Anxiety medications can be life-changing for people with generalized anxiety, panic disorder and obsessive compulsive disorder. But they come with serious tradeoffs. Benzodiazepines are unquestionably effective for anxiety but have adverse neurological effects like memory impairment.
DPDR tends to be chronic and affects between 1% and 2.4% of the population. Despite the prevalence of depersonalization in the general population, it is still assumed to be a rare condition by most clinicians[^11]:
Who wouldn’t like to perform better, think more clearly, and have more “cognitive RAM”?
Food in our Western diet is very different from what our ancestors ate. One remarkable change has to do with polyunsaturated fatty acids (PUFAs). Primarily omega-6 and omega-3.
There's something really fantastic about plant-derived nootropics. I'm a big fan of bacopa, lion's mane and the like.
Could running in high temperatures further boost exercise-induced neurogenesis? Though probably unrelated, I've always felt that workouts in warm weather are more satisfying.
Histamine intolerance is both difficult for patients to bare and also difficult for clinicians to diagnose. The symptoms of histamine intolerance can be nebulous. So it's difficult for physicians to identify the condition.
Cholinergic crisis is a medical condition characterized by excess stimulation of the neuromuscular junction. The neuromuscular junction is between the axon of a motor neuron and a muscle fiber[^1].
It's damn hard to find a reliable sleep aid that can be used in the long-term without fear of ill-health effects.
Darth Vader's Guide to Vyvanse vs Adderall
Vyvanse vs Adderall Summary
- Duration: Vyvanse has a longer duration of action compared to Adderall (12 hours vs 6 hours for instant-release Adderall)
- Formulation: Vyvanse is taken in an inactive form, and the active ingredient, dextroamphetamine, is gradually released throughout the day. This results in smoother onset and offset of the psychological effects of the drug (compared to Adderall).
- Efficacy: Vyvanse may be less effective for certain subtypes of ADHD (those patients that respond better to more noradrenergic drugs like Strattera)
- Cost: Since Shire’s patent for Vyvanse has not expired, expect that Vyvanse will be much more expensive compared to generic Adderall (mixed amphetamine salts)
- Side-Effects: Vyvanse is associated with fewer cardiovascular side effects (increased blood pressure, heart palpitations) compared to Adderall
- Potency: Overall, Vyvanse is less potent than Adderall, requiring a higher dosage to achieve the same ADHD symptom control
- Sleep: Patients who are predisposed to insomnia may prefer Adderall, because Vyvanse’s longer duration of action may make it more difficult to sleep at night
- Chemical composition: Vyvanse releases pure dextroamphetamine, whereas Adderall is comprised of levoamphetamine and dextroamphetamine in a 1:3 ratio.
What About Adderall XR vs Vyvanse?
The difference between these two formulations is subtle because they’re both extended release. This is a completely different comparison than Adderall IR (instant release) vs Vyvanse.
Adderall XR delivers half of the payload instantly, and the other half four hours later. Vyvanse is a little more gradual.
Another key difference is that Adderall XR delivers both d-amphetamine and l-amphetamine, whereas Vyvanse is metabolized gradually into pure d-amphetamine.
Adderall and Vyvanse are Increasingly Prescribed
Adderall is one of the most widely-used prescription stimulants for the treatment of ADHD. It has been one of the top five most searched drugs on Google in recent years, rivaling highly general searches like “antibiotics.”
As the employment and academic landscape becomes increasingly competitive, some students are using prescription psychostimulants to enhance productivity. The shift away from blue to white collar work may also be contributing to the increased diagnosis rates of ADHD in the United States.
The basic difference between Vyvanse vs Adderall is that Vyvanse is delayed release dextroamphetamine, while Adderall is instant release dextroamphetamine plus levoamphetamine. Both drugs are classified as psychostimulants, and are used clinically for the treatment of ADHD.
Is Vyvanse Better Than Adderall?
Adderall is the precedessor to Vyvanse. Humans are biased to believe that newer is synonymous with better. So is Vyvanse a big improvement on Adderall?
Not exactly. It depends on your individual needs.
Whereas Vyvanse is long-acting (12hr) with a gradual onset of effects, Adderall is short-acting (6hr). Adderall has slightly worse cardiovascular side effects than Vyvanse, and is described as having more “kick.” (Adderall is more likely to give you a jolt of energy due to the added levoamphetamine and the fact that the formulation is instant release.)
Some situations are better suited to either Vyvanse vs Adderall. For example, if you only need to control the inattentive symptoms of ADHD for half of the day, Adderall might be preferable due to its 6 hour duration of effects. If you’re concerned about cost, generic Adderall (mixed amphetamine salts) will almost certainly be cheaper than Vyvanse (which is patented by Shire pharmaceuticals).
Some forms of ADHD seem to respond better to Adderall, putatively due to the levoamphetamine ingredient. If you frequently suffer from psychostimulant-related insomnia, Adderall may be a better choice because it’ll be easier to control the duration of action.
When deciding between Vyvanse vs Adderall, there is also the issue of personal preference and individual neurophysiology. Some individuals consider Vyvanse a major improvement on Adderall–they might feel it has fewer side effects and is “cleaner”–whereas others don’t feel good on Vyvanse at all and would be unable to function without Adderall.
Amphetamine Chemistry: Dextroamphetamine vs Levoamphetamine
Any answer to the question 'what's the difference between Adderall and Vyvanse?' must include a discussion about dextroamphetamine and levoamphetamine.
That's because Adderall contains both d-amp (dextroamphetamine) and l-amp(levoamphetamine). Vyvanse is just metabolized to d-amp - it lacks the l-amp component.
The d or l before the amphetamine signifies the handedness of the molecule. It turns out that (chiral) molecules come in pairs - there are left and right mirror images - just like you have left and right hands.
Because they're just mirror images, you'd think that d-amphetamine would have the same biological effects as l-amphetamine. But this is not the case.
What’s the difference between dextroamphetamine and levoamphetamine? Chemically, these two molecules are mirror images (stereoisomers) of each other and have similar but not identical effects in the brain. Some differences include:
- dextroamphetamine is three to fivefold more potent than levoamphetamine
- dextroamphetamine has greater effects on dopamine than noradrenaline, whereas levoamphetamine affects norepinpehrine slightly more strongly than dopamine
- Both isomers effectively treat ADHD
- Levoamphetamine more specifically improves sustained attention than dextroamphetamine1, which may benefit some subtypes of ADHD
- The 3:1 mixture of dextroamphetamine and levoamphetamine in Adderall was found to have a synergistic effect by enhancing and prolonging the efflux of dopamine produced primarily by dextroamphetamine
How Vyvanse Works
Lisdexamfetamine dimesylate (Vyvanse) is the first long-acting prodrug psychostimulant used in the management of ADHD. Chemically speaking, Vyvanse is lisdexamfetamine. It is comprised of the amino acid lysine bonded to the psychostimulant dextroamphetamine.
The peptide bond which joins these two molecules is gradually hydrolyzed releasing the free dextroamphetamine in a controlled manner. Since the hydrolysis of lisdexamfetamine dimesylate (Vyvanse) occurs primarily in the bloodstream, stomach acidity (gastrointestinal pH) does not effect the release of dextroamphetamine.
Exposure to dextroamphetamine resulting from oral treatment with lisdexamfetamine (Vyvanse) is monophasic and dose-dependent with low variability between patients. Pharmacodynamic studies indicate that the therapeutic effects of lisdexamfetamine are observed for 13 hours per dose in children and 14 hours per dose in adults.
Efficacy of Amphetamines vs Other ADHD Drugs
In randomized controlled trials, Vyvanse and other amphetamine-based stimulants have been demonstrated to be modestly more effective than other stimulants like methylphenidate (Ritalin) in children and adolescents with ADHD 2 Consistent with this result, post-hoc analysis of data from a phase III clinical trial showed that Vyvanse was superior to osmotic-release methylphenidate at controlling the symptoms of of ADHD.3
Crudely speaking, Vyvanse is like “delayed release” Adderall. Except that’s not technically correct, because Adderall is comprised of four different amphetamine salts, in equal proportions.
Composition of Adderall
By contrast, since Vyvanse just contains dextroamphetamine (and not amphetamine proper), Vyvanse has slightly different effects than Adderall.
Compared to amphetamine, dextroamphetamine is associated more potent dopamine release in the brain, and has less of an effect on norepinephrine.
Dopamine is the neurotransmitter associated with reward, pleasure, task salience and the regulation of muscle tone. Norepinephrine is linked to sustained attention, heightened vigilance, and various peripheral nervous system effects. For example, norepinephrine controls sympathetic tone, e.g., heart rate, heart contractility, and blood pressure.
In short, Adderall will be more likely to result in harmful cardiovascular side effects like increased blood pressure and heart rate. The trade-off here is that some subtypes of ADHD respond better to the amphetamine/dextroamphetamine mixture vs dextroamphetamine alone (Vyvanse). This is because norepinephrine plays an important role in sustained attention.
Because dextroamphetamine (think Vyvanse) more potently releases dopamine into the synapse than amphetamine alone, dextroamphetamine is a more potent drug, milligram per milligram.
Therefore, lower doses of dextroamphetamine may be needed as compared to the mixture of amphetamine/dextroamphetamine salts founds in Adderall.
Safety & Tolerability of Vyvanse
Since Vyvanse is a relatively new drug, whereas Adderall was approved decades ago, it’s important to scrutinize Vyvanse’s safety record.
To date, six randomized, double-blind, phase III trials have documented the safety and efficacy of lidexamfetamine. The general rates of adverse events from Vyvanse were commensurate with those previously reported for stimulants in general 4
In all studies, the most common treatment-emergent adverse event was decreased appetite (>25%). Anorexia was reported in about 11% of children and adolescents treated with Vyvanse, but only 5% or less in adults.
Insomnia was commonly reported for all groups, occurring in 11-19% of patients receiving Vyvanse. Dry mouth was a conspicuous treatment-emergent adverse event in adults (~27%), but was experienced by less than 7% of adolescents or children.
2.5-12.5% of patients treated with Vyvanse reported nausea.
For the purpose of comparison, headache, nasopharyngitis and decreased appetite were common (>10%) in patients receiving osmotic-release methylphenidate. For receiving the other active control, atomoxetine, decreased appetite, fatigue, headache, nausea and somnolence were reported by more than 10%.
Vyvanse vs Adderall Sales Statistics
Vyvanse is a bestselling drug, ranked #29. Adderall XR is ranked #99.