Psychiatric Medication Side Effects: Risk/benefit Ratio in the Modern Era

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I am going to share an e-mail exchange with a patient about a medication that is part of the changing for treating depression. Since the replacement of “tricyclic antidepressants” like amitriptyline and desipramine by SSRIs (), approach to medication for depression has been SSRI, second SSRI, SNRI, then augment the SNRI, then augment with something else, and finally consider ECT. There are other treatment choices in the algorhythm, such as psychotherapy, , or mirtazepine, but the general pattern of SSRI, second SSRI, SNRI has been the backbone of treatment in the modern era of psychiatry.

gain,

diabetes

At the same time, there have been other medications that are thought of as “mood stabilizers,” including a group of medications known as the atypical antipsychotics, including Zyprexa, Risperdal, Seroquel, Geodon, and Abilify. Recently, two of these medications have received FDA indications for uses other than bipolar mania or schizophrenia; and there are signs that the lines between medications thought of as “antidepressants” and those considered “mood stabilizers” will become more blurred going forward. This should be a good thing, as we are gaining additional options to treat mood disorders, a group of illnesses that cause considerable suffering in the country and world. But the new medications have powerful effects, and so, like most medications, have potential side effects, in this case the risk of increasing blood glucose, cholesterol, triglyceride levels, weight and .

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The e-mail exchange relates to the issue of , and when should a person disregard the scary print at the bottom of the (or the ridiculously fast-spoken list of side effects at the end of a TV commercial). The patient has struggled with depressive symptoms for a number of years, and has been treating the symptoms with the “safest” medications (ie, SSRIs), avoiding medications with greater risks and side effects. I have been her psychiatrist for a short period, and we are not yet certain whether her symptoms are part of depressive disorder or are instead the depressive side of bipolar disorder. I recently suggested to the patient that we look at the big picture—that the depression is taking a toll on her life, that the depression has affected her relationships and career path, and that the depression has even put her at risk for suicide. I think I will let the exchange finish the point I tried to make. She is a bright patient who reads up on whatever we discuss, something that sometimes makes my work easier, and other times makes my work more challenging, albeit in way that medicine SHOULD be challenging.

I suggested considering a more potent medication, such as Seroquel. She sent a message that included the following comment:

http://www.usatoday.com/news/health/2009-04-08-fda-seroquel_N.htm

I looked up Seroquel…and get freaked out by things like this:

I will let interested readers go to the link—to an article questioning the wisdom of the FDA in giving Seroquel the new indications—on their own. As I mentioned earlier, I think that more choices are a good thing, providing we have bright doctors who take the time to educate their patients, who take the time to learn enough about their patients, and who make reasoned decisions based on “risk to benefit ratios,” assumptions that may or may not be valid. I have written about my disdain for psychiatric practices that do “7-minute med checks,” and I believe that those practices may serve their patients more safely by sticking to the SSRIs!

My long-winded response to the patient was as follows:

I am not pushing Seroquel- only suggesting that when you look objectively, there may be a case for more aggressive treatment of your depression. I want to point out a couple things in the

USA Today

article, an article that is clearly written by someone with certain preconceptions.

First, the article correctly reports that the FDA found that the risk/benefit ratio of Seroquel does not favor using the medication as a first-line agent. But it is important to note that after reviewing all of the data, the FDA DOES favor approving the use of the medication for treating depression in people who (like you) do not achieve remission of mood symptoms from first-line treatments like Prozac.

blood sugars

There are a couple comments in the article that I find misleading; for example, the quote of lawyers who said ‘the company knew Seroquel caused diabetes.’ Seroquel doesn’t ‘cause diabetes’. There is an increased risk of diabetes in people taking Seroquel, but the risk varies with dose and length of time taking the medication. The drug is used at 600-800 mg for mania or schizophrenia but only 300 mg for depression, and people who take it for a short period of time at a lower dose are at lower risk. The risk of diabetes in patients taking Seroquel goes from around 3% to around 6%. For an individual, the risk of NOT getting diabetes goes from 97% to 94%. The effect can be worded in a scary way—‘the risk of diabetes doubles’- but going from 97% to 94% odds of NO diabetes is less frightening—especially when the odds ratio takes into account the risk and pain of experiencing years of depression. The risk of diabetes can be greatly reduced, by the way, by monitoring and stopping the medication if glucose tolerance changes.

It is important to distinguish between the risk to an individual vs. the risk to a population. The FDA looks at the latter, but the individual should look at the former. For example, much has been made of the risk of suicidal ideation in children and adolescents taking antidepressants. The result of the FDA black-box warning of this issue has been a significant drop in antidepressant prescriptions for children and adolescents, and at the same time (coincidentally?) a significant increase in suicides in the same age group. The warning came because retrospective evaluation of pooled research data showed that ‘suicidal ideation and behavior almost doubled’ in depressed patients starting antidepressants compared to depressed patients starting placebo tablets. A ‘doubling’ sounds bad… but there was no increase in actual suicides, and the data may reflect something benign. For example, perhaps kids on antidepressants talk about their thoughts more. Looking at the data beyond the ‘doubling’ headline, in the placebo group about 2% of the depressed patients had increased suicidal thoughts. In the treatment group the number was around 4%. This is in fact a ‘doubling’ of suicidal thoughts, but we can look at the exact same data in a different way. In the placebo group, 98% of the patients did not report increased thoughts of self-harm, and in the treatment group 96% had no increased thoughts of self-harm. This way of looking at the data is much less likely to scare a mother into dumping her child’s Prozac down the drain… but is also less likely to catch your eye in the check-out aisle where the papers are sold!

Singulair

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I will again point out that no suicides were attributed to antidepressants. But meanwhile, suicide IS one of the leading causes of death in that age group, and most of those suicides occur in adolescents with untreated depression. There has been less dramatic reporting of similar increases in suicidal ideation in patients taking virtually any of the anti-seizure medications, and in similar effects from other medications—like , a .

Government health agencies look at fractional risk multiplied times 200 million people. A 5% risk of diabetes means an additional ONE MILLION people with diabetes! But an individual still has a 95% chance of NOT having the illness. I remember going through a similar calculation back in med school, when I contemplated giving up the bacon that I loved to lower my risk of heart disease. For now, I am still eating bacon!

I want to leave this discussion making two primary points. First, it is important that patients know the true balance of risk-to-benefit for any treatment or medication, and that they try to learn the truth behind the headlines. This point is a perfect segue for a plug for my practice. I see, at most, two patients per hour for follow-up visits and find that even the 30 minutes that I set aside at minimum is a short period to adequately explain all that the patient should know— particularly when most of the appointment must be used to collect information from the patient, not the other way around. I have no idea how people gain anything from the typical, 7-minute appointment. If you are a dissatisfied patient, give me a call through my telepsychiatry practice!

Second, at some point, it may become time to treat a mood or anxiety disorder or some other psychiatric condition with more potent medication, including medication that has temporary side effects. When a person develops gallstones, he or she usually ends up with either a number of small scars from laparoscopy or one big scar under the right ribcage from an open procedure. In either case, the person experiences significant pain for a number of days. I sometimes think about the different tolerances people have for the treatment of different conditions, from the financial perspective and from the perspective of tolerable side effects. People think little of spending thousands of dollars for anything involving a scalpel or anesthesia… my teenage daughter’s broken arm took 10 minutes to cast, and the orthopedist charge was almost $1,000, but I will get nowhere asking an insurer to pay $140 for an hour of my time with a patient! Likewise, mild nausea from Effexor will keep a patient from taking the medication, even when the illness is so severe that the person is homebound from panic attacks. After several days of mild dysphoria (at most), the medication has a good chance of eliminating the anxiety entirely!

What are the reasons for the differences? I have a few guesses, including the stigma of mental illness, the difficult nature of change, and the powerful effects of denial. In all cases, I don’t see significant changes in “how things are” on the horizon… so noncompliance and unwillingness to accept proper treatment will likely remain an issue for psychiatrists to understand and to consider as part of the entire illness.

I’m sorry for the hiatus in posting; there always seem to be tons of paperwork this time of year— not to mention the need to get things together for the tax season. With taxes in mind, perhaps it is appropriate to write a post that has to do with the FDA.