Andrews G, Bell C, Boyce P, Gale C, Lampe L, Marwat O, Rapee R, Wilkins G (2018) Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for the treatment of panic disorder, social anxiety disorder and generalised anxiety disorder. Aust N Z J Psychiatry 52:1109–1172

Google Scholar 

Baldinger P, Höflich AS, Mitterhauser M, Hahn A, Rami-Mark C, Spies M, Wadsak W, Lanzenberger R, Kasper S (2015) Effects of Silexan on the serotonin-1A receptor and microstructure of the human brain: a randomized, placebo-controlled, double-blind, cross-over study with molecular and structural neuroimaging. Int J Neuropsychopharmacol 18:1–9

CAS  Google Scholar 

Bandelow B (2020) Current and novel psychopharmacological drugs for anxiety disorders. Adv Exp Med Biol 1191:347–365

CAS  Google Scholar 

Bandelow B, Michaelis S (2015) Epidemiology of anxiety disorders in the 21st century. Dial Clin Neurosci 17:327–335

Google Scholar 

Bandelow B, Michaelis S, Wedekind D (2017) Treatment of anxiety disorders. Dial Clin Neurosci 19:93–107

Google Scholar 

Bandelow B, Sher L, Bunevicius R, Hollander E, Kasper S, Zohar J, Möller HJ (2012) Guidelines for the pharmacological treatment of anxiety disorders, obsessive-compulsive disorder and posttraumatic stress disorder in primary care. Int J Psychiatry Clin Pract 16:77–84

CAS  Google Scholar 

Bandelow B, Werner AM, Kopp I, Rudolf S, Wiltink J, Beutel ME (2021) The German Guidelines for the treatment of anxiety disorders: first revision. Eur Arch Psychiatry Clin Neurosci 1–12

Bartova L, Dold M, Volz HP, Seifritz E, Möller HJ, Kasper S (2022) Beneficial effects of Silexan on co-occurring depressive symptoms in patients with subthreshold anxiety and anxiety disorders: randomized, placebo-controlled trials revisited. Eur Arch Psychiatry Clin Neurosci

Bonnet U, Scherbaum N (2017) How addictive are gabapentin and pregabalin? A systematic review. Eur Neuropsychopharmacol 27:1185–1215

CAS  Google Scholar 

Burke DL, Ensor J, Riley RD (2017) Meta-analysis using individual participant data: one-stage and two-stage approaches, and why they may differ. Stat Med 36:855–875

Google Scholar 

Carl E, Witcraft SM, Kauffman BY, Gillespie EM, Becker ES, Cuijpers P, Van Ameringen M, Smits JAJ, Powers MB (2020) Psychological and pharmacological treatments for generalized anxiety disorder (GAD): a meta-analysis of randomized controlled trials. Cogn Behav Ther 49:1–21

Google Scholar 

Collins KA, Westra HA, Dozois DJ, Burns DD (2004) Gaps in accessing treatment for anxiety and depression: challenges for the delivery of care. Clin Psychol Rev 24:583–616

Google Scholar 

Covi L, Rickels K, Lipman RS, McNair DM, Smith VK, Downing R, Kahn R, Fisher S (1981) Effects of psychotropic agents on primary depression. Psychopharmacol Bull 17:100–103

Google Scholar 

Deeks JJ, Higgins JPT, Altman DG (2020) Analysing data and undertaking meta-analyses. In: Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA (eds.) Cochrane handbook for systematic reviews of interventions version 6.1 (updated September 2020). The Cochrane Collaboration. http://www.training.cochrane.org/handbook. Updated Sept 2020

Donelli D, Antonelli M, Bellinazzi C, Gensini GF, Firenzuoli F (2019) Effects of lavender on anxiety: a systematic review and meta-analysis. Phytomedicine 65:153099

CAS  Google Scholar 

Doroshyenko O, Rokitta D, Zadoyan G, Klement S, Schläfke S, Dienel A, Gramatté T, Lück H, Fuhr U (2013) Drug cocktail interaction study on the effect of the orally administered lavender oil preparation Silexan on cytochrome P-450 enzymes in healthy volunteers. Drug Metab Dispos 41:987–993

CAS  Google Scholar 

Fava GA (2020) May antidepressant drugs worsen the conditions they are supposed to treat? The clinical foundations of the oppositional model of tolerance. Ther Adv Psychopharmacol 10:1–11

Google Scholar 

Fava GA, Cosci F (2019) Understanding and managing withdrawal syndromes after discontinuation of antidepressant drugs. J Clin Psychiatry 80:19com12794

Google Scholar 

Gastpar M, Müller WE, Volz HP, Möller HJ, Schläfke S, Dienel A, Kasper S (2017) Silexan does not cause withdrawal symptoms even when abruptly discontinued. Int J Psychiatry Clin Pract 21:177–180

CAS  Google Scholar 

Gautam S, Jain A, Gautam M, Vahia VN, Gautam A (2017) Clinical practice guidelines for the management of generalised anxiety disorder (GAD) and panic disorder (PD). Indian J Psychiatry 59:S67–S73

Google Scholar 

GBD Diseases and Injuries Collaborators, 2020 (2020) Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet 396:1204–1222

Google Scholar 

Generoso MB, Soares A, Taiar IT, Cordeiro Q, Shiozawa P (2017) Lavender oil preparation (Silexan) for treating anxiety: an updated meta-analysis. J Clin Psychopharmacol 37:115–117

Google Scholar 

Gomez AF, Barthel AL, Hofmann SG (2018) Comparing the efficacy of benzodiazepines and serotonergic anti-depressants for adults with generalized anxiety disorder: a meta-analytic review. Expert Opin Pharmacother 19:883–894

CAS  Google Scholar 

Griebel G, Holmes A (2013) 50 years of hurdles and hope in anxiolytic drug discovery. Nat Rev Drug Discov 12:667–687

CAS  Google Scholar 

Grigorova O (2009) P01–156 Estimation of placebo effect in therapy of generalized anxiety disorder. Eur Psychiatry 24:S544

Google Scholar 

Hamilton M (1959) The assessment of anxiety states by rating. Br J Med Psychol 32:50–55

CAS  Google Scholar 

Harris MG, Hobbs MJ, Burgess PM, Pirkis JE, Diminic S, Siskind DJ, Andrews G, Whiteford HA (2015) Frequency and quality of mental health treatment for affective and anxiety disorders among Australian adults. Med J Aust 202:185–189

Google Scholar 

Heger-Mahn D, Pabst G, Dienel A, Schläfke S, Klipping C (2014) No interacting influence of lavender oil preparation silexan on oral contraception using an ethinyl estradiol/levonorgestrel combination. Drugs R D 14:265–272

CAS  Google Scholar 

Hidalgo RB, Tupler LA, Davidson JR (2007) An effect-size analysis of pharmacologic treatments for generalized anxiety disorder. J Psychopharmacol 21:864–872

CAS  Google Scholar 

Kang H-J, Nam ES, Lee Y, Kim M (2019) How strong is the evidence for the anxiolytic efficacy of lavender?: Systematic review and meta-analysis of randomized controlled trials. Asian Nurs Res (Korean Soc Nurs Sci) 13:295–305

Kasper S (2006) Anxiety disorders: under-diagnosed and insufficiently treated. Int J Psychiatry Clin Pract 10:3–9

Google Scholar 

Kasper S (2015) Phytopharmaceutical treatment of anxiety, depression, and dementia in the elderly: evidence from randomized, controlled clinical trials. Wien Med Wochenschr 165:217–228

Google Scholar 

Kasper S, Anghelescu I, Dienel A (2015) Efficacy of orally administered Silexan in patients with anxiety-related restlessness and disturbed sleep—a randomized, placebo-controlled trial. Eur Neuropsychopharmacol 25:1960–1967

CAS  Google Scholar 

Kasper S, Dienel A (2015) Effects of Silexan on daily living skills and health related quality of life in patients with generalized anxiety disorder—results from a randomized, double-blind, placebo controlled trial, Annual Congress of the German Society for Psychiatry and Psychotherapy (DGPPN), Berlin, Germany

Kasper S, Gastpar M, Müller WE, Volz H-P, Möller H-J, Dienel A, Schläfke S (2010) Silexan, an orally administered Lavandula oil preparation, is effective in the treatment of “subsyndromal” anxiety disorder: a randomized, double-blind, placebo controlled trial. Int Clin Psychopharmacol 25:277–287

Google Scholar 

Kasper S, Gastpar M, Müller WE, Volz H-P, Möller H-J, Schläfke S, Dienel A (2014) Lavender oil preparation Silexan is effective in generalized anxiety disorder—a randomized, double-blind comparison to placebo and paroxetine. Int J Neuropsychopharmacol 17:859–869

CAS  Google Scholar 

Kasper S, Möller H-J, Volz H-P, Schläfke S, Dienel A (2017) Silexan in generalized anxiety disorder: investigation of the therapeutic dosage range in a pooled data set. Int Clin Psychopharmacol 32:195–204

Google Scholar 

Kasper S, Müller WE, Volz H-P, Möller H-J, Koch E, Dienel A (2018) Silexan in anxiety disorders: clinical data and pharmacological background. World J Biol Psychiatry 19:412–420

Google Scholar 

Kasper S, Volz H-P, Dienel A, Schläfke S (2016) Efficacy of Silexan in mixed anxiety-depression—a randomized, placebo-controlled trial. Eur Neuropsychopharmacol 26:331–340

CAS  Google Scholar 

Katzman MA, Bleau P, Blier P, Chokka P, Kjernisted K, Van Ameringen M (2014) Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress and obsessive-compulsive disorders. BMC Psychiatry 14(Suppl. 1):S1

Google Scholar 

Kehr J, Yoshitake T, Koch E, Noeldner M (2010) Effects of intraperitoneal administration of Silexan, an essential oil from flowers of Lavandula angustifolia on extracellular levels of noradrenaline, dopamine and serotonin in the prefrontal cortex of freely moving rats. Planta Med 76:1316

Google Scholar 

Maier W, Buller R, Philipp M, Heuser I (1988) The Hamilton Anxiety Scale: reliability, validity and sensitivity to change in anxiety and depressive disorders. J Affect Disord 14:61–68

CAS  Google Scholar 

Matza LS, Morlock R, Sexton C, Malley K, Feltner D (2010) Identifying HAM-A cutoffs for mild, moderate, and severe generalized anxiety disorder. Int J Methods Psychiatr Res 19:223–232

Google Scholar 

Möller H-J, Volz H-P, Dienel A, Schläfke S, Kasper S (2019) Efficacy of Silexan in subthreshold anxiety: meta-analysis of randomised, placebo-controlled trials. Eur Arch Psychiatry Clin Neurosci 269:183–193

Google Scholar 

Möller H-J, Volz H-P, Seifritz E, Müller H, Kenntner-Mabiala R, Kaussner Y, Schoch S, Kasper S (2021) Silexan does not affect driving performance after single and multiple dose applications: results from a double-blind, placebo and reference-controlled study in healthy volunteers. J Psychiatr Res 136:543–551

Google Scholar 

Müller WE, Sillani G, Schuwald A, Friedland K (2021) Pharmacological basis of the anxiolytic and antidepressant properties of Silexan®, an essential oil from the flowers of lavender. Neurochem Int 143:104899

Google Scholar 

National Institute for Health and Care Excellence (NICE) (2019) Generalised anxiety disorder and panic disorder in adults: management

National Institute of Mental Health (1970) 12—CGI. Clinical global impressions. In: Guy W (ed) EDCEU assessment in psychopharmacology. U.S. National Institute of Mental Health, Psychopharmacology Research Branch, Rockville, Md., pp 217–222

Pies RW (2019) Antidepressant discontinuation: a tale of two narratives. J Clin Psychopharmacol 39:185–188

Google Scholar 

Riley RD, Lambert PC, Abo-Zaid G (2010) Meta-analysis of individual participant data: rationale, conduct, and reporting. BMJ 340:c221

Google Scholar 

Rutherford BR, Bailey VS, Schneier FR, Pott E, Brown PJ, Roose SP (2015) Influence of study design on treatment response in anxiety disorder clinical trials. Depress Anxiety 32:944–957

CAS  Google Scholar 

Sartori SB, Singewald N (2019) Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders. Pharmacol Ther 204:107402

CAS  Google Scholar 

Satpute AB, Mumford JA, Naliboff BD, Poldrack RA (2012) Human anterior and posterior hippocampus respond distinctly to state and trait anxiety. Emotion 12:58–68

Google Scholar 

Sayed AM, Morsy S, Tawfik GM, Naveed S, Minh-Duc NT, Hieu TH, Ali ZA, Shinkar A, Doheim MF, Hashan MR, Huy NT (2020) The best route of administration of lavender for anxiety: a systematic review and network meta-analysis. Gen Hosp Psychiatry 64:33–40

Google Scholar 

Schjerning O, Pottegard A, Damkier P, Rosenzweig M, Nielsen J (2016) Use of Pregabalin—a nationwide pharmacoepidemiological drug utilization study with focus on abuse potential. Pharmacopsychiatry 49:155–161

CAS  Google Scholar 

Schuwald AM, Nöldner M, Wilmes T, Klugbauer N, Leuner K, Müller WE (2013) Lavender oil-potent anxiolytic properties via modulating voltage dependent calcium channels. PLoS ONE 8:e59998

CAS  Google Scholar 

Seifritz E, Möller H-J, Volz H-P, Müller WE, Hopyan T, Wacker A, Schläfke S, Kasper S (2021) No abuse potential of Silexan in healthy recreational drug users: a randomized controlled trial. Int J Neuropsychopharmacol 24:171–180

Google Scholar 

Seifritz E, Schläfke S, Holsboer-Trachsler E (2019) Beneficial effects of Silexan on sleep are mediated by its anxiolytic effect. J Psychiatr Res 115:69–74

Google Scholar 

Ströhle A, Gensichen J, Domschke K (2018) The diagnosis and treatment of anxiety disorders. Dtsch Arztebl Int 115:611–620

Google Scholar 

Volz H-P, Saliger J, Kasper S, Möller H-J, Seifritz E (2021) Subsyndromal generalised anxiety disorder: operationalisation and epidemiology—a systematic literature survey. Int J Psychiatry Clin Pract 27:1–10

Google Scholar 

von Känel R, Kasper S, Bondolfi G, Holsboer-Trachsler E, Hättenschwiler J, Hatzinger M, Imboden C, Heitlinger E, Seifritz E (2021) Therapeutic effects of Silexan on somatic symptoms and physical health in patients with anxiety disorders: a meta-analysis. Brain Behav 11:e01997

Google Scholar 

Ware JE Jr, Sherbourne CD (1992) The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care 30:473–483

Google Scholar 

Yap WS, Dolzhenko AV, Jalal Z, Hadi MA, Khan TM (2019) Efficacy and safety of lavender essential oil (Silexan) capsules among patients suffering from anxiety disorders: a net