Unfortunately, the same drugs with high potential for abuse are also the ones that work best for certain individuals with neurobehavioral conditions. According to GlobalData, penetrating the stimulant-dominated pharmaceutical market remains challenging without comparable efficacy from non-stimulants.
The attention deficit hyperactivity disorder (ADHD) market is a lucrative business: Stimulants, amphetamines, and methylphenidates continue to dominate the ADHD drug market across the seven major markets, Express Pharma reports. (The seven major markets are in France, Germany, Italy, Spain, the UK, the US, and Japan.)
Non-addictive drugs demonstrate a “crippling lower” efficacy in treating ADHD.
Drug makers are in a race to develop safer alternatives. Three out of the four late-stage pipeline drug candidates in Phase III development within those markets have non-stimulant properties: Axsome Therapeutics Inc’s solriamfetol, Otsuka Pharmaceutical Co Ltd’s centanafadine and Neurocentria Inc’s L-Threonate Magnesium Salt.
The lower abuse potential of solriamfetol and centanafadine is a major selling point created by developers, but without displaying efficacy comparable to stimulants, they will struggle to penetrate the market—even if they are approved.
The use of stimulants for ADHD treatment is increasing.
The key opinion leaders (KOLs) in the treatment of ADHD say that patients and parents have been hesitant to use stimulants for the treatment of ADHD in children and adolescents, but this is changing with time, and the use of stimulants for ADHD treatment is increasing.
“Marketing emphasis on abuse potential is common in non-stimulates both marketed and pipeline; this is despite KOLs viewing the abuse potential of ADHD stimulants as overstated,” said Lorraine Palmer, Pharma Analyst at GlobalData. “The KOLs interviewed by GlobalData were not concerned about whether a treatment is a stimulant or a non-stimulant, rather they are focused on the pharmaceuticals efficacy and side-effect profile.”
Four non-stimulants are commonly marketed: guanfacine, clonidine, atomoxetine and viloxazine. Sleep disturbances and a decreased appetite have been reported from both clonidine and atomoxetine.
“All four display cripplingly lower efficacy in the treatment of ADHD than stimulants,” Express Pharma reports.
“Rather than an emphasis on abuse potential, a better alternative strategy to penetrate the saturated ADHD market would be to target key unmet needs in ADHD treatment such as improving compliance or providing coverage into the evening without affecting sleep.”
Part of this challenge likely includes the impact of addiction itself. Regarding the popular ADHD drug Adderall, adults and children 6 years of age and older are eligible to take Adderall, beginning at 5 milligrams, while children 3 to 5 years of age are able to start at 2.5 mg per day. Only children under the age of 3 are prohibited from being prescribed the drug in all cases.
Adderall’s active ingredients are dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate. Columbia University psychiatry professor Carl Hart famously wrote for Vice in 2016 that meth is “almost identical to Adderall” in terms of chemistry and its effects on the brain.
A 2016 study published in the Journal of Clinical Psychiatry indicates that an increasing number of young adults have been checking into emergency rooms over the past few years due to accidental overdoses on Adderall and similar drugs.
Other Reasons for Stimulant Alternatives
High Times reported last September that leading drug makers and pharmaceutical companies are having little luck addressing nationwide shortages of stimulant-based ADHD medications like Adderall, Vyvanse, and Ritalin.
The Adderall shortage began in Fall of 2022, marked by an FDA notice acknowledging the shortages with an estimate that things would be resolved in a month or two. That is not the case, however, as issued a joint notice on August 1 acknowledging that the shortage had been “understandably frustrating” for patients and providers.
“The current shortage of stimulant medications is the result of many factors. It began last fall due to a manufacturing delay experienced by one drug maker,” the joint notice said. “While this delay has since resolved, we are continuing to experience its effects in combination with record-high prescription rates of stimulant medications. Data show that, from 2012 to 2021, overall dispensing of stimulants (including amphetamine products and other stimulants) increased by 45.5 percent in the United States.”
Teva Pharmaceuticals, Adderall’s biggest manufacturer, reported shortfalls. Teva CEO Richard Francis told Bloomberg that the company is operating at “full capacity” at the moment and blamed their decreased output in previous years to COVID-induced work shortages which they have only just barely recovered from. Should they wish to increase the amount of Adderall they produce, they would have to buy or build more factories as their current infrastructure cannot handle bigger output. The company has declined to comment on whether or not they plan to invest in such infrastructure.
This adds to the multiple reasons less addictive non-stimulant drugs are needed to treat ADHD.
Correction both Solriamfetol and Centanafadineis are in fact structural derivatives of Amphetamine!
They are also both stimulants, via Norepinephrine and Dopamine reuptake inhibition, exactly the same as Amphetamine, Methamphetamine and Methyphenidate. However Amphetamine and Methamphetamine are more powerful stimulants because they also act directly on Epinephrine and Dopamine receptors.
The irony is that it is this more potent stimulant action that actually makes Amphetamine and Methamphetamine more efficacious in ADHD.
Solriamfetol is actually also considered to have some ‘abuse’ potential, though less than thee amphetamines.
… Atomoxetine is also a stimulant via, you guessed it, Norepinephrine and Dopamine reuptake inhibition. It is also, you guessed it, very similar to Amphetamine in structure, being an N-methyl-Phenylethylamine. Methamphetamine, for reference, is N,alpha-Dimethyl-Phenylethylamine and Amphetamine is just alpha-Methyl-Phenylethylamine.