Depression and Bipolar Flashcards
What are the 2 main symptoms of depression?
- Persistent low mood
- Loss of interest or pleasure
What are other symptoms of depression?
- Low energy/fatigue
- Worthlessness/excessive or inapp guilt
- Sucidal thoughts/plans etc
- Poor concentration
- Restlessness, agitation or slowed down in movt and thinking
- Change in sleep
- Change in appetie
- Concern over impeding death
Explain on the neuroanatomy of depression
- ↓ in patients suffering from severe depression (imaging studies)
- Prefrontal cortex
- Amygdala
- Hippocampus
What monoamine hypothesis of depression?
- Tricyclic antidepressants (Tacs) and monoamine oxidase inhibitors (MAOIs) heralded as 1st generation antidepressants
- Act by impacting NA and 5-HT neurotransmission
Why is the monoamine hypothesis of depression a poor hypothesis?
- Doesn’t meet all the other complexities associated with depression
- Limited in its link to depression
How is the HPA axis involved in depression?
Depressed patients displayed HPA hyperactivation:
* ^ Cortisol in saliva, plasma and urine
* ^ CRH in CSF and in limbic brain region
* ^ Size (as well as activity) of pituitary and adrenal glands
- Impaired negative feedback loop
- Antidepressants enhance the negative feedback and ↓ HPA axis hyperactivity
What is BDNF?
- Brain Derived Neurotrophic Factor:
- Regulates neurogenesis, development, dendritic growth, survival and maturation
What does the neurotrophic hypothesis of depression state?
- Proposes that depression is associated with reduced brain BDNF levels
- Antidepressants treatments alleviate depressive behaviour and ^ BDNF levels
What Neurotransmitters are involved in depression?
-
5-HT - Anxiety, obsessions, compulsions
* Depression due to ↓ 5-HT
2.NA - Alertness, anxiety, interest in life
* Role in reward and stress
3.DA - Attention, motivation, reward
* ↓ tyrosine (precursor to DA)
What are non-pharmacological managements of depression?
- CBT - Objective is to stop cycle of negative thinking that influences emotion and behaviour
- E.g.
1. Feeling: I feel anxious
2. Thoughts: I cant do this, whats wrong with me etc
3. Behaviour: Get away from the situation, avoid it in future
These can all interact back and forth with eachother.
What are the negatives of pharmacological managements of depression?
- Adverse effect profile
- Toxicity in overdose
- Interaction with other treatments
- Cost
What are 3 main modes of action antidepressants?
- Reuptake
- Receptor blockade
- MAO enzyme inhibition
What are the main classes of antidepressants?
- Tricyclic (TCA) antidepressant
- Monoamine Oxidase Inhibitor
- SSRIs
- Serotonin-Noradrenaline reuptake inhibitor
- Noradrenaline Reuptake inhibitor
- Mirtazapine
What are Tricyclic (TCA) antidepressants?
- Inhibit serotonin and noradrenaline reuptake
- E.g. Amitripyline
- Sedative properties
- Anticholinergic side effects (dry mouth, blurred vision etc)
- CV effects can be fatal on overdose
What are MAO?
E.g. Phenelzine
- Cheese reaction - tyramine displaces noradrenaline from vesical storage
What are SSRIs?
- First line option
- E.g. Fluoxetine, Paroxetine
- Favourable ‘side effects’ profile and less toxic in overdose
What are SNRIs?
- E.g. Venlafaxine
- Similar to SSRIs
What are Noradrenaline reuptake inhibitors?
E.g. Reoxetine
What is Mirtazapine?
- Enhances NA and 5-HT transmission
- Presyn a2-adrenoceptors responsible for inhib noradrenaline release
- Presyn 5-HT2 responsible for inhib 5-HT release are also blocked
How do you treat mild depression in < 18Yo?
- Psychologcal therapy e.g. CBT
How do you treat moderate-severe depression in < 18Yo?
- Psychological therapy
- Combined therapy i.e. psyho+Fluoxetine (SSRI)
- If unresponsive to combined therapy - consider alternative psychological therapy
- If experiencing side effects to fluoxetine –> Sertaline or citalopram
Explain the delay of clinical effects
- The main theory of delayed response to antidepressants: increasing neurotransmitters will increase activation of autoreceptors
- Which will cause less neurotransmitter to be released
- However, as a person continues to take the drug, the autoreceptors will become desensitised, so more neurotransmitters will be released
What is Bipolar disorder?
- Cycle between depressed mood and mania
Diagnosis:
* Eliminate misdiagnosis of bipolar disorder –> Differential diagnosis
* Confirmed by a specialist mental health professional
What are pharmacological interventions for bipolar?
Managing Mania
Acute:
* Antipsychotics - Haloperidol
* Longer term: Lithium
Managing Bipolar depression
* SSRI Fluoxetine combined with olanzapine
* Quetiapine alone
* Olanzapine alone
* Lamotrignine alone
What are the problems of Lithium?
- Narrow therapeutic window
- Must be tightly regulated
What are experimental treatments?
Ketamine (NMDA antagonist): Dysfunction of glutamatergic neurotransmission is found in patients with MDD
BDNF target: Recent findings demonstrated that TRKB was a target for antidep
