Data Based Medicine Paper: Dependence and Withdrawal

Transcription

1 Data Based Medicine Paper: Dependence and Withdrawal Author: Dr. David Healy Date Last Revised: 7 June 2012 Contents TREATMENT GROUPS... 2 DRUG GROUPS... 2 ALL DRUGS ACT ON EVERYTHING... 3 DRUG WITHDRAWAL IS NEVER IN THE MIND... 3 STRESS SYNDROMES... 3 Drug withdrawal may involve rebound effects... 3 Drug withdrawal may involve legacy effects... 4 Drugs withdrawal may involve stress effects... 4 Drugs can have lithium- like effects on the underlying illness... 4 Drugs can have catastrophic effects... 4 IS THIS WITHDRAWAL?... 4 DBM: TERMINATOR ALGORITHM... 5 PROMINENT WITHDRAWAL SYMPTOMS... 6 HOW TO WITHDRAW... 7 Simple taper... 8 The reduced potency approach... 8 The half- life approach... 8 Tapering steps... 8 PREGNANCY... 9 COMPLEXITIES OF WITHDRAWAL... 9 OTHER TREATMENTS Liquids In the UK In the US In Canada Elsewhere Copyright 2012 Data Based Medicine Americas Ltd. Page 1 of 10

2 Dependence and Withdrawal The commonest queries to RxISK have been about dependence on and withdrawal from a range of drugs, from statins to anticonvulsants. There are a number of principles that can be outlined to cover the management of these various conditions. Treatment groups Within each apparent treatment group, there may be a number of drug groups. Thus within the antihypertensives, there are thiazides, beta- blockers, ACE- inhibitors and others. When asking the question about dependence, we need to ask do beta- blockers cause dependence and withdrawal rather than do antihypertensives cause withdrawal. This is also important because some drug groups may be used for a few different reasons; thiazides are used for hypertension and heart failure and if they cause withdrawal for one use they are likely to cause it for others also. The mood- stabilizers break- down into at least 3 different drug groups antipsychotics, anticonvulsants and lithium. The anticonvulsants in turn break down into 4 groups - sodium channel blockers, drugs that act on the GABA system, carbonic anhydrase inhibitors and at least one more group with an unknown mechanism of action. The antidepressants include five groups: serotonin reuptake inhibitors, norepinephrine reuptake inhibitors, receptor blockers, monoamine oxidase inhibitors and others. We need information on and strategies specific to each drug group. Drug groups If a drug group is linked to withdrawal problems, there are likely to be some drugs within the group that are worse than others. In the case of sodium channel blockers lamotrigine appears to be the worst In the case of antipsychotics clozapine, olanzapine and trifluoperazine are much worse than haloperidol or sulpiride. Denial is not helpful. Until the pharmaceutical industry and academia concede there can be problems it is difficult to investigate agents and find out which is the worst and why. If companies ever offer explanations it is usually in terms of the half- life of the drug. Drugs with a short half- life supposedly cause more problems than those with a long half- life. This is almost certainly not the explanation in most cases. Copyright 2012 Data Based Medicine Americas Ltd. Page 2 of 10

3 All drugs act on everything It should be assumed that all drugs act on everything. There is a myth that SSRIs act on the brain only when in fact 95% of our serotonin lies outside our brains. Similarly most of our cholesterol and lipids are in our brains rather than in our blood. It is good marketing that gets us to think that cardiac drugs aren t also altering our behavior. The effects of stopping drugs may arise from areas other than the brain. Some of the most distressing effects of drug withdrawal even ones that appear to come from the head in all likelihood do not come from the brain. In the case of antidepressants, dizziness likely arises from the inner ear and a variety of head zaps and other disturbances come from the blood vessels to the scalp, eyes and other areas of the head. Drug withdrawal is never in the mind There is a common assumption that drug withdrawal is a mental phenomenon and can be treated with psychotherapy. A behavioral activation program or physiotherapy may be appropriate but sitting down to talk through your problems with someone is more likely to make things worse. Motivational interviewing can do something to establish whether someone is willing to face the difficulties of withdrawal. Stress syndromes Drug withdrawal arises after the medicine has produced a change in the body aside from its effect on the illness. The medicine induces what has been called dependence but might be better called a stress syndrome There are the classic withdrawal problems linked to alcohol, antidepressants, opiates, antipsychotics, benzodiazepines and anticonvulsants, but also comparable problems arise with steroids, statins, many antihypertensives and other medicines. These withdrawal problems are likely a combination of rebound, stress and legacy effects. Drug withdrawal may involve rebound effects Rebound effects happen with beta- blockers given for heart failure, hypertension or other reasons and lead to increased heart rates and hypertension on stopping. Beta- agonist inhalers for asthma almost certainly lead to an increase in wheezing on treatment that persists after treatment stops. Copyright 2012 Data Based Medicine Americas Ltd. Page 3 of 10

4 Rebound effects also happen with SSRIs, aspirin and statins leading to increased clotting (thrombosis) rates on rebound. Rebound effects are time limited manifestations of a stress syndrome Drug withdrawal may involve legacy effects The thiazide diuretics can lead to enduring acidosis after stopping. Oral contraceptives can lead to a failure of ovulation after stopping. SSRIs can lead to persistent sexual dysfunction after stopping Biphosphonates leave bone architecture altered for years after stopping Drugs withdrawal may involve stress effects These are the states of long- lasting motor and stress disturbances that may emerge first while on treatment but are most obvious after stopping it. The best known are tardive dyskinesia and tardive dysthymia. Drugs can have lithium- like effects on the underlying illness Stopping Lithium can precipitate a new episode of a mood disorder, either mania or depression earlier than it would have otherwise happened. It is difficult to characterize this effect other than as an effect on the underlying illness. While lithium is normally prophylactic, it may convert some people into having much more frequent episodes than they would otherwise have. Drugs can have catastrophic effects There are a small number of people who have a severe syndrome with neurological and other features that may start within weeks of starting almost any drug. Even if only exposed to these drugs for a few weeks, the aftereffects may endure for months or years. Is this withdrawal? There are three ways to distinguish drug dependence and withdrawal from other problems an illness or drug may cause. 1. If the problem begins immediately on reducing or halting a dose or begins within hours or days or perhaps even weeks of so doing then it is more likely to be a withdrawal problem. If the original illness has been treated and you are doing well, then on discontinuing treatment no new problems should show up for several months or indeed years. Copyright 2012 Data Based Medicine Americas Ltd. Page 4 of 10

5 2. If the difficulties that appear on reducing or halting the drug clear up when you are put back on the drug or the dose is put back up, then this also points towards a withdrawal problem rather than a return of the original illness. When original illnesses return, they take a long time to respond to treatment. The relatively immediate response of symptoms on discontinuation to the reinstitution of treatment points towards a withdrawal problem. 3. While the features of withdrawal may overlap with some of the features of the problem for which you were first treated, withdrawal will also often contain new features not in the original state such as pins and needles, tingling sensations, electric shock sensations, pain and a general flu- like feeling. Before starting to withdraw, it should be noted that many people will have no problems on withdrawing. Some will have minimal problems, which may peak after a few days before diminishing. Symptoms can remain for some weeks or months. Others will have greater problems. Yet others will have problems that wax and wane and this waxing and waning can be confusing Finally however there will be a group of people who are simply unable to stop whatever approach they take. Some others will be able to stop but will find problems persisting for months or years afterwards. It is important to recognise this latter possibility in order to avoid punishing yourself. Specialist help may make a difference for some people in these two groups, if only to provide possible antidotes to attenuate the problems of ongoing SSRIs such as loss of libido. DBM: terminator algorithm On the RxISK.org site we ask and score a series of questions to see if your problem might be linked to stopping a drug. These are the questions. 1. Are there previous reports of withdrawal effects from this drug in the manufacturer s literature, FDA database, or RxISK database? 2. Did you reduce the dose of the drug? Did the problem start before or after reducing? 3. Was the problem different to your original condition? 4. Did you stop the drug? Did the problem start after stopping? 5. Did you restart the drug? Copyright 2012 Data Based Medicine Americas Ltd. Page 5 of 10

6 Did the problem clear up? 6. Did you increase the dose of the drug? Did the problem improve? 7. How soon after restarting the drug or increasing the dose did the problem improve? 8. Did you try a related drug? Did the problem clear up? 9. Have you ever had withdrawal effects before on another drug? Was it on the same type of drug? 10. Have you had other drugs of the same type as this? Did you have a similar withdrawal effect on them? 11. Could anything else be causing this event? A score of: 9+ points strongly to a linkage points to a linkage suggests not enough information to confirm a linkage 0 at present unlikely to be a withdrawal effect Prominent withdrawal symptoms Different drugs will lead to a different profile of symptoms but many drugs will lead to some combination of the following which are found in both SSRI and benzodiazepine withdrawal. Symptoms unlike anything you have had before: Dizziness when I turn to look at something I feel my head lags behind. Electric head - which includes a number of strange brain sensations its almost like the brain is having a version of goose pimples Electric shock- like sensations zaps like being prodded with a cattle prod Other strange tingling or painful sensations Nausea, diarrhoea, flatulence Headache Muscle spasms/ tremor Dreams, including agitated dreams or other vivid dreams Copyright 2012 Data Based Medicine Americas Ltd. Page 6 of 10

7 Agitation Hallucinations or other visual or auditory disturbances Sensitivity to noises or visual stimuli Symptoms that may lead you or your physician to think that all you have are features of your original problem. These include: Depression and Anxiety these are the commonest withdrawal symptoms Labile Mood emotions swinging wildly Irritability Confusion Fatigue/ Malaise Flu- like Feelings Insomnia or Drowsiness Sweating Feelings of Unreality Feelings of being Hot or Cold Change of Personality An intolerance of stress. How to withdraw If there are any hints of problems on withdrawal from any drug, you may wish to show this to your doctor. Over- rapid withdrawal may be medically hazardous, particularly in older persons. Faced with hints of a withdrawal problem, many doctors suggest you withdraw by taking one pill every other day for a few weeks before stopping. This is a recipe that will usually make things worse. The first principle behind withdrawal is tapering. Tapering can be done from 10 pills per day to 1 or less but is difficult to do if you are only on 1 or 2 pills to begin with. The first step to consider is getting a liquid formulation of your medicine. This can be done by asking your doctor or local pharmacist who can make an application to one of the specialist companies that can make up a liquid formulation of almost any medication you might be on see below. There are three different approaches to tapering. 1. One approach hinges on the widely held idea that withdrawal problems are commoner in short half- life drugs. This leads to a withdrawal strategy that advocates switching Copyright 2012 Data Based Medicine Americas Ltd. Page 7 of 10

8 from short- acting to long- acting drugs. In the case of the antidepressants, this means switching from paroxetine to fluoxetine for instance. 2. The second approach hinges on the likelihood that it is potency of the problem drug that is the problem and a first step might be to switch to a less potent drug from the same class. This might lead for instance to a switch from lorazepam to chlordiazepoxide for instance or from an SSRI to imipramine of a serotonin reuptake inhibiting antihistamine like chlorpheniramine. This is more likely to be a better approach than the short half- life approach in most cases, although they will sometimes amount to the same thing. 3. The third approach hinges on the hunch that the dependence and withdrawal problems stem from another action that the drug has rather than its primary action. For instance the antipsychotics that have the worst withdrawal profile also block calcium channels and accordingly a calcium channel blocker may offer relief. All of these approaches are facilitated by having access to treatment in liquid form. If you are having problems you should insist on access to the liquid form of the drug you are on. Simple taper Convert to a liquid form of the drug you are on. In the initial weeks of treatment you can reduce by a quarter of your current dose every week or two. See schedule below. The reduced potency approach Taking this approach, the best option is to change to a liquid form of a related drug or a combination of your original drug and the related drugs and slowly switch from the original to the related drug. Your pharmacist will be able to suggest related drugs. The half- life approach Convert the dose of the drug you are on to the equivalent dose of a long- acting related drug ideally in liquid form. Your pharmacist will be able to help you with this. Again you can combine both short and long acting drugs initially while switching from one to the other. One drawback to both the reduced potency and half- life approach is that switching to a new drug may cause its own problems. If new problems emerge on switching you may need to go for simple taper of the liquid form of your original treatment. Tapering steps 1. Stabilise on one of these options for up to 4 weeks before proceeding. Copyright 2012 Data Based Medicine Americas Ltd. Page 8 of 10

9 2. For uncomplicated withdrawal, it may be possible to then drop the dose by a quarter of the original. 3. If there has been no problem with step 2, a week or two later, the dose can be reduced to half of the original. 4. Alternatively if there has been a problem with the original drop, the dose should be reduced by 1 mg amounts in weekly or two weekly decrements. 5. At the lowest dose levels, consider reducing by 1mg every week over the course of several weeks or months. (A syringe is helpful in reducing the dose evenly). 6. If there are difficulties at any particular stage the answer is to wait at that stage for a longer period of time before reducing further. Pregnancy The single most important group who need to be aware of all these issues are women of child- bearing years. A very large number of pregnancies happen in an unplanned fashion and are several weeks advanced before the woman is aware of the situation. An increasing number of drugs are now linked to problems in pregnancy, among which are an increased frequency of birth defects, an increased rate of miscarriage, premature birth, low birth weight, neonatal withdrawal problems and other difficulties in the newborn infant. Complexities of withdrawal Withdrawal and dependence are physical phenomena. You may feel anxious but psychotherapy or cognitive therapy will not help this anxiety. Some people get phobic about withdrawal particularly if the experience is literally shocking. Behaviour therapy may be able to help you to manage any phobic element. Self- help support groups can be invaluable. Join one. If there is none nearby, consider setting one up. There will be lots of others with a similar problem. If withdrawal problems appear to ease off and then come back, it is worth checking whether this is because you have co- incidentally been treating yourself with something related to what you were on. For instance St John s Wort or an antihistamine may inhibit serotonin reuptake. In the case of enduring problems, being active is important. An enduring problem is likely to be underpinned by some physical changes in the brain and elsewhere in the body. Gentle but regular exercise and involvement in social activities rather than withdrawal may compensate for this. Copyright 2012 Data Based Medicine Americas Ltd. Page 9 of 10

10 If it seems impossible to withdraw, one option is to stabilise on the lowest dose of the treatment you are on. Other treatments There can be a range of other drugs that may help such as the triptans for SSRI withdrawal, calcium channel blockers for antipsychotic withdrawal and other drugs. See the specific withdrawal protocols for each drug group. Liquids In the UK 1. Rosemont Pharmaceuticals (Tel ) 2. Cardinal Health, Martindale (Tel ) 3. Large chain pharmacies like Boots. In the US Please help us by sending us details. In Canada Please help us by sending us details. Elsewhere Please help us by sending us details. Copyright 2012 Data Based Medicine Americas Ltd. Page 10 of 10