WHAT ARE BENZODIAZEPINES?
Some benzodiazepines are widely and successfully used in certain settings such as in hospitals as pre-medication before operations, as one-off treatment only for nervous patients before a dental procedure, and in the treatment of some forms of epilepsy and movement disorders. They are also used in the management of alcohol withdrawal.
They work by enhancing the activity of the neurotransmitter, GABA (gamma-aminobutyric acid). GABA is the most important and widespread messenger in the brain. When benzodiazepines bind to the benzodiazepine sites on the GABA receptors they increase GABA’s efficiency and cause a calming effect. There are different receptor subtypes and with selectivity they cause varying effects: sedation/hypnotic (sleep-inducing), anxiolytic (anti-anxiety), muscle relaxant, anticonvulsant and amnesiac (memory disruption).
GABA is an inhibitory neurotransmitter, calming or slowing down the nervous system like the brakes function in a car. There are other neurotransmitters in the brain such as Norepinephrine (noradrenaline), dopamine, serotonin, glutamate and acetylcholine. Excitatory neurotransmitters like glutamate function like a car’s accelerator. While GABA’s inhibitory activity is being enhanced, the activity of other neurotransmitters – some of which are necessary for many essential functions including heart rate and blood pressure control, normal alertness, memory and emotional responses – is affected.
DOWNREGULATION OF RECEPTORS
In the cases of both antidepressants and benzodiazepines, the longer the drug is taken the more the receptors in the brain change to accommodate the raised levels of neurotransmitters. The neuroplasticity of the brain (brain’s ability to reorganize itself by forming new neural connections) causes it to try to maintain normal equilibrium through homeostasis (the body’s natural ability to maintain balance within its internal environment. So the receptors decrease in density and become less sensitive or ‘down-regulated’. They remain this way during the time of the medication is taken.
When the medication is discontinued, the cells then take time to re-adapt to the changes or ‘up-regulate’. During this period of readjustment withdrawal symptoms can be experienced. The reversible damage or compromised brain that we refer to is really this down-regulated state of the receptors.
HALF-LIFE
When medication is taken on a regular basis, there is an ongoing process of drug absorption and elimination. The time it takes for half of the drug to be eliminated or for the blood concentration level to fall by half is known as the half-life. This may vary according to individual, particularly in the elderly.
When someone on a longer acting half-life drug misses several doses or abruptly discontinues the drug, it can take days before withdrawal symptoms surface. This is important to know as some people who stop taking the medication abruptly spend a brief period thinking that they will not have withdrawal symptoms only to be unpleasantly surprised days later.
Inter-dose Withdrawal
People who use benzodiazepines and antidepressant sporadically or those who take the ones with a short half-life can experience ‘inter-dose withdrawal’. When this happens, they begin to feel withdrawal effects between doses.
TOLERANCE
When the receptors in the brain adapt or become habituated to the action of the drug, more is needed in order for the desired therapeutic effect to be achieved. This often develops when the drug is taken regularly and for more than 2 to 4 weeks. As tolerance sets in, physical dependency occurs and withdrawal symptoms usually then appear.
With addictive substances there is a need to keep increasing dosage because of this. A good example is the use of alcohol where a new drinker is able to feel an effect after one or two glasses but eventually, as tolerance sets in, will need increasing amounts. In the case benzodiazepines, z-drugs and antidepressant, successive increases in dosage may be periodically needed in order for the required effect to be maintained. Tolerance develops more rapidly with drugs with a short half-life and can lead to additional drugs being prescribed when a safe maximum dose of the one being taken is no longer effective.
Most people in withdrawal can relate to the concept of tolerance. It is not unusual to have had multiple visits to the doctor plagued by tolerance withdrawal effects. In many cases the withdrawal effects are mistaken for other medical conditions, with misdiagnoses and prescription of additional drugs resulting. This has become a familiar story for me in my support work, over the years, and it is rarely the case that tolerance withdrawal is identified early enough to avoid this predicament.
TAPERING – IN A NUTSHELL
If you have received conflicting advice about tapering, don’t let this confuse you. Despite claims that some tapering protocols are more successful than others, people who have used similar methods can have varying results – ranging from good to challenging. The worst accounts are from those who either stopped abruptly or rushed their tapers. But once you wean off gently and slowly under medical supervision, decide the pace at which you will proceed, and keep the mindset that you can and will succeed, you will find that coming off your medication is attainable.
There are different recommended methods for tapering, some of which are successfully used. For anyone who has taken the drug long-term, it is advisable to not rush the process. The schedules must be flexible and reduction rate should be based on your withdrawal reactions and intensity of symptoms. For short-term users, tapering over very long periods will prolong the period in which the receptors remain down-regulated.
The Ashton Manual recommends the use of diazepam (Valium) to taper off other benzodiazepines because it is more slowly eliminated from the body. Diazepam comes in liquid form and in doses of 10 mg, 5 mg and 2 mg which makes it easy to make very minute reductions in doses.
If you have decided to discontinue taking your medication, there are a few factors which will determine the duration and pace of your taper and how well you are likely to cope:
- If you are on a high dose, you will take longer to withdraw. The drug will be reduced in very small increments periodically in order to allow your body to readjust to the new doses at each stage of reduction.
- The tapering schedule should be used only as a guide. If you require a longer period to taper, you can discuss this with your doctor and adjust it accordingly.
- Many people use razor blades or the milk or water titration method to make the smallest possible cuts. It is believed that the smaller the cut, the gentler it is and the easier it will be for your central nervous system to adjust.
- Drugs differ in potency. If you are on a highly potent one you will need a longer time to reduce.
- Your personal circumstances, overall general health, the stressors in your life, stamina, support available and previous experience with drugs, if any, may also influence how you cope and determine the pace at which you can realistically taper.
If you are faced with additional stress such as a bereavement, admission to hospital or other crisis while tapering, it is acceptable and in some cases necessary to remain on the same stage of the withdrawal for a longer period. It is also important to avoid increasing the dose at this time, if possible. Once your circumstances are more settled, a further reduction in dose can be made.
You will need the cooperation of your doctor. If using the substitution or any other method, she or he will also be prescribing the medication required and will also be supervising your taper.
Having a support system in place is best. It would be good if you had a reliable family member or friend who is willing to learn about your medication and withdrawal. It is extremely important that you set the pace for your taper and not feel rushed to complete it or have anyone pressure you into weaning off quicker than you’re comfortable with. You can do it!
Benzodiazepines, Commonly Used
| Generic Name | Brand Name |
| alprazolam | Xanax |
| bromazepam | Lexotan, Lexomil |
| chlordiazepoxide | Librium |
| clobazam | Frisium |
| clonazepam | Klonopin, Rivotril |
| clorazepate | Tranxene |
| diazepam | Valium, Ducene |
| flunitrazepam | Rohypnol |
| flurazepam | Dalmane |
| lorazepam | Ativan |
| nitrazepam | Mogadon |
| nordazepam | Nordaz, Calmday |
| oxazepam | Serax, Serepax, Serenid |
| temazepam | Restoril, Euhypnos, Normison |
| triazolam | Halcion |
‘Z’ drugs – These have similar effects:
| zaleplon | Sonata |
| zolpidem | Ambien, Stilnoct |
| zopiclone | Zimovane, Imovane |
| eszopiclone | Lunesta |
Caution: Never stop taking a benzodiazepine or antidepressant abruptly or rush your taper. In the case of benzodiazepines the risks of quitting cold turkey include seizures and psychosis. Always taper off slowly using the Ashton or other recommended method, under the supervision of your doctor.
Ref:
Ashton, C. H. (2007). Benzodiazepines: How They Work and How to Withdraw. Newcastle upon Tyne: School of Neurosciences.
Frederick, V. B. (2014) Recovery and Renewal: Your essential guide to overcoming dependency and withdrawal from sleeping pills, other ‘benzo’ tranquillisers and antidepressants. London: Jessica Kingsley Publishers.
Rang, H.P., Dale, M.M. & Ritter, J.M. (1999). Pharmacology. 4th ed. Edinburgh: Churchill Livingstone.
