Skip to main content
Deutsches Ärzteblatt International logoLink to Deutsches Ärzteblatt International
. 2014 Jul 7;111(27-28):473–480. doi: 10.3238/arztebl.2014.0473

The Diagnosis of and Treatment Recommendations for Anxiety Disorders

Borwin Bandelow 1, Thomas Lichte 2, Sebastian Rudolf 3, Jörg Wiltink 4, E Manfred Beutel 4,*
PMCID: PMC4187407  PMID: 25138725

Abstract

Background

Anxiety disorders (panic disorder/agoraphobia, generalized anxiety disorder, social phobia, and specific phobias) are the most common mental illnesses. For example, the 12-month prevalence of panic disorder/agoraphobia is 6%.

Methods

This guideline is based on controlled trials of psychotherapy and pharmacotherapy, retrieved by a systematic search for original articles that were published up to 1 July 2013. Experts from 20 specialty societies and other organizations evaluated the evidence for each treatment option from all available randomized clinical trials and from a synthesis of the recommendations of already existing international and German guidelines.

Results

403 randomized controlled trials were evaluated. It was concluded that anxiety disorders should be treated with psychotherapy, psychopharmacological drugs, or both. Response rates to initial treatment vary from 45% to 65%. Cognitive behavioral therapy is supported by higher-level evidence than any other psychotherapeutic technique. Psychodynamic therapy is recommended as a second-line treatment. Among anxiolytic drugs, the agents of first choice are selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors. The patient's preference should be considered in the choice of treatment. Drug treatment should be continued for 6 to 12 months after remission. If psychotherapy or drug treatment is not adequately effective, then the treatment should be switched to the other form, or to a combination of both.

Conclusion

The large amount of data now available from randomized controlled trials permits the formulation of robust evidence-based recommendations for the treatment of anxiety disorders. Future work should more closely address the necessary duration of psychotherapy and the efficacy of combined psychotherapy and drug treatment.


Anxiety disorders are the most common mental illnesses (1). Women are much more frequently affected than men. Specific phobias, with a 12-month prevalence of 10.3%, are the most common type of anxiety disorder (2), although persons suffering from them rarely seek treatment. The next most common type is panic disorder/agoraphobia (6.0%), followed by social phobia (2.7%) and generalized anxiety disorder (2.2%). Anxiety disorders have not become more common in recent years and decades (3, 4). They often arise in combination with other anxiety disorders, major depression, somatoform disorders, and addictive disorders (5). They are now thought to originate from an interaction of psychosocial, genetic, and neurobiological factors.

The S3 guideline on anxiety disorders

The S3 guideline on anxiety disorders (6) is available free of charge, in both short and long versions, on the website www.awmf.org/leitlinien (in German). S3 guidelines are required to meet the highest qualitative requirements of the DELBI criteria (7). This guideline was issued by 20 specialty societies and other organizations (etable 1). It was created over the period 2008–2014 by a guideline committee of 36 persons, including specialists, general practitioners, and patient representatives (etable 2). After ten working sessions, the final text of the guideline was created by a steering committee (B. Bandelow, M. Beutel, T. Lichte, S. Rudolf) and put to a vote of the remaining participants in two consensus conferences. Each participating group had one vote; recommendations were accepted if they received at least 75% of all votes cast. The resulting guideline was presented to the boards of the participating societies. Professor Ina Kopp of the Association of Scientific Medical Societies in Germany (Arbeitsgemeinschaft der wissenschaftlichen medizinischen Fachgesellschaften, AWMF) assisted in the creation of the guideline and moderated all working sessions and consensus conferences.

eTable 1. Participating medical societies, professional associations, and other organizations.

No. Abbrev. Organization
1 APK Aktion psychisch KrankeSupport for the Mentally Ill
2 BPTK Bundespsychotherapeutenkammer Federal Chamber of Psychotherapists in Germany
3 BVVP Bundesverband der VertragspsychotherapeutenFederal Association of Contract Psychotherapists
4 DAG SHG Deutsche Arbeitsgemeinschaft SelbsthilfegruppenGerman Working Group Self-help Groups
5 DASH Deutsche Angst-SelbsthilfeGerman Self-Help Association for Anxiety Sufferers
6 DÄVT Deutsche Ärztliche Gesellschaft für Verhaltenstherapie German Medical Society of Behavioral Therapy
7 DEGAM Deutsche Gesellschaft für Allgemeinmedizin und FamilienmedizinGerman College of General Practitioners and Family Physicians
8 DGPM Deutsche Gesellschaft für Psychosomatische Medizin und Ärztliche Psychotherapie German Society for Psychosomatic Medicine and Medical Psychotherapy
9 DGPPN Deutsche Gesellschaft für Psychiatrie, Psychotherapie, Psychosomatik und Nervenheilkunde German Association for Psychiatry, Psychotherapy and Psychosomatics
10 DGPPR Deutsche Gesellschaft für Klinische Psychologie und Psychosomatische RehabilitationGerman Society for Clinical Psychology and Psychosomatic Rehabilitation
11 DGPs Deutsche Gesellschaft für PsychologieGerman Psychological Society
12 DGPT Deutsche Gesellschaft für Psychoanalyse, Psychotherapie, Psychosomatik und TiefenpsychologieGerman Society for Psychoanalysis, Psychothera py, Psychosomatic Medicine, and Depth Psychology
13 DGRW Deutsche Gesellschaft für RehabilitationswissenschaftenGerman Society for Rehabilitation Sciences
14 DGVM Deutsche Gesellschaft für Verhaltensmedizin und VerhaltensmodifikationGerman Society for Behavioral Medicine and Behavior Modification
15 DGVT Deutsche Gesellschaft für Verhaltenstherapie German Society for Behavioral Therapy
16 DKPM Deutsches Kollegium für Psychosomatische MedizinGerman College for Psychosomatic Medicine
17 DPG Deutsche Psychoanalytische GesellschaftGerman Psychoanalytic Society
18 DPV Deutsche Psychoanalytische VereinigungGerman Psychoanalytic Association
19 DVT Deutscher Fachverband für VerhaltenstherapieGerman Professional Association for Behavior Therapy
20 GAF Gesellschaft für AngstforschungSociety for Anxiety Research

eTable 2. Members of the consensus group and of the steering committee (designated with an asterisk); abbreviations as in eTable 1.

Name Specialty society / organization Abbreviation
Prof. Dr. rer. nat. Georg W. Alpers German Psychological Society DGPs
Prof. Dr. med. Borwin Bandelow, Dipl.-Psych.* German Association for Psychiatry, Psychotherapy and Psychosomatics; Society for Anxiety Research DGPPN; GAF
Prof. Dr. phil. Cord Benecke German Psychoanalytic Society DPG
Prof. Dr. med. Manfred E. Beutel, Dipl.-Psych.* German College for Psychosomatic Medicine DKPM, coordination
Prof. Dr. med. Jürgen Deckert German Association for Psychiatry, Psychotherapy and Psychosomatics DGPPN
Prof. Dr. med. Annegret Eckhardt-Henn German Psychoanalytic Association DPV
Dr. med. Christian Ehrig German Medical Society of Behavioral Therapy DÄVT
Dr. med. Kerstin Engel German Association for Psychiatry, Psychotherapy and Psychosomatics; Society for Anxiety Research DGPPN; GAF
Prof. Dr. med. Peter Falkai German Association for Psychiatry, Psychotherapy and Psychosomatics DGPPN
Prof. Dr. med. Franziska Geiser, Dipl.-Psych. German Society for Psychosomatic Medicine and Medical Psychotherapy DGPM
Prof. Dr. Alexander L. Gerlach German Society for Behavioral Medicine and Behavior Modification DGVM
Prof. Dr. phil. Stephan Hau, Dipl.-Psych. German Psychoanalytic Association; German Society for Psychoanalysis, Psychotherapy, Psychosomatic Medicine, and Depth Psychology DPV; DGPT
Dipl.-Psych. Timo Harfst Federal Chamber of Psychotherapists in Germany BPTK
Prof. Dr. med. Peter Joraschky German College for Psychosomatic Medicine DKPM
Prof. Dr. med. Michael Kellner German Association for Psychiatry, Psychotherapy and Psychosomatics; Society for Anxiety Research DGPPN; GAF
Prof. Dr. med. Volker Köllner German Society for Psychosomatic Medicine and Medical Psychotherapy DGPM
Univ.-Doz. Dr. med. Gernot Langs German Society for Behavioral Therapy in Medicine DÄVT
Prof. Dr. med. Thomas Lichte* German College of General Practitioners and Family Physicians DEGAM
Dr. rer. nat. Heinz Liebeck German Society for Behavioral Therapy DGVT
Dipl.-Psych. Jürgen Matzat German Working Group Self-help Groups DAG SHG
Dipl.-Psych. Markus Reitt Research
Dr. med. Sebastian Rudolf* German Professional Association for Behavior Therapy DVT
Prof. Dr. med. Heinrich Peter Rüddel German Society for Clinical Psychology and Psychosomatic Rehabilitation DGPPR
Hr. Gerhard Schick German Self-Help Association for Anxiety Sufferers DASH
Prof. Dr. med. Ulrich Schweiger German Professonal Association for Behavior Therapy DVT
Dr. Regine Simon Federal Association of Contract Psychotherapists BVVP
Prof. Dr. med. Andreas Ströhle German Association for Psychiatry, Psychotherapy and Psychosomatics; Society for Anxiety Research; Support for the Mentally Ill DGPPN; GAF; APK
Dipl.-Psych. Anne Springer German Society for Psychoanalysis, Psychotherapy, Psychosomatic Medicine, and Depth Psychology DGPT
Prof. Dr. med. Hermann Staats German Psychoanalytic Society DPG
Dr. Walter Ströhm German Professonal Association for Behavior Therapy DVT
Dipl.-Psych. Benedikt Waldherr Federal Association of Psychotherapists BVVP
Prof. Dr. phil. Birgit Watzke German Society for Rehabilitation Sciences DGRW
Dr. med. Dirk Wedekind German Association for Psychiatry, Psychotherapy and Psychosomatics; Society for Anxiety Research DGPPN; GAF
PD Dr. med. Jörg Wiltink, Dipl.-Psych. Coordination
Dipl.-Soz.-Päd. Christian Zottl German Self-Help Association for Anxiety Sufferers DASH
Prof. Dr. med. Peter Michael Zwanzger German Association for Psychiatry, Psychotherapy and Psychosomatics; Society for Anxiety Research DGPPN; GAF

This guideline, like other guidelines, is explicitly not intended to serve a regulatory function; it neither mandates nor forbids anything. Rather, it provides important contextual information for individual treatment decisions, which should also properly depend on the treating person?s experience and on the preference of the patient.

It is planned that this guideline will be disseminated through presentations by members of the guideline committee at scientific conferences and at continuing medical education sessions, and by providing a patient version (www.awmf.org/leitlinien). An update in 5 years is projected.

Because of the large number of clinical trials evaluated for the guideline, references will not be given for every statement in this article; rather, the reader is referred to the long version of the S3 guideline (in German only) for more information.

Methods

Already existing guidelines on the subject were sought by electronic search. Guidelines meeting the specified quality criteria were selected in a peer-review process (etable 3). The guideline committee performed its own literature searches when discrepancies between existing guidelines were found, when subject areas were not adequately covered, or when new trials potentially resulting in different evidence levels were found to have been published since the appearance of the reference guidelines. All available randomized controlled trials (RCTs) on the treatment of anxiety disorders published up to 1 July 2013 were examined. The inclusion criteria were: original publication in a peer-reviewed journal; therapeutic trials of anxiety disorders defined according to ICD or DSM (panic disorder/agoraphobia, generalized anxiety disorder, social phobia, or specific phobia) in adults; not exclusively subgroup analysis; use of a control group (for drug trials, a placebo or reference drug; for psychotherapy trials, a waiting list, an active control [i.e., a supportive conversation with the patient, without applying specific therapeutic techniques], or treatment as usual [TAU]); for drug trials, use of a commercially available and approved drug.

eTable 3. Existing guidelines on the treatment of anxiety disorders that were used in the creation of the present guideline, in order of publication date. The four columns at right indicate which of the four disorders discussed in the present guideline (panic disorder, generalized anxiety disorder, social phobia, specific phobia) were covered by the guideline in question.

Guideline Society Authors PD GAD Social phobia Specific phobia
Recommendations on the treatment of anxiety and obsessive-compulsive disorders Medicines Committee of the German Medical Association (Arzneimittelkommission der deutschen Ärzteschaft, AkdÄ) (20) x x x x
Evidence-based guidelines for the pharmacological treatment of anxiety disorders British Association for Psychopharmacology (BAP) (21) x x x x
Clinical Practice Guidelines, Management of Anxiety Disorders Canadian Psychiatric Association (22) x x x x
Guidelines for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Post-Traumatic Stress Disorders – First Revision World Federation of Societies of Biological Psychiatry (WFSBP) (23) x x x x
Practice guideline for the treatment of patients with panic disorder American Psychiatric Association (24) x
Evidence-based guidelines on psychotherapy for panic disorder with or without agoraphobia and for agoraphobia without panic disorder German Psychological Society (Deutsche Gesellschaft für Psychologie, DGPs) (25) x
Evidence-based guidelines on psychotherapy for social anxiety disorder German Psychological Society (Deutsche Gesellschaft für Psychologie, DGPs) (26) x
Management of Anxiety (Panic Disorder, with or without Agoraphobia, and Generalised Anxiety Disorder) in Adults in Primary, Secondary and Community Care National Institute for Health and Clinical Excellence (NICE) (27) x x

As an example, the literature search on panic disorder/agoraphobia was carried out in the following way, according to the PRISMA Statement (8): PubMed search algorithm: ([“panic disorder”Title] OR [“agoraphobia”Title]) AND [“randomized”All fields] AND [“treatment” OR “therapy”All fields]; date: 1980/01/01 to present; in ISI Web of Science: Title=[panic disorder OR agoraphobia] AND Topic=[randomized] AND Topic=[therapy]; timespan: >1979; Search language=English, German). 1296 publications were retrieved by this search, and 21 further ones were identified by a manual search. Of the 1317 publications found in total, 1100 were excluded after screening of the titles and abstracts. The full texts of the remaining 217 articles were obtained. 48 were excluded because they met specifically defined exclusion criteria (e.g., double publication, subgroup analysis only, sample size <10 for each arm at study baseline, and lack of an adequate control group, among others); 169 were included in the analysis. A similar procedure was followed for the remaining anxiety disorders (see the long version of the guideline). Finally, a total of 403 RCTs were evaluated for the guideline.

The quality of each trial was evaluated according to the criteria enunciated in the SIGN Statement (9). Methodological flaws led to the exclusion of trials or to downgrading of their evidence level. Common reasons for downgrading the evidence level included small sample size (particularly in non-inferiority comparisons), failure to state the primary efficacy measure, or respectively failure to apply a Bonferroni correction for multiple testing, and inappropriate methods of statistical analysis.

Decisions to base guideline recommendations on the results of RCTs alone have often met with criticism in the past, and, indeed, in the case of the present guideline, this decision was controversial within the guideline committee itself. It was pointed out that RCTs generally involve a selected group of patients: patients with comorbidities are often excluded, and suicidal patients are as a rule excluded. Yet an analysis of psychotherapy and drug trials evaluated for the guideline did not indicate that these types of treatment differed systematically with respect to the inclusion of comorbid patients. In uncontrolled studies, it cannot be determined whether an observed improvement was due to the treatment itself or to spontaneous remission, tendency of regression to the mean, or non-specific attention effects; therefore, the guideline committee agreed that the recommendations should, essentially, be based on the results of RCTs. Although, according to the protocol, results from open studies, case series, and single case reports were also admissible, there was no concrete case in which a decision about an evidence level had to be made on the basis of such publications. This was due to the lack of sufficiently informative non-randomized studies, and the sufficient availability of controlled trials.

While the evidence categories were based exclusively on the efficacy of the various treatments studied, the recommendation grades also took risks into account, e.g., drug adverse effects (etable 4).

eTable 4. Evidence levels (from Eccels and Mason, 2001 [28]) and recommendation grades.

Level of evidence Definition
Ia Evidence from a meta-analysis of at least three randomized controlled trials (RCTs)
Ib Evidence from at least one RCT or a meta-analysis of fewer than three RCTs
IIa Evidence from at least one methodologically sound, non-randomized controlled trial
IIb Evidence from at least one methodologically sound, quasi-experimental descriptive study
III Evidence from methodologically sound, non-experimental observational studies, e.g., comparative studies, correlation studies, and case studies
IV Expert committee reports or expert opinion and/or clinical experience of recognized authorities
Recommendation grade Positive recommendation Negative recommendation
A “Must” recommendation: at least one RCT of good overall quality and consistency supports the recommendation directly, without extrapolation (evidence levels Ia and Ib) “Must not”: recommendation against the measure in question based on level Ia and Ib evidence.
B “Should” recommendation: well-conducted clinical trials, other than RCTs, support the recommendation either directly (evidence levels II or III) or by extrapolation (evidence level I) if the studies do not directly address the subject in question. “Should not”: recommendation against the measure in question based on level II and III evidence.
0 “May” recommendation: expert committee reports or expert opinion and/or clinical experience of recognized authorities (evidence level IV) or extrapolation from evidence of levels IIa, IIb, or III. This recommendation grade indicates that no directly applicable clinical studies of sufficiently high quality are available for consideration. Recommendation against the measure in question based on level IV evidence or extrapolation from evidence of levels IIa, IIb, or III.

Diagnosis

In Germany, anxiety disorders are evaluated in the outpatient and inpatient settings according to the 10th edition of the International Classification of Diseases in its German modification (ICD-10 GM) (10; see brief description in Table 1). In primary care, the diagnosis “mixed anxiety and depressive disorder” (ICD-10 F41.2) is often made; according to ICD-10, however, this diagnosis is impermissible if either anxiety or depression is severe enough to merit being diagnosed in itself. As no clinical trials have been conducted on the treatment of this entity according to its proper, restricted definition, the present guideline does not contain any recommendations about its treatment.

Table 1. Brief descriptions of the main anxiety disoders according to ICD-10 (29).

Anxiety disorder: ICD-10 classification Description Diagnostic tips
Panic disorder F41.0 Anxiety attacks of sudden onset, with physical manifestations of anxiety (palpitations, irregular heartbeat, sweating, tremor, trembling, dry mouth, dyspnea; feeling of choking or of tightness in the throat; chest pain, pressure, or tightness; nausea or other abdominal discomfort; dizziness, unsteadiness, lightheadedness, or faint feelings; feeling of unreality, as if in a dream, or as if “not really there”; chills or hot flashes; numbness, paresthesia) and fear of losing control, going mad, losing consciousness, or dying. These panic attacks develop abruptly and reach a peak within 10 minutes. Panic attacks can arise out of the blue; in the majority of cases, however, panic disorder is associated with agoraphobia.
Agoraphobia
F40.0
without panic disorder
F40.00
with panic disorder
F40.01
In agoraphobia with panic disorder, patients experience not only panic attacks as described above, but also fear of places where it might be difficult or embarrass ing to escape if a panic attack should occur. Such patients most commonly have panic attacks in crowds, on public transport, or in confined spaces (e.g., elevators). Fear of being alone is also common. Having an accompanying person on hand lessens anxiety. When a patient reports agoraphobia, the diagnosis of panic disorder should be considered.
Generalized anxiety disorder
F41.1
Patients suffer from somatic anxiety symptoms (tremor, palpitations, dizziness, nausea, muscle tension, etc.) as well as from difficulty concentrating, nervousness, insomnia, and other psychic symptoms. They usually cannot say what, in particular, they are afraid of, yet they are plagued by constant worry, e.g., that they (or a relative) might have an accident or become ill. They also worry about being in a permanently worried state (“meta worries”). In contrast to panic disorder, the physical manifestations of anxiety do not arise together in the form of an attack, but rather in shifting combinations, as a more or less permanent state. Patients with panic disorder fear for their own health; patients with generalized anxiety disorder worry more about the health of close persons or relatives.
Social phobia
F40.1
These patients are afraid of situations in which they are the center of attention – e.g., public speaking, visits to authorities, conversations with superiors on the job, or with persons of the opposite sex. They are afraid of appearing clumsy, embarassing themselves, or being judged negatively. In many cases, the affected persons are ashamed to discuss their social fears, with the result that the condition remains undiagnosed.
Specific (isolated) phobias
F40.2
Such phobias are restricted to individual, circumscribed situations, often related to animals, or other natural phenomena (e.g., cats, blood, heights). Patients very rarely seek professional help for isolated phobias.
Mixed anxiety and depressive disorder
F41.2
The simultaneous presence of anxiety and depression, with neither predominating. However, neither component is sufficiently severe to justify a diagnosis of anxiety or depression in itself. If the criteria for both an anxiety disorder and major depression are fulfilled, both diagnoses should be made, rather than mixed anxiety and depressive disorder.

Anxiety disorders often go unrecognized, partly because patients frequently complain of pain, sleep disturbances, or other somatic problems as their main symptom, rather than of the underlying anxiety (11). The differential diagnosis of anxiety disorders must include other common mental disorders, such as other anxiety disorders, major depression, and somatoform disorders, as well as somatic diseases such as coronary heart disease, bronchial asthma, and others (table 2).

Table 2. Summary of recommendations on the treatment of anxiety disorders.

Treatment Recommendation Level of evidence Recommendation grade
Psychotherapy and psychotropic drugs Patients with P/A, GAD, or SPh should be offered:
– Psychotherapy
– Medication
The preference of the well-informed patient should be respected. The patient should be informed, in particular, about the onset and duration of action, side effects, and availability of treatment modality.
Ia A
If psychotherapy or psychotropic drugs are not effective, the other form of treatment or a combination of both should be offered. Expertconsensus CCP
Psychotherapy and other measures
Cognitive behavioral therapy (CBT) Patients with P/A, GAD, SPh, or specific phobias should be offered CBT. Ia A
Psychodynamic psychotherapy Patients with P/A, GAD, or SPh should be offered psychodynamic psychotherapy if CBT is unavailable or ineffective, or if they express a preference for psychodynamic psychotherapy after being informed about all available types of treatment. IIa B
Exercise (endurance training, e.g., jogging 5 km three times a week) Patients with P/A can be given a recommendation for exercise (endurance training) as an adjunctive measure to other standard treatments. Expertconsensus CCP
Patient self-help and family support groups Patients and their families should be informed about self-help and family support groups and encouraged to participate, if appropriate. Expertconsensus CCP
Psychotropic drugs
Anxiety disorder Daily dose
Drug P/A GAD SPh
Citalopram*1 x 20–40 mg Ia A
Escitalopram*2 x x x 10–20 mg Ia A
Paroxetine x x x 20–50 mg Ia A
Sertraline x x 50–150 mg Ia A
Duloxetine x 60–120 mg Ia A
Venlafaxine x x x 75–225 mg Ia A
Tricyclic antidepressants Clomipramine (if drugs with a grade A recommendation are ineffective or poorly tolerated) x 75–250 mg Ia B
Calcium modulators Pregabalin x 150–600 mg Ia B
Tricyclic anxiolytics Opipramol (if drugs with a grade A or B recommendation are ineffective or poorly tolerated) x 50–300 mg Ib 0
Azapirones Buspirone (if drugs with a grade A or B recommendation are ineffective or poorly tolerated) x 15–60 mg Ib 0
RIMA Moclobemide (if drugs with a grade A or B recommendation are ineffective or poorly tolerated) x 300–600 mg Expert consensus CCP

P/A = panic disorder/agoraphobia; GAD = generalized anxiety disorder; SPh = social phobia; CCP = clinical consensus point; RIMA = reversible monoamine oxidase A inhibitor.* 1 Do not exceed recommended dose (QT C interval prolongation). Maximal dose with diminished hepatic function 30 mg/day, for older patients 20 mg/day. * 2 Do not exceed recommended dose (QT C interval prolongation). Maximal dose for persons over age 65, 10 mg/day

Health care provision

The primary care physician is often the first doctor contacted by the patient, and therefore plays a major role in its care. Some 15% of patients remain exclusively under the treatment of their primary care physicians and do not consult a specialist (12). Psychotherapy is provided by psychotherapists, who can be either physicians or certified psychologists in Germany. If the symptoms fail to improve sufficiently, if the patient becomes suicidal, or if other complications arise, the patient should be referred to a psychiatrist. Anxiety disorders can usually be treated on an outpatient basis. Indications for hospitalization include suicidality, lack of further options for outpatient management, very severe anxiety, and marked comorbidity.

Treatment recommendations

The accepted indications for treatment are: the presence of an anxiety disorder as defined by ICD-10 GM, moderate to severe subjective distress as perceived by the patient, and psychosocial problems and other complications resulting from the anxiety disorder (e.g., substance abuse). The treatment recommendations are summarized in Table 2 (for a more detailed version, cf. Table 1 in the text of the guideline [in German]). Anxiety disorders can be treated with psychotherapy and/or drug treatment and other interventions. In meta-analyses, both psychotherapy and medication have been found to have moderate to high effect sizes in pre–post comparisons and in comparisons with control groups. Response rates for the form of treatment initially chosen are in the range of 45% to 65%.

The treatment plan should be chosen after careful consideration of individual factors (the patient?s preference, previous treatment attempts, severity, comorbidity including substance abuse, suicide risk, and others). All interventions should be performed on the basis of a functioning and sustainable therapeutic relationship. Treating physicians and psychologists must inform patients of the diagnosis and the likelihood of improvement with each potential treatment, in the light of the available evidence. They must also inform them of the alternatives when multiple treatments, any of which may be indicated, are associated with markedly different burden of distress, risks, or chances of improvement.

The patients? relatives should be integrated into the treatment, and the economic aspects of treatment should also be considered. A detailed discussion of the treatment of generalized anxiety disorder can be found in Bandelow et al. (2013) (13).

Psychotherapy

The large number of RCTs of cognitive behavioral therapy (CBT) carried out to date for each of the four types of anxiety disorder have documented the efficacy of CBT in comparison to active controls and to waiting lists. CBT should be based on empirically validated treatment protocols (manuals). Patients with avoidance behavior (e.g., agoraphobic patients) should receive CBT with exposure, i.e., confrontation with anxiety-inducing situations. Exposure therapy was found to be more effective when the patient was accompanied by the therapist (14).

As psychodynamic methods have rarely been considered in previous guidelines due to a lack of studies, the guideline group carried out an independent literature search in order to integrate recently published studies of manualized short-term psychodynamic therapy. The RCTs on psychodynamic therapy were markedly fewer in number, and lower in quality, than those on CBT, and some comparison studies have shown CBT to be superior. It is thus recommended that patients with panic disorder/agoraphobia, generalized anxiety disorder, or social phobia should be offered psychodynamic psychotherapy if CBT is ineffective or unavailable, or if the (adequately informed) patient expresses a preference for psychodynamic treatment. For specific phobias, the available studies are exclusively of behavioral therapy, which should be performed as exposure treatment.

The current state of the data does not permit any valid generalization about the necessary duration of psychotherapy, as most trials were conducted for periods of 10 to 24 weeks, and only a few of them involved a comparison of the efficacy of treatment when carried out for a shorter or longer time. The duration of treatment should be planned individually depending on the severity of illness, comorbidities, and the overall psychosocial situation. For specific phobias, the available studies show that exposure treatment can be performed successfully in a few sessions.

The guideline committee also investigated nontherapist-supported techniques that are performed via computer or over the Internet. Many studies of such treatments have been published in the last few years, but there is, as yet, insufficient evidence to conclude that they are as effective as individual CBT. Moreover, treatments without personal contact are not reimbursable by the statutory health insurance carriers in Germany. Medicolegal problems can also arise (e.g., in case of suicidality), and the matter of data privacy has not yet been adequately addressed. Patients with panic disorder/agoraphobia can be offered therapist-unsupported interventions based on CBT and involving books, audio material, computers, or the Internet as a form of self-help, to bridge the time interval before therapy is scheduled to begin or as adjunctive treatment to face-to-face therapy.

Group CBT has also been studied in randomized controlled trials, but there is still too little evidence to conclude that group CBT is as effective as individual treatment. It seems reasonable, however, to conduct self-assurance training in groups, e.g., for patients with social phobia; in such cases, the treatment should involve both individual and group therapy. Offering group therapy is also justified if individual therapy is unavailable.

The guideline committee found too little evidence to support any recommendation about other forms of psychotherapy (applied relaxation, interpersonal therapy, client-centered therapy, others).

Pharmacotherapy

Grade A recommendations were issued for drugs from two categories: the selective serotonin reuptake inhibitors (SSRI) and the serotonin-norepinephrine reuptake inhibitors (SNRI). Grade B recommendations were issued for the tricyclic antidepressant clomipramine (for panic disorder) and for pregabalin (for generalized anxiety disorder). Benzodiazepines, though effective, should not be prescribed, as they have major side effects (including the development of dependence). Only in exceptional cases—e.g., in the setting of severe heart disease, contraindications for the standard drugs, suicidality, and other situations—benzodiazepines can be given for short-term use after their risks and benefits have been carefully weighed.

Drug treatment should be conducted according to generally accepted medical standards. The patient must be informed about adverse effects, possible interactions, contraindications, and warnings; the prescriber should obtain this information from the current summary of product characteristics for the drug in question. Patients starting treatment with antidepressants should be told that they generally take effect after a latency period of about two weeks (range, 1 to 6 weeks).

SSRI and SNRI have a relatively flat dose-response curve, i.e., about 75% of patients respond to the initial (low) dose. For some patients, it is reasonable to begin treatment at half of the usually recommended dose. Dose adjustment may be necessary in patients with impaired hepatic function. To prevent agitation and insomnia at the start of treatment, the drug should be given in the morning or at midday. Some patients will need doses at the upper end of the indicated range and should be given them if necessary. Treatment with an SSRI or an SNRI should be continued as maintenance therapy at the same dose that was successful in acute treatment. Once remission has been achieved, pharmacotherapy should be continued for 6 to 12 months, or even longer if drug discontinuation leads to recurrent anxiety, if the anxiety disorder is especially severe, or if the patient's history indicates that prolonged treatment may be needed. The dose should be slowly tapered at the end of treatment to avoid discontinuation syndromes.

There is too little evidence to support any recommendation for drug treatment for specific phobias.

Combined psychotherapy and drug treatment, and the management of refractory anxiety

There have been a number of comparative studies of psychotherapy, drug treatment, and a combination of both in the treatment of panic disorder; most have indicated that a combination is superior to monotherapy of either type. For generalized anxiety disorder, studies of this type are lacking; for social phobia, the evidence is inconsistent. No study indicated that combination therapy was worse. If either psychotherapy or drug treatment is ineffective in an individual case, there should be a switch to the other type of treatment, or to a combination of the two. If there is no response to the first drug after 4 to 6 weeks of treatment, a second standard drug should be given instead. In case of a partial response, raising the dose can be considered first. Table 3 contains a stepwise plan for drug treatment options in case of drug inefficacy or intolerance. If a switch to a different standard drug is unsuccessful, there can be another switch to drugs recommended as a second-line treatment, e.g., tricyclic antidepressants or pregabalin. Medicolegal issues should be considered whenever drugs that have not been approved for the treatment of anxiety (e.g. quetiapine [in Europe]) are given off label.

Table 3. Stepwise plan for alternative drug treatment if the drug initially used to treat an anxiety disorder is ineffective or poorly tolerated*(modified from [30]).

Measure Procedure
Switch from one standard drug to another – Switch from one SSRI to another – Switch from an SSRI to an SNRI, or vice versa – Switch to a TCA – Switch to pregabalin (only in GAD)
Switch to non-standard drugs
Switch to a drug that is approved for other anxiety disorders – Switch to pregabalin – Switch to moclobemide, opipramole, or hydroxyzine – Switch to a benzodiazepine (only in rare cases, when clinically justified)
Switch to a drug that is not approved for the anxiety disorder in question but has been found effective in RCTs – Panic disorder: – GAD: – Social phobia: Mirtazapine, quetiapine, phenelzine, valproate, inositol Quetiapine; in refractory cases, addition of risperidone or olanzapine to treatment with an antidepressant Mirtazapine, gabapentin, pregabalin, olanzapine
Switch to a drug (or drug combination) that has been found effective in open studies – Panic disorder: – GAD: – Social phobia: Combined SSRI and TCA, olanzapine monotherapy, combined SSRI and olanzapine or a TCA, addition of pindolol to an SSRI, combined valproate and clonazepam. In refractory cases, open studies have documented the efficacy of olanzapine and of the addition of fluoxetine to a TCA, of a TCA to fluoxetine, and of olanzapine to an SSRI. Ziprasidone levetiracetam, topiramate, tranylcypromine; in refractory cases, addition of buspirone to an SSRI
Switch to a drug (or drug combination) that has been reported to be effective in case reports – Panic disorder: The addition of lithium to clomipramine and the combination of valproate and clonazepam have been reported to be effective in refractory cases

* Not all drugs mentioned in this article are currently approved in all countries for the indications, in the populations, or at the doses being discussed. Refer to your local prescribing information.SSRI, selective serotonin reuptake inhibitor; SNRI, selective serotonin norepinephrine reuptake inhibitor; TCA, tricyclic antidepressant; GAD, generalized anxiety disorder

The treatment of anxiety disorders in older patients

The treatment of older patients has been studied only in generalized anxiety disorder, probably because the other anxiety disorders are less commonly seen in older patients. The few available studies on CBT in persons over age 65 have shown a lower degree of efficacy than in adults aged 18 to 65. As for drug treatment in older patients, a few studies have shown efficacy for duloxetine, venlafaxine, pregabalin, and quetiapine. In older patients, possible drug interactions and contraindications must be considered carefully, along with the following additional factors: increased sensitivity to anticholinergic effects, the increased risk of orthostatic hypotension and ECG changes, the increased risk of falling, and possible paradoxical reactions to benzodiazepines.

Pregnancy and breastfeeding

For pregnant women, the risk of an untreated anxiety disorder must be weighed against the risk of damage to the unborn child as a result of treatment. The physician should consider whether psychotherapy may be preferable to drug treatment for this reason. Some authors report increased risks with antidepressant drugs (1517), which should, therefore, be given with caution. Likewise, a risk assessment has to be done when the patient is breast feeding.

Exercise

Exercise is recommended as a treatment for panic disorder (aerobic training, e.g., jogging 5 km three times a week). There is, however, too little evidence to support a recommendation for exercise as monotherapy. In the studies performed to date, exercise was less effective than a drug (18) and no more effective than relaxation as a control treatment (19).

Self-help groups

Patients should be informed about self-help and family support groups and encouraged to participate if appropriate.

Key Messages.

  • Anxiety disorders should be treated with psychotherapy, medication, or both.

  • Of all psychotherapeutic techniques, cognitive behavioral therapy is supported by the highest-level evidence.

  • Psychodynamic therapy is recommended as second-line treatment.

  • The anxiolytic drugs of first choice are the selective serotonin reuptake inhibitors (SSRI) and the serotonin-norepinephrine reuptake inhibitors (SNRI).

  • If either psychotherapy or psychotropic drugs are inadequately effective, the treatment should be switched to the other form, or to a combination of both.

Acknowledgments

Translated from the original German by Ethan Taub, M.D.

Footnotes

Conflict of interest statement

All participants in the creation of this guideline have declared their conflicts of interest (e.g., having received lecture honoraria from drug companies or having been an advocate for a particular form of treatment). The guideline committee tried to base its recommendations exclusively on objective evaluation of the scientific evidence despite these potentially distorting influences. Participants with a relevant conflict of interest abstained when recommendations were put to a vote.

Prof. Bandelow has served as a paid consultant to Lilly, Lundbeck, Otsuka, and Pfizer and has received reimbursement of meeting participation fees and of travel and accommodation expenses from Pfizer and Servier. He has received honoraria for lectures at scientific meetings and continuing medical education events from AstraZeneca, Glaxo, Janssen, Lilly, Lundbeck, Meiji-Seika, Otuska, Pfizer, and Servier.

Prof. Beutel has received payment from Pfizer, Servier, and Boehringer-Ingelheim for preparing scientific meetings and continuing medical education events.

Dr. Rudolf, Prof. Lichte, and PD Wiltink declare that no conflict of interest exists.

References

  • 1.Kessler RC, Berglund P, Demler O, Jin R, Merikangas KR, Walters EE. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry. 2005;62:593–602. doi: 10.1001/archpsyc.62.6.593. [DOI] [PubMed] [Google Scholar]
  • 2.Jacobi F, Hofler M, Strehle J, Mack S, et al. Mental disorders in the general population: Study on the health of adults in Germany and the additional module mental health (DEGS1-MH) Nervenarzt. 2014;85:77–87. doi: 10.1007/s00115-013-3961-y. [DOI] [PubMed] [Google Scholar]
  • 3.Kessler RC, McGonagle KA, Zhao S, Nelson CB, et al. Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States Results from the National Comorbidity Survey. Arch Gen Psychiatry. 1994;51:8–19. doi: 10.1001/archpsyc.1994.03950010008002. [DOI] [PubMed] [Google Scholar]
  • 4.Kessler RC, Demler O, Frank RG, Olfson M, et al. Prevalence and treatment of mental disorders, 1990 to 2003. N Engl J Med. 2005;352:2515–2523. doi: 10.1056/NEJMsa043266. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Jacobi F, Wittchen HU, Holting C, Hofler M, et al. Prevalence, co-morbidity and correlates of mental disorders in the general population: results from the German Health Interview and Examination Survey (GHS) Psychol Med. 2004;34:597–611. doi: 10.1017/S0033291703001399. [DOI] [PubMed] [Google Scholar]
  • 6.Bandelow B, Wiltink J, Alpers GW, Benecke C, et al. Deutsche S3-Leitlinie zur Behandlung von Angststörungen. www.awmf.org/leitlinien.html. 2014 (last accessed on 26 May 2014) [Google Scholar]
  • 7.ÄZQ/AWMF: Deutsches Instrument zur methodischen Leitlinien-Bewertung. (DELBI) 2008:468–519. [Google Scholar]
  • 8.Moher D, Liberati A, Tetzlaff J, Altman DG, Group P. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. J Clin Epidemiol. 2009;62:1006–1012. doi: 10.1016/j.jclinepi.2009.06.005. [DOI] [PubMed] [Google Scholar]
  • 9.SIGN: Scottish Intercollegiate Guidelines Network. www.sign.ac.uk. 2012 (last accessed on 26 May 2014) [Google Scholar]
  • 10.DIMDI: Internationale statistische Klassifikation der Krankheiten und verwandter Gesundheitsprobleme, 10th revised edition. German Modification. 2013 (ICD-10-GM) [Google Scholar]
  • 11.Wittchen HU, Kessler RC, Beesdo K, Krause P, Hofler M, Hoyer J. Generalized anxiety and depression in primary care: prevalence, recognition, and management. J Clin Psychiatry. 2002;63:24–34. [PubMed] [Google Scholar]
  • 12.Wittchen HU, Jacobi F. Die Versorgungssituation psychischer Störungen in Deutschland Eine klinisch-epidemiologische Abschätzung anhand des Bundes-Gesundheitssurveys 1998. Bundesgesundheitsbl Gesundheitsforsch Gesundheitsschutz. 2001;44:993–1000. [Google Scholar]
  • 13.Bandelow B, Boerner RJ, Kasper S, Linden M, Wittchen HU, Möller HJ. The diagnosis and treatment of generalized anxiety disorder. Dtsch Arztebl Int. 2013;110:300–310. doi: 10.3238/arztebl.2013.0300. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Gloster AT, Wittchen HU, Einsle F, Lang T, et al. Psychological treatment for panic disorder with agoraphobia: A randomized controlled trial to examine the role of therapist-guided exposure in situ in CBT. J Consult Clin Psychol. 2011;79:406–420. doi: 10.1037/a0023584. [DOI] [PubMed] [Google Scholar]
  • 15.Oyebode F, Rastogi A, Berrisford G, Coccia F. Psychotropics in pregnancy: safety and other considerations. Pharmacol Ther. 2012;135:71–77. doi: 10.1016/j.pharmthera.2012.03.008. [DOI] [PubMed] [Google Scholar]
  • 16.Udechuku A, Nguyen T, Hill R, Szego K. Antidepressants in pregnancy: a systematic review. Aust N Z J Psychiatry. 2010;44:978–996. doi: 10.3109/00048674.2010.507543. [DOI] [PubMed] [Google Scholar]
  • 17.Tuccori M, Testi A, Antonioli L, Fornai M, et al. Safety concerns associated with the use of serotonin reuptake inhibitors and other serotonergic/noradrenergic antidepressants during pregnancy: a review. Clin Ther. 2009;31:1426–1453. doi: 10.1016/j.clinthera.2009.07.009. [DOI] [PubMed] [Google Scholar]
  • 18.Broocks A, Bandelow B, Pekrun G, George A, et al. Comparison of aerobic exercise, clomipramine, and placebo in the treatment of panic disorder. Am J Psychiatry. 1998;155:603–609. doi: 10.1176/ajp.155.5.603. [DOI] [PubMed] [Google Scholar]
  • 19.Wedekind D, Broocks A, Weiss N, Engel K, Neubert K, Bandelow B. A randomized, controlled trial of aerobic exercise in combination with paroxetine in the treatment of panic disorder. World J Biol Psychiatry. 2010;11:904–913. doi: 10.3109/15622975.2010.489620. [DOI] [PubMed] [Google Scholar]
  • 20.Therapieempfehlungen der Arzneimittelkommission der Deutschen Ärzteschaft. Empfehlungen zur Therapie von Angst- und Zwangsstörungen. 2. Auflage. AKDÄ. 2003 [Google Scholar]
  • 21.Baldwin DS, Anderson IM, Nutt DJ, Bandelow B, et al. Evidence-based guidelines for the pharmacological treatment of anxiety disorders: recommendations from the British Association for Psychopharmacology. J Psychopharmacol. 2005;19:567–596. doi: 10.1177/0269881105059253. [DOI] [PubMed] [Google Scholar]
  • 22.Canadian Psychiatric Association. Canadian Psychiatric Association Clinical Practice Guidelines, Management of Anxiety Disorders. Canadian Journal of Psychiatry. 2006;58:1–92. [PubMed] [Google Scholar]
  • 23.Domschke K, Hohoff C, Jacob C, Maier W, et al. Chromosome 4q31-34 panic disorder risk locus: association of neuropeptide Y Y5 receptor variants. Am J Med Genet B Neuropsychiatr Genet. 2008;147:510–516. doi: 10.1002/ajmg.b.30629. [DOI] [PubMed] [Google Scholar]
  • 24.American Psychiatric Association (APA): Practice guideline for the treatment of patients with panic disorder. 2nd ed. Washington (DC): American Psychiatric Association (APA) 2009 Jan; [Google Scholar]
  • 25.Heinrichs N, Alpers GW, Gerlach AL. Evidenzbasierte Leitlinien zur Psychotherapie der Panikstörung mit und ohne Agoraphobie und der Agoraphobie ohne Panikstörung im Auftrag der Fachgruppe Klinische Psychologie und Psychotherapie in der Deutschen Gesellschaft für Psychologie (DGP) Göttingen: Hogrefe. 2009 [Google Scholar]
  • 26.Heinrichs N, Stangier U, Gerlach A, Willutzki U, Fydrich T. Evidenzbasierte Leitlinie zur Psychotherapie der Sozialen Angststörung. Göttingen: Hogrefe. 2010 [Google Scholar]
  • 27.Anxiety: Management of Anxiety (Panic Disorder, with or without Agoraphobia, and Generalised Anxiety Disorder) in Adults in Primary, Secondary and Community Care. NICE. National Institute for Health and Clinical Excellence (NICE) 2011 [PubMed] [Google Scholar]
  • 28.Eccles M, Mason J. How to develop cost-conscious guidelines. Health Technol Assess. 2001;5:1–69. doi: 10.3310/hta5160. [DOI] [PubMed] [Google Scholar]
  • 29.World Health Organisation. Geneva: 1991. WHO. World Health Organisation: Tenth Revision of the International Classification of Diseases, Chapter V (F): Mental and Behavioural Disorders (including disorders of psychological development). Clinical Descriptions and Diagnostic Guidelines. [Google Scholar]
  • 30.Bandelow B, Zohar J, Hollander E, 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. doi: 10.1080/15622970802465807. [DOI] [PubMed] [Google Scholar]

Articles from Deutsches Ärzteblatt International are provided here courtesy of Deutscher Arzte-Verlag GmbH

RESOURCES