Contraindications in psychiatric medication

Absolute and relative, in real terms

An absolute contraindication means there's no reasonable situation where the benefit outweighs the risk. The treatment shouldn't be used. A relative contraindication means the risk is higher than usual, but it can sometimes be outweighed by the benefit or managed with extra precautions. NIH's clinical glossary draws the line the same way.

In practice, the FDA label is where a prescriber starts. Section 4 of every modern prescribing label is titled Contraindications, and it lists the situations the manufacturer and FDA agreed should rule the drug out. The warnings and dosing sections carry many of the relative ones. Knowing that helps make sense of what happens next.

Example: MAOIs and serotonergic drugs

Monoamine oxidase inhibitors, like phenelzine, tranylcypromine, and isocarboxazid, are older antidepressants that are used less often today. They block the enzyme that breaks down serotonin, norepinephrine, and dopamine.

Put one together with an SSRI and serotonin can build up to dangerous levels. The FDA label for sertraline says it's contraindicated in anyone taking an MAOI, or within 14 days of stopping one, because of the risk of serotonin syndrome. That includes two drugs people don't think of as MAOIs at all: the antibiotic linezolid and intravenous methylene blue. This is a true hard stop. The fix is a planned washout between medications, not a lower dose. The serotonin syndrome page covers what that reaction looks like, and the MAOI class page and MAOI and tyramine page cover the food side of MAOI safety.

The same sertraline label lists a second absolute contraindication that surprises people: pimozide, an older antipsychotic, because sertraline raises its blood levels and that can cause dangerous heart rhythm changes.

Example: bupropion and seizure risk

Bupropion is a widely used antidepressant, approved for major depression and for preventing seasonal depression. It can lower the seizure threshold. Its FDA label lists these contraindications:

A seizure disorder.

A current or past diagnosis of bulimia or anorexia nervosa, because seizures were more common in people with eating disorders who took it.

Abruptly stopping alcohol, benzodiazepines, barbiturates, or antiepileptic drugs, since withdrawal itself raises seizure risk.

Taking an MAOI, or being within 14 days of one, because of the risk of dangerous blood pressure spikes. Starting bupropion in someone on linezolid or intravenous methylene blue is contraindicated too.

The eating disorder point is a good example of why history matters and not just current diagnoses. Someone who recovered from bulimia years ago might not think to mention it. It still changes the decision.

Example: lithium and kidney function

Lithium is the opposite case, and it shows why the word "contraindication" can mislead. On the current FDA label, the only formal contraindication is an allergy to an inactive ingredient in the tablet. Yet no prescriber would start lithium without checking kidney function first.

That's because the risks live in the warnings and dosing sections. The label carries a boxed warning that lithium toxicity can happen at levels close to the therapeutic range. It tells prescribers to evaluate kidney function before starting, to start lower and go slower with frequent blood levels in mild to moderate kidney impairment, and to avoid lithium in severe kidney impairment. Dehydration, heavy sweating, and some common medications can push levels up too. Regular ibuprofen and naproxen use is a well known one, covered on the lithium and NSAIDs page.

So kidney problems act like a relative contraindication that becomes close to absolute as function worsens. Shrinkopedia's lithium overview explains why lithium is still worth that effort for many people with bipolar disorder.

How prescribers weigh a relative contraindication

When the answer isn't a clear no, the decision comes down to what the medication could do for you against what it could cost, and whether the risk can be reduced.

Picture someone with bipolar disorder who has done well on lithium for ten years and whose kidney function has started to slip. Stopping lithium carries its own serious risk of relapse. The prescriber might lower the dose, check levels and kidney labs more often, bring in a kidney specialist, or plan a gradual move to another mood stabilizer. None of that is a failure. It's the job.

Your preferences count in that weighing too. Some people accept more monitoring for a drug that has worked well. Others would rather switch. A good prescriber lays out the options and decides with you.

Why your full medication list matters

Many contraindications are about combinations, and the dangerous partner is often something nobody thought of as a medication. The sertraline label's warning on serotonin syndrome names tramadol, triptans for migraine, fentanyl, lithium, buspirone, amphetamines, tryptophan, and St. John's wort as serotonergic drugs that raise the risk. Several of those are sold over the counter or prescribed by a different doctor.

So bring everything to your appointments: prescriptions from every clinician, over-the-counter medicines, supplements, and anything you take only now and then. A photo of the bottles works. So does the list your pharmacy can print. Also mention past diagnoses, including ones that feel resolved, like an eating disorder or a seizure years ago. The CYP450 interactions guide and the appointment sheet can help you prepare.

Don't start, stop, or change a medication because of a contraindication you read about. If something here worries you, call your prescriber or pharmacist. Some changes, like stopping certain medications suddenly, are risky on their own.

Common questions

What's the difference between a contraindication and a side effect? A side effect is something a medication can cause. A contraindication is a reason not to use the medication in the first place, or to use it only with extra care, because of your health history or other medications.

If my medication has a contraindication I have, does that mean my prescriber made a mistake? Not necessarily. Many are relative, and a prescriber may have weighed the risk and decided the benefit was worth it with precautions. It's always fair to ask. If it's an absolute contraindication they didn't know about, tell them right away.

Can a supplement really be a problem? Yes. St. John's wort, for example, is named on the sertraline label as a serotonergic product that raises the risk of serotonin syndrome. Tell your prescriber about every supplement.

Do contraindications ever change? Yes. Labels are updated as new safety data comes in, and your own situation changes too. That's one reason prescribers review your medications and history over time.

If you're having thoughts of harming yourself, call or text 988 in the U.S. to reach the Suicide and Crisis Lifeline, or go to the nearest emergency room.

Sources

1. NIH Clinical Info glossary. Absolute contraindication. and Relative contraindication.
2. DailyMed. Zoloft (sertraline) prescribing information.
3. DailyMed. Wellbutrin XL (bupropion) prescribing information.
4. DailyMed. Lithium carbonate tablets prescribing information.
5. National Institute of Mental Health. Mental health medications.