I ran across a quite interesting article this past week that had been recently published in the Lancet.
Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis. Leucht S, et.al., Lancet. 2013 Sep 14;382(9896):951-62. doi: 10.1016/S0140-6736(13)60733-3.
This is a meta-analysis of randomized trials comparing 15 different anti-psychotics and asking the questions:
1. Which is the most effective antipsychotic in treating schizophrenia?
2. Which antipsychotic has the most (and least) number of side effects?
The answers are quite interesting. Unless you are a psychiatrist, you may not have intuitively known this information before.
Which is the most effective antipsychotic?
The antipsychotic most effective in relieving the symptoms of schizophrenia, by far, is Clozapine. I actually already knew this. The problem is that clozapine is too toxic to use in most cases. Like chemotherapy for cancer, clozapine is not a drug that I would prescribe myself without an expert holding my hand.
The second most effective antipsychotic on the list is amisulpride. What, you’ve never heard of that one? Me neither. It has never been marketed in the United States.
Anyway, here is where the list gets interesting. Third in efficacy on the list is olanzapine (Zyprexa) and fourth is good old risperidone (Risperdal). Right after risperidone is Paliperidone (Invega), which is basically the same thing as risperidone.
The complete ranking from most efficacious to least is:
(I have removed those medications that are not marketed in the US)
1. Clozapine (Clozaril)
2. Olanzapine (Zyprexa)
3. Risperidone (Risperdal)
4. Paliperidone (Invega)
5. Haloperidol (Haldol)
6. Quetiapine (Seroquel)
7. Aripiprazole (Abilify)
8. Ziprasidone (Geodon)
9. Chlorpromazine (Thorazine)
10. Asenapine (Saphris)
11. Lurisidone (Latuda)
12. Iloperidone (Fanapt)
I think the single most interesting thing about this list is that the two most effective commonly used antipsychotics are also two of the three least expensive medications. Here is the list again (less Clozaril) with medication prices listed according to the most recent Idaho Average Actual Acquisition Cost List.
Olanzapine (Zyprexa) 10 mg $ 0.21
Risperidone (Risperdal) 1 mg $ 0.18
Paliperidone (Invega) 3 mg $23.59
Haloperidol (Haldol) 5 mg $ 0.41
Quetiapine (Seroquel) 100 mg $ 0.20
Aripiprazole (Abilify) 20 mg $35.34
Ziprasidone (Geodon) 20 mg $ 2.08
Chlorpromazine (Thorazine) 100 mg $ 2.00
Asenapine (Saphris) 10 mg $12.03
Lurisidone (Latuda) 20 mg $22.79
Iloperidone (Fanapt) 8 mg $12.33
It seems obvious (to me, anyway) that from a price/efficacy standpoint, it makes no sense to prescribe something like Abilify ($35.34 per tablet), when it is actually LESS effective than risperidone ($0.18 a tablet). But I sure see a lot of Abilify prescriptions coming into my jails, so what do I know?
To be fair, the difference in efficacy between these drugs (less clozaril) was not that striking. There is more difference between them in terms of side effects.
Which Anti-Psychotic has the Fewest Side Effects?
Well, the answer to this question depends on what side effect you have in mind. These drugs differ markedly in their side effect profiles.
For example, if we are looking at dystonic reactions, haloperidol is the worst offender. Olanzapine is least likely to cause dystonia.
If, however, we want to know about weight gain, the incidence is almost exactly reversed. Olanzapine is the most likely to cause weight gain, haloperidol the least.
Risperidone and paliperidone are most likely to cause gynecomastia, Quetiapine and Abilify the least likely to have this side effect.
Chlorpormazine and Geodon are the most sedating, Paliperidone/risperidone are the least sedating.
One way to try to get a handle on the overall troublesome-ness of side effects is to look at drug discontinuation rates. Which drug in this list is most likely to cause a patient to stop taking it because of side effects? The answer to that question, according to this meta-analysis, is Haloperidol, followed closely by Geodon. The drugs least likely to be discontinued due to side effects are olanzapine, risperidone and paliperidone.
So there you have it. According to this meta-analysis out of the Lancet, olanzapine and risperidone are the most effective anti-psychotics (excluding clozapine). The are also the least likely to be discontinued due to side effects. And finally, they are the least expensive antipsychotics, to boot.
What’s not to like about that?
‘Which drug on this list is most likely to cause a patient to stop taking it because of side effects?’
I’m not sure I agree with your emphasis here. So patients tend to stop taking haloperidol due to the dystonic reactions, which are extremely unpleasant and take effect quickly. Simple enough. On the other hand, they won’t necessarily stop taking olanzapine because the weight gain, and its painful consequences, take effect slowly! This doesn’t, IMHO, mean the side effects of olanzapine shouldn’t be taken seriously by the prescriber. Maybe they take it today without complaining too much, and it’s relatively easy on the taxpayer’s wallet, but 20 years down the road, when have a bad back, bad knees and diabetes due to being morbidly obese, they may ask as they hobble into your office, ‘why did you ever put me on this crap?’
Good comments, Jeff! The more overarching concern (in my mind, at least) is the over-prescribing of these drugs to patients who should probably not be getting them! The common practice of using Seroquel as a sleeping pill comes to mind. . .
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Good info. In thirty years of practice, I’ve found the best anti-psychotics to be pretty much as above. The larger problem, however, is the overuse and abuse of anti-psychotics. I suspect this is partly because they are called “major tranquilizers” due to their sedative effects, and, since most of our inmates tend to be impulsive and will willingly either gobble down or sell anything that is called a tranquilizer, they will malinger symptoms to get them. And too many doctors are just too happy to oblige – either to dope them up, shut them up, or because they’re afraid of inmates/lawsuits. I always restrict neuroleptics to treat psychosis only, never for mood, “anxiety” or other minor symptoms.