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.

“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.

If you or anyone you know is considering suicide or self-harm or is anxious, depressed, upset, or needs to talk, there are people who want to help:

In the US:

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The National Suicide Prevention Lifeline: 1-800-273-8255

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Outside the US:

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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 to 2014, 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 were 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 shot 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, five 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 jumped 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 Penn‘s 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

Abacavir/Lamivudine

Other

Depressive Symptoms

Acebutolol

Other

Depressive Symptoms

Acetaminophen/Hydrocodone

Analgesics

Depressive Symptoms

Acetaminophen/Tramadol

Analgesic

Suicidal Symptoms

Acitretin

Other

Depressive Symptoms

Amantadine

Other

Suicidal Symptoms

Amitriptyline

Antidepressant

Suicidal Symptoms

Amitriptyline/Chlordiazepoxide

Antidepressant

Suicidal Symptoms

Amitriptyline/Perphenazine

Antidepressant

Suicidal Symptoms

Amphetamine/Detroamphetamine

Other

Depressive Symptoms

Anastrozole

Hormone Modifiers

Depressive Symptoms

Aripiprazole

Other

Suicidal Symptoms

Armodafinil

Other

Suicidal Symptoms

Asenapine

Other

Suicidal Symptoms

Atenolol

Antihypertensives

Depressive Symptoms

Atenolol/Chlorthalidone

Antihypertensives

Depressive Symptoms

Atomoxetine

Other

Suicidal Symptoms

Atropine/Diphenoxylate

Gastrointestinal Agents

Depressive Symptoms

Baclofen

Other

Depressive Symptoms

Bendroflumethiazide/Nadolol

Antihypertensives

Depressive Symptoms

Benzphetamine

Other

Depressive Symptoms

Betamethasone

Corticosteroids

Depressive Symptoms

Betaxolol

Antihypertensives

Depressive Symptoms

Bicalutamide

Hormone Modifiers

Depressive Symptoms

Brimonidine

Antihypertensives

Depressive Symptoms

Brimonidine/Timolol

Antihypertensives

Depressive Symptoms

Bupropion

Antidepressant

Suicidal Symptoms

Butabarbital

Anxiolytic

Suicidal Symptoms

Cabergoline

Hormone Modifiers

Depressive Symptoms

Carbamazepine Clonazepam

Anticonvulsant

Suicidal Symptoms

Carbidopa/Entacapone/Levodopa

Other

Suicidal Symptoms

Carbidopa/Levodopa

Other

Suicidal Symptoms

Cetirizine6

Respiratory Agent

Depressive Symptoms

Chlordiazepoxide

Anxiolytic

Suicidal Symptoms

Cimetidine

Gastrointestinal Agents

Depressive Symptoms

Cinacalcet

Other

Depressive Symptoms

Ciprofloxacin

Other

Suicidal Symptoms

Citalopram

Antidepressant

Suicidal Symptoms

Clomipramine

Antidepressant

Suicidal Symptoms

Clonazepam

Anxiolytic

Suicidal Symptoms

Clonidine

Other

Depressive Symptoms

Clorazepate

Anxiolytic

Suicidal Symptoms

Conjugated Estrogens

Hormone Modifiers

Depressive Symptoms

Conjugated Estrogens/Medroxyprogesterone

Hormone Modifiers

Depressive Symptoms

Cortisone

Corticosteroids

Depressive Symptoms

Cyclobenzaprine

Analgesics

Depressive Symptoms

Cyclosporine

Other

Depressive Symptoms

Dantrolene

Other

Depressive Symptoms

Dapsone

Other

Suicidal Symptoms

Desipramine

Antidepressant

Suicidal Symptoms

Desogestrel/Ethinyl Estradiol

Hormone Modifiers

Depressive Symptoms

Desvenlafaxine

Antidepressant

Suicidal Symptoms

Dexamethasone

Corticosteroids

Depressive Symptoms

Dexlansoprazole

Gastrointestinal Agents

Depressive Symptoms

Dexmethylphenidate

Other

Depressive Symptoms

Diazepam

Anticonvulsant

Suicidal Symptoms

Diazepam

Anxiolytic

Suicidal Symptoms

Dienogest/Estradiol

Hormone Modifiers

Depressive Symptoms

Donepezil

Other

Depressive Symptoms

Dorzolamide/Timolol

Antihypertensives

Depressive Symptoms

Doxepin

Antidepressant

Suicidal Symptoms

Doxepin

Anxiolytic

Suicidal Symptoms

Dronabinol

Other

Depressive Symptoms

Drospirenone/Ethinyl Estradiol

Hormone Modifiers

Depressive Symptoms

Drospirenone/Ethinyl Estradiol/Levomefolate

Hormone Modifiers

Depressive Symptoms

Duloxetine

Antidepressant

Suicidal Symptoms

Efavirenz

Other

Suicidal Symptoms

Efavirenz/Emtricitabine/Tenofovir

Other

Suicidal Symptoms

Emtricitabine

Other

Depressive Symptoms

Enalapril

Antihypertensives

Depressive Symptoms

Erlotinib

Other

Depressive Symptoms

Escitalopram

Antidepressant

Suicidal Symptoms

Esomeprazole

Gastrointestinal Agents

Depressive Symptoms

Esterified Estrogens

Hormone Modifiers

Depressive Symptoms

Esterified Estrogens/Methyltestosterone

Hormone Modifiers

Depressive Symptoms

Estradiol

Hormone Modifiers

Depressive Symptoms

Estradiol/Norethindrone

Hormone Modifiers

Depressive Symptoms

Estropipate

Hormone Modifiers

Depressive Symptoms

Eszopiclone

Anxiolytic

Suicidal Symptoms

Ethinyl Estradiol/Ethynodiol

Hormone Modifiers

Depressive Symptoms

Ethinyl Estradiol/Etonogestrel

Hormone Modifiers

Depressive Symptoms

Ethinyl Estradiol/Levonorgestrel

Hormone Modifiers

Depressive Symptoms

Ethinyl Estradiol/Norethindrone

Hormone Modifiers

Depressive Symptoms

Ethinyl Estradiol/Norgestimate

Hormone Modifiers

Depressive Symptoms

Ethinyl Estradiol/Norgestrel

Hormone Modifiers

Depressive Symptoms

Ethosuximide

Anticonvulsant

Suicidal Symptoms

Etonogestrel

Hormone Modifiers

Depressive Symptoms

Exemestane

Hormone Modifiers

Depressive Symptoms

Famotidine

Gastrointestinal Agents

Depressive Symptoms

Fentanyl

Analgesics

Depressive Symptoms

Flecainide

Other

Depressive Symptoms

Fluoxetine

Antidepressant

Suicidal Symptoms

Fluoxetine/Olanzapine

Antidepressant

Suicidal Symptoms

Fluphenazine7

Other

Depressive Symptoms

Flurazepam

Anxiolytic

Suicidal Symptoms

Fluvoxamine

Antidepressant

Suicidal Symptoms

Gabapentin

Anticonvulsant

Suicidal Symptoms

Galantamine

Other

Depressive Symptoms

Goserelin

Hormone Modifiers

Depressive Symptoms

Haloperidol

Other

Depressive Symptoms

Hydrochlorothiazide/Metoprolol

Antihypertensives

Depressive Symptoms

Hydrocodone

Antihypertensives

Depressive Symptoms

Hydropmorphone

Analgesic

Suicidal Symptoms

Hydroxyprogesterone

Hormone Modifiers

Depressive Symptoms

Ibuprofen

Analgesics

Depressive Symptoms

Iloperidone

Other

Suicidal Symptoms

Imipramine

Antidepressant

Suicidal Symptoms

Indomethacin

Analgesics

Depressive Symptoms

Interferon Beta-1a

Other

Suicidal Symptoms

Interferon Beta-1b

Other

Suicidal Symptoms

Isotretinoin

Other

Suicidal Symptoms

Lamotrigine

Anticonvulsant

Suicidal Symptoms

Levetiracetam

Anticonvulsant

Suicidal Symptoms

Lorazepam

Anticonvulsant

Suicidal Symptoms

Lurasidone

Other

Suicidal Symptoms

Maraviroc

Other

Depressive Symptoms

Medroxyprogesterone

Hormone Modifiers

Depressive Symptoms

Mefloquine

Other

Suicidal Symptoms

Megestrol

Hormone Modifiers

Depressive Symptoms

Memantine

Other

Suicidal Symptoms

Methsuximide

Anticonvulsant

Suicidal Symptoms

Methyldopa

Other

Depressive Symptoms

Methylphenidate

Other

Suicidal Symptoms

Methylprednisolone

Corticosteroids

Depressive Symptoms

Metoclopramide

Gastrointestinal Agent

Suicidal Symptoms

Metolazone

Antihypertensives

Depressive Symptoms

Metolazone

Other

Depressive Symptoms

Metoprolol

Antihypertensives

Depressive Symptoms

Metronidazole

Other

Depressive Symptoms

Milnacipran

Antidepressant

Suicidal Symptoms

Mirtazapine

Antidepressant

Suicidal Symptoms

Modafinil

Other

Suicidal Symptoms

Morphine

Analgesics

Depressive Symptoms

Moxifloxacin

Other

Suicidal Symptoms

Nabumetone

Analgesics

Depressive Symptoms

Naltrexone

Other

Suicidal Symptoms

Natalizumab

Other

Suicidal Symptoms

Nefazodone

Antidepressant

Suicidal Symptoms

Nisoldipine

Antihypertensives

Depressive Symptoms

Norethindrone

Hormone Modifiers

Depressive Symptoms

Nortriptyline

Antidepressant

Suicidal Symptoms

Ofloxacin

Other

Suicidal Symptoms

Olanzapine

Other

Suicidal Symptoms

Omeprazole

Gastrointestinal Agents

Depressive Symptoms

Oxcarbazepine

Anticonvulsant

Suicidal Symptoms

Oxybutynin8

Other

Depressive Symptoms

Oxycodone

Analgesics

Depressive Symptoms

Paroxetine

Antidepressant

Suicidal Symptoms

Peginterferon Alfa-2a

Other

Suicidal Symptoms

Pentobarbital

Anxiolytic

Suicidal Symptoms

Phenelzine

Antidepressant

Suicidal Symptoms

Phentermine9

Other

Depressive Symptoms

Phenytoin

Anticonvulsant

Suicidal Symptoms

Pimozide

Other

Depressive Symptoms

Prazosin

Other

Depressive Symptoms

Prednisolone

Corticosteroids

Depressive Symptoms

Prednisone

Corticosteroids

Depressive Symptoms

Pregabalin

Anticonvulsant

Suicidal Symptoms

Propafenone

Other

Depressive Symptoms

Propranolol

Other

Depressive Symptoms

Protriptyline

Antidepressant

Suicidal Symptoms

Quetiapine

Other

Suicidal Symptoms

Quinapril

Antihypertensives

Depressive Symptoms

Raltegravir

Other

Suicidal Symptoms

Ramelteon

Anxiolytic

Suicidal Symptoms

Ranitidine

Gastrointestinal Agents

Depressive Symptoms

Rasagiline

Other

Depressive Symptoms

Ribavirin

Respiratory Agent

Suicidal Symptoms

Risperidone4

Other

Suicidal Symptoms

Rivastigmine5

Other

Suicidal Symptoms

Roflumilast

Respiratory Agent

Suicidal Symptoms

Rotigotine

Other

Depressive Symptoms

Selegiline

Antidepressant

Suicidal Symptoms

Sertraline

Antidepressant

Suicidal Symptoms

Sibutramine

Other

Suicidal Symptoms

Sorafenib

Other

Depressive Symptoms

Tamoxifen

Hormone Modifiers

Depressive Symptoms

Tapentadol

Analgesic

Suicidal Symptoms

Telmisartan

Antihypertensives

Depressive Symptoms

Testosterone

Hormone Modifiers

Depressive Symptoms

Tetrabenazine

Other

Suicidal Symptoms

Timolol

Antihypertensives

Depressive Symptoms

Tizanidine

Other

Depressive Symptoms

Topiramate

Anticonvulsant

Suicidal Symptoms

Tramadol

Analgesic

Suicidal Symptoms

Trandolapril

Antihypertensives

Depressive Symptoms

Trazodone

Antidepressant

Suicidal Symptoms

Triamcinolone

Corticosteroids

Depressive Symptoms

Triazolam

Anxiolytic

Suicidal Symptoms

Valproic Acid

Anticonvulsant

Suicidal Symptoms

Varenicline

Other

Suicidal Symptoms

Venlafaxine

Antidepressant

Suicidal Symptoms

Vilazodone

Antidepressant

Suicidal Symptoms

Zafirlukast3

Respiratory Agent

Suicidal Symptoms

Zaleplon

Anxiolytic

Suicidal Symptoms

Zolpidem

Anxiolytic

Suicidal Symptoms

Zonisamide

Anticonvulsant

Suicidal Symptoms

Source.