Clozapine 200

Armin Moradi

2021-03-04

Table of Contents

Previously on Clozapine…
Effects and side effects
Constipation
Constipation - agents
Constipation - ileus
Constipation - treatment
Sialorrhea
Sialorrhea - scales
Sialorrhea - treatment
Summary

Previously on Clozapine…

amoradi.org/public/clozapine.html

To see what happened in the previous episode, see this url. The slides suck, so press S to see the speaker notes.

Like any self-respecting programme, I release clozapine episodes once every 6 months.

so, let's get on with it!

Effects and side effects

maaaaaaaaaaaany

In the last episode, I said clozapine has very few side effects. I was mostly comparing it to most common side effects of second generation antipsychotics

Also, there aren't many side effects where you throw in the towel and say "it's what it is, just have to deal bro"!

Now, I'm here to tell you that it has maaaaaaaaany side effects. in fact, it has a book's worth of side effect. It's legit an entire book! It's called the clozapine handbook. It's not big, but it is.

We'll go over 2 of the most common side effects today, and in the next episode, we'll go over more, and maybe the most deadly ones.

Constipation

anticholinergic effects
constipation and ileus

Clozapine has anticholinergic side effects before the blood brain barrier, and so it causes constipation and ileus.

Because the effect is anticholinergic in nature, you should also avoid other anticholinergic drugs

So the way you manage constipation in clozapine patients is almost the same as any other constipation patient, the keyword being almost.

evaluate constipation in all patients started on clozapine
remove other anticholinergic or constipation-inducing agents before starting clozapine
start meds with first clozapine prescription for every patient even if constipation is not a current issue, because it will be
many patients need one med from each class of meds, no more than one per class
no bulk-forming agenst (transit time is slow already, don't make it worse)
48 hours tops per med/dose change
watch out for ileus

Constipation - agents

anionic detergent: docusate
osmotic agent: PEG, lactulose
stimulant: Bisacodyl, sennosides

PEG and bisacodyl have the strongest evidence. PEG has strong high quality evidence, so use it.

Constipation - ileus

more people die from ileus than agranulocytosis

We spend a lot of time talking about agranulocytosis, rightfully so.

But clozapine is pretty shitty in other ways.

When to suspect ileus?

moderate to severe abdo pain >1hr OR any abdo pain with any of

vomiting
distension
absent or high pitched bowel sounds
diarrhea, especially if bloody
hemodynamic instability or signs of sepsis

Constipation - treatment

Porirua protocol for clozapine constipation
docusate + senna -> PEG -> poop maestro

start docusate 100mg + senna 16mg per night
48h: every 48 hours, increase both until max 100 bid and 16 bid
48h: DRE, consult re: enemas or disimpaction; if yes, stop all; if no, add PEG 13.125g BID
48h: consult your local poop maestro
if diarrhea develops, reduce and stop
bristol stool chart for monitoring

Sialorrhea

Cholinergize You Mind (TM)

You might say, Armin, didn't you just tell me about anticholinergic effects of clozapine? Are you mad?

Yes, I am, but that's irrelevant!

Bear with me. Clozapine is anticholinergic, NORclozapine does the opposite. so as opposed to anticholinergic effects of clozapine in the body, it has cholinergizes the mind, so you start drooling everywhere.

Sialorrhea may sound like a "deal with it and move on" kind of problem but it really isn't.

It can increase non-compliance rates, it's socially embarrasing, and can result in aspiration pneumonia

Sialorrhea - scales

C D E F G A B
D S F S (<=2) and N H S (<2)
lip > chin > clothing > body
NHS = # of awakening + 1

The first thing to do when trying to treat sialorrhea is to qualify (quantify?) it. That's done with one of Drooling Severity and Frequency Scale (DSFS) or Nocturnal Hypersalivation Rating Scale (NHS).

DSFS has 2 parts, severity is score from 1 to 5, total should be less than or equal to 2:

never drools, dry
mild, only lips
moderate, lips and chin
severe, off chin onto clothing
profuse, off body onto objects

frequency

no
occasional
frequently
constant

NHS focuses on nocturnal drooling, should be 0 or 1:

absent
minimal, on pillow in morning
mild, wakes the patient once during night
moderate, wakes the patient twice during night
severe, wakes up the patient three+ times

Sialorrhea - treatment

DSFS and NHS
atropine -> botox -> clonidine

The first line of treatment should be topical. topical atropine 1% eye drops are effective in taking care of most cases. But I've heard they taste pretty bad, so patients might not like it.

1-3 drops qHS, up to 3 drops tid. or ipratropium 1-3 sprays qHS up to 3 sprays tid

If that doesn't work, then botox injection into salivary glands can be effective. This can be done by anyone who's comfortable, so ENT, plastics, your local drool bender.

Then if that still doesn't work, think about non-anticholinergic options like alpha-adrenergic agents like clonidine (we don't have amisulpride in canada)

Lastly, if nothing works, you're out of options. think about systemic anticholinergic, but watch out for GI hypomotility and ileus (2x increased risk of ileus). glycopyrrolate has been shown to be effective. Loooots of caution needed though.

Summary

many side effects
to be continued!

Clozapine 200Armin Moradi2021-03-04