18.1.4 - Other Antidepressants

Front 1

Miscellaneous antidepressants
- drugs in "class", including buproprion
- how do they work?

Back 1

mianserin & mirtazapine - NaSSA / tetracyclic piperazinoazepines, chemically similar to TCAs. Blocks alpha-2 (primary action with Mirtazapine), increasing NA (and 5HT with Mirtazapine), blocks 5HT 2&3 (decreases nausea, anxiety and insomnia as with SSRIs), and blocks H1 (causes drowsiness, which is ameliorated partially by increased NA).
venlafaxine - SNRI
duloxetine - SNRI
moclobemide - reversible MAOI
buproprion - Inhibits reuptake of NA and Dopamine
reboxetine - NaRI, week inhibition of seritonin reuptake

Front 2

Mianserin
- what conditions may be worsened?

Back 2

Epilepsy, reduced seizure threshold—mianserin may increase seizure frequency; AVOID use.

Bipolar disorder—all antidepressants may provoke a manic episode when used in people with bipolar disorder. Some patients without a history of bipolar disorder may develop an antidepressant-induced manic episode; this does not necessarily imply a diagnosis of bipolar affective disorder.

Front 3

Mianserin
- of the general cautions, which apply (i.e. surgery, elderly, RF, LF, preg, bf)

Back 3

Renal: Start with a low dose in renal impairment.

Elderly: Start with a low dose.

Pregnancy: Human data limited; ADEC category B2.

Breastfeeding: Contact one of the pregnancy drug information centres.

Front 4

Mianserin
- Three common SEs
- How do it's side effects compare to the TCAs?

Back 4

Most common: sedation, dry mouth, dizziness, vertigo
1. More sedation (dose related, may limit usefulness).

2. Less CV effects, weight gain, toxicity in OD (more than SSRIs)

3. Potential for blood dyscrasias (esp neutropenia>> and agranulocytosis), hepatotoxicity

Front 5

Mianserin
- Monitoring required

Back 5

Baseline CBC. Repeat after 4-6 weeks or if there are signs of neutropenia (sore throat, infection) - TG
Baseline and every month for 3 months - AMH
Baseline LFTs - AMH

Front 6

Mianserin
- Drug interactions

Back 6

1. MAOIs but not ss
2. Sedation: Barbituates, alcohol
3. Seizures

Front 7

Mianserin
- dose forms, brands
- dosing, inreasing doses, dd
- PBS

Back 7

- 10mg.50, 20mg.50 tabs (Lumin, Tolvon)
- 30-120mg d (start at 10mg and increase slowly if old, RI)
- Increase at 10-20mg every 2-3 days
- Give as a single dose nocte, or in 2-3 dd if insomnia occurs
- PBS-R for severe depression

Front 8

Mirtazapine
- dose forms
- brands
- dosing
- PBS

Back 8

- 15mg, 30mg, 45mg.30 tabs(Mirtazon, Avanza)
- WAFERS (Avanza SolTab)
- 15-60mg n
- PBS-R for MDD

Front 9

Mirtazapine
- Side effect profile

Back 9

Common
increased appetite, weight gain, sedation, peripheral oedema

Rare
seizures, granulocytopenia, agranulocytosis

Front 10

Mirtazepine
- what conditions worsened?

Back 10

Epilepsy, reduced seizure threshold—mirtazapine lowers seizure threshold; use low doses and titrate slowly.

Bipolar disorder—all antidepressants may provoke a manic episode when used in people with bipolar disorder. Some patients without a history of bipolar disorder may develop an antidepressant-induced manic episode; this does not necessarily imply a diagnosis of bipolar affective disorder.

Front 11

MirtazApine
- Other considerations for use?

Back 11

1. allergy to mianserin (closely related structure)
2. Preg cat B3, contact a PIC re Preg and BF

Front 12

Withdrawal of Mirtazapine

Back 12

Over 1-2 weeks

Front 13

When is Avanza useful?

Back 13

Atypical depression: insomnia, weight loss, anxiety

Front 14

Counselling points for Avanza and Lumin?

Back 14

Avanza: L1, L9
Lumin/Tolvon: L1, L16, L9

Front 15

Moclobemide
- dose forms, brands
- doses, increase ionterval , dd
- PBS

Back 15

- 150mg, 300mg tabs (Aurorix, Arima, Amira, Maosig, Mohexal)
- 450-600mg d (start on 300mg d and increase after 2 weeks); take as 1-2 dd

Front 16

Maosig
- conditions worsened

Back 16

NOT SEIZURES
Bipolar disorder—all antidepressants may provoke a manic episode when used in people with bipolar disorder. Some patients without a history of bipolar disorder may develop an antidepressant-induced manic episode; this does not necessarily imply a diagnosis of bipolar affective disorder.

Front 17

Other considerations for Mohexal?

Back 17

Hepatic: Reduce dose in severe impairment.

Surgery: Stop moclobemide 24 hours before elective surgery. Pethidine and tramadol may cause increased restlessness and agitation.

Pregnancy: Contact one of the pregnancy drug information centres; ADEC category B3.

Breastfeeding: Appears to be safe; contact one of the pregnancy drug information centres.

Front 18

Amira - Side Effects

Back 18

Common
nausea, dry mouth, constipation, diarrhoea, anxiety, restlessness, insomnia, dizziness, headache

Front 19

Arima - Counselling points

Back 19

Moclobemide is best taken with, or soon after, food.

Take doses no later than early afternoon or you may have trouble sleeping at night.

Although moclobemide is unlikely to affect your ability to drive or operate machinery, be careful with these types of tasks until you know how you are affected.

l9

Front 20

Aurorix
- in what other condition is it not a good idea to use this, besides bipolar disorder?
- tyramine diet?
- toxicity in overdose?
- relative risk of sexual dysfunction?

Back 20

- avoid use in acute confusional states (agitation)
- low tyramine diet is not usually required below the maximum dose UNLESS ALSO USING SELEGELINE
- relatively nontoxic in overdose
- and less likely to cause sexual dysfunction than nonselective MAOIs and SSRIs

Front 21

Reboxetine
- dose forms, doses, brands
- PBS

Back 21

Edronax, 4mg.60 tabs
- 2mg-6mg bd; start on 2 if elderly, sig RI or LF; increase from 4mg only after 3 weeks

Front 22

Edronax
- Side effects

Back 22

Common
urinary retention, dry mouth, sweating, paraesthesia, constipation, increase in diastolic BP, increase in heart rate, impotence, insomnia, headache

Front 23

Edronax
- counselling points

Back 23

Be careful driving or operating machinery until you know how reboxetine affects you.

Tell your doctor if you have difficulty urinating.

Front 24

Edronax
- monitoring required

Back 24

monitor BP and heart rate at baseline (and if the dose is increased), then each week until stable, then as clinically indicated

Front 25

Reboxetine
- what conditions worsened?

Back 25

Closed angle glaucoma—weak mydriatic effect.

Epilepsy—may increase seizure frequency.

Hypertension—may alter control of treated hypertension.

Hyperthyroidism—enhanced response to reboxetine.

Prostatic hypertrophy, urinary retention—may precipitate or exacerbate urinary retention.

Bipolar disorder—all antidepressants may provoke a manic episode when used in people with bipolar disorder. Some patients without a history of bipolar disorder may develop an antidepressant-induced manic episode; this does not necessarily imply a diagnosis of bipolar affective disorder.

Front 26

Reboxetine
- other considerations?

Back 26

Renal
Use lower dose in moderate-to-severe renal impairment (clearance reduced).

Hepatic
Use lower dose in moderate-to-severe hepatic impairment (clearance reduced).

Elderly
Reduce initial dose.

Pregnancy & BF: B1, Contact one of the pregnancy drug information centres

Front 27

Reboxetine DIs (3)

Back 27

CYP3A4 inducers and inhibitors (e.g. fluvoxamine)

MAOIs - manufacturer CI COMBINED use but there is no evidence of an interaction... [except hypertensive crisis]

Drugs which increase BP (e.g. moclobemide)

Seizures

Front 28

Mirtazapine DIs (4)

Back 28

1. Fluvoxamine may increase levels
2. CBZ and Phenytoin may decrease levels
3. seizure threshhold

Front 29

Moclobemide DIs (3 main types)

Back 29

1. Increases BP, hypertensive crises (less likely than with MAOIs) - e.g. reboxetine, adrenalin, dopamine, ephedrine, linezolid[weak MAOI], amphetamines, methylphenidate, PSE/PE, selegeline
2. Seritonin syndrome
3. Inhibits breakdown of sumatriptan, increasing risk of ischaemia; although no AEs reported, CI by manufacturer. Use naratriptan instead; do not use sumatriptan within 2 weeks of stopping a MAOI. Avoid zolmitriptan or limit to 5mg d.

After stopping moclobemide allow at least 2 days before beginning drugs which interact

Front 30

What if moclobemide + selegeline is used?

Back 30

moclobemide + selegiline
Selegiline inhibits MAO-B and moclobemide inhibits MAO-A; follow MAOI dietary restrictions if used together, see Counselling.

Front 31

What if moclobemide + sibutramine is used?

Back 31

Moclobemide is a reversible inhibitor of MAO-A; combination with sibutramine increases synaptic serotonin and the risk of serotonin toxicity; combination contraindicated by manufacturer (an interval of at least 2 weeks between treatments is recommended).

Front 32

Arima + tramadol/pethidine

Back 32

Combination may cause CNS excitation or depression, hypertension or hypotension; avoid using tramadol within 2 days of moclobemide treatment. Stop Arima 2 days before surgery in case of use of these drugs.

Front 33

What about Aurorix + TCAs?

Back 33

Not recommended - SS
(risk probably greatest with clomipramine, amitriptyline and imipramine)

Front 34

Amira + Venlafaxine

Back 34

CONTRAINDICATED - SS

Front 35

Venlafaxine
- dose forms, brands, dosing, PBS

Back 35

Efexor-XR: 37.5, 75, 150, tabs
- 75-300mg d MAX
- 37.5mg d if hepatic impairment, renal impairment
- Doses of up to 150-225mg d may be needed for MDD

Front 36

Efexor - counselling

Back 36

Take with food to minimise stomach upsets.

Do not open, crush or chew controlled release capsules, or put them in water.

Be careful driving or operating machinery until you know how venlafaxine affects you.

Do not stop taking this medicine suddenly unless your doctor tells you to.

Front 37

Venlafaxine practice points
- monitoring
- overdose toxicity?
- panic disorder?
- withdrawal schedule?

Back 37

1. BP at baseline et.al. especially with doses >200 mg daily
2. toxic in overdose; ECG changes, arrhythmias and seizures, some fatalities
3. how venlafaxine compares with standard treatments for panic disorder is not known
4. whenever practical, and especially after completing a course of treatment, withdraw over at least 2 weeks; some advise decreasing the dose by 10–15% every 4 days

Front 38

Withdrawal effects of Venlafaxine?

Back 38

Similar to SSRIs: dizziness, nausea, paraesthesia, anxiety, agitation, tremor, sweating, confusion, electric shock-like sensations

Front 39

How do antidepressants compare in terms of toxicity in overdose?

Back 39

SSRIs, reboxetine, mirtazapine, mianserin and moclobemide are probably the least toxic of all antidepressants in overdose.

Venlafaxine is more toxic than the group listed above.

TCAs and MAOIs are the most toxic in overdose; avoid using them if there is a high risk for overdose/suicide.

Front 40

Efexor A/Es

Back 40

Common
nausea, vomiting, anorexia, headache, sweating, anxiety, dizziness, fatigue, hypertension (dose-related), tremor

Infrequent
sexual dysfunction (eg impotence), loss of libido, dry mouth, insomnia, somnolence, constipation, hyponatraemia, ECG changes, palpitations, abnormal LFTs

Front 41

Venlafaxine - what condition is worsened by Efexor, aside from BPD and seizure disorder?

Back 41

Hypertension—may be exacerbated by venlafaxine; manufacturer suggests hypertension be controlled before treatment.

Front 42

Venlafaxine - other considerations

Back 42

Renal: Halve dose in severe impairment

Hepatic: Halve dose in severe impairment.

Pregnancy: Exposure in late pregnancy may result in withdrawal symptoms in newborns. Contact one of the P-DIC, B2.

Breastfeeding: Contact P-DIC

Front 43

Efexor - Indications

Back 43

Major depression

Generalised anxiety disorder

Panic disorder

Social phobia

Front 44

Aurorix - Indications

Back 44

Marketed: Major depression

Accepted
Panic disorder, Social phobia