Anxiety and Related Disorders in Medical Settings

DefinitionTop

The fifth edition of the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders (DSM-5) defines anxiety disorders as “disorders sharing features of excessive fear and anxiety and related behavioral disturbances. Fear is the emotional response to real or perceived imminent threat, whereas anxiety is the emotional response in anticipation of future threat. Fear is more often associated with surges of autonomic arousal necessary for fight or flight, thoughts of immediate danger and escape behaviors, and anxiety more often associated with muscle tension and vigilance in preparation for future danger and cautious or avoidant behaviors.”

DSM-5 introduced a number of changes in the classification of anxiety disorders. The major change was to move the obsessive-compulsive and related disorders and the trauma-related and stressor-related disorders into separate chapters.

In May 2019, the World Health Organization (WHO) ratified the 11th revision of the International Classification of Diseases and Related Health Problems (ICD-11). In ICD-11, the anxiety category includes disorders in which anxiety or fear are the primary clinical feature. Separation anxiety disorder and selective mutism have been moved from the childhood disorders section to the anxiety category. As with DSM-5, a new category has been introduced: obsessive-compulsive and related disorders (OCRD), which in ICD-11 includes obsessive-compulsive disorder (OCD), body dysmorphic disorder, olfactory reference disorder, hypochondriasis (illness anxiety disorder), and hoarding disorder. These conditions have symptoms of repetitive unwanted thoughts and related repetitive behaviors as the primary clinical feature.

For the sake of continuity, this brief chapter will include OCD and posttraumatic stress disorder (PTSD).

Anxiety and fear are experienced by everyone in daily life and are essential in protecting us from realistic dangers. In anxiety disorders the emotions of anxiety and fear are triggered without there being any realistic threat of harm or the threat is perceived to be out of proportion. The diagnosis of an anxiety disorder is made when the symptoms arise and there is impairment in usual behavior. Commonly, the impairment leads to frequent escapes from uncomfortable situations or avoidance of places or tasks that used to be part of the person’s repertoire.

Symptoms of anxiety occur commonly in multiple psychiatric conditions. The term “anxiety disorder” refers to those conditions in which the experience of anxiety forms the central symptom. Anxiety disorders are common, with prevalence rates between 2% and 9%, although social anxiety ranges from 13% to 16%. Anxiety disorders can cause significant disability and frequently have a chronic course.

EtiologyTop

A relatively consistent finding in neuroimaging studies of anxiety is hyperactivity of the amygdala and impairment of frontal emotion regulation circuits. In OCD there is evidence of altered activity in the orbitofrontal-limbic-basal ganglia-thalamic circuitry. Several neurotransmitters have been implicated in anxiety, especially serotonin and gamma-aminobutyric acid (GABA).

Genetic predisposition, inborn temperamental traits, early childhood development, attachment quality, and family and social environment also contribute to etiology.

Psychologic theories initially were based on classical learning theories. Avoidance of anxiety-provoking situations is a major perpetuating factor. Dysfunctional thought patterns leading to misinterpretations and misattributions are evident in all anxiety disorders.

Clinical Features and DiagnosisTop

Diagnostic Features

1. Generalized anxiety disorder (GAD):

1) Key symptoms: Excessive worry focused on plausible possibilities that are highly magnified, leading to distress and preoccupation.

2) Associated physical symptoms: Feeling on edge, restlessness, fatigue, churning, impaired concentration, muscle tension, irritability, and insomnia.

2. Panic disorder (PD):

1) Key symptoms: Rapid surges of intense anxiety that peak within minutes. Intense anxiety in the form of a panic attack is the main feature of PD and may occur in many mental disorders.

2) Associated physical symptoms: Rapid heart rate, palpitations, sweating, subjective shortness of breath, chest pain, trembling, nausea, light-headedness, feeling hot or cold, numbness, tingling.

3) Psychologic symptoms: Fear that one is going to die or lose one’s mind; feelings of unreality and detachment (depersonalization).

3. Agoraphobia: Key symptoms are marked anxiety about specific situations: open, crowded, or enclosed spaces, such as shopping malls, standing in line or on buses. The patient avoids these situations or endures them with intense anxiety. Frequently associated with panic attacks.

4. Social anxiety disorder (SAD): Key symptoms are intense anxiety in social situations, feeling of being judged by others, embarrassment, and inadequacy. Occurs when meeting new people, being at social gatherings, making a presentation, or eating in public. In learners frequently leads to avoidance of going to school, which impedes progression in education.

5. Specific phobia: Key symptoms are intense anxiety about a specific object or situation, for instance, fear of injections, flying, or specific animals. Panic attacks may occur with severe fear. The patient avoids the situation or object. In the medical setting, fear of blood taking and injections has the most clinical relevance.

6. OCD:

1) Key symptoms: Intrusive unwanted thoughts, images or urges of violence, suicide, harm to others; disturbing sexual or blasphemous thoughts. The thoughts are recognized by the patient to arise in himself or herself but they are uncontrollable and may be very alarming.

2) Compulsive behaviors: Behaviors such as repetitive checking, counting, handwashing, touching, rereading, or ordering occur and are aimed at reducing the anxiety triggered by the thoughts or urges. The ritualistic behaviors may occupy many hours each day and lead to very severe impairment in many spheres.

7. PTSD: Key symptoms are intense physiological and emotional hyperarousal: intrusive vivid memories, flashbacks or bodily sensations of the traumatic event. Symptoms are triggered by reminders or cues of the event leading to marked avoidance. Frequently accompanied by mood dysregulation, anger, depression, and suicidal ideation.

Differential Diagnosis

Anxiety disorders are frequently comorbid with other mental disorders, most commonly depression and alcohol and substance use disorders. Additionally, anxiety disorders commonly co-occur in a patient, including OCD and trauma-related disorders and other disorders within the anxiety disorder category.

It is important to exclude endocrine and cardiac disorders. Investigations including a complete blood count (CBC), liver function tests, gamma-glutamyl transferase (GGT) (alcohol), thyroid indices (thyroid-stimulating hormone [TSH]), and electrocardiography (ECG) may be considered.

ScreeningTop

Initial screening for anxiety disorders of patients who appear to be very stressed or jittery can be performed by asking questions about the person’s experience in the previous 2 weeks. There are many brief questionnaires that focus on the specific disorders. As a general brief screen, it is important to ask the following questions: Have you been bothered by the following problems: (1) Feeling nervous, anxious, frightened, worried, or on edge? (2) Feeling panic or being frightened? (3) Avoiding situations that make you anxious?

If there is a positive response, then follow up with questions about the nature of the anxiety, when and where it occurs, and about its impact on functioning.

TreatmentTop

After assessment and necessary investigations (see Psychiatric Examination), the first step in the treatment of anxiety disorders is to provide the patient with information about the diagnosis, available evidence-based treatments, and ways to access further information suited to the patient’s needs and wishes.

Stepped-Care Approach

Stepped care involves increasing levels of intervention based on nonresponse. The first-step interventions are offered to all patients with diagnosed or suspected cases of the specific anxiety disorder and consist of self-management strategies and access to self-help and educational resources.

1. Step 1: Self-management:

1) Reduce or eliminate stimulants, including caffeine-containing drinks such as tea, coffee, and cola drinks.

2) Reduce alcohol to a minimal amount. Alcohol should not be used by patients in attempts to control their anxiety.

3) Reduce or eliminate tobacco use and cannabis intake.

4) Sleep hygiene as well as regular sleeping and waking times reduce anxiety. Educate the patient on the effects of regular aerobic exercise.

5) Introduce relaxation training, deep breathing exercises, Jacobson progressive muscle relaxation, and mindfulness meditation.

6) Provide the patient with information about the management of anxiety disorders. There are many reliable books, manuals, and websites for each of the anxiety and related disorders (eg, www.anxietyBC.ca, www.adaa.org). This information can be used by the patient alone or worked through in brief guided sessions together with a therapist.

7) Internet-delivered cognitive behavior therapy (iCBT) is evidence based and available via the internet. It may be guided, with a health care professional, or unguided, in which case the patient follows the program unassisted.

8) Low-intensity psychoeducational groups, which may be provided by community organizations and peer support services.

2. Step 2: Psychotherapy (for those not responsive to step 1): Psychotherapy is an effective treatment modality and should be considered in all patients with sufficient disorder severity,Evidence 1Strong recommendation (benefits clearly outweigh downsides; right action for all or almost all patients). Low Quality of Evidence (low confidence that we know true effects of the intervention). Quality of Evidence lowered due to unclear risk of bias, imprecision, and indirectness. Pompoli A, Furukawa TA, Imai H, Tajika A, Efthimiou O, Salanti G. Psychological therapies for panic disorder with or without agoraphobia in adults: a network meta-analysis. Cochrane Database Syst Rev. 2016 Apr 13;4:CD011004. doi: 10.1002/14651858.CD011004.pub2. Review. PMID: 27071857. Katzman MA, Bleau P, Blier P, Chokka P, Kjernisted K, Van Ameringen M; Canadian Anxiety Guidelines Initiative Group on behalf of the Anxiety Disorders Association of Canada/Association Canadienne des troubles anxieux and McGill University, Antony MM, Bouchard S, Brunet A, et al. Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress and obsessive-compulsive disorders. BMC Psychiatry. 2014;14 Suppl 1:S1. doi: 10.1186/1471-244X-14-S1-S1. Epub 2014 Jul 2. Review. PMID: 25081580; PMCID: PMC4120194. with cognitive behavioral therapy (CBT) likely being the most effective.Evidence 2Low Quality of Evidence (low confidence that we know true effects of the intervention). Quality of Evidence lowered due to unclear risk of bias, imprecision, and indirectness. Pompoli A, Furukawa TA, Imai H, Tajika A, Efthimiou O, Salanti G. Psychological therapies for panic disorder with or without agoraphobia in adults: a network meta-analysis. Cochrane Database Syst Rev. 2016 Apr 13;4:CD011004. doi: 10.1002/14651858.CD011004.pub2. Review. PMID: 27071857. CBT is usually delivered in a structured format and can be used in an individual or group setting. A course of therapy varies between 12 to 20 sessions delivered ideally once or twice a week. Booster sessions once a month after the initial course help to maintain and reinforce the gains made. CBT requires that the patient take a very active part in the treatment. McMaster University supports an online resource that provides details about the nature and use of CBT at Psychotherapy Training e-Resources.

The specific anxiety and related disorders are treated using variations of CBT methods. OCDs and trauma-related disorders require specialized therapy focused on the core symptoms of the disorders, such as repeated washing, flashbacks, or nightmares that do not occur commonly in other anxiety disorders.

3. Step 3: A combination of psychotherapy and medication (for those with more severe levels of symptoms, comorbidity, and marked impairment of functioning):

1) First-line medications: The medications recommended for anxiety disorders are classified in the antidepressant category but have been found to be effective in anxiety disorders. Antidepressants should be initiated at low doses to lessen adverse effects but may need to be titrated up to doses that are in the higher approved ranges. Specific selective serotonin reuptake inhibitors (SSRIs) are first-line agents (Table 1). The effectiveness of the serotonin-norepinephrine reuptake inhibitors (SNRIs) venlafaxine and duloxetine is less well established. The tricyclic antidepressant clomipramine is one of the most effective medications for OCD but is mostly used as a second-line option because of the greater tolerability of SSRIs. Medications with dopaminergic and noradrenergic effects can exacerbate anxiety; this includes bupropion, venlafaxine, methylphenidate, and other stimulants.

2) Second-line medications:

a) Benzodiazepines can be very effective for acute management of PD and GAD. Drawbacks include tolerance, cognitive adverse effects, and mood changes. Benzodiazepines can reduce the effectiveness of CBT due to their impact on memory consolidation. Additionally, they should be used sparingly, if at all, in the management of PTSD.

b) GABA derivatives (pregabalin or gabapentin) may be prescribed if the first-line medications do not provide sufficient symptom relief and return of function. Although evidence on this is preliminary, gabapentin can be used as an alternative to benzodiazepines to reduce anxiety symptoms and enhance slow-wave sleep.

c) Buspirone is a mild anxiolytic but has the advantage of not causing dependence. Interestingly, it does not cause bruxism (involuntary grinding of teeth), which can be seen as an adverse effect of SSRIs, and its use to alleviate this condition has been described in case reports.

d) Propranolol, a nonselective beta-blocker, can be effective for performance anxiety, which is a subtype of social anxiety by reducing peripheral adrenergic drives. Contrary to the widespread view, propranolol does relieve psychic anxiety in addition to the physiologic symptoms, such as tremor and tachycardia. Asthma is an absolute contraindication.

e) Medical cannabis: As yet, there is limited evidence about the benefits and risks of using cannabidiol (CBD) in anxiety disorders. In jurisdictions where it is legal, patients have been using CBD oil with mixed results.

Novel Approaches

1. There is moderate-quality evidence that iCBT is as effective as in-person CBT for anxiety disorders, and this can increase access to this modality.

2. At present there is inadequate evidence for the use of virtual reality therapy in the treatment of anxiety disorders.

3. There is preliminary evidence for the use of repetitive transcranial magnetic stimulation in obsessive-compulsive disorder, but its use is limited to specialized centers.

Management

After obtaining the patient’s consent and having educated the patient about the expected effects and adverse effects of the medications, a drug suggested for the anxiety disorder can be chosen (Table 1). It is also necessary to make sure that there are no contraindications for use with any other medications that the patient is taking. It is advisable to use a drug interaction program as a general principle when patients are taking multiple medications.

Currently it is recommended that the first choice of medication in the primary care setting should be an SSRI (Table 1). Patients with anxiety disorders can be very sensitive to adverse effects and it is important to begin treatment with a low dose followed by a gradual increase to a therapeutic dose range. Escitalopram can be initiated at 5 mg daily for 1 week and then increased in 5-mg daily doses to 20 mg daily. Similarly, sertraline is started at 25 mg daily increasing in 25-mg doses up to 200 mg daily. There is usually a delay in the response and it may be 4 to 6 weeks before patients report that they are feeling less anxious. If the response is insufficient after 2 trials of an SSRI, the family practitioner may wish to seek the opinion of a psychiatrist about the next steps. When there is a good response to the medication, it is necessary to continue its use for at least 6 months and frequently for longer.

In addition to the above, prazosin is now well established as one of the first-line agents for treatment of PTSD. Prazosin reduces nightmares, hyperarousal, and sleep disturbances. It improves total sleep time and sleep quality.Evidence 3Low Quality of Evidence (low confidence that we know true effects of the intervention). Quality of Evidence lowered due to the risk of bias and indirectness (short-term trials with indirect end points). Singh B, Hughes AJ, Mehta G, Erwin PJ, Parsaik AK. Efficacy of Prazosin in Posttraumatic Stress Disorder: A Systematic Review and Meta-Analysis. Prim Care Companion CNS Disord. 2016 Jul 28;18(4). doi: 10.4088/PCC.16r01943. Review. PMID: 27828694. Taylor FB, Martin P, Thompson C, et al. Prazosin effects on objective sleep measures and clinical symptoms in civilian trauma posttraumatic stress disorder: a placebo-controlled study. Biol Psychiatry. 2008 Mar 15;63(6):629-32. Epub 2007 Sep 14. PMID: 17868655; PMCID: PMC2350188.

The use of antipsychotics is controversial but quetiapine or olanzapine have been used in low doses, with caution and attention paid to the risk of serious adverse effects, such as metabolic syndrome (including type 2), diabetes mellitus, and tardive dyskinesia. These medications should be reserved for treatment-resistant patients under psychiatric care.

TablesTop