Case-based learning: anxiety disorders

Anxiety is a common mental health condition that affects approximately 6.6% of the population in England each week, along with one in six adults experiencing or being identified as having a common mental health condition per week^[1],[2]
. Data suggest that women are almost twice as likely to be diagnosed with anxiety compared with men; however, the reason for this is unclear^[3],[4]
. Although a large number of people are affected by mental health conditions (e.g. anxiety or depression), only 39% of adults aged 16–74 years are accessing treatment for them^[5]
.

Mental health conditions typically worsen over time and can negatively impact on social activities, relationships, career performance, academic work and general quality of life^[6]
. As such, patients that present with conditions, such as generalised anxiety disorder (GAD), are frequently seen in the community, with pharmacists having the opportunity to significantly impact on the patient’s quality of life by providing information on the treatment options that are available^[7]
. While occasional anxiety is a normal aspect of day-to-day life, persistent symptoms can indicate the possible presence of an anxiety disorder, which can often be debilitating. Anxiety has also been known to precipitate physiological responses, such as tachycardia and hyperhidrosis^[8]
. ’Functional impairment’ is a term that is often used to describe the degree to which an illness can limit a person’s ability to carry out some of their normal daily tasks; anxiety can affect this to differing degrees^[9]
.

There are multiple factors that could predispose or potentially encourage the manifestation of anxiety, which are often attributable to a combination of genetic and environmental factors^[10]
. In addition, studies suggest that alcohol and illicit drug use, particularly the use of stimulants and hallucinogens, are associated with higher rates of incidence^[11],[12]
. Instances of childhood abuse and sexual abuse are also identified as potential causative factors for anxiety and depression^[13]
. However, there is a broad range of patients affected by anxiety, for whom there is often an unknown cause.

Types of anxiety

Anxiety disorder is an inclusive term for several disorders, including:

• GAD;
• Panic disorder;
• Phobias;
• Selective mutism;
• Separation anxiety;
• Social anxiety disorder^[14]
  .

The most common types of anxiety disorder include:

• Social anxiety disorder — this is considered to be the most common form of anxiety; in up to 50% of cases, it is present in individuals by age 11 years^[15]
  . Symptoms include a persistent fear of social performance, panic attacks and a large fear of humiliating oneself in public^[15]
  ;
• Phobic disorder — this broadly refers to a fear of places, situations, objects and animals. For example, agoraphobia is often considered to be simply a fear of open spaces, but it is far more serious and can include a fear of being in a place that individuals will find difficult to escape from or receive aid if things go wrong^[16]
  .

Avoidance behaviour is common to both social anxiety disorder and phobic disorder, with patients actively trying not to encounter the feared stimulus (e.g. avoiding going outside, such as in cases of agoraphobia)^{[17],[18],[19]}
. This behaviour can hugely impact on a patient’s ability to maintain functional capacity.

Symptoms and diagnosis

Symptoms may involve feelings of restlessness, palpitations, problems with concentrating, uncontrollable worry, sleep disturbances and general irritability^[6]
.

Diagnosis of anxiety would initially be made by a GP following a comprehensive review of the following:

• Symptomatic presentation of the patient;
• Frequency of symptoms;
• Degree of severity of distress;
• Functional impairment.

History of substance misuse, comorbidities and past medical history should be considered as part of a holistic approach to diagnosis^[20]
.

In addition, differential diagnoses must be considered before a formal diagnosis is made. Anaemia and hyperthyroidism are two conditions that must be ruled out and/or treated as they can both manifest symptoms of anxiety disorders^[21],[22]
. Blood analysis and further tests may be necessary to ensure a correct diagnosis is made^[22],[23]
. As stated by the National Institute for Health and Care Excellence (NICE), diagnostic tools, such as the Diagnostic and Statistical Manual of Mental Disorders, can be utilised for anxiety disorders^[21]
. The criteria include a minimum of six months of incessant and uncontrollable worries, disproportionate to actual risk, and three of the following symptoms:

• Being easily fatigued;
• Irritability;
• Muscle tension;
• Poor concentration;
• Restlessness/nervousness;
• Sleep disturbance^[21]
  .

The ‘International Classification of Diseases, 10th revision’, a disease classification tool, offers a similar criteria^[21]
. There are also other resources available to healthcare professionals to work through with patients, such as the GAD-7 questionnaire for anxiety and the personal health questionnaire-9 (PHQ-9) for depression^[21]
. Questions typically ask how frequently certain symptoms have occurred in the preceding two weeks. Both GAD-7 and PHQ-9 allow assessors to distinguish between anxiety and depression, and provide an indication as to the severity of presentation, which can guide therapy. These are typically asked by a GP during an initial consultation with the patient and may include questions such as: ‘Over the past two weeks, how often have you been bothered by feeling nervous, anxious or on edge?’^[24]

The GAD-7 questionnaire can also be used as a tool to determine the severity of its presentation, with scores of 5 and above, 10 and above, and 15 and above (out of a possible 21) referring to mild, moderate and severe anxiety, respectively^[25]
. Higher scores are strongly associated with functional impairment, although individual characteristics of presentation will affect how the patient is treated.

Treatment

Pharmacological treatment

For patients with mild anxiety, pharmacotherapy is not recommended. However, as per NICE guidelines, pharmacological treatment is recommended where significant functional impairment exists^[26]
. First-line drug treatment involves selective serotonin reuptake inhibitors (SSRIs; e.g. sertraline or fluoxetine)^[26]
.

SSRIs are widely used for GAD and are often well tolerated. In addition, they are considered to be safer in overdose than most other similarly indicated medicines, because they carry a lower risk of cardiac conduction abnormalities and seizures^{[27],[28],[29]}
. Selective serotonin–noradrenaline reuptake inhibitors (SNRIs; e.g. duloxetine and mirtazapine) are a suitable alternative; pregabalin is a tertiary option if the others are unsuitable or poorly tolerated^[26]
.

It is important to manage the patients’ expectations with pharmacological therapies. Providing a clear message that it could take between four and six weeks before the patient notices a benefit from their medicine is essential, as this will help ensure that they take their medication as directed. Patients should also be made aware of side effects and the withdrawal process (e.g. associated side effects) prior to commencing therapy^[26]
.

Common side effects of SSRIs include abnormal appetite, arrhythmias, impaired concentration, confusion, gastrointestinal discomfort and sleep disorders^[27]
. The incidence of side effects is reported to be highest within the first two weeks of starting treatment^[30]
. Although most common side effects tend to improve over time, sexual dysfunction can persist^[31]
. There is an increased risk with SSRIs in certain patient groups (e.g. young adults, children and patients with a previous history of suicidal behaviour) of suicidal ideation and self-harm; therefore, initiation of SSRIs must be reviewed weekly in those under aged under 30 years for the first four weeks of treatment. If the risk of recurrent suicidal behaviour is a concern, the healthcare professional may want to seek advice from the local crisis or home-based treatment team; SSRIs generally have a better safety profile than other drugs used for anxiety, but may require frequent monitoring in this case^[32],[26]
.

SSRIs are one of several classes of medicines that pose a risk for long QT syndrome, which occurs as a result of a prolonged QT interval on the electrocardiogram measurements of the heart. This can lead to torsades de pointes (a specific type of abnormal heart rhythm) and possible sudden cardiac death^{[33]
[34],[35]}
.

It is important that SSRIs are withdrawn slowly to minimise the occurrence of SSRI discontinuation syndrome — an abrupt cessation of treatment that can cause a combination of psychological and physiological symptoms; the most common including nausea, dizziness, headache and lethargy^[36]
. Tapering drug doses slowly over several weeks will mitigate the effects of the withdrawal and minimise unnecessary re-initiation of the SSRI^[37]
.

Considerations for selective serotonin reuptake inhibitors and selective serotonin–noradrenaline reuptake inhibitors

Serotonin syndrome is a serious side effect that can occur with the use of SSRIs and SNRIs. It occurs as a result of overactivation of the 5-HT1A and 5-HT2A receptors, precipitated by serotonergic drug use^[38]
. Symptoms typically range from confusion and agitation to more serious symptoms, such as seizures, arrhythmias and loss of consciousness^[31]
. The risk of the syndrome is higher if patients are taking other medicines that can increase serotonin levels in the brain, such as tramadol and metoclopramide. Taking 5-HT1F agonists, which include sumatriptan, or a combination of medicines with the same effect, can also increase risk^[39]
.

If a decision is made to initiate an SSRI, despite the associated risk, patients should be provided with suitable information concerning the syndrome, which can be found on or printed from the NHS website^[31]
. If a patient experiences symptoms of serotonin sydrome, they should be advised to contact their GP surgery immediately. If this is unavailable, they should call NHS 111 for advice.

Alongside serotonin syndrome, SSRIs have been known to contribute to inappropriate antidiuretic hormone secretion, which is related to hyponatremia and has symptoms including headache, insomnia, nervousness and agitation^[40]
. 

Patients with anxiety disorders should be monitored as frequently as the severity of the disorder demands, which is essential to protect patients and improve their quality of life. Guidance from the British National Formulary states that patients being initiated on an SSRI should be reviewed every one to two weeks after initiation, with response being assessed at four weeks to determine whether continuation of the drug is suitable^[27]
. NICE guidelines expand on this by encouraging three-monthly reviews of drug therapy to assess clinical effectiveness^[20]
.

Non-pharmacological treatment

Patients should be advised to minimise alcohol intake and make time for activities they find relaxing. They should also be encouraged to exercise every day, aiming to do 150 minutes of moderate-intensity exercise (e.g. walking or cycling) per week as exercising has been shown to improve mental health^[41],[42]
. A study has demonstrated that those who exercise had 43.2% fewer days of poor mental health, with team sports having the largest association with reduction in mental health burden^[43]
.

Psychological treatment

Cognitive behavioural therapy (CBT) is a common psychological treatment used for those with anxiety. This therapy aims to transform negative thinking into more structured thought patterns, which then assist the patient in making changes to their thought processes to encourage positive thinking. CBT is suitable for patients that present with ongoing anxiety and does not look at patient history^[34]
. This type of treatment may be useful for patients with mild anxiety, as an addition to medicine or for those who do not wish to take medicine. It can be conducted individually or as part of a group.

Guided self-help — a process by which a patient is able to work through a course with the support of a trained therapist — and counselling are other treatments available through the NHS that may benefit patients with mild anxiety or as an adjunct to prescription medicines^[44]
.

Specialist referral and suicide risk

Specialist referral should be considered if patients:

• Have not responded to initial therapy;
• Have comorbidities, such as alcohol or substance misuse;
• Are at significant suicide risk.

Healthcare professionals should always assess suicide risk by discussing the patients’ feelings about self-harm openly and considering other contributing factors, such as the use of prescribed or illicit drugs. Healthcare professionals must take opportunities to make interventions — for example, referring patients for urgent mental health assessment or in the case of serious concerns, calling emergency services^[23]
.

In the UK, area-specific community programmes and the charity Anxiety UK can provide patients with further advice on managing their anxiety. However, many primary care networks are now recruiting social prescribers, who will have the ability to direct patients to attend local groups that are more suited to individual needs. Community pharmacists are also likely to be aware of local support networks.

Case studies

*All cases are fictional