Specific phobias are the most common anxiety disorders. The second most common type is panic disorder with or without agoraphobia (PAD), followed by social anxiety disorder (SAD) and generalized anxiety disorder (GAD). Abundant high-quality research addressed the neurobiological causes of these disorders; However, at present, none of the putative biomarkers has been shown to be sufficient and specific as a diagnostic tool for anxiety disorders.
A consensus panel of German experts began developing the “S3 guideline” for anxiety disorders in 2008. The term S3 refers to the highest quality requirements as defined by the systematic search for evidence and consensus statements. . The current work presents the first revision of these German Guidelines for Anxiety Disorders, which was published in 2021 and is available online.
In Germany, the costs of treating anxiety disorders are reimbursed by statutory health insurance providers. These disorders are mostly treated on an outpatient basis. Indications for hospitalization include suicidality, chronic anxiety disorders unresponsive to standard outpatient treatment, or marked comorbidity, such as major depression, personality disorders, or substance abuse.
| Results |
> Diagnosis
For Germany, the International Classification of Diseases in its German version (ICD-10 GM) is the official diagnostic system for anxiety disorders. In primary care, these disorders often go unnoticed. Before diagnosing them, other mental disorders, such as depression, personality disorders, and somatoform disorders, as well as physical illnesses such as coronary heart disease or lung disease, must be excluded.
> Treatment
Treatment is indicated when a patient meets the criteria for an anxiety disorder defined by the ICD or the Diagnostic and Statistical Manual of Mental Disorders (DSM), shows marked distress, or suffers sequelae resulting from the disorder (e.g., suicidal tendencies, depression secondary or substance abuse).
Patients should be educated about their diagnosis, possible history, and available treatment approaches. Anxiety disorders can be treated with psychotherapy, drug treatment, and other interventions. It is mandatory for psychologists and treating physicians to inform patients about the risks and benefits of treatments and possible more effective or better tolerated alternatives. The treatment plan should be chosen after careful consideration of individual factors. It is suggested that treatment success be monitored with standard rating scales.
> Psychotherapy
Of all psychological interventions, cognitive behavioral therapy (CBT) has the best body of evidence. In the case of phobic disorders, confronting patients with their feared situations in sessions is crucial in therapy. Group CBT has also been evaluated in randomized controlled trials (RCTs), but there is not enough evidence to conclude that it is as effective as individual treatment. For patients with SAD, it seems reasonable to conduct self-confidence training in groups; therefore, psychotherapy for SAD should include both in-person and group therapy sessions.
Compared to CBT, the evidence for the effectiveness of psychodynamic therapy (PDT) is weaker. RCTs on TPD were fewer in number and of lower quality, and some comparison studies indicated superiority of CBT over TPD. According to the guideline, patients with TPA, GAD, or SAD should be offered TPD only if CBT has been shown to be ineffective or unavailable, or if the appropriately informed patient expresses a preference for TPD.
The few studies on systemic therapy had serious methodological flaws and inconsistent efficacy results; therefore, this modality only received a “0” recommendation, indicating that it should only be offered if standard treatments have failed or are not available.
Most effectiveness studies used treatment manuals that guided the intervention strategy. Therefore, to maintain quality standards, it is also recommended to manualize psychotherapy in routine practice.
The guideline committee did not provide recommendations on the duration or number of psychotherapy sessions needed due to a lack of reliable data. There is not enough evidence that longer therapies are more effective than shorter ones.
Specific phobias can be treated in a few sessions; Most studies only had one session lasting between 1 and 3 hours, demonstrating that short interventions are effective.
> Internet-based psychological interventions (IPI)
Numerous studies have investigated IPIs, most of which were based on CBT approaches. In most RCTs, IPIs were more effective than a waiting list control. However, evidence showing that IPIs are as effective as individual CBT with face-to-face contact is insufficient. Therefore, the committee decided that IPIs should not be used as monotherapy, but to bridge a waiting period until face-to-face psychotherapy is available, or as an additional self-help measure accompanying standard psychotherapy or pharmacological treatment. .
> Virtual and augmented reality exposure treatment
Virtual reality (VR) and augmented reality (AR) technologies have been introduced in the treatment of phobias. In AR exposure therapy, virtual elements merge into the view of the physical world. Thus, the experience is more authentic, and costs are lower, because it is not necessary to program the entire virtual environment.
For TPA, there are not enough studies to support the use of VR. However, for SAD, it can be used as an additional self-help measure. For specific phobias (fear of spiders, heights, or flying), VR exposure therapy can be used when in vivo exposure is not available.
> Pharmacotherapy
A large database of RCTs on the efficacy of medications for TPA, TAD, and SAD is available. For specific phobias, pharmacological studies are scarce, and behavioral treatments should be privileged.
First-line medications for anxiety disorders include selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs). For panic disorder, the tricyclic antidepressant (TCA) clomipramine may be a second-line option, although it has more adverse effects. For GAD, pregabalin has been shown to be effective, but there are concerns about overdose and withdrawal symptoms associated with the drug. Therefore, it should not be used as the first option.
The guideline group advised against the use of benzodiazepines due to their potential for abuse, despite their high effectiveness in treating anxiety. However, in exceptional cases (eg, severe heart disease, suicidality, contraindications to standard medications), they can be used for a limited time after weighing their risks and benefits.
Only in rare cases is emergency drug treatment an option for acute panic attacks. In general, talking calmly with the patient is sufficient. Only in severe cases, lorazepam 1.0–2.5 mg can be administered.
Patients starting treatment with antidepressants (SSRIs, SNRIs, TCAs) should be warned that these medications take effect after a latency period of ~ 2 weeks. During the first weeks, some patients often stop treatment due to initial restlessness and nervousness. Compliance can be improved by informing patients of these potential adverse effects and starting them at half the recommended dose.
According to various studies, it is advisable to continue drug treatment for 6 to 12 months after remission has occurred. In patients with recurrent and/or severe anxiety symptoms, longer treatments may be necessary. To avoid discontinuation syndromes, the dose should be decreased slowly at the end of treatment.
In patients who do not respond to medications, it is recommended to add psychotherapy. If there is no response to the first drug after 4-6 weeks of treatment, a second standard drug should be given instead. In case of partial response after 4 to 6 weeks, the considered dose can be increased.
> Combination of psychotherapy and medication
The guideline does not recommend starting psychotherapy before considering pharmacotherapy or vice versa, as there is no clinical trial evidence to justify a step-by-step approach. Since more data favors combining these modalities, both can be started at the same time. If the response to psychotherapy or pharmacotherapy is insufficient, treatment should be changed to another modality.
> Treatment of anxiety disorders in older patients
Anxiety disorders are less common in patients ≥ 65 years of age, except for GAD, which can be common in the elderly. Some studies in GAD suggest that CBT is less effective than in adults < 65 years. Several studies showed that duloxetine, venlafaxine, pregabalin and quetiapine are effective in patients ≥ 65 years of age. In these patients, the increased sensitivity to side effects and drug interactions should be considered.
> Pregnancy and lactation
When pregnant women suffer from an anxiety disorder, they must weigh the risk of an untreated disorder vs. the risk of harm to the fetus as a result of drug treatment. Antidepressants have been associated with an increased risk of spontaneous abortions, stillbirths, premature births, respiratory distress, and endocrine and metabolic dysfunctions.
However, current evidence suggests that the use of many antidepressants, especially SSRIs, is favorable compared to exposing the mother to the risks of untreated depression or anxiety disorders. The same evaluation needs to be done when a mother is breastfeeding. In such cases, CBT should be considered as an alternative.
> Other treatment options
Exercise has been shown to be effective in the treatment of APD, but only as an additional treatment to standard therapy. According to a meta-analysis of RCTs in patients with anxiety and related disorders, exercise had a small but statistically significant effect compared to control conditions.
Although controlled studies on the usefulness of self-help groups are lacking, it is suggested that patients be encouraged to participate in such activities. It may also be helpful to integrate the family of affected patients into the treatment plan.
The guideline committee did not find sufficient evidence to recommend the following treatments: interpersonal therapy, progressive muscle relaxation, applied relaxation, music/dance/art therapy, yoga, beta blockers, phytotherapeutics, homeopathic formulations, and repetitive magnetic stimulation.
| Discussion |
Since the publication of the first version of the German guideline for the treatment of anxiety disorders in adults, there have been no fundamental changes in the treatment recommendations. Treatment with SSRIs/SNRIs and CBT remains the mainstay for anxiety disorders.
The number of clinical studies examining IPIs for anxiety disorders has surpassed the number of studies on face-to-face psychotherapy in recent years, perhaps because the former are much easier to conduct. These treatment programs have advantages, because personal contact can be avoided during the COVID-19 pandemic, they are less expensive, they save the therapist’s time, they require less organizational efforts, they save travel time, and they can be used at any time of the day. .
However, a closer look at the quality of these studies is warranted. Even if IPI programs are very sophisticated and can be individualized, it is difficult to believe that they can adequately address unique relationships or problems at the same level as "real" therapists.
Since the first version of the guide, more studies have been published with the new Virtual Reality (VR) and Augmented Reality (AR) technologies used in the treatment of specific phobias. As there is insufficient evidence that these methods are as effective as in vivo exposure therapy, the expert panel recommends using only these technologies as an adjunct treatment to standard behavioral therapy or in cases where alternative treatments are not available. However, these methods may play an important role in the treatment of phobias in the future.
Since the 2014 version of the guideline, no new medications for anxiety disorders have emerged. Therefore, there were no changes in psychopharmacological treatment recommendations. Although there are many unmet needs in pharmacological treatment, new anxiolytic agents will not be available in the near future.
The applicability of this guide is not restricted only to the special situation in Germany. It may also be useful for developing evidence-based treatment plans for adults with anxiety disorders in other countries, as it is based on a comprehensive global evaluation of RCTs. Today, most medications are developed for the international market, and the principles of psychotherapy are substantially the same in the global perspective.
