Alternative Benzos for Catatonia, SIB and Aggression in Autism

Layman Summary. Alternative benzodiazepines may be more effective than traditional benzos for self injurious behaviors (SIB), aggressive behaviors and catatonia in autistics. Smith et al (Vanderbilt)., discuss treatment in 5 profound autism cases. [Earlier blog posts on Benzo's]

Traditional benzos were not effective in reducing their symptoms. Two of the five had to be first stabilized with inpatient infusions of midazolam (traditional benzo used in anesthesia) and dexmedetomidine (selective alpha-2 adrenergic receptor agonist used in sedation) due to severity of symptoms.

Therefore, the authors tried using alternative benzos (by which they mean "not-lorazepam"), including clonazolam and etizolam. These drugs were chosen due to their higher potency and ability to cross the blood-brain barrier more easily than traditional benzos. 

Clonazolam is a high-potency benzo that is structurally similar to clonazepam, while etizolam is a thienodiazepine derivative. The paper does not go into extensive detail on the molecular mechanisms of alternative v traditional benzos. However, the authors note that alternative benzos have a higher potency and a different pharmacokinetic profile than traditional benzos. These differences may be due to structural variations in the chemical composition of alternative benzodiazepines that affect their binding affinity and activity at GABA receptor, which is the primary target of benzos.

However, the authors note that there are potential risks associated with using alternative benzos, such as dependence and withdrawal symptoms (due to longer half-life), which must be carefully monitored. Neither clonazolan or etizolan are approved for use in the US though they have been used in other countries. 

And I do want to highlight that withdrawal should not be taken lightly. Psychiatrists seem to have an arbitrary weaning off period for drugs. For example my "specialist" doc, weaned me off  Clonazepam in just 3 days since I had apparently grown tolerant to it. Half doze on day 2, stop on day 3. Day 4 was a massive Grand-Mal seizure. But it doesn't matter if the body is tolerant to the drug or not, you cannot subject body to shock with these quick withdrawals - a longer weaning off period would have been much more advisable instead of subjecting me to unnecessary health complications that impacted me for months. It should be weeks and not days of weaning off in the case of autistics.

In the meantime, the authors find that "clonazepam, diazepam, valproic acid and mematine" and reducing anti-psychotic meds were effective in reducing the severity of SIB and catatonia (see Twitter thread explaining).

Here are some twitter posts around that

• SIB: harm to self that results in physical injury, tissue damage, or pain.eg:  head-banging, self-hitting, and biting oneself. The severity can range from mild to severe and can lead to significant medical complications, such as tissue damage, infections, and scarring.   
• Aggressive behaviors result in harm to others and includes physical aggression (eg, hitting, kicking, biting, or throwing objects) as well as verbal aggression (eg: shouting, cursing, or threatening).
• Catatonia manifests as a state of immobility, stupor, and unresponsiveness, as well as excessive motor activity, agitation, and abnormal postures or movements. 

(GABA-A Receptor)

Reference
Smith JR, York T, Warn S, Borodge D, Pierce DL, Fuchs DC. Another Option for Aggression and Self-Injury, Alternative Benzodiazepines for Catatonia in Profound Autism. J Child Adolesc Psychopharmacol. 2023 Apr 6. doi: 10.1089/cap.2022.0067. Epub ahead of print. PMID: 37023406.

https://pubmed.ncbi.nlm.nih.gov/37023406/