We cannot follow Dr Müller’s conclusion that, in our article about generalized anxiety disorder (GAD), drug treatment is presented as preferential treatment. Psychological therapies have been discussed in detail in our article and were the first subject presented in the text, before pharmacotherapy. We did not mention one or the other therapeutic approach as the preferred option anywhere in the article. The group of authors includes several qualified psychotherapeutic researchers.
We are surprised that correspondents Dr Müller, Dr Schurig and Ms Dannenberg, and Dr Egidi automatically conclude the presence of a scientific bias in the article from our authors’ declarations of cooperation with drug manufacturers. Such an insinuation is irresponsible at least, if not altogether defamatory. It would be unthinkable for pharmaceutical companies not to collaborate with clinically active scientists in the development of medications. The authors of the article are open to any kind of criticism, but the arguments proffered by our correspondents are not supported by scientific evidence. Our recommendations are based exclusively on whether a medication has license approval for GAD and whether it has consistently shown efficacy in several randomized clinical studies. Medications with insufficient evidence have been downgraded. Our aim was to identify the most effective and tolerable treatments for affected patients, and as such we based our evaluation of hundreds of clinical studies on GAD, on strict, consistent, and objective criteria from evidence-based medicine (1). These studies are available to all scientists. Our recommendations are consistent with international expert recommendations, meta-analyses, and guidelines. Furthermore, the majority of the mentioned medications are available from manufacturers of generics.
Some correspondents suggested inappropriate alternatives that do not have license approval or that are not backed up by evidence: citalopram, as suggested by Dr Schurig/Ms Dannenberg and Dr Egidi, is not approved for this indication and can therefore not simply be used as a substitute for escitalopram. Several studies have shown that escitalopram is superior to citalopram for depression (2) and panic disorder (3); for this reason it cannot be assumed that the two medications are identical. Fluoxetine is not licensed either; there is not a single GAD study for the drug (the only fluoxetine study included in the meta-analysis by Baldwin et al., was conducted in depressed patients with comorbid anxiety states). Three GAD studies exist for sertraline, but sertraline does not have license approval for GAD. For promethazine, as recommended by Dr Müller, no studies have been conducted for GAD; and longer term use of antihistamines can result in decreased effectiveness (due to the tachyphylaxis effect). We also urgently advise against not using antidepressants in treating GAD, as suggested by Dr Müller. All guidelines recommend antidepressants such as SSRIs and SNRIs because of their good anxiolytic effects. Furthermore, it is not rare for anxiety patients to also show symptoms of depression.
Evidence is completely lacking to support the statement that the recommended medications that have license approval for GAD have more side effects than others that were not recommended.
A blanket polemic against psychotropic drugs is not in the interests of the millions of GAD patients who have experienced a substantial reduction in their suffering and improvements in their quality of life as a result of drug treatment.
In our article we express a clear critical stance towards the use of benzodiazepines; indeed, our article contains several warnings against inappropriate use of benzodiazepines. However, condemning their use wholesale as malpratice is an inadmissible simplification, because in certain cases, benzodiazepines can reduce the suffering of severely affected and suicidal anxiety patients, provided these drugs are used in a narrow context and in a responsible fashion.
We did not list the side effects of olanzapine and quetiapine because they were not recommended as routine preparations in this setting.
There is not enough evidence from studies to ascribe an “addiction potential” to pregabalin. The cumulative patient exposure in 2012 has been reported by the manufacturer at 16.9 million patient years. Compared with these frequent prescriptions, only few case reports exist about misuse of the drug. The register of the Federal Institute for Drugs and Medical Devices (Bundesinstituts für Arzneimittel und Medizinprodukte, BfArM) includes 55 reports of pregabalin misuse in patients, a large proportion of whom were taking diverse various medications, with or without an addiction potential, because of polytoxicomania (4). Nevertheless, relevant warnings have been included in the summary of product characteristics. These cases of misuse are balanced by several reports and studies in which a dependency of benzodiazepines, alcohol, or other substances was successfully treated with pregabalin.
Prof. Dr. med. Borwin Bandelow
Klinik für Psychiatrie und Psychotherapie
Dr. med. Dr. scient. pth. Dipl.-Psych. Reinhard J. Boerner
Klinik für Psychiatrie und Psychotherapie, Christliches Krankenhaus Quakenbrück
Prof. Dr. med. Siegfried Kasper
Universitätsklinik für Psychiatrie und Psychotherapie, Wien
Prof. Dr. med. Michael Linden
Charité Universitätsmedizin Berlin und Abteilung für psychische und psychosomatische Störungen am Rehazentrum Seehof, Teltow/Berlin
Prof. Dr. rer. nat. Hans-Ulrich Wittchen
Klinische Psychologie und Psychotherapie, Technische Universität Dresden
Prof. Dr. med. Hans-Jürgen Möller
Klinik für Psychiatrie und Psychotherapie, Ludwig-Maximilians-Universität München
Conflict of interest statement
Prof. Dr. Bandelow has received consultant’s fees from Lilly, Lundbeck, Ono, Otsuka, and Pfizer. He has received reimbursement of conference participation fees from Servier and Pfizer. He has received honoraria for lecturing at continuing medical education events from AstraZeneca, Boehringer-Ingelheim, Glaxo, Janssen, Lilly, Lundbeck, Pfizer, Servier, and Wyeth.
Dr. Boerner has received reimbursement of travel and accommodation costs and payment for preparing continuing medical education events from Pfizer. He has received consultant’s fees from Pfizer.
Prof. Kasper has received research support and lecture honoraria from, and has served on advisory boards or as a consultant for, AstraZeneca, CSC, Eli Lilly, Lundbeck, Merck Sharp & Dohme (MSD),Neuraxpharm, Bristol Myers Squibb, GlaxoSmithKline, Organon,Janssen, Novartis, Pierre Fabre, Pfizer, Schwabe, Sepracor, Servier, and Wyeth. He has received honoraria for the advisory board on anxiety disorders and been reimbursed conference participation fees and travel expenses from Pfizer.
Prof. Linden has received consultant’s fees and lecture honoraria from Pfizer, Lilly, Servier, and Janssen-Cilag. He has received payment from Servier for preparing scientific articles.
Prof. Wittchen has received reimbursement of conference participation fees and travel and accommodation expenses from Pfizer. He has received payment for preparing continuing medical education events from Pfizer.
Prof. Möller has received consultant’s fees and payment for preparing continuing medical education events from Pfizer.
|1.||Bandelow B, Zohar J, Hollander E, Kasper S, et al.: World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the pharmacological treatment of anxiety, obsessive-compulsive and post-traumatic stress disorders – first revision. World J Biol Psychiatry 2008; 9: 248–312 CrossRef MEDLINE|
|2.||Auquier P, Robitail S, Llorca PM, Rive B: Comparison of escitalopram and citalopram efficacy: A meta-analysis. International Journal of Psychiatry in Clinical Practice 2003; 7: 259–68 CrossRef|
|3.||Stahl SM, Gergel I, Li D: Escitalopram in the treatment of panic disorder: a randomized, double-blind, placebo-controlled trial. J Clin Psychiatry 2003; 64: 1322–7 CrossRef MEDLINE|
|4.||Gahr M, Freudenmann RW, Hiemke C, Kolle MA, Schonfeldt-Lecuona C: Pregabalin abuse and dependence in Germany: results from a database query. Eur J Clin Pharmacol 2013 CrossRef MEDLINE|
|5.||Bandelow B, Boerner RJ, Kasper S, Linden M, Wittchen HU, Möller HJ: The diagnosis and treatment of generalized anxiety disorder. Dtsch Arztebl Int 2013; 110(17): 300–10 VOLLTEXT|