Bupropion

Is bupropion safe?

For most adults without a seizure risk, yes, but it has a different risk profile from the SSRIs. Bupropion, sold as Wellbutrin for depression and Zyban for quitting smoking, acts on dopamine and noradrenaline rather than serotonin. That is why it rarely causes the sexual side effects and weight gain that make people give up on drugs like sertraline.

Its weak points are elsewhere: a dose-related risk of seizures, higher blood pressure, many interactions and a much worse record in overdose. We score it 60, below the SSRIs on our list (sertraline 72, fluoxetine 70) and close to gabapentin at 66.

The seizure risk

Seizures are the reason bupropion's dose is capped and raised slowly. The Wellbutrin SR label gives the risk as about 0.1% (1 in 1,000) at up to 300 mg a day and about 0.4% at the 400 mg maximum. With the immediate-release form, risk rises almost tenfold between 450 and 600 mg a day.

The current Wellbutrin XL label says the dose should not exceed 300 mg once a day and must be stopped for good after any seizure. It is contraindicatedContraindicationA situation in which a medicine should not be used, because the risk clearly outweighs any benefit, such as a known allergy to it.More in the glossary in people with:

• epilepsy or another seizure disorder
• current or past bulimia or anorexia, where seizure rates were higher
• abrupt withdrawal from alcohol, benzodiazepines, barbiturates or anti-seizure drugs

Head injury, brain tumours, stroke, low blood sugar on diabetes treatment, cocaine or stimulant misuse and heavy drinking also raise the risk. The label lists other bupropion products among the drugs that add to seizure risk, so Wellbutrin and Zyban should never be taken together.

Side effects day to day

In the Wellbutrin SR depression trials at 300 mg a day:

Side effect	Bupropion 300 mg	Placebo
Dry mouth	17%	7%
Nausea	13%	8%
Insomnia	11%	6%
Tremor	6%	1%
Tinnitus	6%	2%
Rash	5%	1%

The label asks for a blood pressure check before starting and during treatment, and hypertension was more frequent when bupropion was combined with nicotine patches. Agitation, anxiety and, rarely, psychosis or paranoia can occur.

Why overdose is a bigger concern

On its own an SSRI overdose is rarely fatal. Bupropion is different. The label says seizures occurred in about a third of reported overdoses, and deaths have followed large ingestions, with multiple seizures, heart rhythm problems and cardiac arrest. A study of 256 overdoses in a US toxicology registry notes that seizures can occur up to 24 hours after ingestion.

A study of US poison centre data on teenagers who overdosed in suspected self-harm from 2013 to 2017 compared bupropion with SSRIs. Bupropion led to a serious outcome in 58% of cases against 19%, seizures in 27% against 9%, and death in 0.23% against none. This matters most when bupropion is prescribed to someone at risk of self-harm, which prescribers weigh carefully. Any overdose needs emergency care: in the US call 911 or Poison Help on 1-800-222-1222; in the UK call 999.

Interactions

Bupropion strongly blocks the liver enzyme CYP2D6CYP450 enzymesA family of liver enzymes that break down many medicines. When another drug or supplement speeds them up or slows them down, drug levels change.More in the glossary, so it can raise levels of several antidepressants, antipsychotics such as risperidone, and beta blockers such as metoprolol. It is contraindicatedContraindicationA situation in which a medicine should not be used, because the risk clearly outweighs any benefit, such as a known allergy to it.More in the glossary with MAOI antidepressants (14 days either way) because of the risk of a hypertensive reaction. Antipsychotics, tricyclics, theophylline, steroids and tramadol lower the seizure threshold. The MHRA has also reported serotonin syndromeSerotonin syndromeA reaction caused by too much serotonin in the body, usually from combining medicines that raise it. Symptoms range from shivering to high fever.More in the glossary when bupropion is combined with SSRIs or SNRIs.

It can also cause false-positive urine screens for amphetamines, which is worth knowing before a workplace drug test.

Misuse

Bupropion is not a controlled substanceControlled substanceA medicine or drug that the law restricts because it can be misused or cause dependence. Countries group them into schedules or classes.More in the glossary and has no recognised withdrawal syndromeDrug dependenceThe body's adaptation to a drug taken regularly, so that stopping it suddenly causes withdrawal symptoms. It is not the same as addiction.More in the glossary. Taken by mouth at normal doses it is unlikely to be misused. Crushed tablets have been snorted or injected for a stimulant effect, and the label reports seizures and deaths from these routes.

Who should be careful

Talk to your doctor or pharmacist before starting bupropion if you have had a seizure or head injury, have or had an eating disorder, drink heavily or are cutting down on alcohol or sedatives, have high blood pressure, are under 25, have bipolar disorder, take any other antidepressant or antipsychotic, or already use a product that contains bupropion (including the weight-loss combination with naltrexone).

How we scored it

Track record (90) is strong. Overdose marginOverdose marginHow far a normal dose is from a harmful one. A wide margin means an accidental extra dose is unlikely to cause serious harm.More in the glossary (45) is the weakest factor, based on the label's seizure data and the poison centre comparison with SSRIs. Interactions (50) reflect the CYP2D6CYP450 enzymesA family of liver enzymes that break down many medicines. When another drug or supplement speeds them up or slows them down, drug levels change.More in the glossary and seizure-threshold combinations, and serious side effects (62) the seizure and blood pressure risks.