Migraine/Depression Flashcards
Outline the synthesis of serotonin
Derived from Tryptophan
Tryptophan -> 5-hydroxytryptophan by tryptophan hydroxylase -> 5-Hydroxytryptamine by DOPA decarboxylase.
List 3 locations where serotonin (5HT) is found in the body
- GI tract (chromaffin cells)
- Platelets
- CNS
List 4 functions of serotonin
- Platelet aggregation
- GI motility (excites ENS + GI smooth muscle)
- Stimulation of peripheral nociceptors
- Mood regulation
List the 4 hypotheses governing anti-depressant medication use
- Mono-amine hypothesis
- Autoreceptor hypothesis
- HPA -axis hypothesis
- Neurogenesis hypothesis (BDNF)
Outline the mono-amine hypothesis for + against
-> Postulates that depression is due to a reduction in mono-amines serotonin, noradrenalin, dopamine.
-> Drugs that decreased mono-amine levels by increasing their metabolism resulted in higher levels of depression.
-> Drugs that increased mono-amines by inhibiting their metabolism (MAOIs) resulted in improved mood.
-> However: Not everyone responds to anti-depressants suggesting a complex aetiology.
-> Difficult to get solid evidence in terms of mono-amine levels/ receptors.
-> The delayed anti-depressant effects of AD’s despite quick onset of side effects suggest that the anti-depressant effects are due to secondary effects and not due directly to the AD’s.
outline the HPA-axis hypothesis
-> Suggests that HPA-axis dysregulation contributes to depression.
-> Dysregulation results in lack of negative feedback from excess cortisol levels, also results in elevated CRH + ACTH.
-> elevated CRH associated with depressive symptoms
-> Elevated cortisol associated with excitotoxicity in the hippocampus/frontal cortex through NMDA (glutamate) receptor activation.
Outline the neurogenesis theory
Refers to role of BDNF
-BDNF levels found to be low in those with depression.
- BDNF’s normal role is neurogenesis/ encouraging synapse + neuronal development.
-Anti depressants thought to increase BDNF synthesis thereby promoting neurogenesis of the hypothalamus thereby offsetting depression.
Outline the autoreceptor theory
Antidepressant’s cause densensitization of serotonin autoreceptor 5-HT1a.
-> These receptors normally function to inhibit serotonin release in response to negative feedback from high serotonin levels in synaptic cleft.
-> By desensitizing these receptors, the autoreceptors no longer respond to the negative feedback, and instead continue to release serotonin.
-> This could potentially explain why anti-depressant effects take weeks to kick in as autoreceptor desensitization occurs only after chronic exposure to the drugs.
What is the criteria to be diagnosed with depression? What is the ICD10 scale.
2x core symptoms need to be present for atleast 2 weeks, most of the day, everyday.
These 2 symptoms are Anhedonia and/or feelings of persistent sadness/depression.
List 4 depression subtypes
- Recurrent depressive disorder
- at least 2 episodes of depression. - Dysthymia/ Persistent depressive disorder
- >2 years of continuous mild depression. - Psychotic depression
- depression with psychosis; hallucinations/delusions.
4.Pre/post natal depression
- affects 7-10% of new mothers.
What is meant by Cyclothymia?
Cyclothymia refers to unstable mood whereby there are fluctuations between depression and hypomania but not severe enough to be classed as Bipolar.
Name 2 areas of the brain thought to be affected in depression and outline their normal role
Frontal cortex
-Behaviour and emotion.
Hippocampus
-Memories and emotions.
What is the first line anti-depressant ? Give 4 examples of this group of AD’s
SSRIs - Selective Serotonin Reuptake inhibitors
-Fluoxetine
-Paroxetine
-Citalopram
-Sertraline.
What anti-depressants are absolute contraindication for cardiovascular disease? Give 2 examples of this group.
MAOI’s Mono-amine oxidase inhibitots
-Tranylcypromine
-Phenelzine
Use sertraline (SSRI) instead
What is the “cheese” reaction in MAOI’s?
MAOI’s can reduce the first pass metabolism of tyramine, found in foods such as cheese/wine.
-> excess tyramine can cause acute rise in BP
List 3 ADR’s for MAOIs
Hypotension
Hypoglycemia
GI upset
List 3 ADRs of TCA’s
Postural hypotension (alpha 1 blocker)
Prolonged QT
Lowers seizure threshold
List 2 TCA’s
Amitryptaline
Clomipramine
List 3 ADR’s of SSRI
Nausea - 5HT stimulates CTZ
GI bleeding due to anti-platelet effects
Hyponatremia (increased ADH)
Sexual dysfunction
-reduced NO
-alpha blocker
-sedation
List 2 SNRIS and 3 ADRs
- Venlafaxine
- Duloxetine
ADRS
-HTN
-Restlessness
-sweating
-sexual dysfunction
What is meant by “Augmentation”? When is it used? List 2 common drugs for augementation
*Augmentation is the addition of another non-antidepressant drug to the patient’s treatment regimen in order to try enhance the overall therapeutic effect/Remission.
*Used in cases of refractory depression whereby patient has failed to achieve remission after atleast 2 different pharmacological AD options.
2 common drugs
- Lithium
-Tri-iodothyronine (T3)
Outline how T3 hormone functions in depression managment
T4 is converted to T3 intracellularly within the CNS:
-> Can alter gene expression of those genes coding for the 5-HT1a/1b receptors
-> This can alter their sensitivity to serotonin thereby ultimately increasing serotonin neurotransmission in synpatic cleft.
-> inhibits the autoreceptor 5-HT1a and so it is no longer responding to negative feedback from high concentrations of serotonin in cleft.
Management approach for mild depression?
NICE guidelines:
Anti-depressants not advocated.
Watchful waiting +/- CBT is advisable.
What is management approach when prescribing anti-depressants?
Titrate drug slowly to therapeutic dose
Trials for 2 weeks then review patient again.
If effective: continue for 6 - 9 months.
If not: trials another drug.
AD’s will fail to achieve remission in 1 in 3 patients.
