Metformin and Atypicals

[zenman]

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What's the latest thoughts on giving metformin with atypical antipsychotics?

 

[masterofmonkeys]

Found a couple of good papers I don't have links to off hand. Obese population on antipsychotics. Showed weight loss on metformin and normalization of A1c. One trial used 500 QDay, one used 850.

I do it frequently in obese patients and especially those with A1c around 5.8 or greater. This is a good move anyway from a prediabetes mgmt standpoint esp in those that have failed lifestyle change (which many of our chronic psychotic pts tend to) as it improves insulin sensitivity AND can be effective in aiding wt loss in insulin resistant pts.

I also will start it on someone who is doing well on an atypical, but gaining weight on it.

 

[whopper]

I try to get the patient on a metabolically neutral regimen (or as close as I can) if possible. Of course you will have patients that will not respond to Abilify or Geodon, but IMHO, if the case is not extreme, why not give it a try?

Also why not try Lamictal vs. Depakote? Where I practice, almost every doctor only uses Depakote.

Metformin can be an option, but in addition or instead to that, how about a dietary/nutrionist consult?

I've had several patients I've successfully switched from Seroquel or Zyprexa to Geodon or Abilify and they lost dozens of pounds within a few months.

 

[nitemagi]

I read some papers a while back that looked at olanzapine, and showed hyperglycemia and insulin resistance in early stages that might have preceded the weight gain. It was suggested that metformin might normalize the early hyperglycemia and thus prevent weight gain.

I don't think there's a body of evidence to make it a standard of care though.

 

[masterofmonkeys]

I read some papers a while back that looked at olanzapine, and showed hyperglycemia and insulin resistance in early stages that might have preceded the weight gain. It was suggested that metformin might normalize the early hyperglycemia and thus prevent weight gain.

I don't think there's a body of evidence to make it a standard of care though.

quetiapine and olanzapine are huge offenders in directly driving insulin resistance. And then there is the antihistaminergic effects which are prominent in both. I've witnessed enough cases first hand of higher FSBGs after starting these drugs. Not to mention the fact that many people, psych or otherwise, are already in the throes of early metabolic syndrome.

Lifestyle intervention is notoriously crappy in people who do not have psychosis or other psychiatric conditions. I doubt it'd be more effective in these cases. Not to mention the fact that if this is a direct drug effect, lifestyle intervention will be of limited utility.

OTOH, I have not had a huge problem with non-antipsychotic antihistaminergic agents and weight gain (i.e. mirtazapine) since I counsel them on increased appetite, and people who I start on meds like mirtazapine are often higher insight.

I don't consider it standard of care, and don't routinely start metformin in patients who haven't demonstrated weight gain, obesity, or impaired glucose tolerance. I also only use it mainly for those on the above two medications.

For those on risperidone or ziprasidone, I don't bother.

But one of my spastic points is that the chronically mentally ill die 20 years earlier for a reason. Given the state of metabolic and HTN care, or lack thereof, that I usually see, I'm not surprised.

 

[whopper]

Zyprexa reps were giving out a bit of data called the "3,4,5" rule. Basically the gist of it goes like this. Data from the CATIE trial (at least according to them) showed that a sizeable number patients do not gain weight from Zyprexa though a sizeable number still does.

So the rule is if the patient is going to gain weight, they usually do so in the first few weeks. If the patient gains over 5 lbs in the first 3-4 weeks of treatment, then you know if they are in the category where they are likely to gain much more weight if they stay on the medication. Some other medications, the weight gain doesn't work this way. The person could end up gaining weight several months after being on it. If they do gain weight, you don't necessarily have to stop the medication but you should tell the patient what's going and and work on possibly changing the treatment either by changing the medication or by implementing some weight control strategies.

Okay, so you got this data, how true is it? Any data from a rep needs to be taken with a grain of salt. After I was told this, I looked up the CATIE studies and I did not see data backing this us. That does not mean this data is not true. I could've overlooked it, and it is possible that even if it was not published, the data the researchers obtained backed this trend. What backs up that theory is the drug manufacturers did assist the researchers in the CATIE trial, so the manufacturer may have some data that was ultimately not published.

I also received a handout backing this data (from the manufacturer) and the source of the information was from a study that I could not find online. I'm not in the habit of keeping every single flyer I receive and I no longer have it.

I have noticed, however, that at least in clinical practice for me, this trend does appear to be true. I always monitor the weights of patients I start on a medication that is known to cause weight gain in outpatient, while in inpatient the staff do it for me. This 3,4,5 rule so far seems to have at least something to it.

Some more tidbits of data is there is reason to believe that Zyprexa Zydis does not cause weight gain or at least as much weight gain as does regular oral Zyprexa. I have not seen any human studies on this but there are animal studies backing this. Zydis, unfortunately, is much more costly and Zyprexa is already the costliest atypical at least as far as I know.