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BupropiDex is not Auvelity

It's just the dex.

This info is intended for prescribers.

Auvelity (dextromethorphan hydrobromide + bupropion ER)

was approved as a prescription drug for treatment of major depression in 2022. All of the details about Auvelity are in a previous post.

Where the prescription version is unavailable or unaffordable, some prescribers are recommending "DIY Auvelity" made from OTC dextromethorphan (DXM) and generic bupropion ER (Wellbutrin SR).

Auvelity = DXM 45 mg + Bupropion ER 105 mg.

Dosing of Auvelity: Start one tablet QD in AM x 3 days, then increase to target dose of 1 tablet BID. Maximum dose equals target dose. With moderate renal impairment the target dose is 1 tab QD. For CYP2D6 poor metabolizers or those taking a strong 2D6 inHibitor, the recommended target dose is 1 tab QD. Avoid use in severe hepatic or renal insufficiency.

DIY Auvelity = DXM 45 mg + Generic bupropion ER 100 mg (which is 5 mg less bupropion)

Until now, buying the right amount of DXM was either cumbersome or relatively expensive, e.g., combining 30 mg & 15 mg pills. The latest OTC DXM product called BupropiDex was obviously made for the purpose of making DIY Auvelity. It contains no bupropion.

BupropiDex Auvelity dextromethorphan without bupropion

In addition to low cost, a potential advantage of using generic bupropion SR with OTC DXM is the ability to titrate DXM HBr from a lower dose, and taper more gradually when DXM is being stopped, which may be in context of continuing the bupropion component.

A potential disadvantage of the DIY approach is that pharmacokinetics of DXM, e.g., rate of absorption, may differ between Auvelity and generic DXM.

For those with commercial insurance, the vouchers make Auvelity cheaper than the generic components, so this is preferred.

Auvelity savings card

Two respondents expressed concerns about liability with recommending DIY Auvelity to patients. Also, a doctor reported submitting a Medicaid prior authorization for Auvelity, which was denied, but the state's Drug Prior Authorization Committee and Drug Utilization Review Board granted approval for reimbursement of the individual ingredients in place of Auvelity. This approach minimizes liability when prescribing the combo to those with government insurance, who are ineligible to use discount vouchers from Axsome.

Any patient taking DIY Auvelity needs to understand that both components should be taken together, i.e., to not take the DXM if they run out of bupropion.

About Auvelity

Auvelity DXM bupropion mascot by Jason Cafer MD psychopharmacology.

Dextromethorphan (DXM) is the main active ingredient. The mechanism of DXM is NMDA antagonist and sigma-1 receptor agonist. DXM also has serotonin reuptake blocking properties.

For context, the antidepressant mechanism of ketamine is NMDA antagonism. DXM has been nicknamed ketamine in a pill, although it is a much less potent NMDA antagonist. Blocking NMDA receptors modulates glutamatergic signaling which, through complicated downstream molecular events, is believed to elicit the expression of genes involved in neuroplasticity.

The bupropion (Wellbutrin) component of Auvelity serves to block metabolism of DXM by CYP2D6 and may provide antidepressant benefit. This strategic use of a kinetic drug-drug interaction is the same concept described with Nuedexta, with bupropion replacing quinidine as the 2D6 inHibitor.

If not for the 2D6 inHibitor (bupropion), dextromethorphan (DXM) is quickly metabolized to dextrorphan, resulting in low serum levels of the parent compound. This metabolite is spelled similarly to dextromethorphan without the “meth”, which makes sense because this biotransformation is a demethylation. Compared to DXM, the metabolite (dextrorphan) is a more potent NMDA receptor antagonist and less potent serotonin reuptake inhibitor (SRI).

Bupropion raises peak levels of DXM 40-fold and the total exposure to the drug (area under the curve) 60-fold.

As with its component medications, Auvelity is not a DEA-controlled substance. However, either component is potentially abusable at high dose—DXM as a dissociative and bupropion as a NDRI stimulant.

Antidepressant efficacy of Auvelity was statistically significant starting at 1 week, which is faster than traditional antidepressants. Auvelity was shown to be more effective than bupropion 105 mg alone around 2 weeks. Auvelity has not been tested in treatment-resistant depression, and efficacy at one month was not statistically superior to bupropion monotherapy. So, Auvelity works faster than other antidepressants but not necessarily better.

Most side effects of Auvelity are attributable to DXM rather than bupropion. The most common adverse reactions were dizziness (16%), headache (8%), diarrhea (7%), somnolence (7%), dry mouth (6%), sexual dysfunction (6%), and hyperhidrosis (5%).

Note that Auvelity did not cause dissociation in clinical trials. Dissociation with DXM is largely due to dextrorphan, the metabolite. 2D6 inHibition by bupropion slows conversion of DXM to dextrorphan, making dissociation a less likely side effect.

Auvelity dextromethorphan dextrophan dissociation

Regarding duration of treatment, one approach is to wait at least six months before tapering DXM slowly over 1 to 2 months. Patients may also need to raise bupropion to the usual dose of 300 mg/day.

See all the interaction mnemonics and more info about bupropion here.

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