Are Antipsychotics Overprescribed?

Larry Culpepper, MD, MPH; Nassir Ghaemi, MD, MPH


February 18, 2011

In This Article

A (Slight) Difference of Opinion

Larry Culpepper, MD, MPH: First, I agree that the data we have available to guide the use of antipsychotics, and particularly the newer atypical antipsychotics, are limited. We have strong evidence for effectiveness in schizophrenia and bipolar mania.[1,2] Beyond those conditions, we have limited evidence for use acutely in bipolar depression and as augmentation for treatment resistant depression, but for only some of the atypicals, and for only a relatively short (weeks) interval.[4,5,6]

But the world primary care physicians (PCPs) live in is significant here. For many chronically ill patients, including those with resistant depression and bipolar depression, the PCPs are also the "quaternary" care physician. By this I mean the PCP is also the professional the patient returns to for long-term care, after they have gone through the often limited specialty care options available. We are the "physicians of last resort" to whom such multiproblem and treatment-resistant patients return after exhausting other sources of care. Most of us in primary care have a fairly small number of such patients compared with psychiatric practices. These are the patients for whom the question about a treatment is not "what does the evidence say?" rather it's "will it help in Mary Jones?"

For such patients, the clinician's "N-of-One" trials are what is left after standard (evidence-based) treatment has been exhausted. They are marked by desperation on the patient's part because of their suffering, and on the physician's part because of limited treatment options. For these patients with resistant depression and bipolar depression, if a clinical trial indicates efficacy, then continued use is reasonable. However, it is reasonable within the framework of careful monitoring of continued efficacy, and of side effects, with potential trials of tapering.

Other uses like for run-of the-mill depression, anxiety, and sleep, are where Dr. Ghaemi and I agree. Use [of antipsychotics] for these conditions should be discouraged. In part, the real issue for the clinician and patient here is the same as the above – one of risk-benefits in comparison to other treatment options. Quite simply, there are well-established medications (and nonpharmacologic therapies) that are at least as effective but with much less risk and costs that should be the mainstay of treatment. While the atypical might be considered novel or cutting edge for some of these conditions, the role of the physician here should be to minimize the potential for harm, rather than uncontrolled experimentation with new options.

Dr. Ghaemi: I think it is important to emphasize that the benefit shown for some of the atypical neuroleptics for both bipolar and unipolar depression is only short term, as Dr. Culpepper noted. The studies were mostly around 2 months (often 6 weeks) long.[4,5,6] This means that these drugs work for up to 2 months, period -- not 2 months and 1 day, nor 2 years, nor 20 years. We cannot assume they have long-term benefits just because they have short-term benefits. There are many examples in medicine where this is not the case: antibiotics come to mind. One might call this the "happily ever after" fallacy. Once a patient gets better, that's no reason to leave all the drugs alone until the Day of Judgment.

For the desperation cases, as Dr. Culpepper mentions, if they are few in number, one might make exceptions and give long-term treatments even though the evidence isn't there, as long as one is constantly monitoring side effects and thinking about stopping the medication if possible, as he notes. But we should be honest: this is faith, not science; if it is medicine, it is the medicine of the believer, not the knower.

We agree, as he says, on garden-variety depression, anxiety, and sleep issues. These expensive drugs are being marketed for use while cheaper therapies are probably just as good and certainly have never been shown to be worse. For instance, at the low doses in which it is used for sleep and anxiety, ie, below 150 mg/d, quetiapine basically has very little dopamine blockade, but it has major antihistamine effects, over 20-fold more potent than Benadryl in animal studies.[7] So low-dose quetiapine is basically like giving 10-20 over-the-counter Benadryl pills (25-mg tablets). Some people might improve with a prescription for 100 mg/d of Benadryl rather than 25 mg/d of quetiapine.


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