First generation antipsychotics

[clausewitz2]

So it has become clear over the past few years that as a profession we were sold a bill of goods about atypical/SGAs and the idea that they were essentially benign compared to older meds. People still argue about whether and exactly how much the EPS risk differs, but it is pretty clear they are significantly more sedating, metabolism-deranging, and weight gain inducing.

So! I would like to get to grips better with the finer nuances of older agents, but it seems like most people who trained since the late 90's aren't super comfortable with these agents with a couple of exceptions. The clinical lore and detaila about how these things might be used has been lost. Do any of you all have recommendations of papers or books that might cover this sort of thing? I can find lots of comparisons of SGAs and SGAs v. haldol (or sometimes Trilafon/Prolixin) but not so much comparing the FGAs to each other. I can sort of take educated guesses from receptors profiles but this is obviously not isomorphic with likely clinical effects.

Any suggestions?

---

Members don't see this ad.

 

[psyguru]

As I work in corrections and only 2 atypical are on the formulary, I do use typicals such as haldol, prolixin, trilafon and stelazine.

Trilafon is medium potency and was used with prozac for agitated depression. However I would probably tend to use atypicals for depression with psychosis.

Stelazine is high potency and can be used in low doses briefly for GAD. Avoid in those with seizures and glaucoma.

In the free world I did use loxapine. In low doses it acts like an atypical and one of its metabolites is amoxopine which is an antidepressant.

Of course there is haldol and prolixin. Haldol decanoate has more reliable dose conversion than prolixin depot. Also, when using haldol dec you can stop the PO right away (I may use the PO for a few days at reduced dosage).

Thorazine recently came off the formulary although it was used quite a bit amongst the incarcerated. Where I work. It has a lot of side effects and would consider it "dirty". I would like to use it at times for non psychotic agitation. It is low potency but highly sedating. Where I used to work in another hospital, it was recommended to be used as an IM in emergencies (along with atypicals) on the child unit. Haldol and prolixin were not options in the order set on the child unit.

I may use atypicals with typicals. Not a fan of using two typicals or two atypicals. I also don't like using abilify with anything else. (there are some reports of using abilify with clozapine. is it because clozapine has no or almost no d2 blockade to interfere with abilify's partial agonism?)

I don't recall prescribing any other typicals. I am not aware of any other typicals being favorable over the above for any specific reasons but I am sure there are. I believe others are not commonly used due to side effects.




Sent from my SM-G965U using Tapatalk

 

[Liquid8]

The typical antipsychotics I have most experience with are zuclopenthixol, chlorpromazine and neulactil.

My understanding is that Zuclo isn’t approved in the US – it comes in a tablet, long acting depot (Zuclo decanoate) and a shorter acting injectable formulation (Zuclo Acetate or Acuphase). The latter takes about 3-4 hours to kick in, but the effect can last for quite a long time. When I worked in the public acute inpatient setting we would sometimes use this in conjunction with IM olanzapine for very aggressive patients. The Olanzapine would kick in immediately, and by the time it had worn off the Acuphase would start to act.

I still remember the first time I saw this used – the patient was an extremely agitated manic young man with wild hair who proclaimed his father was the leader of a megachurch. He had an overbearing barrister representing him at the involuntary treatment hearing who made all sorts of audacious claims too. After the hearing, my boss at the time asked me to prescribe 200mg of Acuphase and told me he’d be back in a couple days. At the time I wasn’t in training yet and not comfortable using such a high dose, so he ended up charting it. The patient slept for a couple of days, and when he woke up, he basically apologized for his behaviour, cleaned himself up and presented as a polite and appropriate individual.

Throughout training I would use this often, but in future jobs the teams were more conservative and would only use 50-100mg, with protocols on the maximum amount that could be used in 24 hours. There is a cardiac risk, and although patients would have a good night, we’d be back in every 4 hours to check on them. I have also heard there is one local psychiatrist who uses Acuphase with her private DID patients as a PRN, but this is not standard practice at all.

As a depot, we would often use this for involuntary schizophrenia outpatients. The other typical depot often used was flupenthixol, but both seemed to go out of fashion in favour of newer atypical depots like paliperidone.

Haloperidol was always the go-to agent for delirium, but I haven’t really used it much since my CL job.

CPZ would often get used in a similar fashion to Seroquel, but probably more often now in smaller doses as a PRN for agitation. Some of the first psych nurses I worked with had done their training in the asylum days, and you’d hear stories about patients being zombified on 300mg QID for life, or them trying out 100mg themselves back in the day and being bombed out for the next 24 hours.

Neulactil or pericyazine is an old medication I was only made aware of by a former professor towards the end of my training. We would use it as a sleeper - compared to other, it is cheap, effective at a low dose, non-addictive and able to be prescribed in large quantities if needed. Here most benzos, Z-drugs and low dose Seroquel are restricted to scripts without repeats. Neulactil is one option I keep in the back of my armamentarium for managing sleep complaints, and quite handy for patients who claim they’ve tried “everything” and only want higher and higher doses of benzos.

 

[clausewitz2]

The typical antipsychotics I have most experience with are zuclopenthixol, chlorpromazine and neulactil.

My understanding is that Zuclo isn’t approved in the US – it comes in a tablet, long acting depot (Zuclo decanoate) and a shorter acting injectable formulation (Zuclo Acetate or Acuphase). The latter takes about 3-4 hours to kick in, but the effect can last for quite a long time. When I worked in the public acute inpatient setting we would sometimes use this in conjunction with IM olanzapine for very aggressive patients. The Olanzapine would kick in immediately, and by the time it had worn off the Acuphase would start to act.

I still remember the first time I saw this used – the patient was an extremely agitated manic young man with wild hair who proclaimed his father was the leader of a megachurch. He had an overbearing barrister representing him at the involuntary treatment hearing who made all sorts of audacious claims too. After the hearing, my boss at the time asked me to prescribe 200mg of Acuphase and told me he’d be back in a couple days. At the time I wasn’t in training yet and not comfortable using such a high dose, so he ended up charting it. The patient slept for a couple of days, and when he woke up, he basically apologized for his behaviour, cleaned himself up and presented as a polite and appropriate individual.

Throughout training I would use this often, but in future jobs the teams were more conservative and would only use 50-100mg, with protocols on the maximum amount that could be used in 24 hours. There is a cardiac risk, and although patients would have a good night, we’d be back in every 4 hours to check on them. I have also heard there is one local psychiatrist who uses Acuphase with her private DID patients as a PRN, but this is not standard practice at all.

As a depot, we would often use this for involuntary schizophrenia outpatients. The other typical depot often used was flupenthixol, but both seemed to go out of fashion in favour of newer atypical depots like paliperidone.

Haloperidol was always the go-to agent for delirium, but I haven’t really used it much since my CL job.

CPZ would often get used in a similar fashion to Seroquel, but probably more often now in smaller doses as a PRN for agitation. Some of the first psych nurses I worked with had done their training in the asylum days, and you’d hear stories about patients being zombified on 300mg QID for life, or them trying out 100mg themselves back in the day and being bombed out for the next 24 hours.

Neulactil or pericyazine is an old medication I was only made aware of by a former professor towards the end of my training. We would use it as a sleeper - compared to other, it is cheap, effective at a low dose, non-addictive and able to be prescribed in large quantities if needed. Here most benzos, Z-drugs and low dose Seroquel are restricted to scripts without repeats. Neulactil is one option I keep in the back of my armamentarium for managing sleep complaints, and quite handy for patients who claim they’ve tried “everything” and only want higher and higher doses of benzos.

Excellent stuff. Sadly both zuclopenthixol, flupenthixol and pericyazine are not approved for sale in the US, though they do seem to be approved in Canada and for a motivated patient I suppose it would not be impossible to get them.

I had heard legends of Acuphase, and this makes me even more wistful about not having access to it. I have seen CPZ used PRN for anxiety, but usually this is someone who's been using it for years and is not interested in changing things up. I have only really gotten to use it once as a scheduled medication for acute mania for a very agitated and violent young man who seemed to be utterly impervious to IM Zyprexa, Ativan, or Haldol. It did the job, but your point about people sampling a small dose and being bombed out is well taken; I once, not thinking, decided to take promethazine due to feeling ill rather than leaving work early, and within an hour I was falling asleep while typing. I believe I had a therapy client that day who I seem to remember kept commenting more than usual on being tired, so I assume I was nodding off during that session as well. Learned my lesson.

 

[clausewitz2]

Thorazine recently came off the formulary although it was used quite a bit amongst the incarcerated. Where I work. It has a lot of side effects and would consider it "dirty". I would like to use it at times for non psychotic agitation. It is low potency but highly sedating. Where I used to work in another hospital, it was recommended to be used as an IM in emergencies (along with atypicals) on the child unit. Haldol and prolixin were not options in the order set on the child unit.

I may use atypicals with typicals. Not a fan of using two typicals or two atypicals. I also don't like using abilify with anything else. (there are some reports of using abilify with clozapine. is it because clozapine has no or almost no d2 blockade to interfere with abilify's partial agonism?)


Sent from my SM-G965U using Tapatalk

Thorazine was recently relicensed as a generic and now is ridiculously expensive; best cash price I can find is 120 dollars a month with a goodrx coupon. This is probably why it disappeared from your formulary.

The data I have seen on Abilify augmenting clozapine actually suggest that Abilify augmentation may reduce the weight gain and metabolic derangement that comes along with clozapine, but I haven't seen a convincing and consistent demonstration of increased efficacy for symptom control. I don't know that anyone has a good explanation of why this is the case.

 

[thoffen]

The data I have seen on Abilify augmenting clozapine actually suggest that Abilify augmentation may reduce the weight gain and metabolic derangement that comes along with clozapine, but I haven't seen a convincing and consistent demonstration of increased efficacy for symptom control. I don't know that anyone has a good explanation of why this is the case.

What's surprising to me is more that it doesn't decrease efficacy. Abilify has higher affinity for D2 thought less or similar to 5HT-2A. The drugs compete with each other, so I really don't expect enhancement in efficacy, although mechanism of action and role of other receptor activity is poorly known. Less metabolic problems might be due to abilify acting differently there. Efficacy-wise, I don't see a clear rationale for benefit since it basically takes over what clozapine was doing, at least as far as mesolimbic dopamine is concerned. Perhaps clozapine's specialness lies elsewhere, e.g. modulating prefrontal dopamine.

 

[clausewitz2]

What's surprising to me is more that it doesn't decrease efficacy. Abilify has higher affinity for D2 thought less or similar to 5HT-2A. The drugs compete with each other, so I really don't expect enhancement in efficacy, although mechanism of action and role of other receptor activity is poorly known. Less metabolic problems might be due to abilify acting differently there. Efficacy-wise, I don't see a clear rationale for benefit since it basically takes over what clozapine was doing, at least as far as mesolimbic dopamine is concerned. Perhaps clozapine's specialness lies elsewhere, e.g. modulating prefrontal dopamine.

I posted in another recent thread a meta-analysis that examined the question of whether it worsened psychotic symptoms of people previously on another agent. It does not appear to, but they did find that it was more likely to be discontinued for lack of efficacy when it was the agent someone was being switched to.

 

[deleted736562]

For what it's worth (not much), my experience with typicals:
- I still don't understand the point of Prolixin. Everything it does, Haldol does better.
- I hate Thorazine. It just tends to sedate people, and I have had quite a few cases with people getting delirious from anticholinergic side effects after getting too many thorazine PRNs.
- Perphenazine gets a bit of hype from some of my attendings. It's mid-potency. Good enough to be an antipsychotic, not as sedating as thorazine, EPS less likely than Haldol. Seems to me the most alluring of the FGAs.

Overall I don't feel FGA are in any way better than SGA. At best, they're just as bad. But really, as bad as the metabolic side effects are for FGAs, they are still *slightly* better off than the higher likelihood of EPS and TDs. Though I definitely think FGAs still have their utility, especially when a patient is not a candidate for clozapine.

 

[pizzicarella]

We see a few being used regularly here in Australia. In the population I work with (which includes an enormous percentage of people with borderline personality disorder), we often see people on low dose regular or PRN chlorpromazine or pericyazine for 'anxiety' or sleep. I think this is largely due to most atypicals only being approved by the pharmaceutical benefits scheme for people with schizophrenia or bipolar disorder - so it can be a very costly prescription if the patient doesn't have one of these conditions. Ocassionally I've seen patients prescribed low dose trifluoperazine for the same "sleep/anxiety" reason.
Haloperidol is obviously also used enough to warrant mention, although I think it's familiar enough to most here to not need explanation.