Lifetime use of antipsychotic medication and its relation to change of verbal learning and memory in midlife schizophrenia


The association between the course of cognition and long-term antipsychotic medication in schizophrenia remains unclear. We analysed the association between cumulative lifetime antipsychotic medication dose and change of verbal learning and memory during a 9-year follow-up.

Forty schizophrenia subjects and 73 controls from the Northern Finland Birth Cohort 1966 were assessed by California Verbal Learning Test (CVLT) at the ages of 34 and 43 years. Data on the lifetime antipsychotic doses in chlorpromazine equivalents were collected. The association between antipsychotic dose-years and baseline performance and change in CVLT was analysed, controlling for baseline performance, gender, age of onset and severity of illness.

Higher antipsychotic dose-years by baseline were significantly associated with poorer baseline performance in several dimensions of verbal learning and memory, and with a larger decrease in short-delay free recall during the follow-up (p = 0.031). Higher antipsychotic dose-years during the follow-up were associated with a larger decrease of immediate free recall of trials 1–5 during the follow-up (p = 0.039). Compared to controls, decline was greater in some CVLT variables among those using high-doses, but not among those using low-doses.

This is the first report of an association between cumulative lifetime antipsychotic use and change in cognition in a long-term naturalistic follow-up. The use of high doses of antipsychotics may be associated with a decrease in verbal learning and memory in schizophrenia years after illness onset. The results do not support the view that antipsychotics in general prevent cognitive decline or promote cognitive recovery in schizophrenia.


I don’t take my meds to prevent cognitive decline nor to promote cognitive recovery. I take them to stay out of the hospital, to keep from ruining my life and the lives of those I love, and to stay alive.


It was that last line that hit me too… not preventing cognitive decline…

I had a feeling that AP’s didn’t prevent cognitive decline… but CBT and vocational training and lifeskill management classes have. Working with people to do memory builders… like luminosity… and working to try and remember what I read after I read it… I feel that has improved my cognitive ability.


Its my understanding that exercise will help.


That’s interesting and it’s more reason to start the meds early and stay on them because that way it’s supposed to be possible to keep the dose low.

But the other day someone posted a link to a YouTube video of a psychiatrist reviewing risperidone and he said at the end that the great thing about it as a medicine is that it actually encourages neurological regeneration. He did say it’s the only anti-psychotic that does that.

Plus there’s another report on the front of this website where they report that fish oil reduces the side effects if anti-psychotics and can lead to lower doses being enough. So if the cognitive decline is a side effect, fish oil may help to halt it (and exercise can reverse it).

Yes, there’s this report out:

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This probably refers to me. Verbal learning isn’t all it’s cracked up to be. But I wonder what will happen in old age.

I’m 55, and I have been on anti-psych. med’s for over 25 years. If anything, these med’s have slowed my cognitive functioning. I can’t remember the names of familiar people. I forget what I wanted to do before I do it. Stress might be the culprit, but I think it is the medication.

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I’m 64. I’ve been on perphenazine, a potent antipsychotic, for approximately 45 years. I also have been on fish oil for a great many years. As far as exercise is concerned, I used to be a great walker until an injury interrupted my routine maybe ten years ago. Now, even though that injury is healed, I find I cannot get back into it.

When I started this journey through schizophrenia, I was brighter than most of the doctors I saw. Now, that is no longer true. What still is true is that I’m brighter than a lot of the counselors I see. Therefore, although some is lost, a lot remains.

When I get with my siblings, it seems they have learned a great deal more since we were teens than I have. Maybe it is because they are a lot more interested in life than I am?

I don’t know if it is the disease or the treatment that causes me the most problems at this time. I do have cognitive difficulties, and I don’t know if that is schizophrenia or the medicines used to treat schizophrenia.

I have badgered my treatment team with the question about the fatigue I have had seemingly for 40 years. They say they don’t know if it is the illness or the meds. I kept asking this question. Finally, one doctor admitted to me, “Well, you do take enough meds to sedate a horse.”


Dear Hatty,

   I was stabilized on a low dose of antipsychotics in 1969.  When things temporarily looked better in 1975, my doctor took me off all meds. Once I was off the meds I refused to go back on them.  That lead to a number of involuntary hospitalizations over the next three years.  Now, I am stabilized these last many years on a much higher dose.


Yes, you must have seen a lot of changes in those 45 years. It’s difficult to sort out what is a symptom and what is a side effect, though, isn’t it? But most people have some cognitive decline as they get older. I suppose we just have to fight it as much as we can.