18.1.3 - Tricyclic Antidepressants

Front 1

TCAs
Drugs in class (7)

Back 1

Imipramine
Clomipramine
Amitriptyline
Doxepin
Dothiepin
Nortriptylin
Trimipramine

Front 2

TCAs
1. Mode of action of group?
2. Clomipramine in particular?

Back 2

Inhibit reuptake of NA and 5HT
Unrelated to their therapeutic effects: block ACh, H1, Alpha-1, 5HT receptors
Clomipramine has a greater effect on serontonin reuptake than other TCAs

Front 3

Indications for TCAs (9)

Back 3

1. Major depression
2. OCD (clomipramine)
3. Panic disorder (imipramine)
** also clomipramine is PBS-R for phobias
4. Cataplexy associated with narcolepst (clomipramine)
5. nocturnal enuresis (Amitryptyline, imipramine, notriptyline)
6. Urinary urge incontinence (amitriptyline, imipramine, notriptyline)
7. 2nd/3rd line treatment of ADHD (imipramine)
8. migraine prophylaxis (amitriptyline)
9. neuropathic pain adjuvant (amitriptyline)

Front 4

TCAs
CIs (1/2)

Back 4

1. Within 14 days of stopping a MAOI
2. Within 2 days of stopping moclobemide

Front 5

TCAs
Conditions worsened by TCAs (8)

Back 5

1. bipolar disease
1.5 suicidal ideation: toxic in OD
2. seizure disorder
3. orthostatic hypotension
4. prostate hypertrophy - may precipitate urinary retention
5. closed angle glaucoma - may ppt, consult opthamologist
6. Prolonged QT interval
7. Angina / CAD - angina pptted by tachycardia from anticholinergic effect and reflex tachycardia from orthostatic hypotension
8. Severe heart block, heart disease, arrythmia - proarythmic effects on conduction
9. DM - increases BGLs

Front 6

TCAs and
1. Hepatic impairment
2. Renal impairment

Back 6

1. Halve the dose if severe; consider using nortriptyline, which has measurable serum concentrations
2. ok

Front 7

TCAs and
1. the elderly (3 points)
2. children (2 points)

Back 7

1. may respond more slowly so increase slowly from a low starting dose. (2) Also, do not use for sedation as risks inc falls outweigh benefits and sedation decreases with time. (3) Nortriptyline has less hypotension, sedation and anticholinergic effects
2. No better than placebo in depressed children. If used, obtain a baseline ECG and repeat ECG for high doses.

Front 8

TCAs and
1. Preg
2. BF

Back 8

1. Cat C ("relatively safe"); if possible reduce the dose in the week before birth. May cause an initial toxic effect with CNS depression (hypotonia,dyspnoea, feeding difficulties) and then a withdrawal effect (irritability, colic, seizures, tremor). Monitor neonate
2. All have been used - avoid doxepine, 1 case of respiratory depression in the neonate

Front 9

TCAs
Common Adverse Effects

Back 9

- Anticholinergic: SLUG: sedation, dry eyes & blurred vision, urinary retention, constipation; anticholinergic delerium esp in the elderly; sinus tachycardia
- Antihistaminic: SEDATION
- Anti-5HT: weight gain
- Anti-alpha-1: orthostatic hypotension
- Impotence, loss of libido, and other sexual A/Es
- Potentially: agitation, anxiety, insomnia

Front 10

TCAs
Notable infrequent and rare A/Es

Back 10

Infrequent:
- Hyperglycaemia
- ECG effects, arrythmias
Rare:
- SIADH
- Prolonged QT interval
- Blood dyscrasias, and hepatitis

Front 11

TCA
- monitoring required

Back 11

Check supine and standing BP at baseline, afterwards, and with dose changes

Children: ECG at baseline and with high doses

ECG where there is pre-existing heart block of prolonged QT interval in adults

Front 12

TCA
- withdrawal effects

Back 12

cholinergic rebound: salivation, lacrimation, urinatin, defecation (SLUD), runny nose, sleep disturbance

Front 13

TCA
- which most likely to cause withdrawal effects?

Back 13

Amitriptyline
Doxepin
Trimipramine

**NB - these are the ones with the greatest risk of SE to begin with = stronger rebound

Front 14

TCA tapering

Back 14

As with all ADs, taper over several weeks if not chaging to another AD

Front 15

What are the clinical implications of the different spectrum of activity of clomipramine?

Back 15

Extra caution with potential SS; more care in changeover

Front 16

TCA in overdose
- which is the most toxic

Back 16

possibly doxepin

Front 17

Of the 3 major side effects (orthostatic hypotension, anticholinergic effects, and sedation):
1. which drugs are the worst?
2. which drug is the best?

Back 17

1. amitriptyline, doxepin, trimipramine
2. nortriptyline (mod sedatin, minor O.H. and anti-ACh)
***dothiepin and clomipramine and imipramine are only moderate for all three

Front 18

Which TCA is more effective in MDD?

Back 18

They are all equally effective

Front 19

Just to remind myself, what are the three indications of clomipramine?

Back 19

1. cataplexy in narcolepsy
2. MDD
3. OCD
Also used for other anxiety disorders, and perhaps one day for PMDD

Front 20

TCA
Class-specific counselling points?

Back 20

1. Take at night to reduce drowsiness during the day
L1 - alcohol, driving
2. L16
3. L12
3. Blurred vision, dry mouth, drowsiness etc may lessen or disappear after 7 days
L9
L5

Front 21

When would a single nightly dose of TCA NOT be used?

Back 21

1. if it caused insomnia
2. anxiolytic effect desired during day
3. urinary urge incontinence
4. ADHD

Front 22

PBS listing of TCAs?

Back 22

- Most general benefits
- Clomipramine PBS-R for cataplexy with narcolepsy, OCD, and phobic disorders NOT MDD
- Nortiptyline is PBS-R for MDD where other antidepressants are inappropriate

Front 23

1. What dose of TCA is used for treatment of MDD?
2. what intervals for increasing the dose initially?

Back 23

75-150, max 300mg d, n.
Start on 25-75mg and increase by 25-50mg every 2-3/7

Front 24

What dose of TCA is used for treatment of
1. urinary urge incontinence
2. nocturnal enuresis

Back 24

1. 10-25mg up to tds
2. if 7-10: 10-20mg 30-60min before bed
if >10 years: 25-50mg 30-60min before bed

Front 25

What dose of amitriptyline is used for pain management and migraine prevention?

Back 25

10–25 mg at night initially; titrate up to a maximum night time dose of 75 mg in migraine and 150 mg in pain management.

Front 26

What dose is used for
1. clomipramine in cataplexy in narcolepsy and OCD
2. imipramine in panic disorder
3. imipramine in ADHD

Back 26

1. same as in MDD
2. same as in MDD
3. in a child >5 years: 10mg bd, increasing slowly in increments of 0.5mg/kg up to a max of 3mg/kg/d in 2-3 d.d.

Front 27

Amitriptyline
4-5 indications

Back 27

MDD
migraine prevention
adjuvant in pain management
nocturnal enuresis and urinary urge incontinence

Front 28

Amitriptyline
- dose forms, brands

Back 28

Endep: 10, 25, 50mg.50 tabs

Front 29

Clomipramine
- dose forms, brands

Back 29

Clomipramine, Placil, Anafranil
25mg.50 tabs

Front 30

Dothiepin
- dose forms, brands
- indications
- special consideration here

Back 30

- MDD only
- 25mg.50 caps
- 75mg.50 tabs
(Dothep, Prothiaden)
- avoid 75mg tabs in suicidal patients!

Front 31

4 special considerations related to Clomipramine

hint: related to
(a) A/Es
(b) treatments

Back 31

1. high rates of sexual A/Es
2. extra SS potential, caution in change over
3. treatment of choice in OCD!
4. may be useful for PMDD - more evidence required

Front 32

Doxepin
- indications
- dose forms
- brands

Back 32

MDD
Deptran, Sinequan
- 10mg.50, 25mg.50 caps
- 50mg.50 tabs
** remember both Prothiaden and Deptran have their lower doses in caps and higher doses in tabs (easier to get it into a tab?)
**Also odd to have such low dose forms when doxepin only indicated for MDD

Front 33

Imipramine
- indications

Back 33

MDD
Urinary urge incontinence and nocturnal enuresis
ADHD
Panic disorder

Front 34

Imipramine
- dose forms, brands

Back 34

Tofranil, Tolerade
10mg.50, 25mg.50 tabs
** high pill burden for depression, panic disorder

Front 35

Nortriptyline
- dose forms, brands

Back 35

Allegron
10mg.50, 25mg.50 tabs
** again, high pill burden

Front 36

Nortriptyline has what advantage? (aside from its better SE profile)

Back 36

Has the most well defined serum concentration, therapeutic effect relationship
Concentration monitoring may be useful in liver impairment, for DIs, or non-compliance

Front 37

In the treatment of nocturnal enuresis with TCAs, what restrictions apply?

Back 37

Do not treat if <7 years
Do not treat for more than 3 months

Front 38

What about imipramine concentrations in ADHD?

Back 38

Do not correlate with therapeutic effects but do correlate with toxicity

Front 39

Trimipramine
- indications
- dose forms
- brands

Back 39

MDD
Surmontil
25mg tab
50mg cap
** The opposite of doxepin and dothiepin

Front 40

TCA - Drug interactions (8-9 main types)

Back 40

Antidepressants: (1) Seizures, (2)Seritonin syndrome
Heart effects
(3) orthostatic hypotension, (4) sympathomimetic (PSE, Adr), (5) QT prolongation
Other side effects
(6) sedation, (7) BGLs, (8) anticholinergic effects
Also, (9) most are CYP2d6 metabolised

Front 41

TCAs - metabolism

Back 41

CYP2D6: all except trimipramine, doxepin and dothiepin

Front 42

TCA + clonidine
TCA + methyldopa

Back 42

TCA may REDUCE the drugs antihypertensive effect (or worsen O.H.) & they are both also CNS depressants... Also methyldopa can cause depression.
Avoid combination

Front 43

Drugs increasing QT interval

Back 43

1. antiarrhythmics: amiodarone, sotalol
2. antipsychotics: amisulpride, droperidol, haloperidol, pimozide
3. anti-infectives: chloroquine, quinine, mefloquine, clarithromycin, erythromycin, fluconazole, moxifloxacin
4. miscellaneous: cisapride, cocaine, methadone, dolasetron, tacrolimus, TCAs, vardenafil