Dr. Ahmed
Wellbutrin is a drug used to treat depression and smoking cessation. It contains Bupropion which is a stimulant antidepressant and causes insomnia and weight loss. In fact, it has been approved as a weight loss drug in combination with Naltrexone by the name Contrave.
Because of its stimulatory effect on the brain, Wellbutrin (Bupropion) is contraindicated in individuals who have a seizure disorder.
The excitatory effect on the brain is also responsible for other side effects such as aggression, palpitations, dry mouth, high blood pressure, and tremors.
One of these side effects is insomnia. Insomnia is difficulty falling asleep, getting up frequently during the night, and an inability to maintain proper sleep.
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What is the association between Wellbutrin and Insomnia:
Wellbutrin (Bupropion), like other antidepressants, alters the neurotransmitters in the brain responsible for the sleep-wake cycle.
However, Bupropion (Wellbutrin) is the only second-generation antidepressant that selectively blocks the reuptake of dopamine and norepinephrine in the brain.
Dopamine and norepinephrine are responsible for arousal and sleep termination, hence, Bupropion is associated with insomnia.
Other antidepressants which cause insomnia may also alter noradrenaline-based signaling in the brain (Dexvenlafaxine).
On the other hand, antidepressants that cause somnolence or daytime sleepiness either act via the melatonin receptors (Agomelatine) or may affect the H1 receptors (Mirtazapine).
The table below lists the risk of insomnia associated with the 14 second-generation antidepressants in descending order [Ref]:
| Antidepressant | Insomnia Rates (In descending order) |
| Bupropion | Highest |
| Desvenlafaxine | Higher |
| Sertraline | Higher |
| Fluvoxamine | Higher |
| Fluoxetine | Higher |
| Reboxetine | Higher |
| Paroxetine | Higher |
| Venlafaxine | Higher |
| Duloxetine | Higher |
| Escitalopram | Higher |
| Citalopram | No difference |
| Milnacipran | No difference |
| Mirtazapine | No difference |
| Agomelatine | Lower risk |
Somnolence or daytime sleepiness was observed mostly with medications that did not cause insomnia. Bupropion was least likely to be associated with Somnolence.
The table below summarizes the effects of these second-generation antidepressants on daytime sleepiness (in descending order):
| Antidepressant | Daytime somnolence |
| Fluvoxamine | Highest risk |
| Mirtazapine | Higher |
| Reboxetine | Higher |
| Paroxetine | Higher |
| Desvenlafaxine | Higher |
| Duloxetine | Higher |
| Venlafaxine | Higher |
| Sertraline | Higher |
| Fluoxetine | Higher |
| Citalopram | Higher |
| Escitalopram | High |
| Milnacaprin | No effect |
| Agomelatine | No effect |
| Bupropion | Lower risk |
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Who is more at risk of developing insomnia with Wellbutrin?
It is not very clear but all patients who are newly initiated on Wellbutrin treatment may develop some sleep-related issues.
Some of the risk factors for developing insomnia with Wellbutrin may include a history of insomnia or sleep problems before starting Wellbutrin treatment, taking higher doses of Wellbutrin, and consuming it after evening meals.
Additionally, people who take stimulant drugs like amphetamine, decongestants, or modafinil alongside Wellbutrin are more at risk of developing insomnia with Wellbutrin.
Lastly, those who consume excessive amounts of coffee and tea, especially after evening meals, may have a higher risk of developing insomnia.
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How to manage Insomnia with Wellbutrin?
If you are unable to sleep or you wake up in the middle of the night frequently after starting Wellbutrin, you may consider following these steps to get a good overnight sleep:
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Switch Wellbutrin to the morning:
It is better to take Wellbutrin during the early hours of the day to reduce sleep-related side effects. Wellbutrin does not cause daytime drowsiness and hence the risks of developing daytime sleepiness are very low.
-
Reduce your Wellbutrin dose:
Taking a higher dose of Wellbutrin (Bupropion) may cause more side effects including insomnia. If you have switched it to morning but still have poor sleep, you may need to reduce your dose from 300 mg to 150 mg daily.
-
Improve your sleep environment:
Your sleeping environment should be quiet, dark, and comfortable. Try not to work or watch movies in the same bed where your sleep.
It is advisable to avoid watching horror movies, engaging with social media platforms like Facebook and TikTok, or playing video games before going to bed.
-
Practice relaxation techniques:
Practice meditation, deep breathing exercises, yoga, or other relaxation techniques before going to bed. These techniques will help you sleep better.
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Reduce consumption of caffeine:
Caffeinated beverages, coffee, tea, and other stimulant drinks should be avoided, especially after evening meals or before bed.
Coffee is a stimulant and makes your brain active. You may also feel palpitations and tremors if you are consuming excessive quantities of coffee.
-
Perform regular exercise:
Wake up early in the morning, perform regular exercises, and do not sleep during the daytime. Regular exercise improves sleep quality.
-
Cognitive behavioral therapy:
You may need to see a healthcare provider for personalized advice on improving sleep quality and addressing negative thoughts which may be causing sleeping disturbances.
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Take sleep medications:
Lastly, you may take OTC or prescription medications depending on the severity of Wellbutrin-associated insomnia.
Some of the OTC medications include:
- Benadryl (Diphenhydramine)
- Unisom Sleep tablets (Doxylamine)
- Melatonin liquid, drops, gummies, and tablets
- Valerian root (mixed with herbal tea)
- Chamomile, Lavender, or Passionflower Teas
- L-Tryptophan tablets
Prescription medications to treat Wellbutrin-associated Insomnia include:
Medication |
Generic Name |
Common Brand Names |
| Benzodiazepines | Temazepam | Restoril |
| Estazolam | Prosom | |
| Triazolam | Halcion | |
| Lorazepam | Ativan | |
| Non-Benzodiazepine | Zolpidem | Ambien, Intermezzo |
| Hypnotics | Zaleplon | Sonata |
| Eszopiclone | Lunesta | |
| Orexin Receptor Antagonist | Suvorexant | Belsomra |
| Lemborexant | Dayvigo | |
| Daridorexant | Quviviq | |
| Melatonin Receptor Agonist | Ramelteon | Rozerem |
| Antidepressants | Trazodone | Desyrel, Oleptro |
| Doxepin | Silenor |
Mirtazapine (Remeron) is another atypical antidepressant, similar to Trazodone but with fewer side effects, that may be used to treat insomnia.
Some sleep medications may lead to more side effects when combined with Wellbutrin. There is an increased risk of serious adverse drug reactions especially when Bupropion (Wellbutrin) is combined with other SSRIs, SNRIs, or drugs affecting serotonin neuronal pathways.
The following medications should be avoided in combination with Wellbutrin:
Drug Class |
Examples |
| Monoamine Oxidase Inhibitors | Phenelzine, Tranylcypromine, Selegiline |
| Selective Serotonin Reuptake Inhibitors | Fluoxetine, Paroxetine, Sertraline, Citalopram, Escitalopram |
| SSRIs and SNRIs | Venlafaxine, Duloxetine, Desvenlafaxine |
| Antidepressants and Other Psychotropic Medications | Amitriptyline, Nortriptyline, Trazodone, Mirtazapine, Quetiapine, Risperidone |
| Anti-seizure Medications | Carbamazepine, Phenytoin, Valproate |
| Medications Metabolized by CYP2B6 (Cytochrome P450 2B6) | Efavirenz, Voriconazole, Fluconazole, Quinidine, Ticlopidine, Ritonavir |
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In Summary:
Wellbutrin is an atypical antidepressant used as an aid to smoking cessation as well as depression. It is the only antidepressant associated with weight loss and hence approved by the FDA for the treatment of obesity in combination with Naltrexone (Contrave).
Bupropion (Wellbutrin) may cause or worsen insomnia in a person with a history of insomnia. It is best to take it after the morning meals. Start with a low dose (150 mg) and increase the dose to 300 mg.
Avoid certain medications and coffee when on Wellbutrin therapy if you are experiencing insomnia.
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