Antipsychotic Medications and Alzheimer's

Throughout his life, my father laughed away any worries. He never locked doors; he trusted everyone. When lightning struck a transformer ten feet from where he stood, he brushed it off. Nothing kept him awake at night.

But when I visited my parents for Dad’s 73rd birthday last year, he was confused and seemed to be hallucinating. “Where are the others?” he asked over and over. “They were here a little while ago – I’m sure I saw them.” I had flown up by myself, and no one was with us in the house.

Later that week, he told Mom he couldn’t sleep because he thought the vibrating box fan in the doorway of the bedroom was going to attack him. He was upset, and it was hard for my mother to reassure him.

Symptoms like Dad’s are common in Alzheimer’s patients, and add to caregivers’ burdens. According to the U.S. National Institute for Mental Health (NIMH), antipsychotic drugs are widely used to treat psychiatric symptoms in people with Alzheimer’s. More than 27% of patients in American nursing homes receive these drugs, which were initially developed for schizophrenia. But, at least in the U.S., these drugs carry “black-box” warnings that they are not approved for the treatment of patients with dementia-related psychosis.

Results of a five year study of antipsychotic medicines in Alzheimer’s patients were published earlier this month in the New England Journal of Medicine. The “Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Alzheimer’s Disease” study tested three antipsychotic medications against a placebo in 421 Alzheimer’s patients living in their own homes, in family members’ homes, or in assisted living. The medications tested were:

- olanzapine (Zyprexa)
- quetiapine (Seroquel) and
- risperidone (Risperdal).

Input from caregivers was used to help with doctors’ assessments of any improvements or side effects. Although these drugs showed some benefit for some patients, the researchers concluded that “adverse effects offset advantages in the efficacy of atypical antipsychotic drugs for the treatment of psychosis, aggression, or agitation in patients with Alzheimer’s disease.”
Side effects seen in some patients included problems with coordination of movement, sedation, confusion and psychotic symptoms. Antipsychotic medicines have also been shown to increase the risk of developing diabetes and stroke.

Despite recent headlines about this research (“Little Benefit Seen in Antipsychotics Used in Alzheimer's,” etc.), it’s hard to say what the study results mean for each individual patient. Dr. Constantine Lyketsos, Chair of Psychiatry at Johns Hopkins Bayview and Vice Chair of Psychiatry at Johns Hopkins Medicine, co-authored the study. “Neither the CATIE study nor other studies suggest that these medicines shouldn’t be used,” he says. “If you look at the CATIE study, it’s not that the medicines weren’t effective, but the risk/benefit ratio has changed. For the sub-groups of trial participants for whom the medications weren’t discontinued because of side effects, they were more effective than placebo. If a patient’s symptoms are high-risk, then doctors can try antipsychotics with careful safety monitoring. If one of these drugs is well-tolerated, then I can tell you from clinical practice that it’s often effective.”

Constantine (Kostas) G. Lyketsos, M.D., MPH

“I think it would be unfortunate if everyone stopped prescribing any medication solely on the basis of one study,” agrees Dr. Ray Ownby, Professor of Psychiatry at the University of Miami Miller School of Medicine. “Contrary to what many people believe about the study results (and I'll agree that the presentation is confusing), I would not argue that it shows that antipsychotics don't work. It simply shows that antipsychotics aren't enormously effective and that they have lots of side effects. Physicians should prescribe what's appropriate for their individual patients while being aware of the risks and benefits of any given treatment.”

In a “Question and Answer” page on this study, the NIMH recommends caution in prescribing these drugs:

Although some patients may benefit greatly from these medications, the evidence from this study suggests these medications hold limited value for the majority of patients. These results further emphasize the challenge of managing behavioral problems in Alzheimer's patients. Prior to prescribing these medications, clinicians must ensure that agitation or aggression in their Alzheimer's patients are not related to medical, social, or environmental factors (e.g., fever from an infection, side effects from another medication) which might be mitigated without resorting to psychotropic medications.

In a future post, I’ll write about potential alternatives to these drugs, and efforts to develop antipsychotic medications with fewer side effects. But right now, there are no easy answers for doctors or for caregivers.

In the weeks after Dad’s birthday, things got better. Although he was still confused sometimes, he didn’t seem to be hallucinating, and wasn’t as agitated. His doctor thought maybe his symptoms were the result of heat exhaustion (he had mowed the lawn in the summer heat just before these incidents). I now wonder if he’d had a small hemorrhagic stroke that day. If my father had lived longer, he might have gone through more periods when he was anxious, agitated and confused. As the anniversary of his death approaches, we all miss him terribly. But I’m glad we didn’t have to agonize over whether antipsychotic medicines would help him or hurt him.

Comments

[Daniel Haszard]

Zyprexa for Alzheimer's related agitation ~

My CC (chief complaint) against Eli Lilly's Zyprexa is it has a TEN TIMES greater incident of causing type two diabetes.

As regards giving it to someone who is terminally ill with late stage Alzheimer's related agitation and aggression i have less problem.

I think (and it's just my opinion) that these 'anti-psychotics' are ineffective for many mental illnesses all they do for most patients is make you sleep so that your aggression is 'turned off'.

For some who have hallucinations they are effective.They gave it to me for PTSD (post traumatic stress disorder) and it had the paradoxical effect of making me worst,because you can't give anti-aggression drugs to patients who are hyper vigilant from PTSD.
-----
Respectfully submitted,Daniel Haszard Bangor Maine zyprexa-victims.com

[Deb Peterson]

Hi Mona
Thanks for this post! My mother has been on Zyprexa for almost two years, and I was aware of some concern over prescribing it for AD sufferers. She was hallucinating when it was originally prescribed. She hasn't had any more hallucinations like the initial one, but I've noticed that she sometimes comments that she sees patterns in unexpected places. We have a large philodendron plant in the living room and she once told me she saw what looked like a face in the pattern of the leaves. I'm not sure if it's connected to her earlier hallucinations, or if it signals a change in her visual abilities. In any case, I have not advocated for stopping the Zyprexa despite my concerns. And there IS a lot to be said for its sedative properties at this stage. It's so complex, isn't it?

[Patty Doherty]

My father was given Risperadol. It had little to no effect on his hallucinations, but totally knocked him out. It was such a small dose that he took, we wondered how it could have such a huge effect on him. But it did.

He was constantly on the look out for "that guy". That guy was his reflection. He would first be nice to it, then be agitated with it and finally, he'd want to fight it. It was quite the complex maneuver to get him past a row of store windows, a mirror in a rest room, or a mirrored elevator. Oh the elevator was the worst. We solved the problem at home by painting over the mirrors, who knew we had so many?! and keeping a sheet over the car in the garage. The blinds were drawn at night and we basically lived like that for years. The amount of medication needed to stop the hallucinations would have put him to sleep for the entire day and night. Instead, we learned to work around it, and bizarre as it may sound to people who haven't experienced this, it became a "normal" part of our lives.

[Ajlouny]

The FDA has a tough line to walk to try and get medications to people that can receive benefit, but not so early as to miss major problems. When side effects occur only in 0.1% of the subjects, you need to have 10s of thousands of subjects to really see it become statistically significant from placebo. Yes, it is sad that this happens, but there is just no way to prove that drugs are conclusively safe before they are approved.