In Collaboration With

THERAPEUTICS

Brands

• Wellbutrin, Wellbutrin SR, Wellbutrin XL
• Zyban
• Aplenzin

Generic?

• Yes (bupropion and bupropion SR)

Class

• NDRI (norepinephrine dopamine reuptake inhibitor); antidepressant; smoking cessation treatment

Commonly Prescribed For

• (bold for FDA approved)
• Major depressive disorder (bupropion, bupropion SR, and bupropion XL)
• Seasonal affective disorder(bupropion XL)
• Nicotine addiction (bupropion SR)
• Bipolar depression
• Attention deficit /hyperactivity disorder
• Sexual dysfunction

How The Drug Works

• Boosts neurotransmitters norepinephrine/noradrenaline and dopamine
• Blocks norepinephrine reuptake pump (norepinephrine transporter), presumably increasing norepinephrine neurotransmission
• Since dopamine is inactivated by norepinephrine reuptake in frontal cortex, which largely lacks dopamine transporters, bupropion can increase dopamine neurotransmission in this part of the brain
• Blocks dopamine reuptake pump (dopamine transporter), presumably increasing dopaminergic neurotransmission

How Long Until It Works

• Onset of therapeutic actions usually not immediate, but often delayed 2 to 4 weeks
• If it is not working within 6 to 8 weeks for depression, it may require a dosage increase or it may not work at all
• May continue to work for many years to prevent relapse of symptoms

If It Works

• The goal of treatment of depression is complete remission of current symptoms as well as prevention of future relapses
• Treatment of depression most often reduces or even eliminates symptoms, but is not a cure since symptoms can recur after medicine stopped
• Continue treatment of depression until all symptoms are gone (remission)
• Once symptoms of depression are gone, continue treating for 1 year for the first episode of depression
• For second and subsequent episodes of depression, treatment may need to be indefinite
• Treatment for nicotine addiction should consist of a single treatment for 6 weeks

If It Doesn’t Work

• Many patients only have a partial response where some symptoms are improved but others persist (especially insomnia, fatigue, and problems concentrating)
• Other patients may be nonresponders, sometimes called treatment-resistant or treatment-refractory
• Some patients who have an initial response may relapse even though they continue treatment, sometimes called “poop-out”
• Consider increasing dose, switching to another agent or adding an appropriate augmenting agent
• Consider psychotherapy
• Consider evaluation for another diagnosis or for a comorbid condition (e.g., medical illness, substance abuse, etc.)
• Some patients may experience apparent lack of consistent efficacy due to activation of latent or underlying bipolar disorder, and require antidepressant discontinuation and a switch to a mood stabilizer, although this may be a less frequent problem with bupropion than with other antidepressants

Best Augmenting Combos for Partial Response or Treatment-Resistance

• Trazodone for residual insomnia
• Benzodiazepines for residual anxiety
• Can be added to SSRIs to reverse SSRI-induced sexual dysfunction, SSRI-induced apathy (use combinations of antidepressants with caution as this may activate bipolar disorder and suicidal ideation)
• Can be added to SSRIs to treat partial responders
• Often used as an augmenting agent to mood stabilizers and/or atypical antipsychotics in bipolar depression
• Mood stabilizers or atypical antipsychotics can also be added to bupropion for psychotic depression or treatment-resistant depression
• Hypnotics for insomnia
• Mirtazapine, modafinil, atomoxetine (add with caution and at lower doses since bupropion could theoretically raise atomoxetine levels) both for residual symptoms of depression and attention deficit disorder

Tests

• None for healthy individuals