PH3113 - Psychiatric Disease and its Pharmacology 7 Flashcards
What are the classes of drugs used to treat depression?
Tricyclic antidepressants
- TCAs
Selective Serotonin Reuptake Inhibitors
- SSRIs
Serotonin and Noradrenaline Reuptake Inhibitors
- SNRIs
Monoamine Oxidase Inhibitors
- MAIOs
- irreversible
- reversible
Atypical antidepressants
- noradrenaline Reuptake Inhibitors
- NRIs
How do antidepressants work?
Increase monoaminergic signalling
Signalling change may bring about numerous cellular changes that result in amelioration of the symptoms of depression including
- receptor desensitisation/downregulation
- autoreceptors
- receptor potentiation
- AMPA
- modification of BDNF expression
- neurogenesis
What is serotonin syndrome?
Rare but potentially life threatening adverse drug reaction as a consequence of excessive stimulation of CNS and peripheral serotonin receptors
- anti-depressants
- SSRI
- SNRI
- TCA
- MAOI
- St. John’s wort
- Lithium
- analgesics
- tramadol
- pethidine
- fentanyl
- dextromethorphan
- anti-emetics
- odansetron
- metoclopramide
- recreational
- cocaine
- MDMA
- amphetamine
- LSD
- others
What is the next step if a patient does not respond to 3 anti-depressants?
Check concordance
Review diagnosis
Consider social problems
Consider augmentation
- mirtazapine
- quetiapine
- aripiprazole
- lithium
- lamotrigine
- electroconvulsive therapy
- ECT
How effective are anti-depressant drugs?
The more severe the symptoms, the more effective the anti-depressant
- compared to placebo
Usually used for moderate - severe illness
- 20% recover with no treatment
- 30% respond to placebo
- 50% respond to anti-depressant
How long does it take for anti-depressants to become effective?
2 - 4 weeks to see response
- longer in elderly
Improvement greatest during weeks 1 and 2
- if no improvement during that period, consider switching to alternative
- extended duration of treatment trial will lead to additional benefit in some
What is the relapse rate when using anti-depressants?
Relapse rate 3-6 months post remission is 50% with no drug treatment
Anti-depressant treatment reduces absolute risk of relapse by about 50%
After 1st episode continue for 6 - 9 months
After 2nd episode continue for 12 months
After 3rd episode continue for 2 years
Give examples of new treatments for depression
Repetitive transcranial magnet stimulation
- rTMS
Vagal nerve stimulation
Light therapy
- useful in seasonal affective disorder
Modulation of glutamate neurotransmission
- ketamine
What is electroconvulsive therapy?
Used in severe treatment resistant depression or treatment resistant mania
- can also be used to treat
- catatonia
- severe post-natal depression
Up to 70% efficacy
- most effective in older people with depression or people with psychotic depression
Uncertain mechanism of action
- possibly causes release of Brain-deprived neurotrophic factor
Patient is given anaesthetic and muscle relaxant and electric current passed through the brain to trigger a seizure
Usually given twice weekly and response seen within the first few weeks
What are the risks associated with electroconvulsive therapy?
General anaesthesia
Can cause short-term memory loss
What is bipolar disorder?
Chronic, severe mental illness affecting approximately 0.5% of the population more common in women
Characterised by two or more episodes where the patient’s mood and activity is disturbed
- elevation of mood with increased energy and activity
- mania bipolar I
- hypomania bipolar II
- low mood with decreased energy/activity
- episodes are separated by a period of euthymia or a switch to the opposite symptom type
What are the features of a manic episode?
Elevated mood out of keeping from person’s circumstances
- increased energy/activity
- pressure of speech
- flight of ideas
- reduced sleep
- distractability
- inflated self-esteem
- grandiose ideas/delusions
- loss of inhibitions
- inappropriate behaviour
- reckless/risk taking behaviour
How common is bipolar disorder?
Usually presents in young adulthood
- causes
- genetic
- stronger inheritance that any other psychiatric disorder
- 10% risk in first degree relatives
- 79% concordance in monozygotic twins
- less evidence for environmental factors/life events
- possible role of hypothalamic-pituitary-adrenal axis
High risk of suicide
- 20x general population
- 1/3 to 1/2 attempt at some point
Significant delay between disease onset and diagnosis
No direct mendelian inheritance or genes of major effects
Long term implications with
- cognitive effects
- cardiovascular disorders
- diabetes
- obesity
What is the pathophysiology of bipolar disorder?
Evidence for involvement of monoaminergic pathways
- no single dysfunction identified
Synaptic and neuroplasticity implicated
Common with
- depression
- brain-derived neurotrophic factor (BDNF)
- spine density
Common genetic pathways implicate aberrant calcium signalling through voltage-gated calcium channels
Pathology supports altered calcium signalling
- alleviated by lithium
How is mania treated?
Increased dopamine activity
- amphetamine can induce a manic state
Antipsychotics are effective anti-manic agents
Lithium withdrawal can precipitate mania
- only an indirect effect on dopamine
Antipsychotic or sodium valproate (or both)
- olanzapine may b slightly superior to valproate
- patients with bipolar may be more susceptible to antipsychotic adverse effects
- usually treat for 2 - 3 months then consider maintenance options
