5. What do we know about withdrawal?

Drugs are foreign substances from the point of view of the body, and therefore the body tries to counteract their effects. This is sometimes referred to as the body ‘adapting’ to the presence of a drug. The adaptation can occur in a variety of ways. In the presence of a drug that reduces the activity of a neurotransmitter, like dopamine, noradrenalin or serotonin, the body may increase the number of receptors for the particular neurotransmitter, or existing receptors may become more sensitive. Such adaptations can mean that, over time, higher and higher doses are required to achieve the same drug effect, as is seen for example with benzodiazepines and alcohol. When this occurs, the individual is said to have developed ‘tolerance’ to the effects of the drug.

If the drug is stopped then the body’s adaptations are suddenly unopposed by the presence of the drug, and they give rise to withdrawal symptoms. For example, people taking dopamine receptor-blocking drugs such as antipsychotics will manufacture more dopamine receptors in their brains, and those receptors that already exist will change and become more sensitive to dopamine. This is the body’s way of trying to increase the activity of dopamine despite the presence of a chemical that tends to reduce its activity. When the drug is stopped, these extra dopamine receptors will still be present, and may increase the activity of dopamine above normal levels until they reduce back down to normal numbers.

Usually the body’s adaptations disappear gradually when the drug is no longer present, and the withdrawal reactions subside. However, we know very little about the body’s response to long-term drug consumption and how the body reacts to the withdrawal of such consumption. It is possible that the adaptations sometimes persist or that it can take a long time for them to revert to normal. Even relatively shorter-term treatment can result in adaptations and resulting symptoms persisting a long time.

For example, we know that the abnormal movements of tardive dyskinesia, a potential effect of long-term antipsychotic use, often get worse when antipsychotics are reduced or stopped. This is likely to be mediated by the increased numbers and activity of dopamine receptors. Sometimes the movements improve with time as the body readjusts to the fact the drug has been stopped. However, sometimes they are permanent, implying that the adaptation of the body’s dopamine system to the presence of antipsychotics can be irreversible. Something similar may be occurring after discontinuation of benzodiazepines or antidepressants, when, in some cases, withdrawal reactions last for long periods.

Most psychiatric drugs affect a range of different brain chemicals or neurotransmitters, and withdrawal effects can reflect the drug’s impact on any of these chemical systems. Withdrawal reactions themselves may be mild and annoying, they may be unpleasant and sometimes they are unbearable. In addition, withdrawal from sedative drugs often causes agitation and insomnia, which can easily be mistaken for early signs of relapse. When drugs have been taken for a long time, such as several years, it is possible that the body will take a considerable time to readjust and withdrawal reactions may go on for some time.

Often the worst withdrawal effects are experienced at the end of the withdrawal process, when dosage has been reduced to almost zero. It has been suggested that repeated attempts at withdrawal may result in what is known as the ‘kindling’ effect where neuronal hypersensitivity results in the progressive worsening of withdrawal symptoms at each subsequent withdrawal episode. It is reported that this can also happen when drugs are reinstated. Therapists should also be aware that withdrawal reactions are not limited solely to during or immediately after the withdrawal process but may last over a period from six to 18 months, and in some cases, several years.

Withdrawing from psychiatric drugs has some similarities to giving up recreational drugs. For example, people may become dependent on psychiatric drugs in both physical and psychological senses as they do with drugs of misuse. One clear difference is that recreational drugs have effects that are pleasurable, and so people crave the drug when they stop taking it. In contrast, people do not usually crave the effects of drugs such as antipsychotics or antidepressants, since these do not cause euphoria. People can, however, have strong beliefs about what such drugs do for them and may become anxious if they withdraw from them. As anxiety can occur as a withdrawal reaction it may not be possible to tell such feelings apart until withdrawal is complete. The danger is that any anxiety may be mistaken for a relapse of the original condition – see 5.4.2 for further discussion of this.

In general, if a drug is stopped suddenly the withdrawal reactions will be more intense than if a drug is gradually reduced, when the withdrawal reactions will usually be less intense, and may not even be noticed by some people. Withdrawal is also generally easier if someone has only been taking the drug for a short period. The way the body reacts is not predictable, however, and therefore withdrawal reactions can sometimes still be severe in cases where the drug is gradually reduced and only taken short-term. Given this it is usually recommended that people taper medication slowly and do not stop abruptly.

Different drugs differ in their ability to cause withdrawal reactions. ‘Short-acting’ drugs that act quickly and are rapidly eliminated from the body cause more intense withdrawal reactions than ‘long-acting’ drugs that stay around in the body for longer. The rate of elimination of a drug is measured in what is called its ‘half-life’. A half-life means the time it takes for the concentration in the body to decline by half. Drugs with a short half-life are eliminated rapidly, while drugs with a long half-life remain in the body for longer.

Heroin, for example, has a short half-life and causes more reactions after stopping than methadone, which has a long half-life. This is the principle behind the practice of prescribing methadone to people who are dependent on heroin to help them withdraw. The antidepressant fluoxetine is another example of a drug with a long half-life. It is eliminated from the body slowly over a period of weeks. Therefore, its effects generally wear off more gradually following cessation than those of drugs with a shorter half-life. In contrast, drugs such as the benzodiazepine lorazepam, antidepressant paroxetine and antipsychotic clozapine are eliminated rapidly from the body – they have short half-lives. That is why you must take repeated doses of them every day to get an even amount of the drug in the body over a daily period. These drugs cause more intense withdrawal reactions when stopped.

When embarking upon any account of how therapists may best support clients either withdrawing or considering withdrawing from psychiatric drugs, we encounter a number of immediate obstacles:

• In the first place, beyond the considerable work undertaken on benzodiazepine withdrawal, it is widely acknowledged that research into antipsychotic and antidepressant withdrawal is comparatively limited. One of the major outcomes of the recent antidepressant withdrawal debates¹ was that numerous admissions made by mainstream psychiatry showed serious gaps in our understanding of withdrawal. It also showed that established thinking on withdrawal (captured by NICE guidelines) is in significant need of revision (a revision which, as we mentioned in the introduction to this guidance, has now taken place).
• While the prescribing professions still have much work to do in deepening our understanding of withdrawal, research into how therapists may best support clients either in or considering withdrawal is even more sparse.

What is therefore offered in this section is largely derived from the combined experience of those who have worked directly with people withdrawing from psychiatric drugs. Although more research on such practices is still needed, experiential knowledge of successful withdrawal management has become sufficiently comprehensive to merit providing a picture of what we know, to date, works best.

This section will first summarise broadly what is known about withdrawal from each class of psychiatric drug, paying especial attention to the incidence, severity and duration of withdrawal. Finally, some background information regarding the medical management of the withdrawal process is provided alongside the definition of key terms.