Generalised Anxiety Disorder

•  Worry about worry: a meta-worry!
• Excessive and persistent worry about a number of areas of life including family, health, job, finances, etc
•  Worrying dominant source of discomfort: spend half an average day worrying – most recognise they worry excessively about minor things but can‟t control it
•  At least six-month duration, chronic fluctuating course
•  Epidemiology: 2 – 8 % of the population, onset 20 – 40 years, male = female
•  Symptoms: restlessness, feeling on edge, difficulty concentrating, mind going blank, irritability, muscle tension, sleep disturbance (esp difficulty getting back to sleep after waking, anticipatory thoughts while awake)
• Co-morbidity/differential: mood disorders, adjustment disorder (clearly identifiable stressor), panic attacks, socially anxious, low self-esteem, avoidant or dependent personality disorder

·   Treatment:

• Education
• Training: relaxation, breathing control, structured problem solving, gradual confrontation of fears 
• Avoid sedatives: they will love them but will become dependent on them and underlying problems won‟t be fixed
• Specialist referral if symptoms persist for a further 3 months

Treatment of Anxiety Disorders

Cognitive Behavioural Therapy (CBT)

• Effective for most anxiety disorders
• Response more long lived than for drug treatment
• Includes: breathing retraining, deconditioning, cognitive restructuring, relaxation, graded exposure, desensitisation

Psychodynamic Psychotherapy

•  Symptoms result from mental processes outside conscious awareness.  Aim is to elucidate these
• Identify and alter core conflicts

Drug Treatment

• Benzodiazepines: may be useful for the short term or acute treatment of acute stress reactions. Due to tolerance and dependence, these are not useful for long-term use
• Antidepressants:

1. For severe panic disorder (with or without agoraphobia), TCA‟s (eg imipramine) are the medication of choice. Suppression of panic attacks may occur after 4 – 6 weeks. Minimum treatment usually 6 months. Maximum is 18 months. Use alternative therapies if it fails after this time
2. For OCD, clomipramine (a TCA) and SSRIs may be a useful adjunct to CBT. Help minimize compulsions and manage the depression often associated with OCD.

• Betablockers: Useful for the treatment of social phobia when performance anxiety is the main problem. These prevent noticeable symptoms (eg blushing or shaking), which are typically interpreted catastrophically by individuals. However, these drugs are not useful if the anxiety is more generalized

Benzodiazepines

• Mode of action: enhance GABA inhibition throughout the CNS
• GABA (gamma-amino-butyric acid) increases membrane Cl- permeability ® hyperpolarisation
• Binding affinity important in governing duration and degree of effect, in addition to elimination and dosage.

• Key pharmacodynamic differences: 

1. Chlordiazepoxide and Diazepam: shorter elimination time than their active metabolites. Doses of benzos with active metabolites should be reduced in the elderly, especially if ¯renal function
2. Midazolam: often used as premed for procedures and GA – relaxes and amnesia 
3. Zopiclone (Imovane): differs from BDZs and barbiturates, but has same actions (sedation, anticonvulsant, anti-aggressive and muscle relaxant). Binds to BDZ binding sites. Peak plasma conc. in 1 hour, T½ of 4 hours. At higher doses: hangover effect, memory disturbance, rebound insomnia, interaction with alcohol

• Metabolism: 

1. Eg: diazepam ® temazepam ® oxazepam
2. Inactive conjugates excreted

• Adverse Effects: 

1. Daytime sedation: with long acting BDZs where slow elimination leads to accumulation of drug and active metabolites
2. Daytime agitation/irritability: with ultra short acting BDZs (triazolam, midazolam), especially in those with anxiety
3. Psychomotor functional impairment: beware if driving or operating machinery
4. Amnesia: with short acting BDZs
5. Physical dependence: All BDZs are addictive
6. CNS effects of BDZs all exacerbated by alcohol
7. Broken sleep patterns are particularly common after withdrawal of hypnotics 
8. Discontinuation of long-term use must be gradual (2 – 3 months) never abrupt. Withdrawal similar to hyperadrenergic state – anxiety, tremor, ataxia, confusion, insomnia, nausea, seizures (especially with lorazepam). Withdrawal syndrome can be prolonged (ie months). Treating withdrawal: change to diazepam (greater dose flexibility), reduce dose by 10% every 2 – 4 weeks. Use counselling and relaxation

• Lorazepam as a hypnotic where insomnia is a complication of anxiety – but never just as a hypnotic