CPD 15: ANXIETY DISORDERS

Types of anxiety disorders

1. Generalised anxiety disorder (GAD)

Generalised anxiety disorder is characterized by persistent anxiety symptoms that are not triggered by any particular event or situation(3). It is sometimes described as “free floating” anxiety. The patient experiences the physical and psychological symptoms of anxiety which can be disabling due to their chronic, unremitting time course. GAD affects up to 5% of the population and accounts for around 30% of psychiatric consultations in general practice.

2. Phobic anxiety disorders

Patients with phobic anxiety disorders experience the same symptoms as someone with generalized anxiety, but they only show symptoms in response to particular circumstances (3). This could be a certain situation (eg a crowded place), an object (eg spiders) or a natural phenomenon (eg thunderstorms). Clinically phobic anxiety disorders are split into three subtypes; Specific phobia, social phobia and agoraphobia.

2a. Specific phobias

If a patient has a specific phobia, they are inappropriately anxious if they encounter one or more object or situation (3). Anticipatory anxiety is common, as is avoidance of the particular situation. For example, a patient who has a phobia of dental treatment may avoid going to the dentist and develop caries. Sometimes patients seek treatment shortly before a particular event – a patient who has a phobia of flying may request treatment before a holiday. In this situation a short course of benzodiazepines may be appropriate. Long term treatment of phobias includes desensitization therapy (gradual exposure to the feared article or situation).

2b. Social phobia

Patients with social phobia experience anxiety

in situations where the person could be criticized (3). For example, the patient may

be very anxious eating in a restaurant, speaking at a meeting or attending a

dinner party. The patient tends to avoid such situations. If they do

encounter the situation any of the usual symptoms of anxiety can occur, but blushing and trembling are common. Some patients use alcohol to relieve symptoms and alcohol misuse is more common in social phobia compared to the other phobias. Co-morbid depression is common.

2c. Agoraphobia

Patients with agoraphobia experience anxiety symptoms

when they are away from home, in a crowded place or somewhere

that they cannon leave easily (3). Panic attacks are common and anxiety

relating to fear of fainting or loss of control can also occur. The syndrome usually begins with a period of anxiety while in a public place. Anticipatory anxiety can then occur the next time a visit to a similar place is planned. Avoidance is common, causing the patient to remain at home, relying on family or friends for help with activities.

3. Panic Disorder

This illness is characterized by sudden attacks of the physical symptoms of anxiety accompanied by the fear of a serious consequence such as a heart attack (3). It sometimes accompanies agoraphobia.

4. Obsessive compulsive disorder (OCD)

Patients may have obsessional thoughts, where words, ideas or beliefs intrude forcibly into the mind (3). These thoughts may lead to compulsive rituals. For example, an obsessional thought that hands are contaminated can lead to the compulsion to wash the hands many times each day. Depression often accompanies OCD.

5. Post traumatic stress disorder (PTSD)

Symptoms of post traumatic stress disorder involve an intense, prolonged and sometimes delayed response to something that an individual perceives as traumatic (3). This could be a natural or man-made disaster such as an earthquake or war, or could be a personal trauma such as a rape or assault. The patient experiences emotional numbness and detachment, followed by flashbacks and vivid dreams. There is considerable co-morbidity with depression, suicide and substance misuse.

6. Mixed anxiety and depressive disorder (MAD)

Patients with a diagnosis of mixed anxiety and depressive disorder do not suffer from either syndrome severely enough to have a diagnosis of either depression or anxiety (3). However the mild symptoms of anxiety and depression together are disabling enough for the patient to be diagnosed with this minor affective disorder. Treatment is generally with antidepressants.

Most people with anxiety disorders will

probably experience more than one form. For example, someone with panic attacks may develop agoraphobia. If left untreated this could then further develop into generalized anxiety disorder. Anxiety disorders commonly have a comorbid diagnosis of depression. In patients who present with anxiety alone, effective treatment may prevent the later development of depression.

Clinical guidelines relating to anxiety disorders

There are several clinical guidelines for primary and secondary care treatment of patients with anxiety disorders. Three key guidelines for Irish pharmacists are;

• “Guidelinesforthemanagementofdepression and anxiety disorders in primary care” Published in 2006 by the Irish College of General Practitioners.(2)

• “Evidence-basedguidelinesforthepharmacological treatment of anxiety disorders: recommendations from the British Association for Psychopharmacology” published in 2005 (UK guidelines).(4)

• NationalInstituteforHealthandClinicalExcellence(NICE)Managementofanxiety(panic disorder, with or without agoraphobia, and generalised anxiety disorder) in adults in primary, secondary and community care. 2007 (UK guidelines). (5)

Treatment of anxiety disorders

Pharmacological Treatments for Anxiety Disorders

For the majority of anxiety disorders benzodiazepines are used for emergency, short term, management. An antidepressant such as an SSRI is used for long term management.

Benzodiazepines

Benzodiazepines are commonly prescribed in IrelandandacrossEurope.Ina2008European-wide study it was noted that over 9% of adults had taken a benzodiazepine over the course of 12 months. (6)

Benzodiazepines provide rapid relief from anxiety states and are useful for immediate relief of symptoms. However, all current guidelines state that they should be reserved only for anxiety states that are severe and disabling due to their potential for physical dependence (4,5). They should only be used for up to four weeks while long term strategies for management are put into place.

Benzodiazepines can be classified as short acting, such as lorazepam, or long acting like diazepam. They can all cause sedation and affect driving performance. Disinhibition is a possible side effect as benzodiazepines increase GABA transmission. This can lead to aggression or a paradoxical increase in anxiety in some patients. (7)

Physical dependence on benzodiazepines is common following long term use. At least one third of patients will experience withdrawal symptoms after taking benzodiazepines for more than 4-6 weeks (7). Symptoms of sudden withdrawal include tension, panic attacks, palpitations and sweating – symptoms which

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CPD 15: ANXIETY DISORDERS

are similar to the anxiety that was initially being treated. Slow discontinuation can help to manage withdrawal symptoms. Some patients respond to being switched to a long acting benzodiazepine such as diazepam before starting the discontinuation process.

NICErecommendsthatbenzodiazepinesshouldnot be used in panic disorder as they have been shown to be less effective than SSRIs. (5)

Selective Serotonin Reuptake Inhibitors

Selective Serotonin Reuptake Inhibitors (SSRIs) are listed as first line treatments in the majority of anxiety disorders (7). Individual SSRIs have licenses for different anxiety states but this is probably more to do with the marketing strategies of the manufacturer than the effectiveness of the particular medication in that disorder. A summary of the current anxiety disorder licenses of SSRIs is shown in Figure 2.

Figure 2 Anxiety licenses for commonly prescribed SSRIs in Republic of Ireland

Doses of SSRIs

When starting treatment for anxiety disorders with an SSRI the dose should be approximately half that used to treat depression (9). This is because anxiety is a possible side effect of SSRIs in the early stages and may exacerbate the original symptoms (called activation syndrome). Adding a benzodiazepine for the first two weeks can help to counteract this initial anxiety. Titrate the SSRI dose upwards into the normal antidepressant dose range. The patient may take up to six weeks to show a response and treatment may be needed for at least one year.

Patients with anxiety disorders tend to be particularly sensitive to discontinuation symptoms with SSRIs. Doses should be titrated slowly downwards before stopping over several weeks or months.

Side effects of SSRIs

Side effects tend to occur in the first weeks of treatment then subside. Common side effects include restlessness, dizziness, Gastrointestinal (GI) upset and increase in sweating. A paradoxical increase in anxiety is sometimes seen in the first two weeks. In rare cases

suicidal ideation can occur in the early stages of treatment with SSRIs. Long term side effects include sexual dysfunction and weight changes (increase or decrease have been reported).

Discontinuation symptoms

Discontinuation symptoms are seen by approximately one third of patients who stop taking antidepressants. Symptoms begin within five days of stopping SSRIs abruptly (7) and include flu like symptoms, “shock-like” sensations, dizziness, insomnia, vivid dreams and irritability. The symptoms can be explained by a “receptor rebound” effect. Paroxetine is most commonly associated with discontinuation symptoms, probably due to its short half life.

Other antidepressants used to treat anxiety states

Venlafaxine and duloxetine both act on serotonin and noradrenaline (as do tricyclic antidepressants such as amitriptyline.). Both are licensed for generalized anxiety disorder and venlafaxine has additional licenses for panic disorder and social anxiety disorder. Venlafaxine should be avoided in patients at risk of cardiac arrhythmia. It has also been associated with

discontinuation symptoms so slow withdrawal is recommended.

Mirtazepine is a centrally acting antidepressant which has sedative properties which may be helpful for patients with co-existing insomnia. It is not currently licensed for anxiety disorders in Ireland, but is recommended as an alternative to SSRIs in the Maudsley Prescribing Guidelines (7).

Pregabalin

Pregabalin (a gamma-aminobutyric acid analogue) is licensed for the treatment of generalized anxiety disorder. It has a rapid onset of action (approximately one week) (10) which is an advantage when compared to the SSRIs. Side effects include dizziness and somnolence in the early stages of treatment. Weight gain has been reported from trial data. It seems to be associated with fewer withdrawal symptoms than lorazepam, when compared in trial patients.

Beta blockers

Beta blockers such as propranolol are used to treat the physical symptoms of anxiety. They control symptoms such as palpitations, tremor sweating and shortness of breath. They do not cause physical dependence so can be used for long term treatment. They are sometimes used in combination with other anxiolytics that treat the psychological aspects of anxiety.

Other pharmacological treatments

Hydroxyzine is an antihistamine which is related to the phenothiazine antipsychotics. There are few studies to show efficacy but it does seem to be of some benefit in the treatment of anxiety. (9)

Antipsychotics are sometimes used as adjunctive treatments for anxiety (usually added to an antidepressant or benzodiazepine). There is little evidence for efficacy, but a significant risk of side effects. Their use should be reserved for treatment resistant cases. (9)

Non-pharmacological treatments

The2007NICEguidelines(5)recommendpsychological therapies such as cognitive behaviour therapy (CBT) as first line treatment for anxiety disorders. However the guidelines do acknowledge that pharmacological therapies are also effective and that the preference of the patient should be taken into account. In some areas of Ireland CBT may not be readily available so pharmacological treatments may be more suitable. Self help using bibliotherapy based on CBT principles is also recommended byNICE.

Lifestyle considerations for patients with anxiety

TheNICEguidelinesforanxiety(5)recommendthat the benefits of exercise as part of good general health should be discussed with all patients as appropriate

High caffeine intake can worsen the symptoms of anxiety and trigger panic attacks. Patients with anxiety should be advised to reduce intake of drinks and food containing caffeine and to be aware that some over the counter analgesics contain caffeine.

Antidepressant

Fluoxetine

Sertraline

Paroxetine

Citalopram

Escitalopram

Generalised Anxiety

Disorder

YES

YES

Panic Disorder

YES

YES

YES

YES

Obsessive Compulsive

Disorder

YES

YES

YES

YES

Social Phobia

YES

YES

YES

Post Traumatic

Stress Disorder

YES

YES

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CPD 15: ANXIETY DISORDERS

Nicotinestimulatesphysiologicalarousal,increasing the heart rate. Smokers tend to be more anxious and sleep less soundly than their non smoking counterparts.

Alcohol is often used as a relaxant by patients with anxiety. However it can lead to dependence and the onset of physical illness such as liver disease if it is chronically misused.

Recreational drugs of misuse such as cocaine and amphetamines can aggravate anxiety and induce panic attacks. They should obviously be avoided.

Advice for the treatment of special patient groups

British Association for Psychopharmacology has the following advice for patients who are in these special groups; (4)

1. Children and adolescents

Use psychological treatments first line. If medication is needed, use an SSRI as first choice – avoid benzodiazepines and tricylics due to risk of side effects. Start with low doses and monitor carefully for side effects.

2.Elderlypatients

Follow same treatment strategy as for adult patients but use lower doses of medication and monitor carefully for side effects. Be aware of physical co-morbidities and increased sensitivity to side effects of medication.

3. Cardiac disease and epilepsy

Avoid tricyclic antidepressants and venlafaxine in patients with cardiac disease.

Avoid antidepressants that lower seizure threshold in patients with epilepsy. Be mindful of possible drug interactions between anxiety treatments and antiepileptics.

4. Pregnancy and Breastfeeding.

Consider potential risks and benefits of treatments, avoiding drug treatment if possible.

Fluoxetine or tricyclics are considered first line as there is most evidence surrounding the use of these drugs in pregnancy.

Consider SSRIs (apart from fluoxetine and citalopram) or tricyclics for breastfeeding mothers as secretion into milk is low.

Further information for patients and families

Choice and Medication website – an internet site written by UK pharmacists for patients in

the UK and Ireland. Discusses the different types of medication available for psychiatric illnesses. Printable leaflets on different medications. Contains useful comparison charts for different treatments.

http://www.choiceandmedication.org/nsft/

Reach Out – an Irish website for young people with mental health difficulties. Has a section on anxiety disorders. www.reachout.com

Royal College of Psychiatry website – has a range of printable leaftlets on mental health issues, including types of medication and information about counselling and alternative remedies. http://www.rcpsych.ac.uk/

Overcoming Anxiety by Helen Kennerley, a self-help guide using Cognitive Behavioural Therapy (CBT) techniques. Other similar books are available and are useful if patients cannot attend CBT therapy in person.

Practice points for community pharmacists

• Beawareoftheoveruseofbenzodiazepines.Look out for patients on long term benzodiazepine treatment. Consider that some patients may attend more than one GP and pharmacy to obtain supplies of benzodiazepines.

• Informpatientsofthelagtimebetweenstarting antidepressants and seeing a benefit. Up to six weeks may be needed to see maximum effect. However side effects can start from day one.

• EncouragecompliancewithlongtermpreventativetreatmentssuchasSSRIs.Earlydiscontinuation could lead to a recurrence of anxiety symptoms. Treatment may be needed for one year or more.

• Counselpatientswithregardstothewithdrawal effects or discontinuation symptoms when near the end of a course of treatment. Encourageslowdownwardstitrationofdosesrather than sudden stopping of medication.

• Givelifestyleadvicetoreducetheriskoffurther episodes of anxiety.

References1. McDonagh, M. Don’t let anxiety get you down. Irish Times2.8.2011.2. Irish College of General Practitioners. Guidelines for the management of depression and anxiety disorders in primary care. 2006. www.icgp.ie 3. Gelder M, Mayou R. Cowen P. Shorter Oxford TextbookofPsychiatryFourthEdition.2001.OxfordUniversity Press.

4. BaldwinDSetal.Evidence-basedguidelinesforthe pharmacological treatment of anxiety disorders: recommendations from the British Association for Psychopharmacology. J.Psychopharm19(6) (2005) 567–5965. NationalInstituteforHealthandClinicalExcellence(NICE)Managementofanxiety(panicdisorder,withorwithout agoraphobia, and generalised anxiety disorder) in adults in primary, secondary and community care. Clinical guideance 22. Amended April 2007 www.nice.org.uk6. Demyttenaere K et al. Clinical factors influencing the prescription of antidepressants and benzodiazepines:resultsfromtheEuropeanstudyoftheepidemiologyofmentaldisorders(ESEMeD).JAffectDisord.2008Sep;110(1-2):84-93.7. Taylor D, Paton C, Kapur S. Maudsley Prescribing Guidelines10thEdition.2009Informa,London.8. SummaryofProductCharacteristicsforeachproduct accessed on www.medicines.ie February 2012. 9. Bazire S. Psychotropic Drug Directory. 2007. Healthcom UK Ltd. Aberdeen.10. Strawn JR, Geracioti TD. The treatment of generalized anxiety disorder with pregabalin, an atypicalanxiolytic.NeuropsychiatricDiseaseandTreatment.2007, 3(2), 237-243.

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Generalised anxiety disorder

Reassurance, Anxiety

management, Exposuretherapy,

Cognitive behaviour therapy

(CBT)

Panic disorder

CBT, Anxiety management,

Relaxation training

Post traumatic stress disorder

Debriefing if desired,

Counselling, Anxiety

management, CBT, especially for avoidance behaviour or

intrusive images

Obsessive compulsive

disorder

Exposuretherapy,Behavioural

therapy, CBT, Combined drug

and psychological treatment most

effective Surgery

Social Phobia

CBT,Exposuretherapy, Combined

drug and psychological

treatment most effective

Figure 3 – Non-pharmacological treatments for anxiety disorders. (7)

EPEU/2012/022