Generalised anxiety disorder

Background of generalised anxiety disorder- GAD is a common disorder
prevalence amongst adults in England is thought to be 4.4 %
Recent Lancet paper mentions lifetime prevalence of about 5.7 % The central feature is excessive worry about a number of different events associated with heightened tension Often chronic if untreated and associated with substantial disability Can be difficult to diagnose as the key symptom -excessive persistent worry might not be well recognised and not well articulated by the patient ie GAD may be under-recognised GAD – one of a range of disorders that includes
○ Panic disorder ( with or without agoraphobia )
○ Social phobias
○ Acute stress disorder GAD can exist in isolation but more commonly occurs with other anxiety and depressive disorders

DSM 5 diagnostic criteria –Excessive anxiety and worry ( apprehensive expectation ) , occurring more days than not for atleast 6 months , about a number of events or activities ( such as work or school performance ) The individual finds it difficult to control the worry The anxiety and worry are associated with three ( or more ) of the following six symptoms ( with at-least some symptoms having been present for more days than not for the past 6 months )
only 1 item is required in children
○ restlessness , feeling keyed or on the edge
○ being easily fatigued
○ difficulty concentrating or mind going blank
○ irritability
○ muscle tension
○ sleep disturbance ( difficulty falling or staying asleep , or restlessness , unsatisfying sleep ) The anxiety , worry or physical symptoms cause clinically significant distress or impairment in social , occupational or other important areas of functioning The disturbance is not attributable to the physiological effects of a substance ( eg a drug abuse , a medication ) or another medical condition ( eg hyperthyroidism ) The disturbance is not better explained by another medical condition

Identify and communicate the diagnosis of GAD as early as possible Consider the diagnosis in
○ people presenting with anxiety or significant worry and
○ in people who attend primary care frequently and
 ♦ have a chronic physical health problem or
 ♦ do not have a physical health problem but are seeking reassurance about somatic ( particularly older people from minority ethnic groups ) or
 ♦ are repeatedly worrying about a wide range of issues

Conduct a comprehensive assessment that does not rely solely on the number , severity and duration of symptoms but also consider the degree of distress and functional impairment Consider factors which may affect the development, course and severity of GAD as
○ comorbid depressive disorder or other anxiety disorder
○ comorbid substance misuse
○ comorbid medical condition
○ h/o mental health disorders
○ past experience of an response to treatments

step 1 interventions- Comorbid depressive or other anxiety disorder
Treat the primary disorder first
( ie the more severe one and in which it is more likely that treatment would improve overall functioning )
 Substance misuse 
○ substance misuse can be a complication of GAD
○ non-harmful substance use should not be a contraindication to the treatment of GAD
○ harmful and dependent substance misuse should be treated first as this may lead to significant improvement in symptoms of GAD
 Following assessment and diagnosis 
○ provide education , treatment options , written information
○ monitor symptoms and functioning ( active monitoring )

 Discuss use of OTC medications – eg potential for interactions with prescribed medications and lack of evidence to support safe use of OTC medications

Step 2 interventions Low intensity psychological interventions  -individual non facilitated self help-written and electronic material be based on treatment principles of CBT instructions to work systematically through the materials over a period of 6 weeks usually minimal therapist contact , for eh an occasional telephone call of no more than 5 mins

individual self help guide –written and electronic material support by a trained practitioner who facilitates the programme and reviews progress and outcome usually 5-7 weekly or fortnightly F2F or tel sessions of 20-30 mins

pyshoeducational groups –based on CBT principles with an interactive design and encourage observational learning presentations and self-help manuals conducted by trained practitioners one therapist for about 12 participants usually 6 weekly sessions of 2 hrs each

Step 3 interventions- High intensity psychological intervention or drug treatment. CBT or Applied relaxation consist of 12-15 weekly sessions lasting 1 hr each ( No of sessions can be less or more ) Drug treatment – SSRI- first line and agent of choice is sertraline
Monitor carefully for adverse reactions
 If sertraline ineffective- try an alternative SSRI or a SNRI
Consider the following when making the choice
○ chance of withdrawal syndrome ( particularly with paroxetine and venlafaxine )
○ SE profile and interactions
○ risk of suicide and toxicity in OD ( particularly with venlafaxine )
○ h/o previous trials with individual drugs
 If SSRI/ SNRI not tolerated consider Pregabalin ( thirdline )
 Guideline advocates not to offer benzodiazepines in 1° or 2° care except as a short term measure during crises
 Do not offer anti-psyhcotics in primary care for GAD

managing risks and side effects- Risk of bleeding with SSRIs – undertake a risk assessment and provide a gastroprotective drug if needed People less than 30 who take SSRI or an SNRI
○ warn ↑ ed risk of suicidal thinking and self harm in a minority of people under 30 and
○ review them within 1 week of first prescribing and
○ monitor the risk of suicidal thinking and self-harm weekly for the first month If people develop SEs- reassure and
○ monitor symptoms closely or
○ reduce the dose or
○ stop and provide an alternative or
○ high intensity psychological intervention First 3 months – review every 2-4 weeks
Every 3 months after that If drug effective advice to continue for atleast 1 year as high risk of relapse 

inadequate reponse to step 3 –If full course of high intensity psychological intervention is not effective- offer drug treatment
 If no response to drug treatment – offer high intensity psychological intervention or an alternative drug treatment
 If partial response to drug treatment drug treatment consider high intensity psychological intervention in addition to drug treatment

Referral –GAD with severe anxiety and marked functional impairment in conjunction with a risk of self-harm or suicide or significant co-morbidity , such as 
○ substance misuse
○ personality disorder or
○ complex physical health problems or self-neglect or an inadequate response to step 3 interventions

Step 4 interventions are for secondary care- for Complex , treatment refractory GAD and very marked functional impairment or high risk of self-harm

A recent large systematic review and network meta-analysis on RCTs in adult outpatients with GAD (Ref 5) has drawn some useful conclusions on pharmacological management of GAD

Duloxetine , pregabalin , venlafaxine and escitalopram were more efficacious than placebo with relatively good acceptability The study concludes that Mirtazepine , sertraline , fluoxetine , buspirone and agomelatine were also efficacious and well tolerated but the findings were limited due to small sample size Quetiapine -largest reduction in anxiety symptoms but poor tolerability in comparison to placebo ( NICE guideline advice not to use anti-psychotics in 1° care ) Benzodiazepines – risk of potentially fatal interactions with alcohol and opioids , addiction and dependence risk and poor acceptability limits use in practice Paroxetine also effective but poorly tolerated

This paper is of significant importance as it is currently the largest review of pharmacological agents for treatment of GAD by use of network analysis. Like most studies it has its limitations for eg the trials included in the network meta-analysis were done across a broad range of settings

References Generalised anxiety disorder and panic disorder in adults : management Clinical guideline 113 Published January 2011 Management of generalised anxiety disorder in adults : summary of NICE guidance Quick reference guide Generalised anxiety disorder and panic disorder ( with or without agoraphobia ) in adults NICE January 2011 CG 113 Generalized anxiety disorder CKS NHS October 2017 Pharmacological treatments for generalised anxiety disorder : a systematic review and network meta-analysis April Slee MS et al Lancet , The , 2019-02-23 , Volume 393 , Issue 10173 , Pages 768-777 Diagnostic and Statistical Manual of Mental Disorders , Fifth Edition American Psychiatric Association.