Sibutramine
Sibutramine is an appetite suppressant, leading to weight loss, inhibiting the reuptake of serotonin, norepinephrine and dopamine. The affinity of its active metabolites to the transporters of norepinephrine and dopamine is even higher than that of Ritalin and its active metabolites (Fig. 5). [12][13] One of the active metabolites of sibutramine N-di-desmethylsibutramine, when administered to rats, is most localized in the cortical structures of the brain, including the prefrontal cortex (Fig. 6; recall, dysfunction of the prefrontal cortex is the dominant hypothesis of ADHD pathomechanism today, most proven effective drugs for ADHD improve the work of the prefrontal cortex). [14] Among other things, it has been found to increase the level of acetylcholine in the prefrontal cortex in rats, which is similar to the effect of many proven effective ADHD drugs and can contribute to their therapeutic effect to varying degrees, in addition, the level of acetylcholine in the prefrontal cortex is closely related to cognitive functions, and especially attention, and ADHD is associated with dysfunction of the cholinergic system. [15][16] In one small, placebo-controlled study in humans, sibutramine, when administered once, improved cognitive function in healthy adults, including attention. [17] Compared with Ritalin with sibutramine in a mouse model of ADHD, with prolonged administration of both drugs, sibutramine, unlike Ritalin, did not improve working memory in the new object recognition test, but they both improved working memory and attention in the T-maze. [18]

As far as can be judged, sibutramine has not been tested in humans for any pathology, including ADHD, other than excessive body weight. However, one of the patents for the use of sibutramine in psychiatric and neurological practice describes several cases of its successful off-label use in various pathologies, including ADHD, including in severe clinical cases, when no other treatment, sometimes consisting of dozens of drugs prescribed all the time before, did not help. It is stated, among other things, that often the symptoms improved quickly, within a few hours after the first intake of the drug, as well as the fact that the drug acts only 4-5 hours and often requires taking 2-3 times a day. [19]

For example:
Case 15. Severe ADHD associated with executive dysfunction, immune to all other drugs.
The 25-year-old had a lifetime of problems with severe hyperactivity, distractibility, disorganization, poor memory, very poor concentration and poor performance in school despite high IQ. There is no history of head injury and other neurological diseases or metabolic problems.
He repeatedly tried to take both individually and in combination the following drugs: Ritalin (psychostimulator), pemolin (psychostimulator), dextroamphetamine (psychostimulator), venlafaxine, valproic acid, carbamazepine, lamotrigine, nefazodone, lithium carbonate, fluoxetine, imipramine, nortriptyline, bupropion.
Finally, he was prescribed sibutramine with a dosage of up to 15 mg three times a day after titration. It was the first drug that made him calm and allowed him to concentrate attentively, calmly and assimilate information. He now plans to enter graduate school, with a sense of complete self-confidence for the first time. The only complaints were that he had become too calm and had lost the high-risk behavior he had experienced in the past. He also noted for the first time a marked improvement in his ability to act in an organized manner, make plans and follow them without distractions and procrastination.