The prevalence of generalized anxiety disorder (GAD) is 6%. The median age of onset was 31 years, and the mean age of onset was 32.7 years. Prevalence in children is 3%, in adolescents – 10.8%. The age of onset of the disease in children and adolescents is between 10 and 14. There is evidence that GAD is 2-3 times more common in women than in men, and that GAD is more common in older people. This disorder often goes unrecognized and less than a third of patients receive adequate treatment. The situation is complicated by the fact that it may be necessary to separate GAD in children from GAD in adults.
GAD is associated with functional impairment and decreased quality of life. When initially visiting a doctor, 60-94% of patients with GAD complain of painful physical symptoms and in 72% of cases this is the reason for seeking medical help.
We present to your attention a review translation of clinical guidelines for the treatment of generalized anxiety disorder, compiled by experts from the Canadian Anxiety Disorders Association. The translation was prepared jointly by the scientific Internet portal “Psychiatry & Neuroscience” and the Psychiatry Clinic “Doctor SAN” (St. Petersburg).
Diagnosis
GAD is characterized by increased anxiety and worry (most days during the past six months) about a variety of events and activities, such as school or work. In addition, GAD is associated with restlessness, muscle tension, fatigue, problems concentrating, irritability and sleep disturbances.
DSM-5 criteria for diagnosing GAD
- Excessive anxiety and worry (anxious anticipation) about a variety of events and activities, such as school or work.
- The person has difficulty gaining control over anxiety
- Excessive anxiety and worry are associated with at least three of the following symptoms, affecting a person most days for at least six months: Restlessness or feeling on edge, fatigue, difficulty concentrating, irritability, muscle tension or sleep disturbances
Reasons for appearance
No one has yet been able to find out the exact origin of this disorder. The reasons for its appearance may be:
- chronic heart disease, regular hormonal imbalances, serious circulatory problems;
- use and abrupt cessation of psychotropic drugs, alcoholism, drug use;
- head injury and complications;
- prolonged stress and depression;
- constant presence in a melancholic mood;
- suffered mental disorders in early childhood or as a result of difficult life situations;
- mental illness (paranoia, schizophrenia).
Psychological help
Meta-analyses clearly show that CBT significantly reduces GAD symptoms. A small number of studies have compared the effects of CBT and pharmacotherapy, which have shown approximately the same effect size. Individual and group psychotherapy are equally effective in reducing anxiety, but individual psychotherapy may be more effective in reducing anxiety and depressive symptoms.
Psychotherapy intensity was assessed in a meta-analysis of 25 studies. For reducing anxiety, a course of psychotherapy lasting less than eight sessions is as effective as a course lasting more than eight sessions. In reducing anxiety and depression, more intensive courses are more effective than courses with a small number of sessions. Several studies have shown the benefits of ICBT.
The meta-analysis found no significant difference between the effects of CBT and relaxation therapy. However, more recent research suggests limited effectiveness of relaxation therapy. A large RCT found that balneotherapy, a relaxation therapy with spa treatments, was better than SSRIs in reducing anxiety; however, there are doubts about the validity of the study.
The effectiveness of behavioral psychotherapy based on acceptance, metacognitive psychotherapy, CBT aimed at correcting the perception of uncertainty, mindfulness-based cognitive therapy has been proven.
Psychodynamic psychotherapy can also provide results, but at the moment there is no clear evidence of its effectiveness.
Adding interpersonal and emotional-process therapy to CBT does not provide significant benefits compared to CBT without the addition. A preliminary conversation before starting a CBT course helps reduce resistance to therapy and improve compliance - this strategy is especially useful in severe cases.
Combination of psychotherapy and pharmacological treatment
Few data are available on the use of combinations of psychotherapy and pharmacological treatment. A meta-analysis showed that the combination of pharmacological treatment with CBT was more effective than CBT alone when comparing results immediately after treatment, but not after six months. Data are available from studies comparing the combination of diazepam or buspirone plus CBT with CBT alone. The small number of studies comparing pharmacotherapy with pharmacotherapy plus psychotherapy has produced conflicting results.
There is currently no rationale for combining CBT with pharmacotherapy. But, as with other anxiety disorders, if the patient does not improve with CBT, the use of pharmacotherapy is recommended. Likewise, if pharmacotherapy does not improve, then CBT can be expected to help. Meta-analyses and several RCTs suggest that psychotherapy benefits are maintained 1-3 years after treatment.
Options for the development of generalized anxiety disorder
Many psychotherapists are of the opinion that there are several models of this disorder.
- psychodynamic - when certain stressful situations arise, the body’s defense mechanisms cannot withstand it;
- sociocultural - a person forced to be in unhealthy or dangerous conditions for his physical condition and psyche is more susceptible to anxiety;
- existential model - the reason for the tendency to experience a state of anxiety is a deep-seated fear of life and responsibility;
- humanistic - for one reason or another, a person simply stops accepting himself as he is. This leads to a kind of “self-denial,” which is dangerous with the most undesirable consequences.
Pharmacological treatment
SSRIs, SSRIs, TCAs, benzodiazepines, pregabalin, quetiapine XR have been proven effective in the treatment of GAD.
First line
Antidepressants (SSRIs and SSRIs): RCTs show the effectiveness of escitalopram, sertraline and paroxetine, as well as duloxetine and venlafaxine XR. The effectiveness of SSRIs and SSRIs is the same. There is evidence that escitalopram is less effective than venlafaxine XR or quetiapine XR.
Other antidepressants: There is evidence that agomelatine is as effective as escitalopram.
Pregabalin: Pregabalin is as effective as benzodiazepines (level 1 evidence).
Second line
Benzodiazepines: Alprazolam, bromazepam, diazepam and lorazepam have been shown to be effective (level 1 evidence). Although the level of evidence is high, these drugs are recommended as second-line treatment and usually for short-term use due to side effects, dependence and withdrawal symptoms.
TCAs and other antidepressants: Imipramine is as effective as benzodiazepines in the treatment of GAD (level 1 evidence). But due to side effects and potentially toxic overdose, imipramine is recommended as a second-line treatment. There is little data on bupropion XL, but there is a study in which it was shown to be as effective as escitalopram (first-line agent), so it can be used as a second-line agent.
Vortioxetine, a so-called serotonin modulator, acts on different serotonin receptors. Research on the effectiveness of vortioxetine is inconsistent, but there is evidence to support its use for GAD.
Quetiapine XR: Quetiapine XR has proven efficacy and is equivalent to that of antidepressants. But quetiapine is associated with weight gain, sedation, and a higher rate of treatment discontinuation due to side effects than antidepressants. Because of problems associated with tolerability and safety of atypical antipsychotics, this drug is recommended as a second-line treatment for patients who cannot take antidepressants or benzodiazepines.
Other drugs: Buspirone has been shown to be as effective as benzodiazepines in several RCTs. There is insufficient data to compare buspirone with antidepressants. Due to its lack of effectiveness in clinical practice, buspirone should be classified as a second-line drug.
Hydroxyzine has shown efficacy close to that of benzodiazepines and buspirone, but there is insufficient clinical experience with the use of this drug for GAD.
Third line
Third-line drugs include drugs with poorly studied efficacy, side effects, and rarely used as a primary treatment for GAD.
Additional drugs
The adjunctive strategy has been studied in patients who have not responded adequately to SSRI treatment and may be used in cases of refractory GAD.
Second-line add-on drugs: Pregabalin, as an adjunct to the main drug, has been shown to be effective in treating patients who have not responded to previous treatment (level of evidence: 2).
Third-line add-on drugs: A meta-analysis showed no improvement with atypical antipsychotics as add-on drugs, but did show an increase in treatment failure. Studies of the effectiveness of risperidone and quetiapine as adjunctive agents show conflicting results.
Due to weak evidence of effectiveness, risk of weight gain, and metabolic side effects, atypical antipsychotics should be reserved for refractory cases of GAD and, with the exception of quetiapine XR, used only as an adjunct to the primary drug.
A drug | Level of evidence |
| SSRIs | |
| Escitalopram | 1 |
| Paroxetine | 1 |
| Sertraline | 1 |
| Fluoxetine | 3 |
| Citalopram | 3 |
| SSRI | |
| Duloxetine | 1 |
| Venlafaxine | 1 |
| TCA | |
| Imipramine | 1 |
| Other antidepressants | |
| Agomelatine | 1 |
| Vortioxetine | 1 (conflicting data) |
| Bupropion | 2 |
| Trazadone | 2 |
| Mirtazapine | 3 |
| Benzodiazepines | |
| Alprazolam | 1 |
| Bromazepam | 1 |
| Diazepam | 1 |
| Lorazepam | 1 |
| Anticonvulsants | |
| Pregabalin | 1 |
| Divalproex | 2 |
| Tiagabine | 1 (negative result) |
| Pregabalin as an adjunctive drug | 2 |
| Other drugs | |
| Buspirone | 1 |
| Hydroxyzine | 1 |
| Pexacerfont | 2 (negative result) |
| Propranolol | 2 (negative result) |
| Memantine | 4 (negative result) |
| Pindolol as an additive drug | 2 (negative result) |
| Atypical antipsychotics | |
| Quetiapine | 1 |
| Quetiapine as an add-on drug | 1 (conflicting data) |
| Risperidone as an add-on drug | 1 (conflicting data) |
| Olanzapine as an add-on drug | 2 |
| Aripiprazole as an add-on drug | 3 |
| Ziprasidone as monotherapy or in combination | 2 (negative result) |
| First line: Agomelatine, duloxetine, escitalopram, paroxetine, pregabalin, sertraline, venlafaxine Second line: Alprazolam*, bromazepam*, bupropion, buspirone, diazepam, hydroxyzine, imipramine, lorazepam*, quetiapine*, vortioxetine Third line: Citalopram, divalproex, fluoxetine, mirtazapine, trazodone Additional drugs (second line): Pregabalin Additional drugs (third line): Aripiprazole, olanzapine, quetiapine, risperidone Not recommended as adjunct drugs: Ziprasidone Not recommended: Beta blockers (propranolol), pexacefront, tiagabine *These drugs have their own mechanisms of action, effectiveness and safety profile. Benzodiazepines are best used as second-line drugs in most cases unless there is a risk of abuse; It is better to postpone bupropion XL for later. Quetiapine XR is a good choice in terms of effectiveness, but given the metabolic problems associated with atypical antipsychotics, it is best reserved for patients who cannot be prescribed antidepressants or benzodiazepines. |
Diagnostics
To date, no analysis or test has yet been developed that could accurately confirm an anxiety disorder. Many symptoms are very similar to other diseases. In this case, the patient must additionally undergo a psychiatrist, neurologist and therapist.
The diagnosis of “anxiety disorder” can be established only after collecting all the information regarding a person’s lifestyle, his emotional reactions, interests and hobbies. For this purpose, various psychological questionnaires are provided.
It is important not to confuse this condition with ordinary stress or organic anxiety.
Stress appears as a reaction to an irritating factor, for example, communication with a bad person. As soon as the situation or circumstances change, the stress will disappear. With anxiety, everything is different - it can appear for no reason. A person can communicate with pleasant people and at the same time experience anxiety.
Organic anxiety appears against the background of endocrine and heart diseases, as well as with pathologies of the central nervous system, including traumatic brain injuries. Patients also develop causeless anxiety, a feeling of helplessness, a drop in self-esteem, self-doubt, and fear of the future. A person is unable to concentrate on any things.
Maintenance pharmacological therapy
A meta-analysis showed that long-term use of SSRIs (6–12 months) was effective in preventing relapse (odds ratio for relapse = 0.20).
Relapse after 6-18 months of duloxetine, escitalopram, paroxetine and venlayaxin XR was observed in 10-20% of cases, compared with 40-56% in the control group. Continuing pregabalin and quetiapine XR also prevents relapse after 6-12 months.
Long-term RCTs have shown that escitalopram, paroxetine and venlafaxine XR help maintain benefit over six months.
