I’ve mentioned the CATIE study before. CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness) was a NIMH-funded double blinded, randomized controlled trial comparing the effectiveness and side effects of newer-generation neuroleptics versus an older neuroleptic.
CATIE-AD was a part of CATIE. The AD stands for Alzheimer’s disease. CATIE-AD was published in the New England Journal of Medicine in October 2006. The results of the study were as follows:
“There were no significant differences among treatments with regard to the time to the discontinuation of treatment for any reason”
“The time to the discontinuation of treatment due to adverse events or intolerability favored placebo.”
“No significant differences were noted among the groups with regard to improvement on the CGIC scale.”
The general conclusion of the study was:
“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.”
CATIE-AD had important treatment implications, in that second-generation neuroleptics were being used extensively to treat psychotic thinking, aggression, and agitation in clients with Alzheimer’s disease, but, as the research team noted, “…their benefits are uncertain and concerns about safety have emerged.”
APA PRACTICE GUIDELINES
In October 2007, the APA published its Practice Guidelines for the treatment of Patients with Alzheimer’s Disease and other Dementia (103 pages). Two months later (December 2007) they published an abbreviated version of this document – A Quick Reference Guide – 24 pages.
In the Practice Guidelines, the APA discusses the importance of a complete and thorough evaluation. They also mention a range of psychosocial interventions that might be helpful, including: environmental changes, stimulation therapy (art therapy, music therapy, etc.), supportive psychotherapy, reminiscence therapy, validation therapy, etc…
Under the heading “Treatment of Psychosis and Agitation,” the guidelines initially mention the importance of evaluating any underlying problems that may be contributing to the problem. Then they go on to say:
“On the basis of good evidence, antipsychotic medications are recommended for the treatment of psychosis in patients with dementia… and for the treatment of agitation… These medications have also been shown to provide modest improvement in behavioral symptoms in general…”
Remember that CATIE-AD had been published only a year before, and had indicated clearly that antipsychotics (neuroleptics) had little or no advantage in this context over placebo, and in general, any marginal gains were offset by the side effects.
So how can the APA recommend these drugs and claim that the recommendation is made “on the basis of good evidence.”?
They answer this question themselves:
“Evidence for the efficacy of these agents is based mostly on 6–12-week trials in nursing home residents and outpatients.”
CATIE-AD participants were followed up for 36 weeks.
SIDE EFFECTS
The guidelines then list the side effects associated with neuroleptics. These include:
“death, cerebrovascular accidents, tardive dyskinesia, neuroleptic malignant syndrome, hyperlipidemia, weight gain, diabetes mellitus, sedation, worsening of cognition…akathisia, parkinsonian symptoms; … confusion, delirium, postural hypotension, and peripheral anticholinergic effects.”
The Quick Reference Guide also lists as side effects: cardiac conduction defects, urinary tract infections, urinary incontinence, and falls.
CURRENT PRACTICE
So, CATIE-AD stated essentially that these products had minimal efficacy in treating psychosis, aggression, and agitation in patients with Alzheimer’s disease, and what minimal gains existed were offset by serious side effects.
The APA then publishes its Practice Guidelines, encouraging its members to conduct thorough evaluations, including the possibility of psychosocial interventions. But they also informed their members that anti-psychotic (neuroleptic) drugs were an appropriate evidence-based treatment.
Nevertheless, neuroleptics (mostly of the newer generation) are being routinely prescribed to people with dementia. Briesacher et al, in an an article in JAMA, February 2013, draw attention to the fact that neuroleptic use in US nursing homes varies considerably with geography, which suggests that the use is not evidence based. They also report that:
“The most common antipsychotics prescribed are often used for off-label indications related to dementia, and the extended durations of use raise concerns about the care of frail elders residing in NHs [nursing homes]”
Smith et al in an article in the Journal of Gerontological Nursing (2013) state:
“Atypical antipsychotic medications have become the mainstay of treatment for behavioral problems among residents with dementia, despite federal ‘black box’ warnings about health risks and research demonstrating their limited effectiveness.”
In January 2013, the Centers for Medicare and Medicaid Services (CMS) published Improving Dementia Care and Reducing Unnecessary Use of Antipsychotic Medications in Nursing Homes. They state:
“According to CMS’s Quality Measure/Quality Indicator report, between July and September 2010, 39.4% of nursing home residents nationwide who had cognitive impairment and behavioral issues but no diagnosis of psychosis or related conditions received antipsychotic medications.”
ANALYSIS
Here’s what I think. In the old days (i.e. pre-1990), neuroleptics were prescribed relatively sparingly, for people with “diagnoses” of “schizophrenia” and/or “bipolar disorder.” These individuals had usually spent some time (in some cases, a great deal of time) in mental hospitals, but were living in the community, taking the neuroleptics, and seeing a psychiatrist at regular interval for drug checks. Neuroleptic drugs are neurotoxic. They have a generally tranquilizing and numbing effect, and have very severe side effects. Including, paradoxically, agitation. They are not medications in any ordinary sense of the term. They do not target psychotic thinking or hallucinations. Rather, they have a generally dampening effect on all thinking.
In the old days, drug reps and psychiatrists used to say that the action of neuroleptics was like throwing wet grass on a fire. That was before the market potential of these products was realized. They would never say that today.
In 1989, the FDA approved clozapine – the first of the newer neuroleptics. It had been temporarily approved in Europe in the early ’70s, but that’s a different story.
I can remember hearing a drug rep in 1989 singing the praises of clozapine. He said that the side effects were minimal. No more tardive dyskinesia; no more akathisia, etc… The only small snag was the need for regular white blood cell counts. At the time, I thought: “Yeah, right!” But the psychiatrists seemed to lap it up. Psychiatrists tend to become excited about new drugs, and to accept the statements of drug reps somewhat uncritically.
Then other second-general neuroleptics began to be approved and promoted by the pharmaceutical industry.
Meanwhile, Harvard Medical School had invented childhood bipolar disorder, creating a new market for these products.
From a business point of view, the biggest problem with neuroleptics is that people hate them. The side effects aren’t just damaging and destructive, they feel dreadful. So people stop taking them.
If there’s one thing you can say about pharmaceutical marketers, they’re creative. Somewhere around the turn of the millennium, they realized that the best place to push these products was in locations where people weren’t entirely free. They already had the market in the mental hospitals, of course. But group homes and nursing homes were obvious candidates for market expansion. Gwen Olsen’s book Confessions of a Rx Drug Pusher has some interesting insights in this area.
And today – as I’ve mentioned earlier – 39% of nursing home residents who have cognitive impairment and behavioral issues, but no diagnosis of psychosis, are receiving neuroleptic drugs. These drugs are not medication in any true sense of the word. They are chemical strait-jackets with devastating side effects. On February 27 of this year, I wrote a post about an 84-year-old man who had been victimized in this way.
In their practice guidelines, the APA pay lip-service to psychosocial interventions for agitation and aggression in people with Alzheimer’s disease. But there is a strong tendency, in many nursing homes, to bypass this and go straight to the drugs. This is often attributed to the fact that the nursing home doesn’t have staff trained in behavioral interventions, but it is also a fact that many have cultures in which drugs are seen as the first line approach to aggression or agitation.
One of the reasons for this, I suggest, stems from the terminology. Aggression and agitation in these individuals is routinely referred to in the nursing homes as BPSD: behavioral and psychological symptoms of dementia.
In medicine generally, if an illness entails problematic symptoms, it is normal practice to treat these symptoms pharmacologically. One of the symptoms of kidney failure, for instance, is chronic anemia, and this is treated, usually very successfully, with EPO, or a synthetic equivalent.
But when an individual with dementia becomes aggressive or agitated, it would seem to me to be more reasonable to think of this in human terms, and explore whether environmental or other stressors might be precipitating the problem. I have worked with nursing home residents who expressed some distress at the general level of noise in the building. I can recall an elderly man with dementia who expressed frustration and distress that they never served buttermilk! I talked to the Director of Nursing about this. She called the kitchen and asked them to offer buttermilk as an option with each meal. The kitchen manager said, “Sure,” and the problem was solved.
There’s often an assumption that once a person has dementia, he can’t engage in any meaningful discussion concerning his needs or preferences or sources of frustration. This isn’t true. Even in severe cases, it is possible to identity sources of irritation and frustration which are often easily remedied.
But if aggression and agitation are conceptualized as symptoms of an illness, then this kind of basic human interaction tends to be bypassed, in favor of drugs. The truly tragic part of all this is that the drugs themselves are often the source of the distress!
One of the great tragedies of our age is that human life itself – at all age levels – is being reduced to a set of so-called symptoms, to be “treated” with toxic chemicals.
Psychiatry, at a very fundamental level, is extremely disrespectful of the value and uniqueness of each human being. An elderly person’s problems are drugged out of existence, and the ensuing damage to the person’s body is dismissed as “outweighed” by the “benefit.”
Total neuroleptic sales in the US in 2011 amounted to $12.6 billion. It’s big business.