 11,710 individuals, 30 post-acute symptoms were identified, several of which were strongly correlated and could be organised into 13 symptom clusters. The most prevalent symptom cluster was ‘fatigue’ (37.2%, including the symptoms of rapid physical exhaustion and chronic fatigue), followed by ‘neurocognitive impairment’ (31.3%), ‘chest symptoms’ (30.2%), ‘smell or taste disorder’ (23.6%), and ‘anxiety/depression’ (21.1%) (Peter et al., 2022).

Neuropsychiatric manifestations of post-COVID-19 syndrome

Psychiatric symptoms associated with post-COVID-19 syndrome include fatigue, cognitive and concentration impairments, sleep disturbances, headache, depression, anxiety, and symptoms of post-traumatic stress disorder (Crook et al., 2021; Kappelmann et al., 2021). In a sample of 425 individuals, assessed 6–9 months after their discharge from a hospital stay for moderate or severe COVID-19, ‘mixed anxiety-depressive disorder’, ‘generalized anxiety disorder’, ‘post-traumatic stress disorder’, and ‘depression’ were present in 15.5%, 14.1%, 13.7%, and 8% of the sample, respectively. Moreover, 51.1% of the participants reported subjective memory decline. With a prevalence of 32.2% the most frequent category was ‘Common Mental Disorder’, defined as a score ≥12 in the sum of all 14-dimensional symptoms identified in a structured psychiatric interview (Damiano et al., 2022). A meta-analysis on the prevalence of post-COVID mental health problems, including anxiety, depression, general distress, and post-traumatic symptoms found that the prevalence of mental health problems decreased from 46.3% during the acute stage (within 1 month) to 38.8% during the post-illness stage (longer than 3 months) (Zürcher et al., 2022). The high prevalence of psychiatric manifestations was confirmed by another meta-analysis on neuropsychiatric symptoms reported at least 3 months after the COVID-19 onset. The most prevalent neuropsychiatric post-COVID-19 symptoms included fatigue (37%), brain fog (32%), memory issues (28%), attention disorder (22%), myalgia (17%), anosmia (12%), dysgeusia (10%), and headache (15%). Psychiatric manifestations included sleep disturbances, anxiety, and depression that were present in 23%, and 12% of the participants, respectively (Premraj et al., 2022). In addition, a recent large cohort study found that the risk of mental health disorders remained elevated for COVID-19 patients during a follow-up period of 12 months in comparison to a control group, even if the control group had been affected by seasonal influenza (Xie et al., 2022).

Notably, mild and mixed forms of psychiatric manifestations have been shown to prevail in patients with post-COVID-19 syndrome (Stein, 2022; Zürcher et al., 2022). The heterogeneity of neuropsychiatric symptoms in patients with post-COVID-19 syndrome suggests that it may be beneficial to organise them into symptom clusters. Based on large cohorts, the psychiatric manifestations can be divided into two broad symptom clusters, one of which includes memory impairment/brain fog/dizziness/fatigue, whereas the other includes anxiety/depression/mood swings/sleep problems (Caspersen et al., 2022; Peter et al., 2022).

Risk factors for the development of a post-COVID-19 syndrome with psychiatric manifestations

The pathophysiological mechanisms underlying the development of post-COVID-19 syndrome, including psychiatric manifestations, have not been completely elucidated. COVID-19 severity, female gender, age, belonging to an ethnic minority, socioeconomic deprivation, smoking, obesity, a wide range of comorbidities, and preinfection psychological distress have been reported as risk factors (Uzunova et al., 2021). Moreover, biological factors might also contribute to post-COVID-19 psychiatric morbidity. Recent studies have highlighted the role of inflammation (Crook et al., 2021). For example, a multiplex assay of serum samples revealed that even in patients with an asymptomatic or moderate SARS-CoV-2 infection, immune response remained significantly elevated for 40–60 days, with an increased expression of proteins related to mitochondrial stress and anti-inflammatory response. These findings indicate that a SARS-CoV-2 infection affects the immune response for a prolonged period of time even in mild or asymptomatic cases (Doykov et al., 2020). Kappelmann et al. demonstrated the role of IL-6, immune activation, and disruptions of T helper 17 and regulatory T cell responses, which can negatively impact central learning and emotional processes. In addition, the resulting promotion of inflammation and mitochondrial dysfunction negatively affects neuronal energy metabolism and ultimately leads to fatigue (Kappelmann et al., 2021).

The anxiolytic properties of Silexan

Lavender oil has traditionally been used for relief of mild symptoms of mental stress and exhaustion and to aid sleep and has been classified as an ‘other anxiolytic’ according to the ATC code of the World Health Organisation (WHO; EMA/HMPC/143181/2010, 2012). Silexan® is a proprietary essential oil produced from flowering tops of the Lavandula angustifolia lavender species cultivated in Southern Europe that exceeds the quality definition of lavender oil in the European Pharmacopoeia (Ph. Eur.). The oil is a multi-ingredient natural preparation containing over 160 components, the main constituents among which are linalool and linalyl acetate (Volz, 2022).

Silexan has consistently demonstrated efficacy in placebo-controlled clinical trials both in patients with generalised anxiety disorder (GAD) and subthreshold anxiety. Kasper et al. (2018) reviewed the anxiolytic efficacy, tolerability, and safety of Silexan in patients with subthreshold anxiety or GAD: After 2 to 4 weeks of treatment at daily doses of 80 mg or 160 mg, the anxiolytic effects of Silexan, measured with changes in the total Hamilton Anxiety Rating Scale (HAM-A) score, were clinically significant for both patient populations. Silexan also beneficially affected accompanying symptoms, including sleep disturbances, somatic symptoms, decreased quality of life, and depressive symptoms. The only adverse effects which were observed for Silexan in the reviewed clinical trials were mild gastrointestinal symptoms. Silexan showed no drug interactions, sedation, or withdrawal symptoms. Thus, Silexan proved to be an effective and safe therapeutic agent for anxiety disorders. The effective dose of Silexan in GAD was found to be 160 mg/day, while 80 mg/day represented the lower therapeutic range (Kasper et al., 2017). A meta-analysis focussing on the anxiolytic effects of Silexan in patients with subthreshold anxiety demonstrated beneficial effects on psychic and somatic anxiety, quality of life, and secondarily on sleep without causing sedation, and Silexan’s effects were superior to those of placebo (Möller et al., 2019).

Efficacy of Silexan against comorbid depressive, somatic, or sleep impairment symptoms in patients with anxiety

Efficacy of Silexan against comorbid depressive symptoms in patients with anxiety

A meta-analysis of Silexan’s antidepressant properties was performed on five placebo-controlled clinical trials, in which Silexan was administered in patients with generalised anxiety disorder (two trials) or subthreshold anxiety disorder (three trials). In all included studies, 80 mg/day Silexan or placebo were administered for 10 weeks. Patients treated with Silexan demonstrated a significantly more pronounced reduction of the mean total Montgomery Åsberg Depression Rating Scale (MADRS) or Hamilton Depression Rating Scale (HAMD) scores. The reduction of the score for the HAMA item ‘depressed mood’ was also significantly more pronounced in the Silexan group than in the placebo group. Thus, Silexan had a beneficial effect on comorbid depressive symptoms in patients with subthreshold anxiety disorders and GAD, which may have therapeutic implications for the treatment of depressive disorders (Bartova et al., 2022a).

Figure 1. Effects of Silexan on psychiatric symptoms in patients with post-COVID-19 syndrome.

Silexan improves troubled sleep in anxiety patients

Silexan has been shown to improve sleep impairment in patients with anxiety via a sedation-independent mechanism (Seifritz et al., 2022). For example, in a double-blind, randomised, placebo-controlled study, including 212 anxiety patients treated for 10 weeks with 80 mg/day Silexan or placebo, Silexan significantly reduced anxiety and sleep impairment symptoms compared to placebo. Positive clinically meaningful differences were detected already after 2 weeks and after 6 weeks for the anxiety and sleep disruption scores, respectively. Further statistical analysis suggested that Silexan’s beneficial effect on sleep was mainly (98.4%) mediated via its effect on anxiety. Thus, Silexan exerts a secondary positive effect on sleep that is almost entirely mediated via its anxiolytic action (Seifritz et al., 2019).

Silexan improves somatic symptoms and physical health in patients with anxiety

A meta-analysis on the therapeutic effects of Silexan on somatic symptoms in patients with anxiety disorders demonstrated that Silexan had positive effects on somatic anxiety and especially on the single HAMA items cardiovascular, respiratory, somatic muscular, and genitourinary symptoms. Similar statistically significant and clinically meaningful positive effects of Silexan were also observed with regards to physical health-related quality of life (HRQoL), assessed with the 36-Item Short Form Health Survey (SF-36), including the components general health, bodily pain, and role-physical. Moreover, clinically meaningful and statistically significant effects of Silexan were observed with regard to reduced insomnia complaints and fatigue. Thus, Silexan proved to positively affect somatic symptoms and physical health in patients suffering from anxiety (von Känel et al., 2021).

Efficacy of Silexan in mixed anxiety and depressive disorder (MADD)

MADD presents with subsyndromal symptoms of both anxiety and depression. In a double-blind, randomised study, including 318 adult outpatients with at least moderately severe MADD, 80 mg Silexan or placebo was administered once daily for 70 days. Patients treated with Silexan had larger reduction of symptoms of both depression and anxiety, a better clinical outcome, and more pronouncedly improved HRQoL and daily living skills. The only observed adverse effect was eructation. These findings indicate that the use of Silexan for the treatment of MADD is efficacious and safe (Kasper et al., 2016).

Silexan reduces functional impairments in patients with anxiety

Patients with anxiety disorders often develop functional impairment in their activities of daily living or in their ability to work. A pooled analysis of data from three clinical trials demonstrated that a 10-week treatment with Silexan was significantly superior to a placebo in decreasing the Sheehan Disability Scale (SDS) total score and all three of the single items work, social life, and family life/home responsibilities. The number of lost workdays and unproductive days was also lower with Silexan than with placebo administration. Thus, Silexan treatment helped patients with anxiety disorders cope with work, social, or family life and responsibilities and led to less lost or underproductive days (Volz and Klement, 2022).

Emerging data on the use of Silexan in patients with mental post-COVID-19 symptoms

Bartova et al. (2022b) recently reported a promising first clinical experience with the safe and effective employment of Silexan in adult patients experiencing subsyndromal as well as full-blown anxiety and depression with cognitive and psychosomatic symptoms that occurred post-COVID-19. Full remission of fatigue and brain fog, which was increasingly accompanied by inner tension, restlessness and sad mood with weepiness was observed in a female patient only after Silexan had been added to psychotherapy. In a 27-years old male outpatient who developed GAD in the context of COVID-19, partial remission was observed with psychotherapy and Silexan 80 mg q.d. and full remission after dose escalation to 80 mg twice daily. A 38-years old female patient with a history of depression developed a major depressive episode after COVID-19 that partly responded to antidepressant treatment with bupropion and hydroxyzine. Because of the re-occurrence of anxiety and psychosomatic symptoms the patient denied further treatment with bupropion or sertraline. A significant and stable remission was finally achieved with Silexan 80 mg twice daily monotherapy.

Biological mechanisms underlying the beneficial effects of Silexan and lavender oil on neuropsychiatric symptoms

Modulation of voltage-operated calcium channels

Silexan has been demonstrated to inhibit N-type, T-type, and P/Q-type voltage-dependent calcium channels (VDCC) with an estimated IC₅₀ value for linalool of about 37 nM. By non-selectively decreasing calcium influx, Silexan might be able to positively influence the molecular mechanisms of anxiety (Schuwald et al., 2013).

Effects on neuroreceptors and transporters

An investigation of the effects of lavender (Lavandula angustifolia) essential oil on several neuroreceptors and transporters revealed that it had a moderate affinity for the glutamate NMDA-receptor (IC₅₀ 0.04 μl/mL) but not for the GABAA-benzodiazepine receptor. Further, lavender essential oil could bind the serotonin transporter (Lopez et al. 2017). In addition, Silexan has been demonstrated to decrease the binding potential of the serotonin 1 A receptor in the limbic system after an 8-week administration at a dose of 160 mg/day (Baldinger et al., 2015).

Neurotrophic properties

In a study on mechanisms underlying the antidepressant activity of Silexan, the antidepressant effect in the rat-forced swimming test (FST) was comparable to that of imipramine. In neuronal cell models, Silexan promoted neurite outgrowth, synaptogenesis, and phosphorylation of protein kinase A and CREB (Friedland et al., 2021). These findings were supported by another preclinical study that demonstrated the positive effect of lavender oil on neurogenesis and neuronal complexity in an animal model (Sánchez-Vidaña et al., 2019).

Anti-inflammatory properties

Anti-inflammatory activity of lavender essential oil has been observed in a number of nonclinical studies. In a study using two models of acute inflammation, namely carrageenan-induced pleurisy and croton oil-induced ear edoema, lavender essential oil exerted an antioxidant effect and ameliorated the induction of an inflammatory response by carrageenan and croton oil. In the same study, a lavender essential oil also exerted an antinociceptive effect (Silva et al., 2015). The anti-inflammatory effects of lavender oil have also been supported by other studies. In a rat model of renal ischemia/reperfusion injury, the administration of lavender oil 1 h after the beginning of reperfusion restored the antioxidant enzyme activity, ameliorated lipid peroxidation, reduced TNF-α and IL-β levels, and increased IL-10 levels in a dose-dependent manner. In addition, lavender decreased the number of TUNEL-positive cells, reduced the damage of peritubular capillaries, and contributed to the preservation of normal renal cell morphology (Aboutaleb et al., 2019). Notably, the anti-inflammatory effects of lavender essential oil apparently depend on its phytochemical composition. Lavender essential oil extracted from plants at the beginning of their flowering period, rich in linalyl acetate but with somewhat lower contents of linalool and terpinene-4-ol, exerted more pronounced anti-inflammatory effects, including stronger inhibition of the synthesis of the proinflammatory cytokines IL-6, TNF-α, IL-8, and IL-β, than oil extracted at the end of the flowering period (Pandur et al., 2021). The relevance of cytokines like IL-6 for the positive effects of antidepressants in COVID-19 patients has been discussed in detail by Müller et al. (2022).

Favourable safety and tolerability profile of Silexan

Silexan has a favourable safety profile with no major concerns regarding potential adverse effects (Volz, 2022). Possible adverse reactions were only observed with regard to gastrointestinal complaints and hypersensitivity reactions which were generally mild (Kasper et al., 2018).

Silexan does not impair fitness to drive

The effect of Silexan on driving performance was analysed in a double-blind, randomised crossover trial including healthy volunteers and using an alcohol-calibrated simulator test. Single Silexan doses of up to 320 mg and multiple Silexan doses of 80 mg/day did not adversely affect the ability to drive (Möller et al., 2021).

Silexan demonstrates no abuse potential

The risk of abuse of Silexan was evaluated in a single-center, double-blind, five-way crossover study including healthy users of recreational CNS depressants. Silexan did not show any abuse potential and was considered unlikely to be recreationally abused (Seifritz et al., 2021).

Silexan does not induce withdrawal symptoms

The potential of Silexan to induce withdrawal symptoms was assessed in a randomised, double-blind, double-dummy clinical trial. Patients with GAD were treated with 80 mg/day Silexan, 160 mg/day Silexan, 20 mg/day paroxetine, or placebo for 10 weeks, with paroxetine being tapered off, and Silexan being discontinued abruptly. Subsequently, a 1-week follow-up phase was included to determine whether the discontinuation of Silexan can induce withdrawal symptoms using the Physician Withdrawal Checklist questionnaire (PWC-20). No withdrawal symptoms were observed, indicating that Silexan does not have a dependence potential (Gastpar et al., 2017).

Silexan shows no interaction potential with major cytochrome P450 enzymes

The interaction potential of Silexan with major cytochrome P450 enzymes was investigated in a double-blind, randomised, two-fold crossover study. 160 mg Silexan or placebo once daily was administered for 11 days. In addition, on Day 11, 150 mg caffeine, 125 mg tolbutamide, 20 mg omeprazole, 30 mg dextromethorphan-HBr, and 2 mg midazolam were administered orally to evaluate the activities of CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4, respectively. The study proved that Silexan intake does not exert a clinically relevant inhibitory or inducing effect on these enzymes in vivo (Doroshyenko et al., 2013).

Discussion

Post-COVID-19 syndrome often presents with psychiatric symptoms, including mixed manifestations, that often do not reach the full diagnostic criteria for psychiatric disorders. This poses a significant challenge regarding the identification of optimal therapeutic strategies. Even when the symptoms do not meet the criteria for a specific psychiatric disorder, they may still interfere with the patients’ quality of life and daily activities. Independent from post-COVID syndrome, the burden of and treatment need for sub-syndromal manifestations of anxiety and depression is evident: Subsyndromal GAD often exhibits a comparable burden of disease to that of the full syndromal disorder and often tends to develop into full GAD (Volz et al., 2021). Likewise, the impact of subsyndromal depression on quality of life appears to be in the range of the respective impact of major depression, and in a considerable number of cases, conversion from subthreshold to major depression takes place (Volz et al., 2022). Thus, there is an urgent need to identify effective and safe therapies for affected patients.

Silexan has demonstrated broad therapeutic activities against subsyndromal anxiety; against comorbid symptoms, such as depression, sleep impairment, and somatic symptoms; and against mixed psychiatric manifestations. Anxiety/depression/mood swings/sleep problems is one of the symptom clusters that is observed in patients with post-COVID-19 syndrome, mainly with mild to moderate severity. Thus, the therapeutic profile of Silexan matches well with this psychiatric manifestation of a post-COVID-19 syndrome. The usefulness of Silexan in this patient population is supported by emerging experience from clinical routine. The wording of the approved/registered therapeutic indication for Silexan differs by country based on differences in the legal and regulatory framework, e.g., in Austria it is ‘temporary anxious mood’, in Switzerland ‘anxiety and restlessness’, and in Germany ‘restlessness in the anxious mood’. Nevertheless, in these and many other countries treatment of the psychiatric manifestation of a post-COVID-19 syndrome discussed in this review can be considered within-label.

Sick leave for post-COVID-19 syndrome is quite common and a significant burden to societies (Westerlind et al., 2021). In addition, even when returning to work, subjects affected by post-COVID-19 syndrome report impaired work ability (Davis et al., 2021). Silexan has been demonstrated to reduce the number of lost workdays and unproductive days in patients with anxiety disorders. Therefore, there is a chance that Silexan could also reduce the economic cost of COVID-19-related work impairments.

Psychiatric manifestations of post-COVID-19 syndrome are likely of multifactorial origin. Social circumstances of the pandemic, such as isolation and stress, traumatic experiences due to severe disease or bereavement, biological affection of the central nervous system by the virus, a prolonged immune reaction, pre-existing vulnerability, and disease can in combination contribute to the development of post-COVID psychiatric manifestations.

Elucidating the pharmacological mechanisms of action of therapeutic agents used to treat psychiatric manifestations is key to optimising their use and identifying new therapeutic targets. The underlying pharmacological actions, via which Silexan exerts its beneficial effects on psychiatric symptoms, are variable and correspond to its broad therapeutic efficacy. A variety of effects, including actions on VDCC, a neurotrophic activity, an anti-inflammatory activity, and effects on neuroreceptors and neurotransmitters, have been identified, and all of them may be relevant for the ability of Silexan to alleviate psychiatric symptoms. The effects of Silexan on the inflammatory response are of particular interest in light of the activated inflammatory response in patients affected by COVID-19 (Phetsouphanh et al., 2022).

In addition to its suitable pharmacological profile, the favourable safety profile of Silexan also supports its potential use for the treatment of psychiatric symptoms of post-COVID-19 patients. In the numerous trials investigating the efficacy and safety of Silexan in patients with psychiatric disorders, only mild adverse effects have been observed (Volz, 2022). In addition, Silexan has demonstrated no dependence or withdrawal symptoms (Gastpar et al., 2017; Seifritz et al., 2021).

The significance of using a stepped approach for the treatment of psychiatric symptoms, including in patients affected by COVID-19, has been emphasised (Stein, 2022). Phytotherapeutic agents, including Silexan, are generally well accepted by patients. The efficacy of Silexan for mixed psychiatric manifestations as well as its safety and high acceptance are all in favour of its use in the treatment of psychiatric symptoms in patients with post-COVID-19 syndrome.

Conclusion

Silexan is a safe therapeutic agent with proven efficacy against anxiety; comorbid depressive, somatic, and sleep impairment symptoms; as well as mixed psychiatric manifestations. First-case reports show very positive results in post-COVID-19-related mental disorders. Together with its high patient acceptance and promising biological mechanisms Silexan might have the potential to help post-COVID-19 patients with a symptom cluster including anxiety, depression, mood swings, and sleep problems.

Acknowledgments

We thank Dr. Zoya Marinova for editorial assistance in manuscript preparation.

Disclosure statement

In the past 3 years Siegfried Kasper has received grant/research support from Lundbeck; he has served as a consultant or on advisory boards for Angelini, Biogen, Esai, Janssen, IQVIA, Lundbeck, Mylan, Recordati, Sage and Schwabe; and he has served on speakers bureaus for Abbott, Angelini, Aspen Farmaceutica S.A., Biogen, Janssen, Lundbeck, Recordati, Sage, Sanofi, Schwabe, Servier, Sun Pharma and Vifor.

Anne Eckert received consulting funds and/or honoraria within the last three years from Schwabe.

Hans-Jürgen Möller has received grant/research support, consulting fees and honoraria within the last years from AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen Cilag, Lundbeck, MSD, Novartis, Organon, Otsuka, Pfizer, Schwabe, Sepracor, Servier, and Wyeth.

Within the last three years, Hans-Peter Volz has served as a consultant or on advisory boards for Astra/Zeneca, Eli Lilly, Lundbeck, Pfizer, Schwabe, Janssen, Otsuka, Angelini, and Sage and has served on speakers’ bureaus for Astra/Zeneca, Eli Lilly, Lundbeck, Schwabe, Janssen, Bayer, Recordati and neuraxpharm.

Erich Seifritz has received honoraria from Schwabe for educational lectures. He has further received educational grants and consulting fees from Janssen Cilag, Lundbeck, Angelini, Otsuka, Servier, Recordati, Vifor, Sunovion, and Mepha.

Additional information

Funding

This work is also supported by Dr. Willmar Schwabe GmbH & Co. KG.