Monoamine reuptake inhibitor

Concerta is an osmotic extended-release formulation of methylphenidate hydrochloride for ADHD. A controlled pediatric comparison found effects lasting through 12 hours and broadly matching immediate-release methylphenidate given three times daily. It is the same active drug as Ritalin, with a different delivery system.

Doxepin is a tricyclic antidepressant first approved in the United States in 1969 that is now also licensed there, at 3 and 6 mg, for insomnia marked by trouble staying asleep: doses 10 to 100 times lower than antidepressant ones. At those doses it acts almost only as a histamine H1 blocker. In industry-funded trials of up to 12 weeks it cut time awake during the night by about 22–23 minutes, with little effect on how quickly people fell asleep, and the American Academy of Sleep Medicine gives it a weak recommendation for sleep maintenance on evidence it rates as very low quality. At 75–300 mg a day it is a sedating antidepressant with the anticholinergic side effects and overdose toxicity of its class.

Ritalin tablets contain immediate-release methylphenidate hydrochloride, a prescription stimulant used for ADHD and narcolepsy. ADHD efficacy is well supported, while its shorter delivery profile means that trial regimens often use multiple daily doses. This page focuses on ordinary tablets, not the separate Ritalin LA formulation.

Tesofensine is not a GLP-1 anything. It is a triple monoamine reuptake inhibitor - it blocks the transporters for norepinephrine, dopamine and serotonin - originally developed for Parkinson's and Alzheimer's disease, where trials failed but participants lost weight. That observation led to a phase 2 obesity trial in 203 patients: 24 weeks at 0.5 mg gave 9.2% weight loss against 2.0% on placebo, with heart rate up 7.4 beats per minute. It never reached phase 3 for obesity. That trial also carries a Lancet expression of concern, issued in 2013 over under-reporting of adverse effects and never withdrawn. A newer formulation combining tesofensine with metoprolol has been tested in hypothalamic obesity, a condition with almost no other options, giving 6.3% more weight loss than placebo in 21 patients.

Trazodone is an antidepressant licensed for major depression in adults that is now prescribed in the United States mainly at low doses as an off-label sleep aid. It blocks 5-HT2A serotonin and alpha-1 adrenergic receptors strongly and the serotonin transporter weakly. Across 44 randomized trials it improved sleep quality and cut night-time awakenings without lengthening how long people felt they slept, at the cost of more side effects, and the American Academy of Sleep Medicine advises against it for chronic insomnia. In depression it beat placebo but ranks among the less effective and less well tolerated antidepressants.