Surprising Medications and Supplements That Could Trigger or Worsen Bipolar Disorder

Certain common medications, OTC products, and supplements may worsen bipolar symptoms — or even lead to a first-time diagnosis if you’re at risk.

After successfully managing her bipolar 2 disorder for two years, Penny S., 63, an artist splitting her time between New Zealand and the United Kingdom, faced an unexpected challenge. While on a trip to New Zealand, she was stung by five bees, causing a severe allergic reaction that threatened to close her throat. Fortunately, she had an EpiPen, which she used promptly to administer epinephrine and save her life.

But the surge of adrenaline from the epinephrine unexpectedly triggered a manic episode, catching her off guard.

“I had no warnings of the possibility of mania being induced by my EpiPen or any other medication,” Penny says. Despite continuing her bipolar treatment, the manic episode required additional medication to help her sleep and stabilize her mood.

Penny’s experience underscores a critical but often overlooked challenge in mental health care: the onset of psychiatric symptoms triggered by external substances. When this happens, it’s called substance- or medication-induced bipolar disorder.

What Is Substance- or Medication-Induced Bipolar Disorder?

Substance- or medication-induced bipolar disorder refers to bipolar symptoms that can emerge after consuming substances such as:

• Prescription medications
• Over-the-counter medications
• Illegal or recreational drugs
• Supplements

“The biggest culprits are both recreational drugs and medications prescribed by other providers who are not aware of a patient’s psychiatric history or who do not know about a medication’s potential to induce bipolar symptoms,” says John Zajecka, MD, professor of psychiatry and director of the Woman’s Board Depression Treatment Research Center at Rush University in Chicago.

Symptoms

The symptoms of medication-induced bipolar disorder are often the same as bipolar disorder itself, Dr. Zajecka says.

“The best example is cocaine or stimulant abuse, as acute intoxication can look like hypomania or mania, and the withdrawal can look like a classic depression,” he says.

It’s also common to see hypomanic or manic-like symptoms after the use of oral or intravenous (IV) steroids in people without a mood disorder, but the symptoms usually resolve once they stop the steroid, Zajecka notes.

The symptoms of substance-induced bipolar disorder are typically temporary and often resolve once the substance is discontinued or the medication is switched, usually within a month, per an article in StatPearls. But if symptoms last beyond this period, that may indicate that an underlying primary bipolar disorder has been triggered or unmasked.

In this way, this condition can affect people who:

• have no prior history of mental health concerns
• have latent or undiagnosed bipolar disorder
• are already diagnosed with bipolar disorder

Diagnosis and Treatment

Understanding the difference between substance- or medication-induced symptoms and primary bipolar disorder is essential because it affects how someone may be treated.

If symptoms are caused by a particular substance or medication, changing the medication or managing the substance use might clear up the symptoms. But if the substance use reveals an underlying bipolar disorder, it means the person will likely need long-term management focusing on stabilizing their mood and other supportive treatments.

The key to diagnosis is to identify when symptoms started, when they resolved, and whether they occurred as clusters or in isolation. Your psychiatrist will take a thorough history and use good clinical judgment to make the proper diagnosis.

How Substances Can Induce or Unmask Bipolar Symptoms

Triggering of a bipolar episode can happen even if the person had used the substance or medication in the past, Zajecka explains.

“The substance or medication, sometimes combined with other triggers such as stress, major life changes, sleep disruption, [or] all alone could result in triggering or unmasking the mood disorder that was just waiting to express itself,” he says.

And an underlying predisposition to bipolar disorder can reveal itself under the right circumstances, like exposure to medications and substances or experiencing induced mania, says psychiatrist Perihan Esra Guvenek-Cokol, MD, medical director of the Support, Treatment, and Resilience program and of the OCD Institute for Children and Adolescents at McLean Hospital in Belmont, Massachusetts.

In addition to triggering a resurgence of bipolar symptoms, certain medications may also precipitate the initial diagnosis. This happened to Melissa S., 45, of Western New York, who does not want to disclose her last name for privacy reasons. Her initial bipolar disorder diagnosis came after she was prescribed an antidepressant to treat depression and anxiety.

She has two younger brothers who were diagnosed with bipolar disorder at the time. Still, her doctor did not tell her that antidepressants could potentially unmask existing undiagnosed bipolar mania symptoms. Melissa also has attention deficit hyperactivity disorder (ADHD) and autism.

What followed was a great deal of trial and error; in some ways, she is still learning what does and doesn’t alter her mood states.

What Substances and Medications Can Trigger Bipolar Symptoms?

Many medications and substances may lead to bipolar symptoms in some people, according to research and case reports. These triggers can be categorized into four main groups.

1. Prescription Medications

Some prescription medications that may induce or trigger bipolar symptoms include:

• Antidepressants Medications for depression, including tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), and serotonin-norepinephrine reuptake inhibitors (SNRIs), can indeed trigger manic episodes in some individuals, particularly those with bipolar disorder or a predisposition to mood disorders, per a consensus statement from the International Society for Bipolar Disorders. Rarely, withdrawal from antidepressants may also lead to manic or hypomanic episodes, according to one paper.
• Antimalarial Drugs Some case reports suggest that medications like chloroquine can induce mania and psychosis.
• Benzodiazepines Benzodiazepines, used to help relieve anxiety, can induce or unmask manic symptoms, some reports suggest.
• Blood Pressure Medications A study published in Hypertension suggested a link between mood changes and the use of beta-blockers and calcium antagonists.
• Epi-Pen (Epinephrine) Epinephrine can significantly affect the central nervous system, potentially leading to mood changes, per Cleveland Clinic.
• Hormonal Contraceptives Some hormonal birth control can decrease the concentration of some bipolar medications (like anticonvulsants) in your body, research shows. This interaction can make your bipolar treatment less effective, which may worsen symptoms.
• Metronidazole This antibiotic has been reported to cause mood changes.
• Opioids Older research suggests that prescription opioid medications, like codeine, hydrocodone, tramadol, and buprenorphine, may induce mania or hypomania in people with and without previously diagnosed bipolar disorder.
• Parkinson’s Disease Medications Medications that increase dopamine availability, such as levodopa, can induce manic symptoms, some research has suggested.
• Steroids Medications such as prednisone, dexamethasone, and other corticosteroids can cause mood swings, mania, or psychosis. This is especially true with long-term use, high doses, or in people who have a family or personal history of the disorder, a study published in Cureus reported.
• Stimulant Medications for ADHD, Narcolepsy, or Weight Loss Stimulants can induce manic symptoms in people who aren’t taking mood stabilizers, some research has shown.
• Testosterone Testosterone and similar androgenic agents may potentially trigger or worsen symptoms of mania or hypomania in some people. Research has found this even in people without a history of mental health issues who started or increased their testosterone treatment.

2. Over-the-Counter Medications

Some known over-the-counter (OTC) medications have the potential to induce, unmask, or trigger bipolar symptoms. These include:

• Antihistamines Used in allergy medications and sleep aids, antihistamines can cause sedation, confusion, and excitation or agitation, which may affect mood stability and potentially trigger manic-like symptoms.
• Cough Suppressants A drug fact sheet from the U.S. Drug Enforcement Administration (DEA) lists dextromethorphan (DXM), a common ingredient in cough suppressants that may cause euphoria, hallucinations, and other mood changes, particularly at high doses.
• Decongestants Ingredients like pseudoephedrine and phenylephrine found in many decongestants can act like stimulants and trigger manic symptoms in people with bipolar disorder, according to one report.
• Medications for Smoking Cessation Nicotine patches and other medications used for quitting smoking are associated with mood swings and agitation in about 6 percent of people with bipolar who use them, according to the findings of a large clinical trial.

3. Supplements

Supplements may be touted as natural remedies, but they can still cause interactions and side effects like bipolar disorder symptoms in some people. Avoid these supplements or be mindful of your mood when taking supplements such as:

• Choline Choline may lead to depressive symptoms, according to the University of Rochester Medical Center.
• Ginseng Often used to improve overall mental and physical well-being, ginseng may induce mania. It can also increase the levels of antipsychotic medications in the blood, which can be dangerous for people with bipolar.
• S-Adenosyl-L-Methionine (SAMe) This supplement, typically used for managing depression and liver disease, can increase the risk of mania in people with bipolar, according to the National Center for Complementary and Integrative Health.
• St. John’s Wort This herb, mainly used for depression, is known to interact with medications and potentially induce mania.
• 5-HTP (5-Hydroxytryptophan) A supplement often used for easing depression, 5-HTP may trigger mania, a case study suggests.

4. Other Substances

Other substances that research suggests may lead to bipolar symptoms include:

• Alcohol As noted by Mayo Clinic, heavy alcohol use in people with bipolar disorder can make mood swings and depression worse. In a study of 584 adults with bipolar disorder over a period ranging from 5 to 16 years, increased alcohol use was linked to higher depression and manic or hypomanic symptoms after the alcohol use.
• Caffeine Consuming too much caffeine may trigger manic-like symptoms in people with bipolar disorder, research suggests.
• Cannabis According to a review article, cannabis use can trigger manic or psychotic episodes, including in people without a previous diagnosis of bipolar disorder.
• Energy Drinks These often contain high levels of caffeine and other stimulants, which could potentially trigger manic episodes.
• Illegal or Recreational Drugs Substances like cocaine, heroin, methamphetamine (meth), and hallucinogens like psilocybin (“magic mushrooms”) mushrooms can cause extreme mood elevation during use and severe depressive crashes during withdrawal.

For Penny, common medications like over-the-counter NSAIDs have triggered her bipolar symptoms, and when she was given morphine after a bicycle accident, it landed her in a psychiatric unit.

Her advice? “Always be cautious with new medications and ask if they could cause mania,” she recommends. “I have found there is little knowledge of medication-induced mania amongst the general practitioners I have seen. I’ve discovered what has induced my mania the hard way.”

How Prevalent Are Substance- or Medication-Induced Psychiatric Symptoms?

It’s not yet known precisely how common substance-induced bipolar disorder is. Overall, the prevalence of all substance-induced mood disorders is thought to be less than 1 percent. By comparison, the prevalence rate for bipolar disorder is 4 percent of American adults, per the National Institute of Mental Health.

Among people who already have bipolar, especially that which is well managed, substance-induced symptoms are a common scenario, Zajecka says. “Close to 50 percent of the time when someone with bipolar disorder is stable for years, and there is a destabilization, it’s because of external things such as medications,” he notes.

Factors That Can Increase the Risk

People with a personal or family history of bipolar disorder are at higher risk for medication- or substance-induced bipolar disorder symptoms, Zajecka says.

Lifestyle factors can also play a significant role in the risk of substance- or medication-induced bipolar symptoms. Lifestyle factors that can affect mood stability include:

• Chronic stress
• Traumatic life events
• Irregular sleep patterns

These factors can also influence how people respond to medications, potentially triggering bipolar symptoms.

What You Can Do to Help Prevent Substance- or Medication-Induced Bipolar Symptoms

Bipolar disorder is a chronic illness, and throughout life, people with bipolar will often need to take other medications for other conditions, says Zajecka. Whether you already have bipolar or not, it’s important to understand how best to keep yourself safe and healthy when there are risks. These tips may help.

Be Mindful of Any Medications and Substance Use

For example, according to StatPearls, experts offer this advice:

• Steer clear of alcohol, cocaine, and legal and illegal opioids, which can increase the risk of substance-induced mental disorders.
• Read the labels on all your medications carefully, including OTC drugs and supplements.
• Ask your prescribing doctor or pharmacist about the risk for medication-induced bipolar symptoms when you begin taking any new prescription or OTC medication.
• Ask about safer alternatives if there is a risk of medication-induced mental disorder with a given drug.
• Make sure all of your doctors are aware of your personal or family history of bipolar disorder or other mental health conditions before taking any new medications.

Alert Your Doctor to Changes in Your Mood and Energy

Having a plan to spot early signs of mood changes is crucial, too, particularly changes in sleep patterns. “If you notice changes in mood, sleep, and energy levels, loop in your psychiatrist and treatment team early to assess if this is something to worry about,” Zajecka says. “The earlier you intervene when symptoms emerge, the shorter the episode is going to be.”

Communicate About Medication Changes

Let your psychiatrist know before you take a needed medication prescribed by someone else if it has the potential to trigger mania or depression. “They can make some transient ‘tweaks’ in your medications, especially to assure sleep is stable while on the steroid or other drug,” Dr. Guvenek-Cokol says.

In cases where symptoms arise, the approach usually involves stopping the problematic medication, if it’s safe, and addressing the symptoms with therapy or other medications, Guvenek-Cokol notes.

Managing substance- or medication-induced bipolar disorder is all about teamwork. Staying in close touch with your doctors to tweak your treatment can help keep your moods stable.

Editorial Sources and Fact-Checking

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