ABC's "Revenge" & Pharmacy

Every Wednesday, the specialty clinical pharmacist in mental health has

a clozapine clinic day. Basically, patients on clozapine come to see the

physician, then the pharmacist for further discussion, and then the

pharmacy to pick up their medication. In light of “clozapine days,” I read

the clozapine patient management protocol that the VA has, and also some

basic background information on the drug. Here it goes…

Clozapine

o        Blocks DA2, 5HT2, and cholinergic receptors (ADR of the latter mechanism

think blind as a bat, dry as a bone, red as a beet, and mad as a hatter,

hot as a hare…)

o        Black box warnings for: agranulocytosis, seizures, myocarditis

(especially during the first month), CV/Respiratory dysfunction (Benzo

drug-drug interaction), dementia.

o        Agranulocytosis is defined as an ANC < 500/mm3, most frequent in first 6

months of clozapine use.

o        Other ADRs: cardiac toxicity, GI hypomotility, hypersalivation (you

would think the patient would have a dry mouth d/t anticholinergic

effects, but the hypersalivation is actually d/t the patient not being

able to swallow appropriately), metabolic syndrome, EKG abnormalities.

o        Therapeutic range at steady state: 0.35-0.60mg/L.

o        Other DDI’s: cisapride and dronedarone causes additive QT prolongation

if either is used with clozapine, and concomitant potassium-salts cause

delay in potassium passage through the GI tract (which causes increased

risk for ulcerative lesions).

o        Limitations of clozapine – it’s reserved for severe schizophrenia

(treatment resistant or treatment intolerant) and in schizophrenia with

emergency suicidal ideations. The ADRs associated with this medication

prevent it from being first line.

o        Off label uses: schizoaffective disorder, bipolar affective disorder,

tremor, and Parkinson’s.

o        Max dose is 900mg/day.

o        May take 8 weeks to see initial effect, and up to 6 months for full effect.

o        For discontinuation, taper must be over 1-2 weeks, and need to monitor

o        WBC and ANC for four weeks after D/C.

When I see something pharmacy-related in pop culture, I tend to get pretty excited. 

The antagonist of my new favorite ABC show was taking clozapine, and when the 

protagonist took his medication bottle, he started experiencing withdrawal symptoms 

(since it wasn’t tapered over how many weeks? That’s right, 1-2 weeks). 

And this is Tyler from ABC's "Revenge" great actor!

In other news, we had a patient call in today asking about sexual dysfunction with his 

newly prescribed SSRI (citalopram). The 5HT2A receptor plays a big role in sexual 

dysfunction. Basically, agonists of this receptor contribute to sexual dysfunction and 

antagonists don’t have this effect. This is a common ADR of SSRI’s, about a 40% 

chance of happening. I called the patient back to find out more about it. Unfortunately, 

he wasn’t at home, but I did have a list of questions prepared: have you noticed any 

benefit from the citalopram? When did these new sx begin? Have you been compliant 

with the medication? Have you ever had an antidepressant in the past? My plan was to 

start off with these questions and then take the conversation wherever it went. Some 

solutions to this ADR include:

o        If patient is on Prozac (the SSRI most associated with sexual dysfunction), 

then consider switching to another SSRI (citalopram or sertraline are least associated 

with this).

o        Decrease the dose – this however may not be acceptable if this affects control of 

depression. This could be a possibility if a patient is already on the maximum dose of 

an SSRI, and is aware enough to correlate the ADR with the last increased taper up. 

o        Change drug to mirtazapine, buproprion, nefazodone, or trazodone – these have 

the lowest incidence of adverse sexual side effects. These have action as a 5HT2A 

antagonist – so it makes sense why there would be fewer incidents. 

o        Add Viagra to patient’s medications. 

That closes out week #1. I’ve pulled all my psych lectures from school (I realize I 

had some pretty amazing pharmacology professors). I’m working on putting together

 presynaptic/synaptic cleft/post synaptic diagrams for all the main neurotransmitters 

for psych medications. I will share as soon as I finish!