Bupropion (Wellbutrin)

Contents

Bupropion is a stimulating antidepressant and a smoking cessation aid (helps people stop smoking). Below are some important points to know about this medication. 

Clinical Information

Generic: Bupropion

Brand: Wellbutrin, Wellbutrin SR, Wellbutrin XL, Zyban

Half-life: 21 hours

Starting doses:

    Immediate Release (IR): 100mg PO BID

    Sustained Release (SR): 150mg PO QAM

    Extended Release (ER): 150mg PO QAM

Target dosing range: 150mg-450mg

Best time to dose: Morning

How to dose:
> IR: Initial 100mg PO BID for 5-7 days then increase to 100mg PO TID. Max daily dose is 450mg. Each dose should be administered at least 6 hours apart with no more than 150mg per dose.
> SR: Initial 150mg PO QAM for 5-7 days then increase to 150mg PO BID. Max daily dose is 400mg. Each dose should be administered at least 8 hours apart with no more than 200mg per dose.
> ER: Initial 150mg PO QAM for 5-7 days then increase to 300mg PO QAM. Max daily dose is 450mg PO QAM.

METABOLISM: Primarily through CYP2B6 (also a potent inhibitor of CYP2D6). Bupropion is an active drug and prodrug as it is metabolized to a number of active metabolites. Some of these metabolites are more potent NET inhibitors than bupropion itself but are equally potent DAT inhibitors. In addition, some of the active metabolites are more concentrated in the brain than bupropion itself. The most potent of bupropion’s metabolites is an enantiomer of the 6-hydroxy metabolite of bupropion, also known as radafaxine.

PREGNANCY: Minimal data on safety. Not a contraindication.

BREASTFEEDING: Minimal data on safety. Not a contraindication.

FDA INDICATIONS:
1) Major Depressive Disorder
2) Seasonal Affective Disorder
3) Smoking Cessation

Side Effects

Nausea, heartburn, diarrhea, upset stomach, sweating, headache, fatigue, initial anxiety, restlessness, jitteriness, insomnia. Some of these side effects are common when starting Bupropion but typically go away after 5-7 days of consistently taking the medication as prescribed.

The following should be monitored while taking Bupropion: Blood pressure, Anxiety Levels, Sleep quality/quantity, irritability, appetite, and hydration status. Bupropion (Wellbutrin) may reduce appetite and thirst drive and it can be tempting to skip meals and forget to hydrate. It is imperative to eat small meals during the day and remain hydrated. Poor nutrition and dehydration may reduce the efficacy of Bupropion (Wellbutrin).

Mechanism of Action

Bupropion is considered a Norepinephrine (NE) and Dopamine (DA) Reuptake Inhibitor (NDRI). Bupropion is a weak inhibitor of the dopamine transporter (DAT) and a weak inhibitor of the norepinephrine transporter (NET). Bupropion enhances norepinephrine and dopamine neurotransmission in specific areas of the brain. Recall that Norepinephrine transporter (NET) blockade increases dopamine’s diffusion radius in the prefrontal cortex (PFC). Increased NE and DA are thought to be the primary mechanisms for an antidepressant response, which usually takes 2-6 weeks of consistently taking it. Human Positron Emission Tomography (PET) scans suggest that about 20–30% of striatal Dopamine Transporters (DATs) are occupied at therapeutic doses of bupropion. NET occupancy would be expected to be in this same range. This is in contrast to Selective Serotonin Reuptake Inhibitors (SSRIs), which require 90% Serotonin Transporter (SERT) occupancy for an antidepressant effect. Lastly, bupropion has actions at nicotine receptors and this may explain its ability to aid in reducing cigarette smoking. The FDA approved Bupropion (branded as Zyban) as a smoking cessation aid. 

Additional Information

  • There is a rare risk of seizures at high doses or with rapid increases in dose
  • There is an increased risk of seizures in patients who 1) abuse bupropion 2) have preexisting seizure disorders 3) have co-morbid eating disorders, and 4) are withdrawing from alcohol or benzodiazepines
  • Bupropion has minimal sexual side effects and is often used to minimize psychotropic induced sexual dysfunction

References

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