The practical process of tapering is outlined in 'Tapering benzodiazepines and z-drugs in practice'. The key elements of a programme of tapering are:
Although the major approach outlined in the drug-specific sections involves making reductions every 1-4 weeks (sometimes called 'cut and hold') 1 an alternative approach is called micro-tapering, whereby a small change in dose is made each day. Theoretically (see Figure 3.4) making smaller reductions should produce smaller disruptions of the homeostatic equilibrium leading to less intense withdrawal symptoms. 2 This process might require further dilutions of a liquid version of the drug and the use of small-volume syringes. It also requires quite complex calculations and record keeping. Micro-tapering allows the patient great flexibility in finding a rate of reduction that is tolerable for them. It also means that doses can be evenly distributed throughout the day, which should minimise any plasma fluctuations that might provoke or exacerbate withdrawal symptoms. Where several doses of a medication are taken each day, these same small-dose reductions can be made to all doses, or sequentially to one dose at a time (e.g. morning, afternoon or night).
Micro-tapering rates can be calculated from the regimens given in the drug-specific sections by dividing the change in dose for each step by 7, 14 or 28 days, depending on the rate of desired taper. For example, if a regimen suggests that a reduction should be made from 60mg to 55mg in one step over 2 weeks, then this could be converted into a reduction of approximately 0.4mg each day for 2 weeks. The rate of tapering per day will reduce throughout the taper (hyperbolically). This rate can be slowed if withdrawal symptoms become too unpleasant. As an example, if a 0.1mg/mL suspension of diazepam is made up, as above, to a volume of 20mL, then 0.5mL less could be taken every day to reduce from 2mg (20mL) by 0.05mg each day, taking 40 days to reach 0mg (a rate that could be adjusted to withdrawal symptoms).
Currently there are no medications approved by the FDA or other drug regulators to alleviate the symptoms of benzodiazepine withdrawal. Pharmacological adjunctive treatments for benzodiazepine withdrawal have had mixed reviews. 3, 4 Many drugs that have been trialled to help people with withdrawal symptoms themselves cause physical dependence and withdrawal. These include pregabalin, paroxetine, tricyclic antidepressants, and trazodone. 4 Ultimately these agents may then in turn need to be tapered, and are, in any case, associated with their own adverse effects. 5 Clearly then, using a dependence-forming agent to assist withdrawal is ultimately likely to be self-defeating. NICE guidance on safe withdrawal of benzodiazepines states explicitly 'Do not treat withdrawal symptoms with another medicine that is associated with dependence or withdrawal symptoms.' 6 The British National Formulary (BNF) cautions: 'The addition of beta-blockers, antidepressants and antipsychotics should be avoided where possible.' 7
When severe withdrawal symptoms occur it is generally preferable to slow the rate of taper to minimise withdrawal symptoms rather than seek to mask them with another medication. The addition of another medication also risks complicating the picture by adding in new adverse effects, and potential interactions with existing medication. In the process of withdrawal, some patients will become sensitised to a range of medications, which may include other psychiatric medications - another reason for a cautious approach to new agents. 5, 8 Professor Ashton said on this issue 'Presumably the general hypersensitivity of the nervous system magnifies the reaction to any foreign substances, but no clear explanation has yet emerged.' 8
In selected cases of severe withdrawal, the addition of an adjunctive medication may be considered. 9 The adjunct agent should be ideally one without a strong withdrawal syndrome and should have less severe adverse effects than the original benzodiazepine. In a Cochrane review, the use of valproate assisted successful benzodiazepine discontinuation, 10 as did carbamazepine. 11 Valproate and carbamazepine are less likely to produce withdrawal effects than benzodiazepines, although withdrawal is reported for both drugs. 12 These drugs also pose risk of blood dyscrasias, hepatic decompensation, and psychiatric and cognitive alterations, amongst other adverse effects, and so require careful monitoring. 13, 14 Also, NICE concluded: 'Do not offer sodium valproate or buspirone to aid withdrawal from a benzodiazepine.' 6 The addition of melatonin may also be more effective 15 than tapering alone, although evidence is mixed. 16 Drugs like propranolol 17, 18 and antihistamines like hydroxyzine 19 have been used in case of unpleasant withdrawal symptoms, with inconclusive findings. 11 Ideally these drugs should be used only for the short term, as some
can also cause physical dependence and withdrawal with chronic use. 20
There has been almost no formal research into the effects of supplements on withdrawal symptoms. Hypersensitivity to adverse effects may also be seen with supplements. 8 Any theories on the possible benefits of supplements in this area are mere speculation.
The use of GABA-affecting supplements (e.g. valerian, cannabinoids and phenibut) 5 seems particularly unwise as these may have similar effects to benzodiazepines. They may or may not help withdrawal but may also themselves result in dependence. Phenibut, a GABA agonist, in particular is known to cause physical dependence and withdrawal effects. 21 Carisoprodol (Soma), is metabolised into a barbiturate-like drug (meprobamate), which binds to GABAA receptors 22 and, like baclofen, a GABA analogue, 23 is associated with a withdrawal syndrome. Alcohol should be specifically avoided as it also interacts with GABAA receptors and can exacerbate withdrawal symptoms, sometimes to a surprising degree. 8