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Synopsis: Some medications are not friendly to your thyroid gland. You would expect that all doctors would be well-informed of the most likely culprits. So, how did Seroquel (quetiapine) slip through the cracks? This article takes a look at Seroquel (quetiapine) – one of the biggest troublemakers of thyroid function – and what can you do to protect yourself and the people you care about.
BY LEN LANTZ, MD, author of unJoy / 10.30.22; No. 61 / 7 min read
Disclaimer: Yes, I am a physician, but I’m not your doctor and this article does not create a doctor-patient relationship. This article is for educational purposes and should not be seen as medical advice. You should consult with your physician before you rely on this information. This post also contains affiliate links. Please click this LINK for the full disclaimer.
How a random issue hit Len’s radar
I admit it. Sometimes I get behind in reading medical journals. And, then, in a flurry, I might read through a year-long backlog of medical journals in a weekend. This happened to me this spring and I was astonished by something I read in a letter to the editor. It wasn’t even a major article or an editorial response to a major article. It showed up – without fanfare – in the “orange journal” of the American Association of Child and Adolescent Psychiatry. The title was, “Quetiapine-Induced Central Hypothyroidism.” (Zenno and Leschek. JAACAP. 2000)
At this point, you might be saying to yourself, “Huh?” I thought the same thing. I guessed that this was going to be some small-time report about a few patients having a random and rare side effect until I read this statement from the authors, “The drug manufacturer reports low T4 without TSH change in up to 50% of adult patients treated with quetiapine in clinical trials, which is suggestive of central hypothyroidism. However, central hypothyroidism is not mentioned as the etiology of low T4 by the drug manufacturer or in any publications to date.”
Translation: Seroquel can screw up your thyroid gland up to 50% of the time, and the manufacturer is not warning doctors about this risk.
I freaked out. Alarm bells started ringing in my brain when I read this information, and a thought that I couldn’t get out of my head was, “Why is this critical information with huge ramifications about Seroquel being published in obscurity?” I thought to myself, “This can’t be right! This is huge! I never heard about this in residency and have never heard this information in a medical conference.” I felt like I must have missed something in medical school or psychiatry residency. So, I sent copies of the letter to my colleagues (these are top-shelf, bright psychiatrists). “Have any of you ever heard about this?” I asked, “How could I have missed this?” Here is the funny thing: nobody had heard about this until I pointed it out to them.
“Big deal!” you might reply, “It’s small potatoes. No harm, no foul, right?” Wrong. Do you know how many prescriptions for Seroquel (quetiapine) there are in America every year?
In 2020 alone, there were 10.5 million prescriptions of Seroquel (quetiapine). This is a darn, big deal.
What are the symptoms of low thyroid (hypothyroidism)?
Hypothyroidism can cause a number of emotional and physical effects. Even without the possible worsening of thyroid function by a medication, the US lifetime prevalence of diagnosed thyroid disease (all types) is around 4% in men and 15% in women (Dzierlenga et al, 2019). These numbers are probably an underestimate as they do not capture all thyroid disease or subclinical thyroid disease. Hypothyroidism is more commonly associated with depression at 18% (Mohammad et al, 2019) compared to hyperthyroidism (elevated thyroid) at 10% (Bang Bové et al, 2014). Some common symptoms of low thyroid function (hypothyroidism) include:
Depression
Fatigue
Weight gain
Intolerance to cold
Constipation
Dry, thinning hair
Dry skin
Heavy or irregular menses
Goiter (an enlarged thyroid that might cause your neck to look swollen)
How doctors measure thyroid function and why the effects of Seroquel (quetiapine) might be missed
Three main blood tests are commonly performed to screen for thyroid disease: TSH, T4, and T3. To save money, the most frequently used screen that doctors order is the TSH and they skip the other tests. Here is the problem with central hypothyroidism: TSH looks normal in central hypothyroidism. In central hypothyroidism, TSH levels are normal when actual circulating thyroid hormone levels (T4 and T3) are low. So, the test (TSH) that most doctors order to check your thyroid function will miss central hypothyroidism caused by Seroquel (quetiapine).
Another reason that doctors might be missing central hypothyroidism with Seroquel (quetiapine) is that they simply don't know to check. Doctors know to screen for common problems related to psychiatric medications, but they rarely screen for rare side effects unless a person is experiencing unexplained symptoms. Most medical databases list “hypothyroidism” as an uncommon, possible side effect of Seroquel, but they do not list “central hypothyroidism.”
An additional problem is that doctors generally are reluctant to prescribe thyroid hormone for low T4 when the TSH is normal, as central hypothyroidism is generally thought to be rare.
As common a problem as lithium?
Several psychiatric medications can cause problems with thyroid function. The most well-known is lithium, which has been found in clinical studies to cause hypothyroidism in up to 52% of people (Bandyopadhyay and Nielson. QJM. 2012). Doctors who prescribe lithium routinely check thyroid labs as they know about this association, however, many other psychiatric medications can cause infrequent thyroid problems. Because the list is long, doctors might not think to check thyroid function because they are screening for more common side effects of these medications instead. Psychiatric medications found to cause thyroid dysfunction (Khalil and Richa. Clinical Neuropharmacology. 2011) less frequently than lithium include:
Typical (older) antipsychotics
Atypical (newer) antipsychotics
Tricyclic (older) antidepressants
Nontricyclic (newer) antidepressants
Carbamazepine and valproic acid (older anticonvulsants)
Should the FDA and the company that originally manufactured Seroquel have done more to warn people and their doctors?
Given what I have discovered since I first learned about this issue, I would say yes. If the FDA knew about this, which they did, then they clearly could have established recommended screening for central hypothyroidism, because screening for central hypothyroidism is not something doctors routinely do even when they are attempting to do an adequate job of testing thyroid function.
I think it also is reasonable to ask why the company that brought Seroquel to the world didn’t warn doctors or patients more effectively. Seroquel is already associated with the undesirable effect of weight gain. Undiscovered central hypothyroidism in up to 50% of patients could worsen this side effect and cause depression.
This spring, one of my colleagues made a written request for information from AstraZeneca, the manufacturer of Seroquel, because AstraZeneca’s web page reference listed in the “orange journal” was no longer available. The request was simple: please provide the incidence of low T4 with normal TSH in treatment with Seroquel. What was the company’s response? Their letter of reply included this statement: “We no longer actively search the published literature in response to inquiries for SEROQUEL® (quetiapine fumarate) Tablets, and we do not have information in our existing product information database to respond to your request.”
You can come to whatever conclusion you want to about AstraZeneca’s denial of having access to information on thyroid function that they previously submitted to the FDA for a pill that the company reportedly made over $37 billion in revenue since 2006 (source: Statistica). I believe it is worth pointing out that in 2010 the company had to pay a fine of $520 million – a small fraction of their profits from Seroquel – due to off-label drug marketing and other ethical breaches including the recruitment of “doctors to serve as authors of articles that were ghostwritten by medical literature companies and about studies the doctors in question did not conduct. AstraZeneca then used those studies and articles as the basis for promotional messages about unapproved uses of Seroquel” (source: US Department of Justice).
While the manufacturer of Seroquel likely has motives for remaining silent on the effects of the medication on the thyroid gland, the lack of labeling/warnings and public awareness could have a negative impact on millions of patients.
What you can do to check your thyroid
If you are taking Seroquel (quetiapine), you might want to educate your doctor about the effects of Seroquel on the thyroid. Many doctors are unaware of the need to pay particular attention to the level of Free T4 when assessing and treating central hypothyroidism. You can request that all 3 thyroid tests (TSH, Free T4, and Total T3) be checked if you are on Seroquel and plan to remain on the medication. I believe that this issue is so important that I have already changed my laboratory screening patterns and discovered the beginnings of central hypothyroidism in more than one patient taking Seroquel (quetiapine). If you discover that you have low Free T4 on Seroquel (quetiapine), you can then work with your doctor to determine if you should switch to a different medication or start a prescription of thyroid hormone (levothyroxine) to make up for the deficit.
Knowing about the possible thyroid effects of Seroquel (quetiapine) could help you and others
Seroquel (quetiapine) is a very helpful medication for many people. Like all prescription medications, there is a certain risk of side effects. When you know all the risks, you know what to watch out for and can do something about it. This issue of high rates of thyroid dysfunction from Seroquel (quetiapine) startled me, but the positive thing is that it opened up new discussions with my patients who are on the medication and benefit from it. Together, we were able to come up with a plan to regularly monitor thyroid function and decide together on any medication changes that might be needed if their thyroid was functioning poorly due to the medication. If you know someone on Seroquel (quetiapine), please share this article with them. We just need to get the word out, so that our doctors, families, and friends are aware of this important information and can do something about it.
For further reading, check out:
Len’s Article, “Medical Causes of Depression”
Len’s Article, “How Record Keeping Can Help Treatment-Resistant Depression”
Len’s Article, “Genetic Testing for Psychiatric Medications”
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