Here is an overview of the state of the art in GAD:<p>TL;DR
Tofisopam appears to be the ideal long term anxiety medication except it's understudied despite being old, which is a real shame.<p>Pregabalin is likely the second best candidate however some people reports horrible anecdotes with it (brain breaker)<p>As always the best blog about the topic is from Scott Alexander:
<a href="https://slatestarcodex.com/2015/07/13/things-that-sometimes-work-if-you-have-anxiety/" rel="nofollow">https://slatestarcodex.com/2015/07/13/things-that-sometimes-...</a><p>Best recent meta analyse of the SOTA
<a href="https://pubmed.ncbi.nlm.nih.gov/30712879/" rel="nofollow">https://pubmed.ncbi.nlm.nih.gov/30712879/</a><p>Anxiety is more prevalant than depression yet is extremely under reported.
While ADHD and depression have <i>relatively</i> safe and effective medications for long term treatment, chronic anxiety doesn't.<p>Some antidepressants are safe long term treatment for anxiety however they are not very potent (compared to benzodiazepines)<p>Benzos are not a long term solution because of tolerance, of their sedative effect and of their persistent impairment of cognitive performance.<p>The ideal medication has the following properties:
Required:
1) no persistent loss of cognitive performance
Studies shows that popular benzos negatively affect cognitive performance even months (years?) after their use.
2) no hypnotic effect at normal dose<p>Desired:
3) no loss of cognitive performance while in use.
4) No or low tolerance
5) no sedative effect<p>It happens that there are at least 2 benzos derivatives that share those properties:<p>Tofisopam (Emandaxin and Grandaxin) and Hydazepam (Gidazepam IC) are drugs that are benzodiazepine derivatives. Like other benzodiazepines, they possesses anxiolytic properties, but, unlike other benzodiazepines, they do not have anticonvulsant, sedative, skeletal muscle relaxant, motor skill-impairing, or amnestic properties.
Moreover Tofisopam (apparently) induce NO COGNITIVE PERFORMANCE LOSS!
See e.g this DOI on scihub
<a href="https://doi.org/10.1007/978-3-642-74031-2_13" rel="nofollow">https://doi.org/10.1007/978-3-642-74031-2_13</a><p>The most interesting NON-benzos:<p>Pregabalin's anxiolytic effect appears after one week of use and is similar in effectiveness to lorazepam, alprazolam, and venlafaxine, but has demonstrated more consistent therapeutic effects for psychic and somatic anxiety symptoms. Long-term trials have shown continued effectiveness without the development of tolerance, and unlike benzodiazepines, it does not disrupt sleep architecture and produces less severe cognitive and psychomotor impairment. Pregabalin also exhibits a lower potential for abuse and dependence than benzodiazepines.[43][44]<p>Hydroxyzine has been shown to be as effective as benzodiazepines in the treatment of generalized anxiety disorder, while producing fewer side-effects.[13]<p>Moclobemide potentially more potent than SSRIs, however much slower to act than benzos.<p>CONCLUSION:<p>* Tofisopam appears to be the clear winner.
<i>Hydazepam might be as well but can't find information on cognitive performance.
</i>Pregabalin appears to be the best non-benzo
* reversible Maois might be the safest/potent well studied medication for long term use and do not destroy libido contrary to SSRIs.
This is a major issue because
anxiety is a major commorbidity of ADHD and given that MAOIs increase norepinephrine/dopamine quantities it might interact badly with concurrent use of stimulants. However some anecdotal studies shows that it can be safe, however the use of beta blockers might be needed (for e.g 50mg of Vyvanse)
A plausible and surprisingly understudied solution for the SSRIs effects on libido might be TRT.