Category:Schedule IV controlled substances: Difference between revisions
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The medicines that populate Schedule IV are dominated by the [[:Category:Benzodiazepines|benzodiazepines]] and the related "Z-drug" non-benzodiazepine hypnotics. The benzodiazepines (chlordiazepoxide, [[wikipedia:Diazepam|diazepam]], [[wikipedia:Lorazepam|lorazepam]], [[wikipedia:Alprazolam|alprazolam]], [[wikipedia:Clonazepam|clonazepam]], [[wikipedia:Midazolam|midazolam]], [[wikipedia:Temazepam|temazepam]], and the longer list of clinically used agents) were introduced in 1960 with chlordiazepoxide and followed shortly by diazepam, both developed at Hoffmann-La Roche by [[wikipedia:Leo Sternbach|Leo Sternbach]] on a screening programme that began with a discarded series of "useless" tricyclic compounds from his earlier work. Diazepam (Valium) became the most prescribed medicine in the world between 1969 and 1982. The class produced rapid and reliable anxiolysis and sedation, but with a tolerance and dependence pattern that emerged over the following decade and led, in the 1980s, to the recognition of benzodiazepine withdrawal syndrome and to a substantial tightening of prescribing practice. The Z-drug hypnotics ([[wikipedia:Zolpidem|zolpidem]] (Ambien, Sanofi, 1992), zaleplon, eszopiclone) were developed in the late 1980s and 1990s as selective alpha-1-subunit GABA-A agonists with hypnotic but reduced anxiolytic and muscle-relaxant action; they share Schedule IV with the benzodiazepines. | The medicines that populate Schedule IV are dominated by the [[:Category:Benzodiazepines|benzodiazepines]] and the related "Z-drug" non-benzodiazepine hypnotics. The benzodiazepines (chlordiazepoxide, [[wikipedia:Diazepam|diazepam]], [[wikipedia:Lorazepam|lorazepam]], [[wikipedia:Alprazolam|alprazolam]], [[wikipedia:Clonazepam|clonazepam]], [[wikipedia:Midazolam|midazolam]], [[wikipedia:Temazepam|temazepam]], and the longer list of clinically used agents) were introduced in 1960 with chlordiazepoxide and followed shortly by diazepam, both developed at Hoffmann-La Roche by [[wikipedia:Leo Sternbach|Leo Sternbach]] on a screening programme that began with a discarded series of "useless" tricyclic compounds from his earlier work. Diazepam (Valium) became the most prescribed medicine in the world between 1969 and 1982. The class produced rapid and reliable anxiolysis and sedation, but with a tolerance and dependence pattern that emerged over the following decade and led, in the 1980s, to the recognition of benzodiazepine withdrawal syndrome and to a substantial tightening of prescribing practice. The Z-drug hypnotics ([[wikipedia:Zolpidem|zolpidem]] (Ambien, Sanofi, 1992), zaleplon, eszopiclone) were developed in the late 1980s and 1990s as selective alpha-1-subunit GABA-A agonists with hypnotic but reduced anxiolytic and muscle-relaxant action; they share Schedule IV with the benzodiazepines. | ||
The Schedule IV tier also includes the wakefulness-promoting medicine [[wikipedia:Modafinil|modafinil]] (Provigil, Cephalon, 1998) and the related armodafinil; the anti-obesity medicines [[wikipedia:Phentermine|phentermine]] (a sympathomimetic | The Schedule IV tier also includes the wakefulness-promoting medicine [[wikipedia:Modafinil|modafinil]] (Provigil, Cephalon, 1998) and the related armodafinil; the anti-obesity medicines [[wikipedia:Phentermine|phentermine]] (a sympathomimetic psychostimulant with substantially lower abuse potential than the Schedule II amphetamines), diethylpropion, and the older phendimetrazine (Schedule III rather than IV); [[wikipedia:Tramadol|tramadol]], the atypical opioid that was unscheduled at U.S. introduction in 1995 and was moved to Schedule IV by the DEA in 2014 in response to accumulating evidence of dependence and overdose; and the GABA-receptor partial agonist [[wikipedia:Suvorexant|suvorexant]] (an orexin-receptor antagonist for insomnia) along with the related lemborexant and daridorexant. Selected anticonvulsants used principally for benzodiazepine indications (carisoprodol, the muscle relaxant metabolically activated to meprobamate, was moved to Schedule IV in 2012) round out the category. | ||
The benzodiazepine class deserves particular clinical attention given its size and its overdose profile. Concurrent prescription of a benzodiazepine and an opioid is associated with a substantial excess of fatal respiratory depression compared to either alone, a finding that is reflected in the FDA boxed warning that has been on these medicines since 2016 and in the contemporary guidelines that recommend against routine co-prescription except in carefully considered circumstances. The benzodiazepines and Z-drugs are also implicated in falls and fracture in elderly patients, in cognitive impairment that may not fully reverse on discontinuation, in motor-vehicle collision risk, and in disinhibition phenomena. The contemporary practice has moved toward shorter courses, lower doses, taper rather than abrupt discontinuation when long use is to be stopped, and increasing use of non-benzodiazepine alternatives for anxiety (the SSRIs and SNRIs for chronic anxiety, propranolol for performance anxiety, the new gepants and antihistamines for situational use). | The benzodiazepine class deserves particular clinical attention given its size and its overdose profile. Concurrent prescription of a benzodiazepine and an opioid is associated with a substantial excess of fatal respiratory depression compared to either alone, a finding that is reflected in the FDA boxed warning that has been on these medicines since 2016 and in the contemporary guidelines that recommend against routine co-prescription except in carefully considered circumstances. The benzodiazepines and Z-drugs are also implicated in falls and fracture in elderly patients, in cognitive impairment that may not fully reverse on discontinuation, in motor-vehicle collision risk, and in disinhibition phenomena. The contemporary practice has moved toward shorter courses, lower doses, taper rather than abrupt discontinuation when long use is to be stopped, and increasing use of non-benzodiazepine alternatives for anxiety (the SSRIs and SNRIs for chronic anxiety, propranolol for performance anxiety, the new gepants and antihistamines for situational use). | ||
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* '''Atypical opioid analgesics''' (less abuse potential than the Schedule II opioids): [[Tramadol|tramadol]] (rescheduled to Schedule IV in 2014); [[wikipedia:Butorphanol|butorphanol]]; [[wikipedia:Pentazocine|pentazocine]] | * '''Atypical opioid analgesics''' (less abuse potential than the Schedule II opioids): [[Tramadol|tramadol]] (rescheduled to Schedule IV in 2014); [[wikipedia:Butorphanol|butorphanol]]; [[wikipedia:Pentazocine|pentazocine]] | ||
* '''Anti-obesity sympathomimetics''': [[wikipedia:Phentermine|phentermine]], diethylpropion | * '''Anti-obesity sympathomimetics''': [[wikipedia:Phentermine|phentermine]], diethylpropion | ||
* '''Other''': [[wikipedia:Carisoprodol|carisoprodol]] (Soma, the | * '''Other''': [[wikipedia:Carisoprodol|carisoprodol]] (Soma, the muscle relaxant metabolised to meprobamate), [[wikipedia:Suvorexant|suvorexant]] and the related orexin antagonists [[wikipedia:Lemborexant|lemborexant]] and [[wikipedia:Daridorexant|daridorexant]] (insomnia) | ||
== Notes on scope == | == Notes on scope == | ||