18.1.2 - Ssris

Front 1

SSRIs
- drugs in class (6) with at least 1 brand name per drug

Back 1

Sertraline (Zoloft, Xydep)
Citalopram (Cipramil)
Fluoxetine (Lovan, Prozac, Auscap)
Fluvoxamine (Faverin, Luvox)
Escitalopram (Esipram, Lexapro)
Paroxetine (Paxtine, Extine)

Front 2

SSRIs
- Mode of action

Back 2

Selective serotonin pre-synaptic re-uptake inhibition

Front 3

SSRIs
- Indications

Back 3

1. Major depression
2. OCD
3. Anxiety disorders
4. Pre-menstrual dysphoric disorder (PMDD)
5. Bulimia nervosa

Front 4

SSRIs
- Indications for
(a) Citalopram
(b) Paroxetine
(c) Fluvoxamine

Back 4

(a) just major depression
(b) MDD, OCD and all types of anxiety (social phobia, PTSD, generalised anxiety and panic disorder)
(c) MDD, OCD and panic disorder

Front 5

Which SSRIs are indicated for
(a) PMDD
(b) OCD
(c) bulimia
(d) PTSD

Back 5

(a) Fluoxetine and sertraline
(b) all except citalopram
(c) fluoxetine
(d) paroxetine is the only one marketed; fluoxetine also used. SSRIs are first choice drugs but poor evidence

Front 6

SSRIs in pregnancy?

Back 6

Pregnancy: Weigh up the benefits and risks of treatment. Only paroxetine has evidence of fetal malformations (in particular increased ventricular septal defects). There may also be NEONATAL toxic/withdrawal effects after use in late pregnancy (esp with paroxetine) - reduce this risk by reducing dose in late pregnancy if possible. Observe neonates carefully for a few days.
They are all cat C except for Paroxetine = Cat D

Front 7

SSRIs in breastfeeding?

Back 7

SSRIs are used in post-natal depression. Some consider sertraline to be the preferred agent. Flouxetine shows signs of being transfered into breastmilk at higher rates (Avoid) - Others appear safe

Front 8

What percentage of women may be depressed in pregnancy?

Back 8

10%

Front 9

What about other treatments for depression in pregnancy?

Back 9

1. PSYCHOTHERAPY: CBT or IPT (interpersonal therapy)
2. ECT can be used
3. TCAs are relatively safe - They are Cat C. Some babies whose mothers have taken TCAs up until delivery have shown symptoms such as dyspnoea, cyanosis, lethargy, feeding difficulties, colic, irritability, seizures, tremor, hypertonia, hypotonia and spasms during the first hours or days after birth. Some symptoms may be due initially to CNS depression, but ongoing symptoms may result from TCA withdrawal. Reducing the dose in the week before delivery may reduce the chance of withdrawal symptoms in the neonate.
4. Reboxetine is cat B1
5. Venlafaxine may cause withdrawal symptoms; little data on the miscellaneous antidepressants

Front 10

What about other antidepressants in breast feeding?

Back 10

Moclobemide and TCAs have low transfer into breast milk and are considered safe but moclobemide has less experience - except doxepin (a single case of neonatal respiratory depression was reported)
Little is known about the other antidepressants

Front 11

What medical conditions can be worsened by SSRIs? (4)

Back 11

1. Epilepsy - use low doses and titrate slowly; stop if seizures occur - SSRIs and venlafaxine have less effect than TCAs; also care with DIs
2. People at risk of bleeding (e.g. >80 years, hx of gastric ulcers, NSAIDs) - avoid; monitor; consider gastroprotection
3. Bipolar disorder
4. Sexual dysfunction
(Temp: anxiety)

Front 12

What about SSRIs in HIV, cancer, cardiovascular disease, diabetes, dementia

Back 12

* Caution in HIV with anxiety and weightloss but gen well tolerated
* May exacerbate weight loss and nausea in cancer
* SSRIs gen considered safest for CVD
* Diabetes - SSRIs preferred
* SSRIs and venlafaxine preferred

Front 13

SSRIs - hepatic or renal impairment?

Back 13

Hepatic - halve dose
Renal - OK

Front 14

SSRIs - children

Back 14

Fluvoxamine and sertraline have marketed indication in children - other SSRIs do not (i.e. OCD, sertraline >6 years)
NO antidepressant is approved in Aus for treatment of major depressive disorder - fluoxetine is approved in US.
A child psychiatrist should begin treatment
There is an increased risk of suicidality and self harm. Strongest association has been found with paroxetine and venlafaxine; fluoetine possibly has a lower risk and fluvoxamine (OCD) has very little data. The effect is stronger in SSRIs than other antidepressants in youth.

Front 15

SSRIs - common adverse effects?

Back 15

Common:
- nausea, diarrhoea, dry mouth
- headache
- dizziness
- tremor, sweating
- agitation, anxiety
- insomnia > sedation
- sexual dysfunction
- weight gain (minimal) or loss

Front 16

SSRIs - notable infrequent / rare adverse effects

Back 16

Infrequent
- EPSE inc TD
- Palpitations, hypotension,
- Hyponatraemia (as part of SIADH)
- platelet effects
Rarely
- seizures
- liver toxicity & dyscrasias

Front 17

Which SSRIs cause insomnia and which sedation?

Back 17

FLUVOXAMINE AND PAROXETINE may need to be given at night.

Front 18

PKKs of SSRIs
- compare half-lives
- clinical consequences

Back 18

(withdrawal unlikely)
1. paroxetine shortest (withdrawal)
2. fluoxetine longest: active metabolite norfluoxetine with a half life of 16 days 3. others ~24hr half lives
*Impacts withdrawal, duration of adverse effects, and wash out periods

Front 19

What is the washout periods for SSRIs; how do you change over?
Group 1: SSRI / TCA/ Mianserine/ Mirtazepine
(1) Group 1 --> to anything
(2) Fluoxetine --> to anything
(3) Reboxetine, Venlafaxine?
(4) MAOIs

Back 19

(1) For MAOIs: 7 days. For the rest: 2-4 days - But note that SSRI inhibition of CYP3A4 may persist, elevating TCA for several weeks
(2) For MAOIs: 5 weeks. For everything else 1 week
(3) For MAOIs: 1 week. Everything else 1-2 days
(4) Moclobemide = nil, the rest are 2 weeks
(n.b. nil days = the next day, the washout is drug free days)

Front 20

What if you want to taper the dose of TCA before changing?

Back 20

The days of tapering are included in the washout period. E.g. taper over 3-4 days and start the new drug the next day. Only do this when switching to other TCAs, SSRIs, mirtazepine or mianserin

Front 21

SSRIs and DIs
- which SSRIs have least potential for CYP450 DIs?
- other broad groups of DIs?

Back 21

1. citalopram, escitalopram, and sertraline (the "s" drugs)
2. seritonin syndrome
3. platelet aggregation
4. seizure threshold

Front 22

Which drugs should be considered for CYP450 interactions for all SSRIs? (x3)

Back 22

1. Pimozide - increased risk of arrythmias; Combos are CI!
2. Clozapine
3. Perhexiline (avoid citalopram, fluoxetine and paroxetine)

Front 23

SSRIs and DIs
- which enzymes does fluoxetine inhibit?
- which drugs is this particularly likely to affect (ref. AMH)

Back 23

CYP2D6
CYP3A4

CBZ, phenyoin, alprazolam, risperidone, haloperidol

Front 24

Which CYP450 enzymes does Fluvoxamine inhibit?

Back 24

CYP1A2
CYPC19
CYP3A4

Front 25

Which CYP450 enzymes does paroxetine inhibit?

Back 25

CYP2D6 - most potent inhibitor of the SSRIs

Front 26

Name some CYP2D6 substrates (paroxetine, fluoxetine)

Back 26

1. TCAs, venlafaxine, mirtazepine, some SSRIs, clozapine (but mostly 1A2), olanzapine, quetiapine, risperidone, haloperidol, CPZ
2. flecainide, mexelitine, propranolol, metoclopramide
3. codeine, oxycodone, tramadol
4. donepezil, galantamine
5. PIMOZIDE, CLOZAPINE, PERHEXELINE

Front 27

Seritonin syndrome
- signs and symptoms

Back 27

1. diarrhoea, vomiting, tachycardia
2. sweating, hyperthermia
3. tremor, hyperreflexia, rigidity, myoclonus
4. mood changes: hypomania, anxiety, delerium, disorientation

Front 28

Seritonin syndrome
- laboratory findings

Back 28

ZERO; a clinical diagnosis

Front 29

Seritonin syndrome
- management

Back 29

- mild tremor and hyperreflexia may consititute a tolerable level of SS; extreme care must be taken not to add other drugs with SS potential
- If severe:
manage vitals; cease drugs; sedate with benzos, give seritonin antagonists (cyproheptadine!! or less proven: atypical antipsychotics such as olanzapine, CPZ), dantrolene for hyperthermia

Front 30

Seritonin syndrome
- which drugs?

Back 30

1. Analgesics: pethidine, tramadol, dextromethorpan
2. Stimulants: sibutramine, phentermine, illicit drugs (ecstacy, cocaine, LSD, etc, amphetamines)
3. FORGETABLE RANDOMS: lithium, selegeline, linezolid,
4. antidepressants: venlafaxine, duloxene, MAOIs, moclobemide, TCAs, SSRIs, St John's wort (not mianserine, mirtazepine, reboxetine)

Front 31

Drugs which lower the seizure threshhold?

Back 31

- Antipsychotics, promethazine, pizotifen
- Theophylline
- TCAs > other antidepressants, buproprion
- cholinesterase inhibitors and memantine
- anti-infectives: quinolones, ertapenem, chloroquine, mefloquine, ganciclovir, valganciclovir, isoniazid

Front 32

Citalopram
- brands
- dose forms
- doses
- PBS

Back 32

- Cipramil, Talam, Celapram, Ciazil
- 10mg, 20mg, 40mg.28 tabs
- 20-60mg d, 20mg is usually adequate for depression, max 40mg in the elderly
- PBS-R for MDD

Front 33

Escitalopram
- brands
- dose forms
- doses
- PBS

Back 33

- Lexapro, Esipram
- 10mg, 20mg.28 tabs
- 10mg/mL.28mL oral liquid
- 10-20mg d (10mg usually enough for MDD)
- PBS-R for MDD

Front 34

Fluoxetine
- brands
- dose forms
- doses (multiple conditions)
- PBS

Back 34

20mg.28 dispersable tabs (Prozac, Lovan)
20mg.28 caps (Auscap, Lovan, Prozac, Zactin)
**Panic disorder: 10-20mg MAX
**OCD: 20-80mg d
**Depression: 20-60mg d (20 usually adequate)
**PMDD: 20mg d, continuous or for 14 days prior to period until day 1 of cycle
- PBS-R for MDD, OCD

Front 35

Fluvoxamine
- brands
- dose forms
- dose
- dose in children with OCD
- PBS

Back 35

- Luvox, Faverin, Movox, Voxam
- 50mg, 100mg tabs
- 50-300mg d (>150mg as d.d) Doses >100mg not usually needed for panic and MDD)
- PBS-R for OCD and MDD

Front 36

Sertraline
- brands
- dose forms
- doses (multiple conditions)
- PBS

Back 36

- Xydep, Zoloft, Sertra, Concorz, Eleva
- 50mg, 100mg.30 tabs
- OCD, Depression: 50-200mg d (>100mg not usually needed for depression)
- Social phobia, panic: 25-50mg d
- PMDD: 50mg d continuous or for days 15-28 of cycle
- PBS-R for MDD, and 2nd line for OCD

Front 37

Paroxetine
- brands
- dose forms
- doses
- PBS

Back 37

Paxtine, Aropax, Extine
20mg.28 tabs
- OCD/MDD: 20-50mg d (over 20 not usually required for MDD)
- Other anxity disorders: 10-20mg d
- PBS-R for MDD, OCD and panic disorders

Front 38

Paroxetine withdrawal: signs and symptoms?

Back 38

dizziness, nausea, paraesthesia, anxiety, agitation, tremor, sweating, confusion, electric shock-like sensations

Front 39

SSRI counselling points (by labels) for class as a whole

Back 39

L9 - expected duration at least 6/12 after amelioration of symptoms if first episode; several years if second; indefinate if third
L12
L5

Front 40

SSRI counselling points for individual members of class

Back 40

Paroxetine & fluvoxamine - Usually morning (sometimes night) with FOOD to minimise stomach upset
Escitalopram & Fluoxetine - Take in the morning
Also for escitalopram: can mix the liquid with water, orange juice or apple juice
Sertraline - usually in the morning

Front 41

Dosing of SSRIs in MDD?

Back 41

in depression, increasing the SSRI dose may not provide further improvement; most people can be maintained with 10 mg escitalopram, 20 mg paroxetine, citalopram or fluoxetine, 50 mg sertraline, or 50–100 mg fluvoxamine, except where some psychiatric comorbidities exist

Front 42

Dosing of SSRIs in anxiety disorders (excluding OCD/bulimia)

Back 42

for the management of anxiety disorders (eg panic disorder), begin with half the normal starting dose and avoid using high maintenance doses as activating effects may exacerbate anxiety

Front 43

Stopping SSRIs?

Back 43

when stopping SSRI treatment taper over several weeks to avoid withdrawal symptoms; reduce the daily dose by half no faster than weekly

Tapering is not usually required for fluvoxamine (TG)

Front 44

What can affect compliance?

Back 44

- Sexual dysfunction - You have to ask! - loss of libido, anorgasmia and ejaculatory disturbance; occurs in up to 60% of patients
- Support of family helps compliance

Front 45

Can you drink alcohol while taking SSRIs?

Back 45

SSRIs do not interact with alcohol (TG)

Front 46

Is it ok to combine SSRI and moclobemide

Back 46

SSRIs should not be given with either reversible selective or irreversible nonselective monoamine oxidase inhibitors (MAOIs). These combinations may produce the serotonin syndrome (see Table 8.1) which has been associated with fatalities. (TG)

Front 47

SSRIs AND VENLAFAXINE and SIADH
- onset?
- age group? sex? other risks?
- signs and symptoms?
- management

Back 47

- usually in first month
- usually >60 years, more often female; diuretics
- primarily hyponatraemia; sometimes neuropsychological effects such as confusion, convulsions, fatigue, delirium, syncope, somnolence, agitation, dizziness and hallucinations; 3 reported deaths
- withdrawal of SSRI, fluid restriction

Front 48

When discussing side effects about SSRIs, what points should be made?

Back 48

1. most are transient, and disappear after 1-2 weeks; If they persist or interfere with normal activities, tell your doctor. There are alternatives
2. Weight gain: may occur because of improvement in depressive symptoms. Maintain a healthy diet and exercise.
3. Increased energy --> anxiety

Front 49

What drug is first line for depression?

Back 49

Some references say SSRIs.
The AMH says all drugs have equal efficacy and tolerability (just different side effects). All first line except the irreversible MAOIs.

Front 50

In summary, regarding SSRIs, what counselling points?

Back 50

1. What it does, how long it takes to work (1. physical imrovements: energy, apetite, 2. mental), likelihood of working.
2. How to take, whether with food, whether morning or night.
3. Side effects:
(a) common side effects are ..., they usually abate in 1-2 weeks, if not or if they interfere with daily activities, see the doctor
(b) increased apetitie and mood -> weight change
(c) increased energy --> anxiety
4. Past the teething phase: all that is needed is to watch for potential for DIs
5. See the doctor when you want to stop because of risk of relapse and risk of withdrawal effects.