Naltrexone is a medication that interferes with the reinforcement mechanism of alcohol, and therefore with the reason why, at a neurological level rather than at the level of conscious effects, a person with alcohol dependence is driven to drink. Alcohol induces an “appetite” for itself: drinking makes one want to drink more, up to a certain point. This point varies in a controlled drinker, who can choose whether or not to become intoxicated, can want to experience the effects of alcohol or stop after a first drink. In a person with alcohol dependence, this mechanism is much more sensitive, and therefore the first drink brings another ten along with it. It matters little what the person’s intentions were, which obviously could not always have been to drink too much or to do so under any circumstances. Alcohol dependence is, in fact, a loss of control that occurs automatically. The medication intervenes in this process and attempts to restore control. It is not so much the effect of alcohol understood as a desired effect, but rather its reinforcing effect, which does not necessarily depend on a pleasant intoxication or on a useful effect. Like other substances, alcohol has the ability to drive a person to consume it again and to continue drinking even when intoxication is occurring and even when the person intends not to drink. Reinforcement is a “subliminal” mechanism that is not always linked to a desired effect.
Pathological craving for alcohol can also arise “cold,” that is, before the first drink. This may occur either because the person is urgently seeking some function of alcohol, or despite the intention to avoid drinking, independently of the reason the person may subsequently give for having drunk.
Naltrexone can also be used in people with alcohol dependence who are unable to stop drinking at the moment they seek help. This is true, but it requires some consideration. Medications for alcohol dependence start from the premise that, even if the person has stopped drinking, relapse will occur, and they use relapse as an opportunity to move the person away from a state of “loss of control.” Some treatments are started after a period of abstinence for technical reasons, and not because this is the general principle on which treatment for alcohol dependence is initiated. In the case of naltrexone, the person drinks, and as this happens, the desire to continue drinking beyond that point gradually decreases. Over time, this effect becomes increasingly consolidated, eventually keeping the person detached from alcohol and protecting them if they drink again because residual craving may reappear.
Naltrexone can also be used on an as-needed basis, only when the risk of relapse increases, by taking it before exposure to alcohol. This is true, but the same principle applies to naltrexone, so there is nothing fundamentally new about it. Moreover, it is not so simple for a person with alcohol dependence to understand how to use this approach: most people with alcohol dependence who are not drinking regularly try to control themselves, and when they fail, they have not taken the medication in time, before drinking. In trying to prevent relapse, in fact, one often fails to manage it effectively. The “as-needed” approach instead requires psychological preparation, through which the person stops trying to control relapse—something they cannot do—and instead focuses on how to manage it, which they can do. Managing relapse means knowing how to behave if it occurs and understanding that relapse begins with the desire to drink, even before drinking actually occurs. Thus, if the idea is to hold out until one drinks, on the assumption that drinking must not happen, one never succeeds in managing the relapse and, obviously, cannot prevent it either. If, instead, one avoids “holding out” under the illusion of having control or of being able to regain it alone—which is precisely what does not work in alcohol dependence—one can manage the first relapses and, over time, also prevent them through the use of medication.
These treatments have been shown to work better when the person is drinking and when psychotherapy is oriented toward relapse management rather than toward controlling craving. If no alcohol is consumed, treatment with naltrexone will work—but its effect will be assessable only later.
Naltrexone does not treat alcohol withdrawal syndrome. Therefore, starting this treatment while abruptly stopping alcohol consumption is both inappropriate and risky. It is risky because alcohol withdrawal must be treated and should not be left unmanaged. It is inappropriate because, if no alcohol is present, the mechanism of action of naltrexone is not being engaged; therefore, stopping drinking is not necessarily the first step, nor is it necessarily the appropriate first step for this type of treatment.
So how does naltrexone work? It acts through the brain’s opioid system, which naturally exists to transmit signals along specific neural circuits. These signals involve what are sometimes called “internal morphines.” More precisely, morphine, heroin and similar substances can be understood as the “external” versions of substances naturally present in the brain, although the endogenous substances act in a more controlled manner. Opioid antagonists block the action of both external and endogenous opioids. In the case of alcohol, there are two mechanisms. One is the more obvious one: alcohol stimulates the production of endogenous opioids, a mechanism through which alcohol is encoded as pleasurable and increases the desire to continue drinking. Opioid blockade interferes with the tendency to encode alcohol as pleasurable and with the tendency to persist in drinking once consumption has begun. This is not a dissociation between effect and behavior—that is, “I like the effect but I do not drink more.” Rather, it is an association between effect and behavior: “I do not drink more because the reasons I have for not overdoing it outweigh the desire I would otherwise have to continue drinking.” In other words, the ability to exercise control improves. This effect develops over time, and therefore relapses become progressively less frequent and progressively shorter.
Not all patients respond to this treatment. Not everyone manages to achieve complete control, but even partial control can lead to improvements in the management of one’s life.
The treatment program can begin in two ways: either with regular daily administration or on an “as-needed” basis. It is possible to begin with a period of regular administration and then move to the second approach.
“As needed” means when drinking is imminent. When a person with alcohol dependence, who is by then drinking very little, feels that the desire is increasing or notices that they are thinking about drinking and struggling to resist, there are two practical options. The first is to try to resist with all their strength, use distraction techniques, revive the memory of the negative consequences of the most recent drinking episodes—in short, try to prevent the drink from occurring. The second option is instead to abandon the mental effort to prevent the drink and prepare a shield against the drinking episode that may occur, so that it stops there and does not progress into a full relapse.
At least in people receiving treatment with opioid antagonists, the second method works better. Since a person with alcohol dependence essentially lacks control, when faced with the likelihood of relapse it is wiser to focus on how to manage it rather than on how to prevent it. Act with a shield rather than a sword. A person with alcohol dependence who adopts this approach carries the medication with them and, when they feel at risk of drinking, takes it, thereby reducing the likelihood of progressing to a full relapse after the first drink.
The most difficult part is getting the patient to adopt this way of thinking, because most patients believe that they must demonstrate control to others, that they must resist and succeed through their own efforts, or at least develop their willpower. This strength develops through controlled relapses—with the treatment in place—and does not develop through frustrating attempts to restrain oneself.
The first objective is to reduce severity: to prevent the situation from “degenerating.” The ideal objective is restoration of control, and this has a very different meaning depending on whether the diagnosis is alcohol dependence or alcohol abuse. In other words, it also depends on how much the person with alcohol dependence has come to “hate” the presence of alcohol in their life and on how much control they can exercise over it. Once control has been regained, it can be exercised according to what makes sense. In the case of alcohol dependence, control means maintaining abstinence, because a balanced level of alcohol consumption is no longer realistically possible.
The time required to obtain results is measured in months, with monthly or more frequent appointments to monitor the development of the situation. During the first few weeks, there may even be a temporary increase in drinking, or a return to drinking in someone who had stopped. This should not lead to premature conclusions, let alone to the belief that the treatment has failed in comparison with an attempt the person had already begun independently before seeing the doctor or after hospitalization. The results that matter are those observed over a period of time, not at the beginning, and they do not appear immediately. Whatever happens immediately, whether positive or negative, is not representative of the eventual outcome.
For this reason, appointments and therapy sessions are intended to support the person in carrying out the treatment correctly and also in understanding its progress and mechanisms as the treatment unfolds.