[6] Generalised Anxiety Disorder Flashcards
What is generalised anxiety disorder?
A syndrome of ongoing, uncontrollable, widespread worry about many events or thoughts that the patient recognises as excessive or inappropriate.
How often must symptoms be present to classify as generalised anxiety disorder?
Must be present on most days for at least 6 months duration
What can the aetiology of GAD be divided into?
Biological and environmental
What can the biological causes of GAD be further divided into?
- Genetics
- Neurophysiological
How does having a first degree relative with the condition affect the incidence of GAD?
The incidence is 5x higher
What is the neurophysiological component of the aetiology of GAD?
- Dysfunction of the autonomic nervous system
- Exaggerated responses in the amygdala and hippocampus
- Alterations in GABA, serotonin, and noradrenaline
What environmental factors are involved in the development of GAD?
- Stressful life events, including childhood abuse
- Problems with relationships
- Personal illness
- Employment/finances
- Substance dependance, including alcohol and benzodiazepines
- Exposure to organic solvents
What are the predisposing risk factors for GAD?
- Genetics
- Personality type and demands for high achievement
- Divorced
- Living alone or as a single parent
- Low socioeconomic status
What are the precipitating risk factors for GAD?
- Domestic violence
- Unemployment
- Relationship problems
- Personal illness
What are the maintaining risk factors for GAD?
- Continuing stressful life events
- Living alone
- Ways of thinking which perpetuate anxiety
What are the chest and abdomen symptoms of GAD?
- Chest pain and discomfort
- Difficulty breathing/hyperventilation
- Feeling of choking
- Nausea
- Abdominal distress/pain
- Loose motions
What are the brain and mind symptoms of GAD?
- Feeling dizzy/light headed
- Fear of dying
- Fear of loosing control
- Derealisation and depersonalisation
- Tremor
What are the general symptoms of GAD?
- Hot flushes or cold chills
- Numbness/tingling
- Headache
What symptoms of tenson might be present in GAD?
- Muscle tension/aches
- Restlessness
- Feeling on edge
- Difficulty swallowing
- Sensation of lump in throat
What non-specific symptoms might be present in GAD?
- Being startled
- Concentration difficulty and mind blanks
- Persistent irritability
- Sleep problems
- Excessive, uncontrollable worry
- Autonomic hyperactivity, resulting in sweating, increased pupil size, increased HR
What is the ICD-10 diagnostic criteria for anxiety?
A period at at least 6 months with prominent tension, worry, and feelings of apprehension about everyday events and problems, alongside at least 4 symptoms, and at least one symptom of autonomic arousal (palpitations, sweating, shaking/tremor, dry mouth)
How is generalised anxiety disorder investigated?
- History
- MSE
- Blood tests - FBC, TFTs, glucose
- ECG
- Questionnaires - GAD-2, GAD-7, Beck’s Anxiety Inventory
What are the differential diagnoses of GAD?
- Other neurotic disorders, including panic disorder, specific phobias, OCD, PTSD
- Depression
- Schizophrenia
- Personality disorder, especially anxious or dependant
- Excessive caffeine of alcohol consumption
- Withdrawal from drugs
- Organic causes, including anaemia, hyperthyroidism, phaeochromocytoma, hypoglycaemia
What is GAD managed based on?
The bio-psycho-social mdel
What co-morbid conditions should also be treated in anxiety disorders?
- Depression
- Substance misuse
What is the first line drug treatment for GAD?
SSRI (sertraline is recommended)
What is the second line drug treatment in GAD?
SNRI (venlafaxine or duloxetine)
What is the third line drug treatment for the management of anxiety?
Pregabalin
How long should medication be used in GAD?
At least a year
Should benzodiazepines be used in GAD?
No, apart from as a short-term management during crisis
Why should benzodiazepines not be used long term?
Due to the risk of dependance
When are beta-blockers used in the treatment of anxiety?
When there are symptoms like palpitation, sweating, and tremor
Give two examples of benzodiazepines
- Diazepam
- Lorazepam
What are the targets for benzodiazepam action?
GABAA receptors
What is GABA?
A major inhibitory neurotransmitter in the CNS
What does the way that GABA receptors are activated depend on?
The type, number of subunits, and the brain region localisation
What does different drugs activating GABA receptors in different ways produce?
Different pharmacological effects
How do benzodiazepines modulate GABA effects?
Benzodiazepines are positive allosteric modulators of GABA receptors - they bind to a specific, high-affinity site located at the interface between the alpha subunit and gamma2 subunit of the GABAA receptor (the benzodiazepine binding site is separate from the GABA binding site), which potentiates the effect of GABA
What is the result of GABA binding to GABAA receptors?
It triggers an opening of chloride channels, which leads to an increase in chloride conductance. The influx of chloride ions causes a small hyperpolarisation that moves the postsynaptic potential away from the firing theshold, and therefore inhibits the formation of action potentials.
By increasing the action of GABA, benzodiazepines increase this action, and that is how they exert their effects
What are the actions of benzodiazepines?
- Reduction of anxiety
- Sedative and hypnotic actions
- Anti-convulsants
- Muscle relaxant
At what doses do benzodiazepines have anxiolytic properties?
Low doses
What causes the anxiolytic properties of benzodiazepines?
Thought to be due to inhibition of neuronal circuits in the limbic system of the brain
What is hyponosis?
Artificially produced sleep
Do all benzodiazepines have sedative and hypnotic actions?
All have sedative actions, some have hypnotic actions at higher doses
How can the anti-convulsant activity of some benzodiazepines be utilised?
They can be used to treat epilepsy, status epilepticus, and other seizure disorders
At what doses can benzodiazepines act as muscle relaxants?
High doses
How do benzodiazepines exert their muscle relaxant action?
They relax the spasticity of skeletal muscle, probably by increasing pre-synaptic inhibition in the spinal cord
Where are benzodiazepines effective in the treatment of anxiety?
When the anxiety symptoms are secondary to;
- Generalised anxiety disorder
- Social anxiety disorder
- PTSD
- Performance anxiety
- Specific phobias
It can also be useful in treating the anxiety that accompanies some forms of depression and schizophrenia
What benzodiazepines are preferred for use in anxiety?
The longer acting agents, such as diazepam and lorazepam
What should the use of benzodiazepines in anxiety be reserved for?
Severe anxiety
Other than anxiety, what disorders can benzodiazepines be used for?
- Skeletal muscle spasms
- Spasticity from degenerative disorders such as MS and CP
- Pre-medication for anxiety-provoking and unpleasant procedures such as endoscopy, bronchoscopy, and some dental procedure
- Sleep disorders
What are the most common side effects of benzodiazepines?
Drowsiness and confusion
What side effects of benzodiazepines occur at higher doses?
Ataxia
What is the result of ataxia being a side effect of benzodiazepines?
It precludes activities that require fine motor coordination, such as driving
What other side effects of benzodiazepines?
Cognitive impairment (decreased long-term recall and retention of new knowledge)
When might psychological and physiological dependance to benzodiazepines occur?
If high doses of benzodiazepines are given over a prolonged period
What does abrupt discontinuation of benzodiazepines cause?
Withdrawal symptoms
What withdrawal symptoms may occur with abrupt discontinuation of benzodiazepines?
- Confusion
- Anxiety
- Agitation
- Restlessness
- Insomnia
- Tension
- Seizures
Why might withdrawal symptoms occur slowly after discontinuation of therapy with some benzodiazepines?
Because some benzodiazepines have long half lives
When should caution be taken with giving benzodiazepines?
- Liver disease
- Narrow angle glaucoma
- Concurrent alcohol and other CNS depressant use
Are benzodiazepines hydrophilic or lipophilic?
Lipophilic
Describe the absorption of benzodiazepines
They are rapidly and completely absorbed after oral administration
Describe the distribution of benzodiazepines after absorption
They distribute throughout the body
Why is the half-life of benzodiazepines useful clinically?
Because the duration of action may determine their therapeutic usefulness
Why are agents such as diazepam and lorazepam long acting?
Because they form active metabolites with long half-lives
How are the benzodiazepines metabolised?
Most, including dizepam, are metabolised by the hepatic microsomal system to compounds that are active
How are the actions of benzodiazepines terminated?
Excretion and redistribution
How are the benzodiazepines excreted?
Excreted in urine as glucuronides or oxidised metabolites
Are benzodiazepines safe in pregnancy?
No, all benzodiazepines cross the placental barrier and may depress the CNS of a newborn if given before birth
Are benzodiazepines safe in breastfeeding?
No, nursing infants may become exposed through breast milk
What are the differences between diazepam and lorazepam?
- Diazepam can have interactions with other medications. Lorazepam is less likely to have interactions
- Diazepam has a longer half life
- Lorazepam is more likely to cause withdrawal symptoms, whereas diazepam has less severe withdrawal symptoms
- Diazepam works quicker
- Diazepam is more dangerous in liver problems
- Both are available in pill and liquid form, but lorazepam is also available in injection form
What is pregabalin?
Pregabalin is a CNS depressant
What is the mechanism of action of pregabalin?
It binds to voltage gated calcium channels in neurons, and increases extra-celluluar amounts of the enzyme responsible synthesis of GABA, and therefore increases GABA concentrations in tje brain
What are the indications for pregabalin?
- Anxiety
- Neuropathic pain
- Epilepsy
Can pregabalin be misused?
It has less potential for misuse for dependance than benzodiazepines, but is still misused, so the BNF recommends that is used for short term use only
What are the adverse effects of pregabalin?
- Sedation
- Weight gain
How do beta-blockers work in anxiety?
Reducing the autonomic nervous system activation
Which beta-blocker is most commonly used in anxiety?
Propanolol
Where are beta-blockers in the use of anxiety contraindicated?
Asthma
Where are beta-blockers of limited effectiveness in anxiety disorders?
In enduring anxiety disorders
Give an example of a low-intensity psychological intervention that can be used in GAD?
Psychoeducational groups
Give two examples of high intesity forms of psychological intervention that can be used in GAD?
- CBT
- Applied relaxation
What is applied relaxation?
Learning of techniques that lead to muscular and bodily relaxation, which can be applied in situtations that trigger anxiety and worry
What social interventions can help with GAD?
- Self-help methods, such as writing down worrying thoughts and analysing them objectively
- Support groups
- Exercise
What is the Stepped Care model for the management of GAD?
- Identification and assessment - psychoeducation about GAD and active monitoring
- Low intensity psychological interventions
- Individual non-guided self-help, psychoeducational group-based therapy
- High intensity psychological interventions - CBT or applied relaxation, or drug treatment
- Highly specialised input, combination of drug and psychological therapies. May need involvement of crisis team