Document Title Pharmacological Management of Generalised Anxiety Disorder Document Description Document Type Policy Service Application Trust Wide Version 1.1 Policy Reference no. POL 201 Lead Author(s) This policy was developed by members of the Medicines Management Committee Change History Version Control Version Date Comments 0.1 20/12/2011 Initial document drafted and developed in line with comments from Dudley and Walsall Mental Health Partnership NHS Trusts Medicines Management Committee 1.0 15/02/2012 Policy Agreed for ratification by Policies and Procedures Focus Group and formally ratified by Governance and Quality Committee 15/02/2012 1.1 29/01/2016 Guidance updated and reviewed by MMC. Ratified by Policies and Procedures Group 31/03/2016 Link with National Standards National Health Service Litigation Authority Care Quality Commission National Institute for Health and Clinical Excellence National Patient Safety Agency West Midlands Quality Review Essence of Care Aims Standards Key Dates Day Month Year Ratification Date 31 03 2016 Review Date 31 03 2019 1
Executive Summary Sheet Document Title: Pharmacological Management of Generalised Anxiety Disorder Please tick ( ) as appropriate This is a new document within the Trust This is a revised document within the Trust What is the purpose of this document? To promote evidence based prescribing in the treatment of generalised anxiety disorder What key issues does this document explore? The pharmacological and non-pharmacological treatment of generalised anxiety disorder. Who is this document aimed at? Doctors and non-medical prescibers. What other policies, guidance and directives should this document be read in conjunction with? British National Formulary (BNF) Medicines Management Policy Trust policies and national guidance on the management of violence and aggression Resuscitation Policy Consent to treatment guidance How and when will this document be reviewed? This policy will be subject to review every 2 years. This review will be coordinated by nominated members of the Medicines Management Committee. 2
Document Index Pg 1 Introduction 4 2 Scope 4 3 Roles and Responsibilites 4 4 Support Training 4 5 Prescribing Guidance for Generalised Anxiety Disorder 5 6 References 6 Document Appendices Pg 1 Specialist pharmacological treatment for generalised anxiety 8 disorder 2 Prescribing guidance for generalised anxiety disorder 10 3
1. Introduction 1.1 The prescribing guidance for generalised anxiety disorder is designed to support the treatment of this disorder in primary and secondary care. It is intended to outline what is perceived as best practice and specifies the prescribing responsibilities of clinicians within primary and secondary care. 2. Scope 2.1 The prescribing guidance covers the pharmacological treatment of generalised anxiety disorder including non-pharmacological therapy. 2.2 This policy applies to all Dudley and Walsall Mental Health Partnership NHS Trust staff and is of particular interest in relation to those involved within the management of generalised anxiety disorder within primary and secondary care. 3. Roles and Responsibilities / Duties 3.1 The Chief Pharmacist and Medical director hold overarching responsibility for ensuring the development, management and implementation of a policy regarding the pharmacological treatment of generalised anxiety disorder. 3.2 The Heads of Medicines Management with local CCGs are responsible for the appropriate pharmacological management of generalised anxiety disorder within their relevant organisations. 3.3 Prescribers should ensure that they are aware of the recommendations and adhere to the guidance outlined within this document. Adherence will be monitored by audit and regular review of patient treatment as inpatients. 4. Support Training 4.1 There is no formal training available into the pharmacological management of Generalised Anxiety Disorder. 4.2 This guidance will be disseminated to all Consultants and teams across the organisation. 4
5. Prescribing Guidance for Generalised Anxiety Disorder 5.1 Pharmacological interventions 5.1.1 Most evidence for the efficacy of treatment in GAD is based on short-term trials. The choice of medication can depend on the potential adverse effect profile, the presence of co-existent depressive symptoms and the need for a rapid onset of action. 5.1.2 Benzodiazepines are suitable for short term use only and can be effective within 15-60mins. 5.1.3 NICE recommend that antidepressants should be the only pharmacological intervention used in the long term management of GAD. Antidepressants can take up to 4 weeks to show effectiveness but clinical effectiveness has been noted after as little as 2 weeks. 5.2 n-medical interventions 5.2.1 Psychological therapies (CBT) and self help strategies have been shown to be effective and should be offered to patients instead of pharmacological therapies or with pharmacological therapies where appropriate. There is also limited evidence to suggest that regular exercise can be beneficial (NICE 2011) 5.3 Acute Treatment (up to 4 weeks) should only be used short term in severe disabling and stressful anxiety. longer than 2 4 weeks with regular reviews. Benzodiazepines are effective and rapid in the treatment of GAD. However the benzodiazepines have limited efficacy against co-morbid depressive symptoms. The problems of tolerance, dependence and potential withdrawal symptoms limit the use of the benzodiazepines to short term use (up to 4 weeks). Treatment with a benzodiazepine should be tapered off after 2-4 weeks when the antidepressant becomes effective. 5.4 First Line Pharmacological treatment The SSRIs sertraline - (off license indication, but recommended first line by CKS), citalopram, fluoxetine and paroxetine are recommended as first line treatments. Paroxetine and escitalopram are licensed for the treatment of GAD and have shown efficacy in relapse prevention studies and have demonstrated long-term efficacy with response rates continuing to increase over 6 months of treatment. The current NICE guidance recommends the use of an SSRI in the treatment of GAD acknowledging that not all SSRIs are licensed for this indication. Review patient in first week, counsel patient out initiation of SSRIs e.g. symptoms may get worse initially, may take a few weeks to start showing benefit. If in 2 months, no improvement, titrate to optimum dose or consider switching to another SSRI or SNRI (venlafaxine and duloxetine licensed for GAD) 5.5 Second Line agents: 5
If SSRIs not effective (titrated to optimal dose and switched to alternative SSRI), then consider SNRI (venlafaxine and duloxetine) 5.6 Third Line: If SSRI / SNRI not effective / not tolerated, consider prescribing pregabalin (this should be categorised under specialist treatments and only initiated by a specialist and is not mentioned in NICE guidance). 5.7 Other licensed agents include (Initiation by specialists only): Trazodone, buspirone, hydroxyzine The agents should only be used by specialists for the treatment of GAD. These agents should only be used where patients have failed to respond to first and second line agents or where their use is considered inappropriate. The above agents are not recommended as first or second line agents due to either a lack of efficacy data. Hydroxyzine has been shown in trials to be similar in efficacy to the benzodiazepines without discontinuation symptoms. Hydroxyzine is indicated for short term use only as there is no long term data. Safety information EMA (April 2015), hydroxyzine is associated with a small risk of QT prolongation. The EMA make the following recommendations: Hydroxyzine is contraindicated in patients with a prolonged QT interval Avoid use in the elderly due to increased susceptibility of side effects Consider the risks of QT prolongation and Torsade de Pointes in patients taking medications with lower heart rate or plasma potassium concentration In the elderly the maximum dose used in 50mg The lowest effective dose for the shortest period of time should be prescribed 5.8 Specialist Treatment 5.8.1 Patients may take up to 6 months for remission of symptoms following treatment with pharmacotherapy. If a patient fails to respond to first, or second line agents then, following a review of the diagnosis, alternative agents as listed above should be considered (see specialist pharmacological treatment for generalised anxiety disorder). 5.8.2 Augmentation strategies have limited supporting evidence for use in the treatment of GAD and care should be taken to minimise adverse events when using this approach. 6
6. References See Guidance Baldwin D S, Anderson I M, Nutt D J, et al. Evidenced-based guidelines for the pharmacological treatment of anxiety disorders: recommendations from the British Association for Psychopharmacology. J of Psychopharmacology 2005; 19(6): 567-596. Baldwin D S, Polkinghorn C. Evidence-based pharmacotherapy of generalised anxiety disorder. International J of Neuropsychopharmacology 2005; 8: 293-302. BNF 57, Chapter 4. BMJ Group/RPSGB Publishing. March 2009 Carter N J, McCormack P L. Duloxetine a review of its use in the treatment of generalized anxiety disorder. CNS Drugs 2009; 23 (6):523-541. Clinical Knowledge Summaries (Generalised anxiety disorder). Found at: http://cks.nice.org.uk/generalized-anxiety-disorder accessed 21/01/2016 Feltner D, Crockatt J, Dubovsky S, et al. A randomized, double-blind, placebo-controlled, fixed-dose, multicenter study of pregabalin in patients with generalized anxiety disorder. J Clin Psychopharmacol 2003;23:240 9. Flint A J. Generalised anxiety disorder in elderly patients. Drugs aging 2005; 22(2): 101-114. Fricchione G. Generalized Anxiety Disorder. N Engl J Med 2004; 351:675-82. JOINT FORMULARY COMMITTEE, 2015. British National Formulary. 69. London: BMJ Group and Pharmaceutical Press. Kapczinski F F K, Silva de Lima M, Santos Souza J J S S, et al. Antidepressants for generalised anxiety disorder (review). Cochrane Database Syst Rev 2009. Montgomery S A. Sheehan D V, Meoni P et al. Characterization of the longitudinal course of improvement in generalised anxiety disorder during long-term treatment with Venlafaxine XR. J Psychiatr Res 2002; 36(4): 209-217. NICE (2011) Generalised anxiety disorder and panic disorder (with or without agoraphobia) in adults. Management in primary, secondary and community care (NICE guideline). Clinical guideline 113. National Institute for Health and Care Excellence. Rickels K, Downing R, Schweizer E, et al. Antidepressants for the treatment of generalized anxiety disorder: a placebo-controlled comparison of imipramine, trazodone, and diazepam. Arch Gen Psychiatry 1993;50:884 95. 7
Rickels K, Pollack M H, Feltner D E, et al. Pregabalin for treatment of generalized anxiety disorder: a 4-week, multicenter, double-blind, placebocontrolled trial of pregabalin and alprazolam. Arch Gen Psychiatry 2005;62:1022 30. The Canadian journal of psychiatry. Clinical practice guidelines. Management of anxiety disorders. 2006; 51(suppl 2): 51-55s. 8
Appendix 1 Primary Care - Pharmacological management of generalised anxiety disorder Step 1 Step 2 Step 3 Step 4 Focus of the Intervention All known and suspected Presentations of GAD Diagnosed GAD that has not improved after education and active monitoring in primary care GAD with an inadequate response to step 2 interventions or marked function impairment Complex treatment-refractory GAD and very marked functional impairment, such as self neglect or a high risk of self harm Nature of the Intervention Identification assessment; education; active monitoring. Low intensity psychological interventions; self help, individual guided self help psycho educational groups High intensity psychological intervention (CBT/applied relaxation) Or drug treatment Refer to Specialist Does the patient meet the criteria for a diagnosis of depression? Is immediate pharmacological management necessary? Refer to the Depression Guidance Consider offering: Benzodiazepines do not use for more than 2-4 weeks Sedative antihistamines do not use for more than 4 weeks Pharmacological therapy Before prescribing, consider: age previous treatment response risks of deliberate self-harm or accidental overdose tolerability possible interactions with concomitant medications the patients preference cost Considerations when prescribing a) Offer an SSRI, unless otherwise indicated b) If one SSRI is not suitable or there is no improvement after a 12-week course (including dose titration to optimum dose, and a further medication is appropriate, another SSRI should be offered. c) Inform patients, at the time treatment is initiated, about: - potential side effects (including transient increase in anxiety at the start of treatment) - possible discontinuation/withdrawal symptoms. - delay in onset of effect - time course of treatment - need to take medication as prescribed (this may be particularly important with short half-life medication in order to avoid discontinuation/withdrawal symptoms) d) Written information appropriate for the patient s needs should be made available e) Side effects on initiation may be minimised by starting at a low dose and slowly increasing the dose until a satisfactory therapeutic response is achieved. Long-term treatment and doses at the upper end of the indicated dose range may be necessary ª Paroxetine and escitalopram has a licence for the treatment of generalised anxiety disorder Drug Dose First Line Sertraline initially 50 mg daily, increased after 1 week to 100mg daily; (Unlicensed) if response partial and drug tolerated, increased in steps of 50 mg at least weekly. Max 200 mg daily. Monitoring: Review efficacy and side effects within 2 weeks of starting treatment and again at 4,6 & 12 weeks Review at 8-12 week intervals if drug used for more than 12 weeks Follow Summary of Product Characteristics for all other monitoring required Use short, self-complete questionnaires to monitor outcomes wherever possible Citalopram Patients should be started on 10 mg/day and the dose gradually increased in 10 mg (Unlicensed) steps according to the patient's response up to the recommended dose. The recommended dose is 20-30 mg daily. (Please monitor for QT prolongation in line with recommendations from the MHRA) Fluoxetine 20 mg each morning higher doses on specialist advice only. Paroxetine 20 mg each morning, higher doses on specialist advice only Has there been an improvement after 12 weeks of treatment? E Ongoing management Use with appropriate monitoring for 6 months after optimal dose reached: then dose can be tapered When stopping, reduce the dose gradually over an extended period Review Reassess the patient and consider trying another SSRI 9 Is this at least the second intervention tried? Review and offer referral to specialist mental health services if appropriate
Appendix 2 Specialist Pharmacological Treatment for Generalised Anxiety Disorder Ongoing management Use with appropriate monitoring for 6 months after optimal dose reached: then dose can be tapered When stopping, reduce the dose gradually over an extended period Review diagnosis, if depression is a prominent feature then treat according to depression guidance. Has the patient responded to prior treatment? Ensure that first and second line agents have been tried if suitable for an adequate period of time. If so, then switch to alternative agent. First line agents Sertraline, Citalopram, Fluoxetine and Paroxetine Second line agents Venlafaxine, Duloxetine Third Line agents (under specialist supervision - Pregabalin Fourth line agents (Specialist Only) Trazodone, Buspirone and Hydroxyzine Consider offering: 1a Duloxetine Venlafaxine Escitalopram Does the patient exhibit any depressive symptoms? Monitoring Review efficacy and side effects within 2 weeks of starting treatment and again at 4,6 and 12 weeks Review at 8-12 week intervals if drug used for more than 12 weeks Follow Summary of Product Characteristics for all other monitoring required Use short, self-complete questionnaires to monitor outcomes wherever possible - Consider offering: 1b Pregabalin* If using an agent from 1a consider use of an agent from 1b or under fourth line agents Has there been an improvement after 12 weeks of treatment? Ongoing management Use with appropriate monitoring for 6 months after optimal dose reached: Continue to review treatment. Pharmacotherapy should be used in conjunction with CBT where appropriate. Duloxetine should be offered in preference to trazadone due to greater likelihood of patient tolerability. If a patient fails to respond to treatment from 1a consideration should be given to treatment from 1b, or visa versa. If the patient fails to respond fully to either agent consideration should be given to augmentation therapy. # Buspirone should be used in preference to pregabalin due to greater long term data and lower acquisition cost. * Pregabalin should be used by Consultant Psychiatrists only and we would not routinely support its initiation by General Practitioners. Unlicensed Use: Atypical antipsychotics olanzapine and risperidone may be effective adjunctive agents for patients who are refractory to other therapies. However due to the risk of weight gain and metabolic side effects, their use should be reserved for treatment refractory cases. 10