- duration of action
- side effects
Chemically speaking, focalin isdexmethylphenidate, whereas Adderall is comprised of 25% levoamphetamine and 75% dextroamphetamine.
For those interested in the chemistry: dexmethylphenidate is one diasteriomer or “mirror” image of racemic methylphenidate.
Racemic methylphenidate contains both l-threo-methylphenidate and d-threo-methylphenidate (aka dexmethylphenidate or Focalin) in equal proportions. The l-threo-methylphenidate isomer is much less biologically active. For this reason, Focalin (pure dexmethylphenidate) is about twice as potent as the racemic methylphenidate.
In summary, Focalin is a longer-acting, slightly less potent version of Adderall. In terms of the drug’s mechanism, Focalin is more specific: it mostly “works” by inhibiting dopamine reuptake. Amphetamine on the other hand has many mechanisms, the most important of which is as a highly potent dopamine-releasing agent.
Focalin and Adderall have different upsides and downsides. Clinical studies have demonstrated equivalent efficacy, though some individuals anecdotally report that Adderall works better for them.
Adderall is more popular than Focalin, despite the fact that Adderall has a more troubling side effect profile (possible neurotoxicity from long-term use, cardiovascular side effects). We think that Adderall is more frequently prescribed for a reason and is rightly used as a first-line agent for the treatment of ADHD.
Similarities Between Focalin vs Adderall
Both medications share the following features:
- Classification: psychostimulant
- Potency: equivalent; both drugs pack nearly the same punch (5mg Focalin is equivalent to 5mg Adderall)
- Legal status: schedule II (United States)
- Indication: first-line agent for the treatment of ADHD
- Duration of effects: 4-6 hours (IR)
- Forms: both immediate release (IR) and extended release (ER) available
- Addiction: notable abuse liability
- Sleep: should be taken in the morning or afternoon to limit insomnia
- Generic Availability: Focalin is available as the generic dexmethylphenidate hydrochloride, Adderall is available as the generic mixed amphetamine salts
- Pricing: the cost of the IR generics of both drugs is nearly identical. Generic Adderall XR is slightly cheaper than Generic Focalin XR.
Both medications have the following box warning (US):
Give dexmethylphenidate cautiously to patients with a history of drug dependence or alcoholism. Long-term abusive use can lead to marked tolerance and psychological dependence with varying degrees of abnormal behavior. Frank psychotic episodes can occur, especially with parenteral abuse. Careful supervision is required during drug withdrawal from abusive use because severe depression may occur. Withdrawal following long-term therapeutic use may unmask symptoms of the underlying disorder that may require follow-up.
Key Differences Between Focalin vs Adderall
- Indications: Adderall is FDA approved for ADHD and narcolepsy, while Focalin is only approved for ADHD
- Half-Life: Focalin has a half-life of about 2-2.5 hr vs 11-13 hr for Adderall
- Efficacy: Studies indicate that both drugs are equally effective. but anecdotally, some individuals report that they respond better to Focalin
- Side Effects: Adderall has worse cardiovascular side effects (e.g., hypertension, increased heart rate, peripheral vasoconstriction)
- *Abuse potential: *Both Focalin and Adderall are habit-forming, but Adderall may have greater abuse liability
- Chemical composition: Focalin is dextromethylphenidate, whereas Adderall is four different amphetamine salts with a ratio of 1:3 dextroamphetamine to levoamphetamine.
- Neurotoxicity: Adderall may have a greater risk of neurotoxicity than Focalin, but this topic remains controversial.
- Mechanism: Adderall “works” by promoting dopamine and norepinephrine release from storage sites (vesicles), Focalin inhibits the re-uptake of dopamine and norepinephrine, increasing their concentrations (in the extra-neuronal space).
- Popularity: More prescriptions are written for Adderall than Focalin
Subjective Differences (Anecdotal)
- Focalin may be more anxiety-promoting than Adderall for some individuals
- Adderall is associated with more euphoria and therefore has greater abuse liability
Focalin and Adderall are approximately equivalent in terms of potency and efficacy. A study conducted in 2011 comparing Focalin vs Adderall reported that Adderall reduced symptoms by 80% and Focalin reduced symptoms by 79%.
Adderall has a reputation for being more effective than Focalin because Focalin is less widely known and Adderall may have a greater propensity for inducing euphoria in some individuals. Adderall is more commonly used as a performance enhancing drug and is popular among college students to gain an academic edge.
Whether or not psychostimulants like Adderall or Focalin actually improve cognitive performance in healthy individuals remains controversial. Some reports suggest modest improvement in certain types of cognitive tasks, but this effect is most robust in lower-performing individuals and vanishes among high-performing individuals.
Mechanism of Action
Focalin and Adderall are both potent psychostimulants and therefore share a similar mechanism of action. Since psychostimulants have been around for over fifty years and have been used clinically for decades, their mechanism of action is among the most well-characterized of any drug.
Focalin inhibits the re-uptake of the catecholamines dopamine and norepineprhine. Re-uptake is the process by which catecholamines are removed from the synapse. Therefore, inhibiting re-uptake increases the synaptic concentration of dopamine and norepinephrine, resulting in the enhancement of catecholaminergic neurotransmission.
Adderall, by contrast, is a catecholamine-releasing agent. Adderall is a relatively weak reuptake inhibitor of dopamine, norepinephrine and to a lesser extent serotonin. Adderall also inhibits vesicular monoamine transporter 2 (VMAT2) and weakly and reversibly inhibits monoamine oxidase (MAO).
|Neuronal target||Focalin Binding affinity||Adderall* binding affinity|
|NET (Ki nM)||206||40,000-50,000|
A smaller binding affinity (Ki) indicates that the ligand binds more tightly to the receptor. DAT = dopamine transporter. NET = norepinephrine transporter.
*Technically, these binding affinities only apply to dextroamphetamine, which comprises Adderall by 75%
Focalin Side Effects
- Central nervous system: Headache (25% to 39%), insomnia (children 5% to 17%), restlessness (adults 12%), anxiety (5% to 11%);
- Gastrointestinal: Appetite decreased (children 30%), xerostomia (adults 7% to 20%), abdominal pain (children 15%)
- Central nervous system: Dizziness (adults 6%), fever (children 5%), irritability (children ≤5%), depression (children ≤3%), mood swings (children ≤3%)
- Dermatologic: Pruritus (children ≤3%)
- Gastrointestinal: Nausea (children 9%), dyspepsia (5% to 9%), vomiting (children 2% to 9%), anorexia (children 5% to 7%), pharyngolaryngeal pain (adults 4% to 7%)
- Respiratory: Nasal congestion (children ≤5%)
Adderall Side Effects
- Cardiovascular: Systolic hypertension (adolescents 7% to 35%; dose related; transient)
- Central nervous system: Insomnia (12% to 27%), headache (adults ≤26%)
- Gastrointestinal: Decreased appetite (22% to 36%), xerostomia (2% to 35%), abdominal pain (11% to 14%)
- Cardiovascular: Tachycardia (adults ≤6%), palpitations (2% to 4%)
- Central nervous system: Emotional lability (2% to 9%), anxiety (adults 8%), agitation (adults ≤8%), dizziness (2% to 7%), nervousness (6%), drowsiness (2% to 4%), speech disturbance (2% to 4%), twitching (2% to 4%)
- Dermatologic: Diaphoresis (2% to 4%), skin photosensitivity (2% to 4%); Endocrine & metabolic: Weight loss (4% to 10%), decreased libido (2% to 4%), dysmenorrhea (2% to 4%)
- Gastrointestinal: Nausea (2% to 8%), vomiting (2% to 7%), diarrhea (2% to 6%), constipation (2% to 4%), dyspepsia (2% to 4%), teeth clenching (≤4%), tooth infection (≤4%), anorexia (2%)
- Genitourinary: Urinary tract infection (5%), impotence (2% to 4%)
- Infection: Infection (2% to 4%)
- Respiratory: Dyspnea (2% to 4%)
- Miscellaneous: Fever (5%)
Focalin vs Adderall Comparison Table
|Brand Names||Flocalin; Focalin XR||Adderall; Adderall XR|
|Pharmacologic Category||Central Nervous System Stimulant||Central Nervous System Stimulant|
|Date of FDA Approval||November 2001 (IR); May 2005 (XR)||February 1996|
|Off-label uses||Treatment-resistant depression||Treatment-resistant depression|
|Dosing||2.5mg-20mg (immediate release); 10mg-40mg (extended release)||5-40mg (Adderall); 20-60mg (Adderall XR)|
|Contraindications||Agitation or marked anxiety; glaucoma; motor tics; Tourette syndrome, concurrent use with monoamine oxidase inhibitor (MAOI)||moderate-to-severe hypertension, agitated states, glaucoma, during or within 14 days following MAO inhibitor, cardiovascular disease, hyperthyroidism, patients with a history of drug abuse, arteriosclerosis, hypersensitivity to sympathomimetics|
|Warnings||Cardiovascular events, hypersensitivity reactions, peripheral vasculopathy (e.g., Reynaud’s syndrome), priapism, Tourette syndrome or tics, visual disturbance, abuse potential, hypertension, psychiatric disorders, seizure disorders||Cardiovascular events, CNS effects, peripheral vasculopathy, visual disturbance, abuse potential, hypertension, psychiatric disorders, seizure disorder, Tourette syndrome|
|Mechanism||Dexmethylphenidate is the more active enantiomer of racemic methylphenidate. It is a psychostimulant that blocks reuptake of dopamine and norepinephrine and enhances their release.||l- and d-amphetamine promote the release of catecholamines (dopamine, norepinephrine) from their storage sites|
|Absorption, Distribution, Metabolism||Absorption – Immediate release: rapid; extended release: biomodal. Distribution – Vd: 1.54 to 3.76 L/kg. Metabolism: de-esterification to the inactive metabolite d-ritalinic acid||Absorption – Well-absorbed.|
|Half-Life||2.2hours||9hr for d-amphetamine, 11hr for l-amphetamine (children); d-amphetamine 11hr, l-amphetamine 13-14hr (adolescents); 10hr for d-amphetamine, 13hr for l-amphetamine|
|Time to Peak||1-1.5hr (immediate release); first peak 1.5hr, second peak 6.5hr (extended release)|