Depression

Question 1

Pathophysiology
Depression

Answer 1

A depletion of the neurotransmitters serotonin, norepinephrine or dopamine in the central nervous system

Question 2

Rationale for drug use
Depression

Answer 2

Relieve psychological and physical symptoms.

Improve functional capacity.

Reduce the likelihood of self-harm or suicide.

Question 3

Diagnostic criteria
Depression

Answer 3

Pervasive depressed mood (or irritable mood in children) and/or marked loss of interest or pleasure unexplained by personal circumstances, eg grief, plus 4 or more of the following:

• marked change in weight or appetite
• insomnia/hypersomnia nearly every day
• psychomotor agitation/retardation nearly every day
• fatigue/loss of energy nearly every day
• feelings of worthlessness, excessive/inappropriate guilt
• indecisiveness or diminished concentration
• feelings of hopelessness
• thoughts of death, suicidal ideation/attempt.

Question 4

What to consider when choosing an antidepressant

Answer 4

• Previous response
• adverse effects
• Drug interactions
• Serotonin toxicity

Question 5

Drug treatment
Depression

Answer 5

1. SSRIs
2. Nonselective MAOIs (phenelzine, tranylcypromine) when other treatments are not tolerated

Other:
TCA
SNRI
Melatonin Agonist
TeCA
NaRI

Question 6

Drug class
Monoamine oxidase inhibitors

Answer 6

Antidepressants

Question 7

Generic drug names
Monoamine oxidase inhibitors

Answer 7

Phenelzine
Tranylcypromine

Question 8

MAOI a.k.a.

Answer 8

Monoamine oxidase inhibitors

Question 9

Monoamine oxidase inhibitors a.k.a.

Answer 9

MAOIs

Question 10

Indication
MAOIs

Answer 10

Major depression (third line)
Some anxiety disorders

Question 11

MOA
MAOIs

Answer 11

Nonselective MAOIs irreversibly inhibit monoamine oxidases A and B (MAO‑A and MAO‑B), increasing the synaptic concentrations of adrenaline, noradrenaline, dopamine and serotonin.=

Question 12

Precautions
MAOIs

Answer 12

Overdose carries high risk of fatality; avoid MAOIs if there is a high risk for overdose/suicide.!!!

• Treatment with rizatriptan or sumatriptan—contraindicated (risk of ischaemia is increased as their metabolism is inhibited).
• Angina—MAOIs may reduce pain associated with myocardial ischaemia; use with caution.
• Epilepsy, history of seizures or other risks for reduced seizure threshold, including treatment with drugs that may increase the risk of seizures (table)—MAOIs may increase the risk of seizures (risk less than with TCAs); use low doses and titrate slowly. Note that depression may also increase the risk of seizures.
• Diabetes—MAOIs may reduce blood glucose concentration, possibly affecting control of diabetes; the dose(s) of antidiabetic drugs may need to be reduced.

Question 13

Adverse effects
MAOIs

Answer 13

orthostatic hypotension, sleep disturbances (including insomnia and less commonly hypersomnia), headache, drowsiness, fatigue, loss of libido

Question 14

Counselling
MAOIs

Answer 14

• It is best to take your last dose of the day before 3 pm or you may have trouble sleeping at night.
• Sometimes people who take large amounts of caffeine feel jittery or get headaches when they take this medicine. If this happens, reduce the amount of caffeine you take.
• This medicine may cause drowsiness and increase the effects of alcohol; do not drive or operate machinery if you are affected.
• significant interactions with other medicines (eg hay fever or cold treatments and weight-reducing products). Do not use non-prescription medicines (even nasal sprays) or herbal products, eg St John’s wort, without discussing these with a pharmacist.

Question 15

Practice points
MAOIs

Answer 15

MAOIs are third-line antidepressants, and are usually reserved for use by psychiatrists; they may be useful in atypical depression and psychotic depression; some specialists use MAOIs for post-traumatic stress disorder

Question 16

Drug class and indication

Phenelzine

Answer 16

Antidepressants - MAOIs
Major depression

Question 17

Drug class and indication

Tranylcypromine

Answer 17

Antidepressants - MAOIs
Major depression

Question 18

Drug interactions
MAOIs

Answer 18

MAOIs can cause hypotension; administration with other drugs* that can also reduce BP may result in an additional effect; monitor effect of combinations closely.
MAOIs can cause serotonin toxicity; administration with other drugs that may contribute to serotonin toxicity (table) may increase likelihood; avoid combinations or monitor carefully

Bad / many drug interactions with any drugs such as adrenaline that act on sympathetic nervous sytem

adrenaline + MAOIs
cocaine + MAOIs
dopamine + MAOIs
noradrenaline + MAOIs
pseudoephedrine + MAOIs
SSRIs + MAOIs

Question 19

“pram”, “ine” suffix

Answer 19

SSRIs
Selective serotonin reuptake inhibitors

Antidepressants

Question 20

Suffix
SSRIs / Selective serotonin reuptake inhibitors

Answer 20

“pram”, “ine”

Question 21

Drug class
SSRI

Answer 21

Antidepressants

Question 22

SSRI a.k.a.

Answer 22

Selective serotonin reuptake inhibitors

Question 23

Generic drug names
SSRIs

Answer 23

Citalopram
Dapoxetine
Escitalopram
Fluoxetine
Fluvoxamine
Paroxetine
Sertraline

Question 24

Indication
SSRIs

Answer 24

Major depression

Question 25

**MOA** SSRIs

Answer 25

SSRIs selectively inhibit the presynaptic reuptake of serotonin

Question 26

**Precautions** SSRIs

Answer 26

**Bipolar disorder**—all antidepressants may provoke a manic episode when used in people with bipolar disorder **Risk of bleeding**

Question 27

**Adverse effects** SSRIs

Answer 27

nausea, diarrhoea, agitation, insomnia, drowsiness, tremor

Question 28

**Counselling** SSRIs

Answer 28

SSRIs are usually taken in the **morning** to **minimise insomnia**, but if somnolence occurs, they can be given in the evening. **Do not drive** or operate machinery until you know how this medicine affects you. **Do not stop** taking this medicine suddenly

Question 29

**Practice points** SSRIs

Answer 29

* **SSRIs are less likely to alter ability to drive** or operate machinery than TCAs in depression, * increasing the SSRI dose may not provide further improvement * **increased suicidal thoughts** and behaviour can occur soon after starting antidepressants, particularly with some SSRIs in young people; monitor patients frequently and carefully early in treatment * **sexual dysfunction** is an adverse effect that may affect compliance

Question 30

# Drug class and indication Citalopram

Answer 30

**SSRI** Major depression

Question 31

# Drug class and indication Escitalopram

Answer 31

**SSRI** Major depression GAD Social phobia OCD

Question 32

# Drug class and indication Fluoxetine

Answer 32

**SSRI** Major depression OCD Premenstrual dysphoric disorder

Question 33

# Drug class and indication Fluvoxamine

Answer 33

**SSRI** Major depression OCD

Question 34

# Drug class and indication Paroxetine

Answer 34

**SSRI** Major depression OCD Panic disorder GAD PTSD Social phobia | GAD = generalised anxiety disorder

Question 35

# Drug class and indication Sertraline

Answer 35

**SSRI** Major depression OCD Panic disorder Social phobia Premenstrual dysphoric disorder

Question 36

**Drug interactions** SSRIs

Answer 36

* SSRIs can cause **serotonin toxicity**; administration with other drugs that may contribute to serotonin toxicity * SSRIs can **affect platelet aggregation** so that combinations with other drugs* that affect the clotting process may increase the risk of bleeding * MAOIs + SSRIs = Serotonin toxicity * SNRIs + SSRIs = Serotonin toxicity * tricyclic antidepressants + SSRIs = Serotonin toxicity * triptans + SSRIs = Serotonin toxicity * warfarin + SSRIs = risk of bleeding

Question 37

Serotonin and noradrenaline reuptake inhibitors **a.k.a.**

Answer 37

SNRIs

Question 38

SNRIs **a.k.a.**

Answer 38

Serotonin and noradrenaline reuptake inhibitors

Question 39

**Generic drug names** SNRIs

Answer 39

Desvenlafaxine Duloxetine Venlafaxine

Question 40

**Indication** SNRIs

Answer 40

Major depression

Question 41

**MOA** SNRIs

Answer 41

Inhibit serotonin and noradrenaline reuptake.

Question 42

**Precautions** SNRIs

Answer 42

* **Bipolar disorder**—all antidepressants may provoke a manic episode when used in people with bipolar disorder * **High risk of bleeding** * SNRIs may cause palpitations, tachycardia, increased BP and orthostatic hypotension * **Serotonin toxicity**

Question 43

**Adverse effects** SNRIs

Answer 43

**nausea, dry mouth, constipation**, yawning, sweating, **dizziness**, increased BP (infrequent with duloxetine), weakness, **sexual dysfunction**

Question 44

**Practice points** SNRIs

Answer 44

* **check BP** before starting treatment * increased **suicidal thoughts** and behaviour * **Do not stop** suddenly

Question 45

# Drug class and indication Desvenlafaxine

Answer 45

**SNRIs** Major depression

Question 46

# Drug class and indication Duloxetine

Answer 46

**SNRIs** Major depression GAD Painful diabetic peripheral neuropathy

Question 47

# Drug class and indication Venlafaxine

Answer 47

**SNRIs** Major depression GAD Panic disorder Social phobia | GAD = Generalised anxiety disorder

Question 48

**Drug interactions** SNRIs | Serotonin and noradrenaline reuptake inhibitors

Answer 48

**Antihypertensives** * effects BP control * Further decrease BP = hypotension **Serotonin toxicity** * Antidepressants * Opioids * MDMA, LSD **Anticoagulants** * increased risk of bleeding