Antidepressants II

Question 1

Names of SSRI drugs

Answer 1

• Fluoxetine (currently the most widely prescribed antidepressant)
• Citalopram

Question 2

Adverse effects of SSRI drugs

Answer 2

• Nausea
• Insomnia
  » Citalopram still has some histamine receptor antagonism leading to sedation.
• Sexual dysfunction
  » Men = delayed ejaculation
  » Women = delayed or blocked orgasm
  » Occurs due to increased stimulation of 5HT2 receptors, rarely leads to discontinuation
  »> Cyproheptadine or other 5HT2 blockers can be given to prevent SSRI-induced sexual dysfunction.

- Serotonin syndrome 
>> Severe reaction can result from drug-drug interactions with other drugs increasing serotoninergic activity (e.g. MAOIs). 
>> Effects include: 
>>> Tremor 
>>> Hyperthermia 
>>> Cardiovascular collapse

Question 3

Advantages of SSRIs

Answer 3

• Greater 5-HT reuptake selectivity than TCAs
• Possibly very wide therapeutic range (e.g. fluoxetine, 50-fold selectivity for 5-HT, citalopram, 1000-fold selectivity for 5-HT).
• Fewer adverse effects than TCAs
• Pharmacological features -> Clinical Benefits
  > Low affinity for α -adrenoreceptors -> lack of cardiovascular effects, safer in overdose.
  > Lack of effect at histamine receptors -> reduced sedation
  > low affinity for muscarinic cholinergic receptors -> minimal anticholinergic side effects (e.g. dry mouth and constipation)
• Overall SSRIs are safer in overdose and less side effects lead to better compliance.
• Improved adverse effects profile of SSRIs leads to better compliance and prescription of more adequate doses.

Summary of benefits of SSRIs
- SSRIs can offer better: 
>> Efficacy 
>> Safety 
>> Tolerability 

• First-line therapy

Question 4

Disadvantages of SSRIs

Answer 4

• 2/3 of the patient population gets remission
• Adverse effects especially at the start
• Discontinuation can be a problem in some

Question 5

Names of NARI drugs

Answer 5

Reboxetine, maprotiline

Question 6

Adverse effects of maprotiline

Answer 6

• TCA-like adverse effects
• Occasionally caused seizures
• Due to α-adrenoreceptor and histamine receptor effects.

Question 7

Adverse effects of reboxetine

Answer 7

• Dry mouth
• Constipation
• Insomnia
  » Due to increased NA activity in the CNS
• Tachycardia
  » Due to increased availability of NA at sympathetic “fright, flight or fight” synapses.

Question 8

Advantages of NARIs

Answer 8

• Greater NA reuptake selectivity than TCAs.

- Fewer adverse effects than TCAs and SSRIs

Question 9

Names of SNRI drugs

Answer 9

Venlafaxine, duloxetine

Question 10

Mechanism of Action of SNRI drugs

Answer 10

Similar dual 5-HT and NA reuptake inhibition profiles to non-selective TCAs.

Question 11

Adverse effects of SNRI drugs

Answer 11

• Serotoninergic adverse effects like SSRIs:
  » Nausea
  » Insomnia
  » Sexual dysfunction
• “Serotonin syndrome” when combined with other serotoninergic drugs and MAOIs.
• Withdrawal effects are more common and stronger than for SSRIs and TCAs.

Question 12

Advantages of Venlafaxine (SNRIs)

Answer 12

• Different structure to TCAs and fewer adverse effects than TCAs.
• Claimed to work slightly faster than other antidepressants.
• Claimed to work better in treatment-resistant patients.

Question 13

Mirtazapine

Answer 13

norepinephrine and specific serotonin antidepressant (NaSSA)

Question 14

Bupropion

Answer 14

norepinephrine-dopamine reuptake inhibitor

Question 15

Agomelatine

Answer 15

agonist of melatonin MT1 and MT2 receptors

Question 16

Ketamine

Answer 16

glutamate NMDA receptor antagonist

Question 17

Vortioxetine

Answer 17

novel class multimodal serotonergic antidepressant

may be efficacious to patients resistant to other antidepressants.

may cause suicidal thoughts and actions in children