Well, I can’t seem to let this topic lie. After my last two posts, I ran across a letter to the editor in the American Journal of Psychiatry from Dr. Bernard Carroll, a frequent commenter here, written back in 2009 in response to the meta-analysis by Nelson and Popakostas [Atypical Antipsychotic Augmentation in Major Depressive Disorder: A Meta-Analysis of Placebo-Controlled Randomized Trials]. I’m posting it here with his permission for several reasons. First, he anticipates the cautions expressed in the 2013 meta-analysis by Spielmans et al [Adjunctive Atypical Antipsychotic Treatment for Major Depressive Disorder: A Meta-Analysis of Depression, Quality of Life, and Safety Outcomes] as well as my own concerns about this whole augmentation strategy. In addition, he fleshes out the risk/benefit ratio equation with some actual estimates:
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Antipsychotic Drugs for Depression?
Bernard J. Carroll, M.B.B.S., Ph.D., F.R.C.Psych. American Journal of Psychiatry. 2010 167[2]:216. |
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To the Editor: The Review and Overview by J. Craig Nelson, M.D., and George I. Papakostas, M.D., published in the September 2009 issue of the Journal, concluded that atypical antipsychotic drugs "are effective augmentation agents in major depressive disorder but are associated with an increased risk of discontinuation due to adverse events". This meta-analysis did not demonstrate effectiveness, only nominal efficacy against placebo. Moreover, the review is unbalanced because risk was not adequately considered.
The authors called the risk of tardive dyskinesia a "rare but serious" concern. Tardive dyskinesia is serious but not rare with atypical antipsychotic drugs. A rate of 8% has been seen in delusional depression. Many cases are persistent, and depressed patients are especially at risk. For aripiprazole, which was the first atypical antipsychotic drug approved for augmentation in depression, a 1.1% rate of dyskinesia within 6 weeks was reported [study #CN138165; ClinicalTrials.gov registry number, NCT00105196]. This translates to 11,000 cases per million exposures. Should we really give this drug to millions of nonpsychotic depressed patients? The marketer’s aggressive media advertising appears to have that aim. There is insufficient evidence of benefit to offset such risk. The trials of aripiprazole were unblinded by akathisia [25%] and other side effects that can introduce rater bias. Aripiprazole was not efficacious by self-report depression measures, i.e., patients did not find it effective. In one study cited, efficacy was lacking in male subjects. In the meta-analysis, the number needed to treat was nine, signifying only borderline utility in this therapeutic context. The corresponding number needed to treat for lithium is four to five. The larger numbers of patients in the evidence base for atypical antipsychotic drugs, as noted by the authors, reflect the commercial interest in penetrating the depression market, but the manufacturers of these drugs have studiously avoided testing their products against lithium. These concerns about efficacy and relative efficacy were not addressed. Finally, there is no evidence that augmentation with atypical antipsychotic drugs is useful in the long-term. Drs. Nelson and Papakostas did not note that a study of depressive relapse prevention with risperidone augmentation was negative. No long-term safety or efficacy data have been posted for aripiprazole in the treatment of depression, even though a 52-week study was completed in November 2007 [ClinicalTrials.gov registry number, NCT00095745]. On the basis of the presently available data, psychiatrists should be more forthright in pointing out the limited effectiveness as well as the risks and adverse effects of atypical antipsychotic drugs in the treatment of depression, especially in primary care.
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Can we copy and paste this and email it to every doctor working in the VA?
Just in case readers are interested, way back in the 1990s, before all these atypical / novel antisychotics came out, we were told that using anti psychotics in people with mood disorders was a transient or temporary
Intervention
Now that was based on medications that were the original ones, like Haldol or Thorazine., I think the atypicals seem to have the same risks.
Also, it was drummed into my head that anti psychotics used in nonpsychotic people end up making them impaired to a point of cognitive disruptions, that antipsychotics dull people down per mood.
Now let’s jump back to 2015, and see what I have seen with the use of Seroquel, abilify, risperdal, zyprexa, and you fill in the blank with whatever new antipsychotic is out there.
These patients come in looking drugged / impaired / depressed. So, do these drugs really help people who are depressed, or did they just really help these big pharma companies continue their multi billion dollar profits on a yearly basis?
What’s more pathetic. Denying the truth, or propagating a lie?
Trick question!
It’s an astonishing lack of clinical judgment and clinical risk assessment that the same physicians who would be terrified to start someone on an MAOI or Prazosin hand out Abilify and Seroquel like candy.
Other than herd mentality, I don’t get it.
Well put. I don’t know either. This morning I saw a woman who was on Seroquel [prescribed by telepsychiatrists at a mental heath clinic] with big time TD [mouth, hands, legs]. The closer I get to getting her off of Seroquel, the worse it gets. It’s just a tragedy in that this patient has never been psychotic. Her primary diagnosis would probably best be characterized as an attachment disorder. How that translated to Depakote/ Prozac/ Seroquel/ Cogentin/ Neurontin/ Xanax/ Trazadone [all over max doses] is beyond my understanding. I say “telepsychiatrist[s]” because it was a different one every time. I’m rarely at a loss for words, but I felt speechless this morning when she asked, “What was the Seroquel for, anyway?”
Yep, I’ve got those people too, on a ridiculous basket of drugs, with horrible side effects. None have been prescribed by telepsychiatry yet — they’ve all gotten their prescriptions from PCPs or psychiatrists in person.
What was the Seroquel for? To shush an annoying, high-maintenance female.
Or so I am tempted to reply … I know plenty of males are mal-treated in the same way. But at least as a male it seems you have to be somewhat Disruptive, not just Annoying, to get the Big Shush. Many state prison systems have shoveled it out in alarming quantities.
Johanna,
It’s not shut up the woman, it’s shut up the patient who can’t sleep. If you think it is just a shut up the women thing, look at the staggering numbers of male veterans who are placed on these drugs:
http://www.nydailynews.com/life-style/health/sleepless-vets-prescribed-seroquel-nightmare-beginning-article-1.206526
And yet no off label Prazosin trial? Even when they have BPH and hypertension (FDA indications) too, a potential triple threat drug?
We can all agree that it’s a “shut up” ploy – “somebody shut up.” I might have more sympathy than some since I work in a too-high-volume clinic. I’ve learned some things in this very unfamiliar environment for me compared to my former life. One of them is that many patients appear with an agenda. Other are lobbying for a medication that doesn’t exist except in the minds of some Mercedes-driving KOL who doesn’t see patients or an ad designer making DTC ads.
I’ve actually taken an old psychoanalytic principle [Michael Baliant] and adapted it to an Appalachian charity clinic. It’s the “repairative fantasy.” He said [wisely], that every patient has a fantasy about what will make them well [“if only…”], and you need to know what that is and deal with its irrationality/rationality before you can get anywhere. I’ve taken to querying patients who have some medication agenda, exploring what they think this pill they need would do for them if they had it [or I had it]. They often start with “anxiety” or “depression” and it takes a moment to get under that, but it usually gets us on the same page. It doesn’t take as long as it sounds. I started it when people would come in already on a sack-full and I insisted on their going through it and saying why and how long for each. It has gotten to be kind of a hobby, but more productive than I would’ve thought.
My sense of things is that a lot of bad prescribing comes from doctors thinking “What can I give now?” with Johanna’s aside – “to shut her/him up.” I could feel that happening at the end of a long clinic. If you confront that, you can often get on a much more productive path. How many times have I said something like, “You know, you’re the kind of person that doctors throw medicine at. It doesn’t seem to have helped because you have a sack full, and you seem to be looking for more, or a silver bullet. Let’s back up and start over.” I jokingly call it “country psychiatry,” but it has sure helped me stay out of the rut so many fall into.
I worked today and saw a waiting-room full, and it was fun. I don’t think the over-prescribers have any fun…
Hmm, reading these above “shut up” comments, makes me wonder why it is so scary to see antipsychotics being given to characterologically disordered patients.
Frankly, I firmly believe that medicating Axis 2 is detrimental until proven otherwise.
Ironic isn’t it, that personality disorder issues seem to have reactions to meds, that could give some question of a biological marker to something that really doesn’t deserve medication…
Thanks, Dr. Joel, for mentioning that other disastrous excuse for prescribing Seroquel — “because the patient can’t sleep” due to PTSD symptoms, physical pain or both. Both military veterans and injured workers have had their health wrecked this way. And once you become dependent on Seroquel for sleep, quitting it can cause some fierce “rebound insomnia.”
As for the folks with screwed-up ways of coping with terribly screwed-up life experiences: The current concepts of “Bipolar Disorder” and “Borderline Personality Disorder” resemble each other so closely that the individual doc can simply take his or her choice. Bipolar is likely to win out, both because the treatment can be quick and almost exclusively chemical, and because the insurer is more likely to pay.
A depressing sign of the times: In order to win treatment and “respect” for folks on the borderline spectrum, groups like NAMI have embarked on a crusade to prove that BPD is indeed a Biological Brain Disease …
Re the “shut up” ploy, a lot of it has to do with the sociology of medicine. What concrete thing can I give this person to address his complaint? This kind of thinking favors meds (and procedures), and is exacerbated by time pressure. In an era of 5-day inpatient stays and 15-minute med checks, it’s hard to think outside this box.
James, I like your point comparing atypicals to MAOIs and prazosin.
Johanna, the crusade to argue (not prove) that BPD, and everything else, is a biological brain disease is an odd turn indeed. As I see it, it conflates a trivial philosophical position with a scientific breakthrough, and only serves rhetorical and political purposes. Little or none of this serves the patient.
I’m surprised at the lack of discussion on antipsychotics shrinking cortex, which was the result from Ho et al. study published in 2011 in Archives of General Psychiatry and in the work with the primates (Dorph-Petersen et al., 2005). I just finished reading Cotel et al.’s Microglia activation in the rat brain following chronic antipsychotic treatment at clinically relevant doses scheduled for publication in European Neuropsychopharmacology. The Cotel et al. article examines the mechanism through which antipsychotics destroy brain cortex. Please, tell your friends.