Science

Depression and suicide risk are side effects of more than 200 common drugs

The recent suicides of celebrities Anthony Bourdain and Kate Spade have prompted many of us to look more closely at what may drive people to depression or to end their own lives.

One risk factor has gotten little attention in this discussion: the medications people take.

More than a third of American adults are using medications that have the potential to increase their risk of depression, a study published this week in JAMA finds, and nearly a quarter use medications that have suicidal symptoms as side effects.

The 203 drugs the researchers identified aren’t obscure; they include some of the most commonly prescribed medications around — like birth control, beta blockers for high blood pressure, and proton pump inhibitors for acid reflux. (You can see the full list at the end of this article.)

Strikingly, the researchers from the University of Illinois and Columbia University discovered, people using these drugs had an elevated risk of depression compared to the general population. And the more medications with depression as a side effect people took, the more their risk of the disease increased.


Javier Zarracina/Vox

“It’s remarkable to know just how common it is that people might be at higher risk because of medicines they take,” said University of Pennsylvania psychiatry professor Michael Thase, who was not involved in the study. “Thinking about these [potential side effects] should be [doctors’] second or third step before they prescribe antidepressants. Sometimes de-prescribing [other drugs] is what’s needed.”

Since depression affects more than one in 20 adults in the US every year, and suicide rates have been steadily climbing here for years, these new findings are an important reminder that the drugs a person takes for one health condition may be making them sick in other ways.

Americans commonly use more than 200 drugs that carry depression or suicidal symptoms as side effects

Every medication comes with many possible side effects, and most of those side effects are rare. (Just think about the warnings highlighted on the drug commercials on TV.) If a side effect is listed on a package insert, it generally means at least 1 to 2 percent of people will experience it, said lead study author Dima Mazen Qato, a pharmacist and assistant professor of pharmacy at the University of Illinois Chicago.

To figure out how common depression and suicide-related symptoms (including suicide, or suicidal thoughts and behaviors) side effects were among the drugs Americans take, the researchers turned to the National Health and Nutrition Examination Survey, a government-run study that’s been tracking health trends in a representative sample of Americans since the 1970s.

They combed through the drug use data on more than 26,000 people who participated in the study between 2005 and 2014 and found that Americans reported using 203 medications with depression and suicidal symptoms listed among their side effects. As of 2013-’14, 38 percent of adults reported taking drugs with depression as a potential side effect within the past 30 days, while 23 percent were using drugs that carried the risk of suicidal symptoms.

After the researchers figured out that these drugs were common, they wanted to see if there was any relationship between the people taking the drugs and an elevated risk of depression. To find this out, they turned to the NHANES survey again, which also tracks mental health. They discovered that the more drugs people reported taking, the higher their risk of depression and suicide.

There was a tripling of depression risk among people on three or more medications that have depression as a potential side effect

To get a sense for how much of a risk of depression and suicide taking these drugs was associated with, let’s walk through the numbers.

In the total study population of more than 23,000 people (excluding the people on antidepressants), 6 percent reported depression. Among the users of just one of the drugs that have depression as an adverse effect, the prevalence increased to 7 percent. Among people taking two or more of the potentially depression-inducing drugs, the prevalence went up to 10 percent. And among people taking three or more of the drugs, the prevalence was 15 percent. (Again, for all these figures, the researchers excluded antidepressant users since they’d inflate the results.)

They found similar associations in non-antidepressant users who were taking medications with suicide symptoms. In the total study population, who weren‘t using medications with suicidal symptoms, 5 percent of participants reported suicidal symptoms. Among adults on one of these medications, the prevalence rose to 8 percent and among adults using three or more, the prevalence increased to 18 percent.

“One can say you’d expect that finding because people who have more medical problems are more likely to take more medications and are more likely to be depressed,” said study co-author Mark Olfson, a professor of epidemiology and psychiatry at the Columbia University Medical Center.

But when the researchers looked at drugs that weren’t associated with depressive side effects, they found no dose response like the one they discovered in people taking one or more drugs with depressive or suicidal side effects. In other words, simply taking more medications, when the medications don‘t have depression or suicide listed as a side effect, was not associated with an increased risk.

“It didn’t surprise me that there are a large numbers of drugs [with these side effects] and that these drugs are commonly prescribed,” said Olfson. “But what surprised me is that you can see this connection [to depression] in the general population, how strong it was, and that it builds up with each additional medication a person uses.”

Penn’s Thase called the findings “very suggestive” and ”strong circumstantial evidence” that taking one or more medications with depression as a potential side effect may increase a person’s risk of depression. While these medications work through different mechanisms, he said, it’s possible that when they‘re combined, those risks increase.

While the researchers did their best to statistically control for factors that may confound their results, like sex, age, race, and employment status, there were some things the paper can’t tell us.

Because this is an observational study and not an experimental study, the researchers stopped short of saying the medications caused the depression. To find that out, they’d need to do a follow-up study where they track people who start taking these medications over time and see if their risk of depression increases.

What’s more, there are many factors that can increase a person’s risk of depression and suicide, including one’s personal and family medical history and major life upheavals, and the researchers couldn‘t account for those. The sample in the study was also too small to drill down into the individual medications and their depression patterns.

But for now, the study is a powerful reminder that people know that certain medications carry the risk of depression and suicidal thinking, and that they should talk to their doctors about that when starting on a new drug.

“When you have a patient,“ said Thase, “and their story doesn’t fit the usual pattern — there are no setbacks in the person‘s life, no broken heart, no job difficulty, [doctors] should think of other possible masquerading causes — and the chance that medication could be the cause.”

For patients concerned about the side effects of their medications, this database from the National Institutes of Health lets you search for the side effects for most drugs and drug classes. We’ve also created a table of the 203 drugs the researchers found that had depression or suicidal symptoms as side effects:

Drugs with depression and suicide risks

Name: Type Risk
Name: Type Risk
Acetaminophen/Tramadol Analgesics Suicidal Symptoms
Hydropmorphone Analgesics Suicidal Symptoms
Tapentadol Analgesics Suicidal Symptoms
Tramadol Analgesics Suicidal Symptoms
Carbamazepine Anticonvulsants Suicidal Symptoms
Clonazepam Anticonvulsants Suicidal Symptoms
Diazepam Anticonvulsants Suicidal Symptoms
Ethosuximide Anticonvulsants Suicidal Symptoms
Gabapentin Anticonvulsants Suicidal Symptoms
Lamotrigine Anticonvulsants Suicidal Symptoms
Levetiracetam Anticonvulsants Suicidal Symptoms
Lorazepam Anticonvulsants Suicidal Symptoms
Methsuximide Anticonvulsants Suicidal Symptoms
Oxcarbazepine Anticonvulsants Suicidal Symptoms
Phenytoin Anticonvulsants Suicidal Symptoms
Pregabalin Anticonvulsants Suicidal Symptoms
Topiramate Anticonvulsants Suicidal Symptoms
Valproic Acid Anticonvulsants Suicidal Symptoms
Zonisamide Anticonvulsants Suicidal Symptoms
Amitriptyline Antidepressants Suicidal Symptoms
Amitriptyline/Chlordiazepoxide Antidepressants Suicidal Symptoms
Amitriptyline/Perphenazine Antidepressants Suicidal Symptoms
Bupropion Antidepressants Suicidal Symptoms
Citalopram Antidepressants Suicidal Symptoms
Clomipramine Antidepressants Suicidal Symptoms
Desipramine Antidepressants Suicidal Symptoms
Desvenlafaxine Antidepressants Suicidal Symptoms
Doxepin Antidepressants Suicidal Symptoms
Duloxetine Antidepressants Suicidal Symptoms
Escitalopram Antidepressants Suicidal Symptoms
Fluoxetine Antidepressants Suicidal Symptoms
Fluoxetine/Olanzapine Antidepressants Suicidal Symptoms
Fluvoxamine Antidepressants Suicidal Symptoms
Imipramine Antidepressants Suicidal Symptoms
Milnacipran Antidepressants Suicidal Symptoms
Mirtazapine Antidepressants Suicidal Symptoms
Nefazodone Antidepressants Suicidal Symptoms
Nortriptyline Antidepressants Suicidal Symptoms
Paroxetine Antidepressants Suicidal Symptoms
Phenelzine Antidepressants Suicidal Symptoms
Protriptyline Antidepressants Suicidal Symptoms
Selegiline Antidepressants Suicidal Symptoms
Sertraline Antidepressants Suicidal Symptoms
Trazodone Antidepressants Suicidal Symptoms
Venlafaxine Antidepressants Suicidal Symptoms
Vilazodone Antidepressants Suicidal Symptoms
Alprazolam Anxiolytics, Hypnotics and Sedatives Suicidal Symptoms
Butabarbital Anxiolytics, Hypnotics and Sedatives Suicidal Symptoms
Chlordiazepoxide Anxiolytics, Hypnotics and Sedatives Suicidal Symptoms
Clonazepam Anxiolytics, Hypnotics and Sedatives Suicidal Symptoms
Clorazepate Anxiolytics, Hypnotics and Sedatives Suicidal Symptoms
Diazepam Anxiolytics, Hypnotics and Sedatives Suicidal Symptoms
Doxepin Anxiolytics, Hypnotics and Sedatives Suicidal Symptoms
Eszopiclone Anxiolytics, Hypnotics and Sedatives Suicidal Symptoms
Flurazepam Anxiolytics, Hypnotics and Sedatives Suicidal Symptoms
Pentobarbital Anxiolytics, Hypnotics and Sedatives Suicidal Symptoms
Ramelteon Anxiolytics, Hypnotics and Sedatives Suicidal Symptoms
Triazolam Anxiolytics, Hypnotics and Sedatives Suicidal Symptoms
Zaleplon Anxiolytics, Hypnotics and Sedatives Suicidal Symptoms
Zolpidem Anxiolytics, Hypnotics and Sedatives Suicidal Symptoms
Metoclopramide Gastrointestinal Agents Suicidal Symptoms
Finasteride Hormones/Hormone Modifiers Suicidal Symptoms
Leuprolide Hormones/Hormone Modifiers Suicidal Symptoms
Levonorgestrel Hormones/Hormone Modifiers Suicidal Symptoms
Oxandrolone Hormones/Hormone Modifiers Suicidal Symptoms
Progesterone Hormones/Hormone Modifiers Suicidal Symptoms
Montelukast Respiratory Agents Suicidal Symptoms
Ribavirin Respiratory Agents Suicidal Symptoms
Roflumilast Respiratory Agents Suicidal Symptoms
Zafirlukast Respiratory Agents Suicidal Symptoms
Acamprosate Other Suicidal Symptoms
Amantadine Other Suicidal Symptoms
Armodafinil Other Suicidal Symptoms
Aripiprazole Other Suicidal Symptoms
Asenapine Other Suicidal Symptoms
Atomoxetine Other Suicidal Symptoms
Carbidopa/Entacapone/Levodopa Other Suicidal Symptoms
Carbidopa/Levodopa Other Suicidal Symptoms
Ciprofloxacin Other Suicidal Symptoms
Dapsone Other Suicidal Symptoms
Efavirenz Other Suicidal Symptoms
Efavirenz/Emtricitabine/Tenofovir Other Suicidal Symptoms
Iloperidone Other Suicidal Symptoms
Interferon Beta-1a Other Suicidal Symptoms
Interferon Beta-1b Other Suicidal Symptoms
Isotretinoin Other Suicidal Symptoms
Lurasidone Other Suicidal Symptoms
Memantine Other Suicidal Symptoms
Mefloquine Other Suicidal Symptoms
Methylphenidate Other Suicidal Symptoms
Modafinil Other Suicidal Symptoms
Moxifloxacin Other Suicidal Symptoms
Naltrexone Other Suicidal Symptoms
Natalizumab Other Suicidal Symptoms
Olanzapine Other Suicidal Symptoms
Ofloxacin Other Suicidal Symptoms
Peginterferon Alfa-2a Other Suicidal Symptoms
Quetiapine Other Suicidal Symptoms
Raltegravir Other Suicidal Symptoms
Risperidone4 Other Suicidal Symptoms
Rivastigmine5 Other Suicidal Symptoms
Sibutramine Other Suicidal Symptoms
Tetrabenazine Other Suicidal Symptoms
Varenicline Other Suicidal Symptoms
Cyclobenzaprine Analgesics Depressive (Non-Suicidal) Symptoms
Fentanyl Analgesics Depressive (Non-Suicidal) Symptoms
Acetaminophen/Hydrocodone Analgesics Depressive (Non-Suicidal) Symptoms
Ibuprofen Analgesics Depressive (Non-Suicidal) Symptoms
Indomethacin Analgesics Depressive (Non-Suicidal) Symptoms
Morphine Analgesics Depressive (Non-Suicidal) Symptoms
Nabumetone Analgesics Depressive (Non-Suicidal) Symptoms
Oxycodone Analgesics Depressive (Non-Suicidal) Symptoms
Atenolol Antihypertensives Depressive (Non-Suicidal) Symptoms
Atenolol/Chlorthalidone Antihypertensives Depressive (Non-Suicidal) Symptoms
Betaxolol Antihypertensives Depressive (Non-Suicidal) Symptoms
Bendroflumethiazide/Nadolol Antihypertensives Depressive (Non-Suicidal) Symptoms
Brimonidine Antihypertensives Depressive (Non-Suicidal) Symptoms
Brimonidine/Timolol Antihypertensives Depressive (Non-Suicidal) Symptoms
Dorzolamide/Timolol Antihypertensives Depressive (Non-Suicidal) Symptoms
Enalapril Antihypertensives Depressive (Non-Suicidal) Symptoms
Hydrochlorothiazide/Metoprolol Antihypertensives Depressive (Non-Suicidal) Symptoms
Hydrocodone Antihypertensives Depressive (Non-Suicidal) Symptoms
Metolazone Antihypertensives Depressive (Non-Suicidal) Symptoms
Metoprolol Antihypertensives Depressive (Non-Suicidal) Symptoms
Nisoldipine Antihypertensives Depressive (Non-Suicidal) Symptoms
Quinapril Antihypertensives Depressive (Non-Suicidal) Symptoms
Telmisartan Antihypertensives Depressive (Non-Suicidal) Symptoms
Timolol Antihypertensives Depressive (Non-Suicidal) Symptoms
Trandolapril Antihypertensives Depressive (Non-Suicidal) Symptoms
Betamethasone Corticosteroids Depressive (Non-Suicidal) Symptoms
Cortisone Corticosteroids Depressive (Non-Suicidal) Symptoms
Dexamethasone Corticosteroids Depressive (Non-Suicidal) Symptoms
Methylprednisolone Corticosteroids Depressive (Non-Suicidal) Symptoms
Prednisolone Corticosteroids Depressive (Non-Suicidal) Symptoms
Prednisone Corticosteroids Depressive (Non-Suicidal) Symptoms
Triamcinolone Corticosteroids Depressive (Non-Suicidal) Symptoms
Atropine/Diphenoxylate Gastrointestinal Agents Depressive (Non-Suicidal) Symptoms
Cimetidine Gastrointestinal Agents Depressive (Non-Suicidal) Symptoms
Dexlansoprazole Gastrointestinal Agents Depressive (Non-Suicidal) Symptoms
Esomeprazole Gastrointestinal Agents Depressive (Non-Suicidal) Symptoms
Famotidine Gastrointestinal Agents Depressive (Non-Suicidal) Symptoms
Omeprazole Gastrointestinal Agents Depressive (Non-Suicidal) Symptoms
Ranitidine Gastrointestinal Agents Depressive (Non-Suicidal) Symptoms
Anastrozole Hormones/Hormone Modifiers Depressive (Non-Suicidal) Symptoms
Bicalutamide Hormones/Hormone Modifiers Depressive (Non-Suicidal) Symptoms
Cabergoline Hormones/Hormone Modifiers Depressive (Non-Suicidal) Symptoms
Conjugated Estrogens Hormones/Hormone Modifiers Depressive (Non-Suicidal) Symptoms
Conjugated Estrogens/Medroxyprogesterone Hormones/Hormone Modifiers Depressive (Non-Suicidal) Symptoms
Desogestrel/Ethinyl Estradiol Hormones/Hormone Modifiers Depressive (Non-Suicidal) Symptoms
Dienogest/Estradiol Hormones/Hormone Modifiers Depressive (Non-Suicidal) Symptoms
Drospirenone/Ethinyl Estradiol Hormones/Hormone Modifiers Depressive (Non-Suicidal) Symptoms
Drospirenone/Ethinyl Estradiol/Levomefolate Hormones/Hormone Modifiers Depressive (Non-Suicidal) Symptoms
Esterified Estrogens Hormones/Hormone Modifiers Depressive (Non-Suicidal) Symptoms
Esterified Estrogens/Methyltestosterone Hormones/Hormone Modifiers Depressive (Non-Suicidal) Symptoms
Estradiol Hormones/Hormone Modifiers Depressive (Non-Suicidal) Symptoms
Estradiol/Norethindrone Hormones/Hormone Modifiers Depressive (Non-Suicidal) Symptoms
Estropipate Hormones/Hormone Modifiers Depressive (Non-Suicidal) Symptoms
Ethinyl Estradiol/Ethynodiol Hormones/Hormone Modifiers Depressive (Non-Suicidal) Symptoms
Ethinyl Estradiol/Etonogestrel Hormones/Hormone Modifiers Depressive (Non-Suicidal) Symptoms
Ethinyl Estradiol/Levonorgestrel Hormones/Hormone Modifiers Depressive (Non-Suicidal) Symptoms
Ethinyl Estradiol/Norethindrone Hormones/Hormone Modifiers Depressive (Non-Suicidal) Symptoms
Ethinyl Estradiol/Norgestimate Hormones/Hormone Modifiers Depressive (Non-Suicidal) Symptoms
Ethinyl Estradiol/Norgestrel Hormones/Hormone Modifiers Depressive (Non-Suicidal) Symptoms
Etonogestrel Hormones/Hormone Modifiers Depressive (Non-Suicidal) Symptoms
Exemestane Hormones/Hormone Modifiers Depressive (Non-Suicidal) Symptoms
Goserelin Hormones/Hormone Modifiers Depressive (Non-Suicidal) Symptoms
Hydroxyprogesterone Hormones/Hormone Modifiers Depressive (Non-Suicidal) Symptoms
Medroxyprogesterone Hormones/Hormone Modifiers Depressive (Non-Suicidal) Symptoms
Megestrol Hormones/Hormone Modifiers Depressive (Non-Suicidal) Symptoms
Norethindrone Hormones/Hormone Modifiers Depressive (Non-Suicidal) Symptoms
Tamoxifen Hormones/Hormone Modifiers Depressive (Non-Suicidal) Symptoms
Testosterone Hormones/Hormone Modifiers Depressive (Non-Suicidal) Symptoms
Cetirizine Respiratory Agents Depressive (Non-Suicidal) Symptoms
Abacavir/Lamivudine Other Depressive (Non-Suicidal) Symptoms
Acebutolol Other Depressive (Non-Suicidal) Symptoms
Acitretin Other Depressive (Non-Suicidal) Symptoms
Amphetamine/Detroamphetamine Other Depressive (Non-Suicidal) Symptoms
Baclofen Other Depressive (Non-Suicidal) Symptoms
Benzphetamine Other Depressive (Non-Suicidal) Symptoms
Cinacalcet Other Depressive (Non-Suicidal) Symptoms
Clonidine Other Depressive (Non-Suicidal) Symptoms
Cyclosporine Other Depressive (Non-Suicidal) Symptoms
Dantrolene Other Depressive (Non-Suicidal) Symptoms
Dexmethylphenidate Other Depressive (Non-Suicidal) Symptoms
Donepezil Other Depressive (Non-Suicidal) Symptoms
Dronabinol Other Depressive (Non-Suicidal) Symptoms
Emtricitabine Other Depressive (Non-Suicidal) Symptoms
Erlotinib Other Depressive (Non-Suicidal) Symptoms
Flecainide Other Depressive (Non-Suicidal) Symptoms
Fluphenazine Other Depressive (Non-Suicidal) Symptoms
Galantamine Other Depressive (Non-Suicidal) Symptoms
Haloperidol Other Depressive (Non-Suicidal) Symptoms
Maraviroc Other Depressive (Non-Suicidal) Symptoms
Methyldopa Other Depressive (Non-Suicidal) Symptoms
Metolazone Other Depressive (Non-Suicidal) Symptoms
Metronidazole Other Depressive (Non-Suicidal) Symptoms
Oxybutynin Other Depressive (Non-Suicidal) Symptoms
Phentermine Other Depressive (Non-Suicidal) Symptoms
Pimozide Other Depressive (Non-Suicidal) Symptoms
Prazosin Other Depressive (Non-Suicidal) Symptoms
Propafenone Other Depressive (Non-Suicidal) Symptoms
Propranolol Other Depressive (Non-Suicidal) Symptoms
Rasagiline Other Depressive (Non-Suicidal) Symptoms
Rotigotine Other Depressive (Non-Suicidal) Symptoms
Sorafenib Other Depressive (Non-Suicidal) Symptoms
Tizanidine Other Depressive (Non-Suicidal) Symptoms

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