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Lecture 15

Lecture 15 - Anxiety & Insomnia.docx

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University of Otago
Steve Kerr

15. Drug Treatment of Anxiety Disorders and Insomnia 9/3/2013 3:13:00 AM Anxiety:  Normal emotional response to a perceived threat  Sympathetic “fight or flight” response  Becomes a psychiatric “disorder” when symptoms : o Cause distress o Impair everyday functioning Anxiety Disorders: GAD = Generalized Anxiety Disorder SAD = Social Anxiety Disorder PD = Panic Disorder PTSD = Post-Traumatic Stress Disorder OCD = Obsessive Compulsive Disorder Generalized Anxiety Disorder:  Most common  High co-morbidity with depression  Characterized by: o Excessive anxiety and worry occurring more days than not for at least 6 months. o Impairment in:  Social, occupational or other important area of functioning o At least 3 of the following:  Restlessness or feeling on edge  Easily fatigued  Difficulty concentrating or mind going blank  Irritability  Muscle tension  Sleep disturbance Key Receptor System Drug Targets:  GABA: o Barbiturates o Benzodiazepines  Serotonin (5HT) o Buspirone o SSRI’s o SNRI’s (NA reuptake inhibitors)  Noradrenaline (NA) o SSRI’s o SNRI’s Barbiturates:  DIRECT GABA receAtor agonists o (i.e. does not need presence of GABA to open channels)  Largely replaced by benzodiazepines o Now only used for:  Epilepsy – phenobarbital  Anaesthesia – thiopental  HIGH RISK in overdose: o Particularly combined with other CNS depressants (e.g. alcohol) o Leads to respiratory depression (coma/death) o No antidote / selective antagonist Benzodiazepines:  Positive allosteric modulator of GABA reAeptors  Uses include: o Anxiolytic o Muscle relaxant (possibly reduces headaches) o Hypnotic o Amnestic sedative o Anticonvulsant  Advantages: o Fast acting (no therapeutic delay) o Larger therapeutic window o Relatively safer in overdose  Effective antagonist – Flumazenil (also a benzodiazepine)  Wide range available dependent on pharmacokinetic properties: o Short duration of action (acute anxiety & insomnia (12-18 hours)):  temazepam o Long duration of action (short term relief of anxiety (2-4 weeks)):  diazepam  Acute side effects: o Drowsiness o Confusion o Amnesia o Impaired coordination  Accumulation: o Particularly in elderly  Accumulation increases risks of falls etc associated with impaired coordination  Amnesia and confusion can lead to false dementia diagnosis  Tolerance: o GABA reAeptors become less sensitive over time o More drug required for same effect  Dependence: o Withdrawal syndrome if stopped suddenly o Leads to:  Increased anxiety  Insomnia  Tremor  Seizures Buspirone:  Partial agonist at 5HT 1Areceptors  Also low affinity 2 -receptor antagonist – leads to side effects  Originally developed as an anti-psychotic  Only recommended when SSRI’s & SNRI’s fail  Used to treat anxiety o Can be effective as benzodiazepines by 4-6 weeks (therapeutic lag) o Safer long term than benzodiazepines  NO withdrawl syndrome  NO evidence for tolerance or dependence  NO sedation – safer in overdose  Side effects (generally subside over time or with decreased dosage):
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