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Clinical guidelines

Prescribing drugs of dependence in general practice, Part B
Benzodiazepines

2.3 Anxiety disorders

 Key points

  • Anxiety disorders are common and exist as a spectrum of conditions that vary from mild to severe.
  • Comprehensive clinical assessment is the first step in management. Effective management requires obtaining a diagnosis, and recognising that patients may not present with a single disorder (eg patients may experience generalised anxiety, panic disorder as well as depression).
  • Where treatment is indicated:
    • First-line therapy for generalised anxiety disorder (GAD), panic disorder, and panic attacks should include CBT (due to its effectiveness at reducing the symptoms of anxiety in the short and long term.
    • SSRI and SNRI medications are effective across the range of anxiety disorders and generally suitable for first-line pharmacological treatment of anxiety.
    • Short-term benzodiazepines as occasional adjunctive therapy may be effective at reducing worsening of symptoms that can occur in the first days to weeks of initiating antidepressant medication, and therefore aid adherence
    • Benzodiazepine use in anxiety disorders is mostly limited to severe or treatment-resistant cases.
    • Patients who use two or more psychoactive drugs in combination (polydrug use) may be more vulnerable to major harms.

 

Evidence statements

Grade

Rec 6

Cognitive behavioural therapy is recommended as one of the treatments of choice for generalised anxiety disorder, panic disorder, and panic attacks due to its effectiveness at reducing the symptoms of anxiety in the short and long term, although patient preference must be taken into consideration.64

A

Rec 7

Consider an selective serotonin reuptake inhibitor (SSRI) for first-line drug treatment, as SSRIs are effective across the anxiety and related disorders, in short and long term, and are generally well tolerated.128

A

Rec 8

Benzodiazepines have evidence of benefit in generalised anxiety disorder, social anxiety disorder and panic disorder, but not obsessive compulsive disorder or post-traumatic stress disorder.94

A/B

To see the original source of the recommendations and grading, as well as supporting sources, click on the recommendation number in the left column.

2.3.1 Background

Anxiety disorders include GAD, panic disorder, OCD, PTSD, phobias and SAD.

In 2007, anxiety disorders were the most common self-reported mental disorder in Australia, affecting 14% of people aged 16–85 years.129 Anxiety disorders may be prominent in depressive conditions and other chronic health diseases. Anxiety and related disorders often become chronic.

Not all patients with anxiety symptoms require treatment. Anxiety symptoms exist on a continuum and many people with milder degrees of anxiety, particularly recent onset and association with stressful situations will recover without intervention.89 The need for treatment is determined by the severity and persistence of symptoms, the presence of comorbid mental or physical illness, the level of disability and the impact on social functioning. Treatment should aim to achieve full remission of symptoms and return of function, rather than just symptom improvement and distress reduction.130

Randomised controlled trials across a range of anxiety disorders often demonstrate a high placebo response, which indicates that non-specific effects can play a large part in improvement.128

Approaching anxiety disorders systematically involves identifying and treating any comorbidities, providing patient education and appropriate psychological and pharmacological interventions. These should be evidence-based and patients should receive ongoing monitoring to determine whether treatment aims are being achieved.130

2.3.2 Management of anxiety in general practice

For a comprehensive review of management of anxiety disorders, GPs are advised to review individual clinical guidelines.

Benzodiazepine use in anxiety disorders is mostly limited to severe, or treatment-resistant, cases. Patients with a history of significant mental illness who use two or more psychoactive drugs (polydrug use) may be more vulnerable to major harms. Significant caution should be taken if prescribing benzodiazepines to patients with comorbid alcohol or SUDs, or polydrug use. GPs should consider seeking specialist opinion in the management of these patients.

2.3.2.1 Assessment and diagnosis

Comprehensive clinical assessment is the first step to developing a diagnosis and determining the patient’s level of disability. In milder, recent onset anxiety disorders, consider ‘watchful waiting’ (support, addressing social factors and monitoring).89

It is important to detect comorbid depression. Depression should be treated if depressive symptoms are moderate or severe.

Most guidelines recommend CBT as first-line non-drug therapy, while SSRIs and SNRIs are the drugs of first choice. Benzodiazepine recommendations are generally limited to severe or treatment-resistant cases. However, the efficacy of psychological and pharmacological approaches is similar in the acute treatment of mild to moderate anxiety disorders.89,94,131

The selection of an initial treatment modality should be guided by considerations including the patient’s needs and preferences, the risks and benefits for the patient, the patient’s past treatment history, the presence of comorbid general medical and other psychiatric conditions, cost and the local availability of evidence-based psychological interventions.

Where appropriate and available, patients should be offered a choice of evidence-based treatment approaches.

2.3.2.2 Cognitive behavioural therapy

All major guidelines recommend CBT as the first-line intervention for anxiety disorders.64,89,94,130

CBT is a multimodal intervention. Specific techniques used in the therapy include education, self-monitoring, relaxation training, cognitive restructuring, exposure to imagery and anxiety-producing situations, and relapse prevention. CBT has been shown to be an effective stand-alone treatment for GAD.132 Comorbidity does not decrease the treatment effects of CBT.

CBT for most anxiety, and related disorders, can be delivered effectively in individual or group therapy formats.130 There are also an increasing number of self-directed formats that require minimal or no therapist contact, which have been shown to be effective.130 These include bibliotherapy (self-help books) and internet or computer-based programs.133,134

A combination of medication and cognitive behaviour or exposure therapy has been shown to be a clinically desired treatment strategy.94 However, combination therapy results have been conflicting,135,136 and results vary for different anxiety disorders. While current evidence does not support the routine combination of CBT and pharmacotherapy as initial treatment for all anxiety disorders, there is support for combined use in panic disorders, with or without agoraphobia.137,138

Benzodiazepines are generally avoided in patients with anxiety disorders who are undergoing CBT. This is due to their potential interference with motivation and learning, which are required for CBT to be effective. Some authors are now challenging this,73 however there is sparse trial evidence to support a conclusion. More research is needed to ascertain if these treatment modalities can be combined effectively.

CBT protocols for anxiety usually involve 10–14 weekly sessions, but briefer strategies of 6–7 sessions have been shown to be as effective. Unfortunately, a lack of access to trained clinicians may be an issue in some areas and therefore lead to the majority of patients with anxiety being treated with medications.139 Online CBT programs have shown efficacy, and may be suitable for patients who cannot access face-to-face therapy, or who prefer treatment in their own homes, in their own time.

2.3.2.3 Antidepressants

Note that anxiety disorders show a strong placebo response, especially at mild to moderate levels of symptom severity.89 If pharmacotherapy is indicated, the SSRIs and SNRIs are preferred agents.140 Tricylic antidepressants (TCAs) and monoamine oxidase inhibitors (MOAI) are other alternatives.

Although preferred over benzodiazepines, there are limited studies comparing head-to-head effectiveness with antidepressants. Reviews of the studies performed suggest comparative effectiveness of benzodiazepines to older and new antidepressants.141–142

In trials of benzodiazepines and newer antidepressants, benzodiazepines have demonstrated comparable or greater improvements with fewer adverse events in patients suffering from GAD or panic disorder.141 Efficacy of benzodiazepines for panic disorder is comparable to SSRIs, SNRIs and TCAs.143 Similarly, the incidence of withdrawal symptoms from antidepressants seems to occur at similar levels to benzodiazepines.96

Reviewers have suggested the major change in prescribing pattern from benzodiazepines to newer antidepressants in anxiety disorders has occurred in the absence of comparative data of high-level of proof.141,144

However, SSRIs and SNRIs remain recommended first-line treatments by international guidelines for anxiety disorders.143

Short-term benzodiazepines as occasional adjunctive therapy may be effective at reducing worsening of symptoms that can occur in the first days to weeks of initiating antidepressant medication.

2.3.2.4 Benzodiazepines

Benzodiazepines are not indicated for ‘mild’ anxiety.

Benzodiazepines may be used (as monotherapy or in combination with antidepressants) for patients with very distressing or impairing symptoms whom rapid symptom control is critical.143

Benzodiazepines have evidence of benefit for GAD, social anxiety disorder and panic disorder, but not for OCD or PTSD.64,94 Trials have been conducted with clonazepam, diazepam and lorazepam, which have demonstrated the efficacy of these compounds in managing panic disorder clonazepam for SAD, diazepam and bromazepam for GAD.3

The benefit of a more rapid response to benzodiazepines must be balanced against the possibilities of troublesome side effects (eg sedation) and physiological dependence that may lead to difficulty discontinuing the medication.143 Note that:

  • Due to its rapid onset and offset of action, alprazolam is the benzodiazepine most commonly prescribed for panic disorders. However, in a meta-analysis, it has not been shown to have better efficacy than other benzodiazepines for panic disorders, and it does have a greater risk of dependence, problematic use and withdrawal.145
  • Although tolerance is less of an issue with anxiety, patients are at risk of dependence and other harms (eg depression, increased anxiety, accidents).

When benzodiazepines are prescribed short term for severe anxiety, they are generally used in conjunction with other interventions including counselling or antidepressants (where appropriate), to reduce the risk of symptom recurrence89 or to alleviate and prevent the worsening of anxiety130 that may occur at the start of antidepressant therapy.146

Rarely, ongoing therapy with benzodiazepines may be necessary in patients with severe, treatment-resistant anxiety. Although concerns have surrounded the risks of tolerance and SUD with long-term use of benzodiazepines, there is little evidence of tolerance to their anxiolytic effects.35 Problematic use is a risk in those with a history of SUD, but is otherwise uncommon.147

The decision to treat chronic anxiety with benzodiazepines must weigh the risks and benefits of benzodiazepine therapy. Concerns about potential problems in long-term use should not prevent their use in patients with persistent, severe, distressing and impairing anxiety symptoms,147 or in patients who are resistant to, or cannot tolerate, multiple first-line therapies.130 Ongoing supervision is required.

2.3.3 Resources

References

  1. Dell’osso B, Lader M. Do benzodiazepines still deserve a major role in the treatment of psychiatric disorders? A critical reappraisal. Eur Psychiatry 2013;28(1):7–20.
  2. Therapeutic Guidelines. eTG complete [internet.] Melbourne: Therapeutic Guidelines Limited; 2013 [Accessed 26 Decemeber 2013].
  3. Guideline Working Group for the Treatment of Patients with Anxiety Disorders in Primary Care. Clinical Practice Guideline for Treatment of Patients with Anxiety Disorders in Primary Care. UETS no 2006/10 ed. Madrid: National Plan for the NHS of the MSC. Health Technology Assessment Unit; 2008.
  4. Baldwin DS, Anderson IM, Nutt DJ, et al. Evidence-based guidelines for the pharmacological treatment of anxiety disorders: Recommendations from the British Association for Psychopharmacology. J Psychopharmacol 2005;19(6):567–96.
  5. Bandelow B, Sher L, Bunevicius R, et al. Guidelines for the pharmacological treatment of anxiety disorders, obsessive-compulsive disorder and posttraumatic stress disorder in primary care. Int J Psychiatry Clin Pract 2012;16(2):77–84.
  6. Baldwin DS, Anderson IM, Nutt DJ, et al. Evidence-based pharmacological treatment of anxiety disorders, post-traumatic stress disorder and obsessive-compulsive disorder: a revision of the 2005 guidelines from the British Association for Psychopharmacology. J Psychopharmacol 2014;28(5):403–39.
  7. Mental Health: Australian Bureau of Statistics; 2010 [updated 13 November 2013]. Available at www.abs.gov.au/ ausstats/ abs@.nsf/ Lookup/ by%20Subject/ 1370.0~2010~Chapter~Mental%20health%20(4.1.6.7) [Accessed 27 December 2013].
  8. Canadian Agency for Drugs and Technologies in Health. Short- and Long-Term Use of Benzodiazepines in Patients with Generalized Anxiety Disorder: A Review of Guidelines. Ottawa: CADTH; 2014.
  9. National Collaborating Centre for Mental Health. Generalised anxiety disorder and panic disorder (with or without agoraphobia) in adults: management in primary, secondary and community care. National Institute for Health and Care Excellence clinical guideline 113. London: NICE; 2011.
  10. Bystritsky A, Khalsa SS, Cameron ME, Schiffman J. Current diagnosis and treatment of anxiety disorders. P T 2013;38(1):30–57.
  11. The Royal Australian College of General Practitioners. Depression and anxiety: Internet based or computerised CBT (iCBT or CCBT). Melbourne: RACGP; 2014. Available at www.racgp.org.au/ your-practice/ guidelines/ handi/ interventions/ mental-health/ internet-based-or-computerised-cbt-for-depression-and-anxiety [Accessed 4 October 2014].
  12. The Royal Australian college of General Practitioners. Bibliotherapy: Depression. Melbourne: RACGP; 2014. Available at www.racgp.org.au/ your-practice/ guidelines/ handi/ interventions/ mental-health/ bibliotherapy-for-depression [Accessed 4 October 2014].
  13. Bandelow B, Seidler-Brandler U, Becker A, Wedekind D, Ruther E. Meta-analysis of randomized controlled comparisons of psychopharmacological and psychological treatments for anxiety disorders. World J Biol Psychiatry 2007;8(3):175–87.
  14. Hofmann SG, Sawyer AT, Korte KJ, Smits JA. Is it Beneficial to Add Pharmacotherapy to Cognitive-Behavioral Therapy when Treating Anxiety Disorders? A Meta-Analytic Review. Int J Cogn Ther 2009;2(2):160–75.
  15. Furukawa TA, Watanabe N, Churchill R. Psychotherapy plus antidepressant for panic disorder with or without agoraphobia: Systematic review. Br J Psychiatry 2006;188:305–12.
  16. Furukawa TA, Watanabe N, Churchill R. Combined psychotherapy plus antidepressants for panic disorder with or without agoraphobia. Cochrane Database Syst Rev 2007(1):CD004364.
  17. Tyrer P, Baldwin D. Generalised anxiety disorder. Lancet 2006;368(9553):2156–66.
  18. Bystritsky A. Pharmacotherapy for generalized anxiety disorder [internet]. Waltham, MA: UpToDate; 2013. Available at www.uptodate.com/ contents/ pharmacotherapy-for-generalized-anxiety-disorder [Accessed April 2015].
  19. Berney P, Halperin D, Tango R, Daeniker-Dayer I, Schulz P. A major change of prescribing pattern in absence of adequate evidence: Benzodiazepines versus newer antidepressants in anxiety disorders. Psychopharmacol Bull 2008;41(3):39–47.
  20. Bandelow B, Reitt M, Röver C, Michaelis S, Görlich Y, Wedekind D. Efficacy of treatments for anxiety disorders: a meta-analysis. Int Clin Psychopharmacol. 2015 Apr 29; Epub 2015 Apr 29.
  21. American Psychiatric Association. Practice guideline for the treatment of patients with panic disorder. 2nd edn. Arlington VA: American Psychiatric Publishing, Inc; 2009.
  22. Offidani E, Guidi J, Tomba E, Fava GA. Efficacy and tolerability of benzodiazepines versus antidepressants in anxiety disorders: A systematic review and meta-analysis. Psychother Psychosom 2013;82(6):355–62.
  23. Moylan S, Staples J, Ward SA, et al. The efficacy and safety of alprazolam versus other benzodiazepines in the treatment of panic disorder. J Clin Psychopharmacol 2011;31(5):647–52.
  24. Bostwick JR, Casher MI, Yasugi S. Benzodiazepines: A versatile clinical tool. Curr Psychiatr 2012;11(4).
  25. Nutt DJ. Overview of diagnosis and drug treatments of anxiety disorders. CNS Spectr 2005;10(1):49–56.
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