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An overview of the most effective treatment for anxiety disorders

GAD SAD - 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 PDA - The addition of lithium to clomipramine and the combination of valproate and clonazepam have been reported to be effective in refractory cases GAD, generalized anxiety disorder; PDA, panic disorder with agoraphobia; RCT, randomized controlled trial; SAD, social anxiety disorder also known as social phobia ; SNRI, selective serotonin norepinephrine reuptake inhibitors; SSRI, selective serotonin reuptake inhibitors; TCA, tricyclic antidepressant.

Patients should be informed that the onset of the anxiolytic effect of these antidepressants has a latency of 2 to 4 weeks in some cases up to 6 weeks. During the first 2 weeks, adverse effects may be stronger.

Initial jitteriness or an increase in anxiety symptoms may occur, which may reduce the patients' treatment compliance. Lowering the starting dose of the antidepressants may reduce these adverse effects. However, these are much less frequent and severe than the withdrawal reactions observed after terminating benzodiazepine treatment. These adverse reactions may be more frequent with paroxetine than with sertraline or fluoxetine.

The drug has sedating properties. Onset of efficacy is earlier with pregabalin than with antidepressants.

  • The assessment included the treatment of children, adolescents and adults with;
  • These therapies can teach you how to control your anxiety levels, stop worrisome thoughts, and conquer your fears;
  • As noted above, anxiety disorders often co-occur with other disorders that produce symptoms similar to anxiety;
  • Engaging people suffering from anxiety in social, creative, or other activities they find interesting can be very helpful;
  • Professionals working in primary healthcare settings are likely to come into contact with older adults suffering with anxiety disorders.

Pregabalin is not subject to hepatic metabolism and hence does not interact with inhibitors or inducers of cytochrome P450 enzymes. However, there have been concerns about the abuse of pregabalin in individuals suffering from substance abuse and also withdrawal syndromes after abrupt discontinuation.

Thus, these drugs should be tried first before TCAs are used. The dosage should be uptitrated slowly until dosage levels reach those used in the treatment of depression. TCAs should be used with caution in patients considered to be at risk of suicide, due to their potential fatal toxicity after overdose. In contrast to antidepressants, benzodiazepines do not lead to initially increased jitteriness and insomnia. Cognitive functions may be impaired, mainly in elderly patients.

After longterm treatment with benzodiazepines eg, over 4 to 8 monthsdependency may occur in some patients, 41 - 47 especially in patients predisposed for substance abuse.

Current guidelines do not recommend benzodiazepines as first-line treatments. However, patients with a history of benzodiazepine or other substance abuse should be excluded from treatment. In that case, lorazepam melting tablets at a dose of 1.

Current Diagnosis and Treatment of Anxiety Disorders

It is usually sufficient to talk calmly with the patient and explain that the attack is not due to a life-threatening medical condition. Moclobemide Moclobemide is a selective and reversible inhibitor of monoamine oxidase A. It is used in the treatment of SAD. Because not all studies have shown evidence for superiority to placebo, the drug is not recommended as first-line treatment.

Other drugs Some other drugs have shown efficacy in anxiety disorders in randomized controlled studies but are not licensed for the treatment of these disorders in most countries. Medicolegal issues have to be considered whenever drugs that have not been approved for anxiety indications are prescribed off label. Agomelatine The antidepressant agomelatine—which acts as an agonist for melatonin MT1 and MT2 receptors and as an antagonist for serotonin 5-HT2C receptors—was shown to be effective in four studies in GAD.

However, probably due to adverse effects such as the metabolic syndrome, the drug was not licensed for anxiety disorders in most countries. In general, typical adverse events, such as sedation or weight gain, were less frequent in patients receiving lower doses.

INTRODUCTION

The onset of efficacy is earlier than with antidepressants. Vortioxetine A new antidepressant, vortioxetine, was investigated in several controlled studies in GAD. However, according to a meta-analysis, significant improvement for vortioxetine could not be demonstrated compared with placebo. The comparison studies only used low doses of the comparators, eg, 20 mg paroxetine per day 66 or one tablet of lorazepam 0.

Studies with Kava-kava Piper methysticum showed inconsistent results, 70 - 72 and the extract was been withdrawn from the market in some countries due to hepatotoxicity in some preparations. Valerian extract was not effective in placebo-controlled studies in anxious patients. Due to the low quality of these studies, the evidence for the investigated products is not sufficient for a review, see Sards et al 75.

Standardization may be an issue in herbal preparations. For example, it was shown that different preparations of St. John's wort exhibited large differences in the content of the putatively effective ingredients. We simply looked at the absolute difference in anxiety scale scores before and after treatment, without regard to the relative efficacy compared with placebo.

This approach makes it possible to include hundreds of studies in comparisons of differential efficacy of all available drugs and not only the few direct head-to-head comparisons. From the patients' point of view, the improvement in anxiety symptoms as measured by the change from baseline to end point is more relevant than the difference from a control group.

The available medications for anxiety disorders showed considerably large differences in pre-post effect sizes.

Treatment of Anxiety Disorders: A Systematic Review [Internet].

Quetiapine, however, is not licensed for the treatment of any anxiety disorder in most countries. However, these drugs are not recommended for routine treatment. General treatment principles Patients must be informed about possible adverse effects, interactions, safety warnings, and an overview of the most effective treatment for anxiety disorders, as indicated in the current summary of product characteristics.

If patients are educated about the possibility that some early side effects might later decrease in intensity, compliance may improve. Patients with anxiety disorders are often hesitant to take psychotropic drugs because they are afraid of adverse effects.

In particular, patients with PDA may easily discontinue antidepressants because of initial jitteriness and nervousness. Doses for drug treatments are shown in Table II. In patients with severe hepatic impairment, a dosage adjustment or use of medications that are cleared primarily by the kidney eg, pregabalin may be required. For all drugs recommended in this article, relapse prevention studies in at least one anxiety disorder have been conducted in patients who have responded to previous open treatment with a certain drug and were then randomized to placebo or ongoing blind treatment with the same drug for periods of between 6 and 18 months.

All of these studies showed a significant advantage for staying on active medication when compared with switching to placebo. Based on the findings from these relapse prevention studies and clinical experiences, drug treatment should be continued for 12 months or more after remission has occurred. Given the chronic course of anxiety disorders, it is regrettable that there are almost no controlled studies that investigate treatment periods over 12 months.

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To avoid withdrawal syndromes, the dose should be slowly tapered off over a period of 2 weeks at treatment termination. It is a common opinion that patients treated with drugs show immediate relapse after stopping medication, whereas gains of psychological therapies are maintained for months or years after treatment termination.

This would offer psychological therapies considerable advantage over drug treatment. However, in naturalistic studies following up anxiety patients, substantial relapse rates were also found years after CBT treatment. Additive CNS depression may occur when drugs with sedating properties are combined, eg, TCAs, benzodiazepines, or pregabalin, resulting in unwanted sedation, drowsiness, or increased reaction time.

Additive effects at the neurotransmitter level can occur when medications are combined that have antagonistic effects on the same receptors, eg, two drugs with anticholinergic effects. Unresponsiveness to standard treatments Before considering a patient to be treatment unresponsive, it should be ascertained that the diagnosis was correct, adherence to the treatment plan was sufficient, the dose prescribed had covered the full range, and there had been a trial period of adequate duration.

Treatment of anxiety disorders

When patients report previous treatment failures, it often turns out that a drug was only prescribed in the lowest dose or was stopped within the first 2 weeks due to side effects that occurred in the initial phase before the patient could experience improvement. Concurrent drugs may interfere with efficacy, eg, metabolic inhibitors or enhancers.

Psychosocial factors may affect response, and comorbid personality or substance abuse disorders are especially likely to complicate anxiety disorders. When initial treatment fails, the physician has to decide when to change the treatment plan.

There have been few systematic trials of treatment-refractory patients with anxiety disorders. If after treatment at what is considered an adequate dose for 4 to 6 weeks a patient shows no response, the medication should be changed.

If partial response is seen after this period, there is still a chance that the patient will respond after another 4 to 6 weeks of therapy with increased dosages. For some antidepressants, the studies on a potential dose-response relationship are inconclusive, perhaps due to the lack of statistical power for showing a difference between lower and higher doses.

According to clinical experience, however, a trial with a higher dose in patients with insufficient response is warranted.

Identifying and Treating Anxiety Disorders

Elderly patients may take longer to show a response. Table III contains options in case of drug inefficacy or intolerance.

In patients who are unresponsive to psychotropic drugs, the addition of CBT is generally recommended. When all standard treatments have failed, the off-label use of drugs may be considered, for example, drugs licensed for another anxiety disorder or that are not licensed but have shown efficacy in clinical studies. Such drugs include quetiapine and agomelatine.

Therefore, only a few studies for the treatment of GAD have been performed with older patients. Controlled studies have shown the efficacy of duloxetine, venlafaxine, pregabalin, and quetiapine in patients over 65 years old. In the elderly, effect sizes for CBT tend to be somewhat smaller than those found in mixed-age populations.

There are some randomized, placebo-controlled studies of pharmacotherapy for anxiety disorders in children and adolescents showing efficacy of sertraline, fluoxetine, and duloxetine in young patients with GAD, of venlafaxine and paroxetine in SAD, and of sertraline, fluvoxamine, and fluoxetine in mixed samples, including patients with separation anxiety disorder, GAD, and SAD. There is also a paucity of treatment studies for children with selective mutism.

Small studies have shown that psychotherapeutic approaches were at least better than waitlist controls. A large study suggested no substantial increase in the risk of cardiac malformations attributable to antidepressant use during the first trimester. In such cases, CBT should be considered as an alternative to medication treatment. Psychotherapy All patients with anxiety disorders require supportive talks and attention to the emotional problems that are associated with the anxiety disorder.

  1. Based on the findings from these relapse prevention studies and clinical experiences, drug treatment should be continued for 12 months or more after remission has occurred.
  2. The onset of efficacy is earlier than with antidepressants.
  3. Drive to the airport.

Psychoeducation includes information about the physiology of the bodily symptoms of anxiety reactions and the rationale of available treatment possibilities. Many patients may require formal psychological treatment interventions, which are mostly done on an outpatient basis. The treatment of anxiety disorders by CBT is described in more detail in the article by Borza in this issue of Dialogues in Clinical Neuroscience p 203. The efficacy of CBT for all anxiety disorders has been shown in a large number of controlled studies.

If avoidance of feared situations is a relevant factor in phobic disorders, exposure techniques should be included in the treatment schedule, in which patients are confronted with their feared situations.

In comparison with CBT the evidence for psychodynamic therapy is weaker. For specific phobias, there are only studies with behavioral therapy, which should be performed as exposure treatment. In the available treatment studies, it was shown that only a few sessions eg, one to five were necessary for effective treatment of specific phobias. In recent years, many studies have investigated psychological therapies that are performed via the Internet, usually involving minimal or no contact with a therapist.

However, at present, evidence is lacking that these treatments are as effective as individual CBT with face-to-face contact. They are also less expensive than face-to-face psychotherapies.

Combining psychotherapy and medication Both psychotherapy and pharmacotherapy have been shown to be more effective than control groups. Therefore, our research group conducted a large meta-analysis of all available controlled short-term studies for anxiety disorders and compared the pre-post effect size differences before and after treatment between medications and psychotherapies. It was also found that patients included in psychotherapy studies were less severely ill than those recruited for medication trials.