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Tolerance to many of the effects of benzodiazepines (Alprazolam, Ambien, Anxon, Apodorm, Apzepam, Ativan, Bromazepam, Centrax, Chlordiasepin, Clobazam, Clonazepin, Klonazepin, Clorazepain, Dalmane, Diazepan, Diazephane, Doral Dormonol, Estazolam, Euhypnol, Flunitrazepan, Flurazepan, Fluscane, Frisim. Halazepan, Halcion, Ketazolan, Klonopin, Lexomil Lexotan, Librium, Loprazolan, Lorazepan, Lormetazepan, Medazepan, Mogadon, Nitrazepan, Nobrium, Noctamin, Normison, Oxascan, Oxazepan, Paxipan, Prazepan, ProSon, Quazepan, Restoril, Rivotrin, Rohypnol, Seraxat, Serenil, Serepan, Sobril Stesolid, Temazepan, Temesta, Tranxen, Triazolam, Valium, Xanax, Xanor, etc.) develops with regular use: the original dose of the drug has progressively less effect and a higher dose is required to obtain the original effect. This has often led doctors to increase the dosage in their prescriptions or to add another benzodiazepine so that some patients have ended up taking two benzodiazepines at once.
However, tolerance to the various actions of benzodiazepines develops at variable rates and to different degrees. Tolerance to the hypnotic effects (sleeping pill effect) develops rapidly and sleep recordings have shown that sleep patterns, including deep sleep (slow wave sleep) and dreaming (which are initially suppressed by benzodiazepines), return to pre-treatment levels after a few weeks of regular benzodiazepine use. Similarly, daytime users of the drugs for anxiety no longer feel sleepy after a few days.
Tolerance to the anxiolytic effects (calming, anxiety-reducing effect) develops more slowly but there is little evidence that benzodiazepines retain their effectiveness after a few months. In fact long-term benzodiazepine use may even aggravate anxiety disorders . Many patients find that anxiety symptoms gradually increase over the years despite continuous benzodiazepine use, and panic attacks and agoraphobia may appear for the first time after years of chronic use. Such worsening of symptoms during long-term benzodiazepine use is probably due to the development of tolerance to the anxiolytic effects, so that "withdrawal" symptoms emerge even in the continued presence of the drugs. However, tolerance may not be complete and chronic users sometimes report continued efficacy, which may be partly due to suppression of withdrawal effects. Nevertheless, in most cases such symptoms gradually disappear after successful tapering and withdrawal of benzodiazepines.
Tolerance to the anticonvulsant effects of benzodiazepines makes them generally unsuitable for long-term control of epilepsy. Tolerance to the motor effects of benzodiazepines can develop to a remarkable degree so that people on very large doses may be able to ride a bicycle and play ball games. However, complete tolerance to the effects on memory and cognition does not seem to occur. Many studies show that these functions remain impaired in chronic users, recovering slowly, though sometimes incompletely, after withdrawal.
Tolerance is a phenomenon that develops with many chronically used drugs (including alcohol, heroin and morphine and cannabis). The body responds to the continued presence of the drug with a series of adjustments that tend to overcome the drug effects. In the case of benzodiazepines, compensatory changes occur in the GABA and benzodiazepine receptors which become less responsive, so that the inhibitory actions of GABA and benzodiazepines are decreased. At the same time there are changes in the secondary systems controlled by GABA so that the activity of excitatory neurotransmitters tends to be restored. Tolerance to different effects of benzodiazepines may vary between individuals - probably as a result of differences in intrinsic neurological and chemical make-up which are reflected in personality characteristics and susceptibility to stress. The development of tolerance is one of the reasons people become dependent on benzodiazepines, and also sets the scene for the withdrawal syndrome.
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