Anxiety & depression

Question 1

example of Tricyclic antidepressants (TCA)

Answer 1

amitriptyline

imipramine

Question 2

example of SSRI

Answer 2

fluoxetine

citalopram

Question 3

Example of SNRI

Answer 3

venlafaxine

duloxetine

Question 4

Example of MAO-I

Answer 4

Selegiline

Question 5

Name an atypical AD

Answer 5

Buproprion

Question 6

TCA adverse effects

Answer 6

anti-cholinergic (confusion, urinary retention, blurred vision, dry mouth, constipation, tachycardia); anti-histaminic (sedation, weight gain), and alpha-blocking (postural hypotension) side-effects

Question 7

Contra-indications for TCA

Answer 7

closed-angle glaucoma (anti-cholinergic properties), BPH (benign prostatic hyperplasia), MI, arrythmia.

Question 8

Safest TCA in early pregnancy

Answer 8

Amitryptilline

Question 9

Complications in TCA overdose

Answer 9

Cardiac toxicity – sinus tachycardia (due to anticholinergic effect, worsened by hypotension); refractory hypotension (alpha-1 adrenergic receptor blockade with decreased peripheral resistance, impaired sodium input resulting in impaired myocardial contractility thus contributing to hypotension and decreased cardiac output); cardiac conduction abnormalities (due to inhibition of fast sodium channels, delayed AV conduction, risk of arrythmias).

CNS toxicity – delirium, lethargy, seizures, coma (inhibition of fast sodium channels in the CNS, antagonism of GABA A receptors (seizures), antihistaminic effects)

Question 10

MOA of SSRI

Answer 10

In addition to serotonin reuptake inhibition, fluoxetine has NE reuptake inhibition (clinically relevant at high doses), CYP450 2D6 and 3A4 inhibition, and serotonin 2C antagonist actions (activating effects).

CYP450 2D6 and 3A4 needed for some metabolizing processes – need to check for drug-drug interactions

Question 11

Adverse effects SSRI

Answer 11

No cardiac, no anti-cholinergic and no antihistaminic side-effects. Yet, sexual dysfunction (ejaculatory dysfunction, anorgasmia) is a class effect. 
Nausea and vomiting; energising (not sedation - POTENTIATE SUICIDALITY) and initially anxiogenic (start low, go slow). Can cause weight gain / weight loss.

Question 12

Age groups of SSRI

Answer 12

In younger age groups, TCAs rather SSRIs. Contra-indicated in adolescents/children – may potentiate suicidality.

Question 13

Contra-indications of SSRI

Answer 13

Suicidality
Existing sexual dysfunction
Patients of anti-coagulants/warfarin

Question 14

SSRI in pregnancy

Answer 14

SSRIs relatively safe in early pregnancy (late pregnancy risk of neonatal pulmonary hypertension, apnea, floppy syndrome).

Question 15

Why not SSRI when on anticoagulants?

Answer 15

5-HT in brain, gut and platelets – SSRIs block serotonin uptake in platelets, thus increased risk of bleeding; warfarin and SSRI’s contra-indicated.

Question 16

Clinical signs of serotonin syndrome

Answer 16

Neuromuscular hyperactivity:
–tremor, sustained clonus (pathognomonic; mostly if high doses of SSRI’s used, if other serotonergic agents used), hyperreflexia, rigidity
Altered mental state:
–agitation, confusion
Autonomic hyperactivity
–fever, sweating, tachycardia, tachypnoea, diarrhoea

Question 17

Rx of Serotonin syndrome

Answer 17

Stop drug, benzodiazepine

Question 18

Factors when choosing AD

Answer 18

Efficacy similar
Advocate monopharmacy
Safety profile and cost determinants

Question 19

Mianserin - MOA, advantages, side-effect

Answer 19

Mianserin and mirtazepine - tetracyclic antidepressants, alpha 2 antagonists. Not a SSRI, not a TCA. Unlike the tricyclic antidepressants, it does not prevent peripheral reuptake of NE, but releases 5-HT and NE into the synaptic cleft. Free of anticholinergic side-effects (useful in patients with prostatic enlargement; closed-angle glaucoma), not cardiotoxic, no risk of OD. Potentially anti-histaminic side-effect with sedation; and weightgain. Serious risk of neutropenia and agranulocytosis – do baseline and follow-up WCC.

Question 20

Venlaflaxine - MOA, disadvantages, indications, adverse effects

Answer 20

Venlafaxine – SNRI – at lower doses only has serotonin reuptake inhibition; at higher doses has NE reuptake inhibition (not the case with duloxetine, which has uptake inhibition of both at low and high doses). Thus, at lower doses, acts as SSRI. Problem with venlafaxine – discontinuation/withdrawal syndrome; follows interruption/reduction/discontinuation of drug. Can present with paresthesiae, ataxia/dizzyness, lethargy, insomnia, anxiety, agitation. Consider drug only when patient poorly responsive to others.