Hey everyone, welcome to another psych student video.
Today we'll be looking at one of the more complex medications in Psychiatry, Clozapine. Clozapine has several different brand names and is one of the few medications where it's important to remember and prescribe accordingly. These can include Denzapine, Clozaril and Zapponex, but there are others as well.
Clozapine is prescribed for lots of different reasons. Most commonly, treatment-resistant schizophrenia. It can also sometimes be used to reduce suicidal Behaviour within schizophrenia or schizoaffective disorder. It can be helpful where dyskinesia is a difficulty or in Parkinson's disease where there are psychotic symptoms as it can have less extrapyramidal side effects. And in some cases, is used in treatment-resistant bipolar.
So, as I say it's a type of anti-psychotic and this has lots of different mechanisms of action. It's not just dopamine, we look at serotonin receptors, there's Alpha receptors, muscarinic receptors, histamine receptors and then there are specific dopamine targets, particularly both D2 and D4. The action on positive symptoms is antagonism in these dopamine receptors, but for the negative symptoms of schizophrenia, things like cognitive impairment, we're looking actually at serotonin for these effects. Histamine can be linked with some of the side effects of sedation and weight gain. Alpha receptors with hypotension and the muscarinic receptors can have anticholinergic actions. Dry mouth and constipation are also linked to this receptor.
So, when we start clozapine, it's quite a difficult one to begin with because there's lots of factors to think about. So, clearly to start with we need to discuss it with the person and either obtain consent or be treating them within another structure such as mental health law. We need to get Baseline blood tests particularly a full blood count, but also the same kind of tests would need for any type of anti-psychotic because it could have side effects that we need to know about. And we need to inform the Baseline monitoring agency. So, for example, if we had Clozaril we would have to inform the Clozaril monitoring service (CPMS) of our intention to start the drug and our pharmacy team. Only a consultant psychiatrist can authorize commencement of Clozapine.
When we then titrate the drug, we have to start off with a low dose and this will be on a basic regime that goes up usually each day to begin with depending on the response and the side effects experienced throughout that time. We need careful monitoring of blood pressure and heart rate to make sure these effects aren't too high and side effect monitoring for making sure they're not developing really severe constipation or hypersalivation early on. The titration regime happens over a few weeks to get to a therapeutic dose and then we can do blood clozapine levels as well as their FBCs to see if we're at the therapeutic range.
The FBC is really important to monitor because of the potential for clozapine to reduce neutrophil counts and prompt agranulocytosis. So, to help monitor that we have to check their busy weekly for 18 weeks then fortnightly for the rest of that year. And then monthly and those results are fed back to the drugs monitoring service.
So, there's lots of side effects we need to be very careful of, particularly as they can cause people to disengage from treatment. Sedation is particularly a problem. And then we look at things like constipation. So, people can get really severe constipation and to the point where it becomes really difficult for patients, can be very painful and could become obstructive so we need to be very careful and treat that very early. Hypersalivation can actually be a significant risk particularly to obstruction of airways at night-time; and weight gain and metabolic effects could put people at risk of things like diabetes, which are potentially very long-term serious effects. There are movement problems evident in general for antipsychotics so we need to be careful. And clozapine particularly can decrease the blood pressure and increase heart rate. There are life-threatening effects from clozapine things like tardive dyskinesia, which is evident in lots of different antipsychotics. Similarly, NMS that is Neuroleptic malignant syndrome, is something we need to be very careful of. Clozapine particularly has its effects on the cardiac function. So, there's the risk of myocarditis. If someone on clozapine says they have any kind of chest pain, its really important to get an ECG. Seizures particularly if you have got the doses essentially out. So, if they have too high a dose then the level is too high in the blood. Or, if there's metabolic syndrome, things like diabetic ketoacidosis could result. Agranulocytosis is something I mentioned already so we would just need to be very, very, careful of those full blood counts.
So ,there is other information that is really Important to think about when commencing clozapine therapy. One thing that trips up people a lot, particularly if they change hospitals, is missing doses. So, if a patient misses 48 hours’ worth of doses, that’s usually four doses, then we really need to re titrate from scratch. Potentially they've built up quite a lot of tolerance to the medication. And if we restart it too quickly those effects on the cardiac function that they might have developed some tolerance to so, the potential for hypertension or high heart rate, could become much more problematic if suddenly we started a high dose.
If the neutrophils drop the monitoring service for that drug will alert us that it's either an amber or red result and depending on that we might need to increase how often we are monitoring, or stop the drug. And the levels are particularly altered by things like smoking and caffeine. If someone suddenly gives up smoking or starts smoking, we need to be mindful of that as well. And of course, with any drug, there's lots of interactions with need to be monitored.
So, some top tips for you: seek help really early on from a pharmacist particularly if you're working in a non-psychiatric setting, ensure that the monitoring is in place and that side effects are treated early.
Further information can be found in the BNF, there's a great book “essential neuropharmacology” and any local guidelines as well.
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