Depression Flashcards
Major types of drugs used in Depression
In the past:
Monoamine oxidase inhibitors
Tricyclic antidepressants
Now:
Selective serotonin reuptake inhibitor - SSRI
Noradrenaline Reuptake inhibitor - NARI
5-HT and Na Reuptake inhibitor - SNRI
Types of Unipolar depression
- Reactive depression
- non familial
- anxiety and agitation follows - Endogenous depression
- Familial pattern
- not directly related to external stress
Bipolar depression
alternating depression and mania
Mania - Extreme confidence / excitation
- Familial - genetic
- appears in adulthood
Monoamine theory
Deficits in monoamine neurotransmitters causes depression
Limitation:
- Initially devised with noradrenaline in mind -> Serotonin
- Monoamine deficits are not the only cause of Depression -> could be due to pure reduction of serotonin
What does Monoamine oxidase do?
MAO-A: Breaks down serotonin
MAO-B: Breaks down Dopamine
Inhibitors for MAO-B: Selegiline - used in Parkinsons
Parkinsons: Accumulation of Dopamine
Name a MAOI
Phenelzine
Characteristics of Phenelzine
- Nonselective MAOI
- Irreversible MAOI
Adverse effects of MAOI
- Postural hypotension
- Sympathetic block - Dopamine accumulation (MAO-B inhibition) at cervical ganglia -> inhibitory transmitter
- Restlessness / Insomnia -> more neurotransmitters available
Name the TCAs
Nonselective:
1. Imipramine
2. Amitrityline
3. Nortrityline - 2nd gen
milder effects + increased compliance
Selective for NET:
1. Desipramine
MOA of Tricyclic antidepressants
Nonselective for Serotonin Transporter (SERT) and Noradrenaline Transporter (NET) blocker
Adverse effects of TCA
- Sedation - H1 histamine receptor antagonism
- Postural hypotension - alpha-adrenoreceptor sympathetic block
- Parasympatholytic effects
- dry mouth
- blurred vision - DDI - protein bound = high bioavailability
Pharmacological benefits of SSRI
- fewer side effects than TCA
- Greater selectivity for 5-HT
- More efficient and tolerable - 66% undergo remission
MOA of SSRI
Targets serotonin transporters - block them
2 example of SSRI
- Fluoxetine - 50 fold
- Citalopram - 1000 fold
Adverse effects of SSRI
Rebound symptoms when plasma levels drop
- nausea
- insomnia
- sexual dysfunction
What is something to look out for while using SSRI / SNRI
Serotonin syndrome
What is serotonin syndrome?
Serotoninergic drugs that results in accumulation of Serotonin
- Tremor
- Hyperthermia
- CVS collapse
2 examples of NARI
- Reboxetine - 1000 fold selectivity
- Maprotiline - TCA-like action + adverse effects
MOA of NARI
Targets noradrenaline transporters - blocks it
Pharmacological benefits of NARI
- Greater selectivity for NA
- Fewer adverse effects than TCA and SSRI
Adverse effects of NARI
- Parasympatholytic effects
- Insomnia
- Tachycardia - increased availability of NA - sympathetic neurotransmitter
MOA of SNRI
Targets SERT and NET
3 examples of SNRI
- Venlafaxine
- Desvenlafaxine - synthetic metabolite of venlafaxine
- Duloxetine
Pharmacological benefits of SNRI
- Fewer side effects than TCA
- works faster than other antidepressants
- works better in treatment resistant patients
Adverse effects of SNRI
- Increased risk of Serotonin syndrome
- Serotoninergic AE - nausea, insomnia, sexual dysfunction
Name a norepinephrine-dopamine reuptake inhibitor (NDRI)
Bupropion
Name a Noradrenaline and specific serotonin antidepressant (NaSSA)
Mirtazapine
Name a Melatonin receptor agonist and its MOA
Agomelatine - works on MT1 and MT2
- less TCA and SSRI-associated AE
Helps in sleep disorders
Name a N-methyl-D-aspartate(NMDA) antagonist and its MOA
Ketamine - glutamate thats used as an anasthetic
- Rapid onset antidepressant effect
