ABSTINENCE OR MAINTENANCE TREATMENT IN SUBSTANCE USE DISORDERS? (Addiction, 2016)
Autoren: Marc Walter & Michael Soyka
(pp, 16.07.2016)
Hier handelt es sich um einen Kommentar von Walter & Soyka zu einer Veröffentlichung von Darke & Farrell (Addiction, 2016), in der Letztere die medikamentöse Behandlung der Alkoholkrankheit mittels Agonisten anzweifeln.
Struktur des Inhalts
Kommentar zum Text von Darke & Farrell (Addiction, 2016)
Agonist maintenance treatment may not be suitable for all drugs of abuse. A favourable agonist maintenance treatment requires good pharmacological potential, as well as suitable clinical and neurocognitive characteristics.
Darke & Farrell [1] propose several criteria for agonist maintenance treatment, including the most frequently abused substances, such as opioids, nicotine, benzodiazepines, cannabis, psychostimulants and alcohol. According to their analysis, opioids and nicotine meet the criteria sufficiently for amaintenance drug,whereas psychostimulants and alcohol do not. The major clinical concern for maintenance treatment is the toxicity of stimulants and alcohol.
Stimulant use may actually increase anxiety and depression, and toxic reactions (e.g. cerebrovascular disorders) can occur, irrespective of the dose and frequency of use or route of administration. In acute alcohol intoxication, higher alcohol levels are related to cognitive decline, disinhibition and negative emotional states. Moreover, alcohol use has numerous physiological consequences, including chronic liver, cardiovascular and pancreatic disease and neuronal atrophy [1].
However, all these criteria regarding the different substances are based clinically, and ‘to some degree…subjective’. Moreover, there is a lack of possible future directions for the agonist maintenance treatment.We offer some comments. Last week, a colleague from internal medicine asked why we do not give alcohol as a substitution treatment for chronic alcoholics when we already give heroin to drug addicts. It was a somewhat ironic statement after a presentation of different maintenance treatment strategies in opioid use disorders. The answer was that this difference — abstinence or maintenance — is mainly for pharmacological reasons. One drug or medication has good potential, whereas another drug does not.
As the term implies, substitution or agonist maintenance treatment means that a pharmacologically similar agent is substituted for the abused substance. From a pharmacological perspective, there are three major strategies to stop or reduce intake of drugs of abuse: antagonism or blockade of rewarding effects (naloxone, naltrexone) or reducing tolerance (disulfiram), vaccination against the drug or ‘substitution’ of its effects by a less harmful drug. Of course, abstinence is always an adequate strategy and usually preferred for patients suffering from severe substance use disorders and, in most cases, better than ongoing and long-term substitution with addictive drugs and possible side effects. However, abstinence in alcohol or drug use disorders is often not a realistic treatment goal, irrespective of the specific substance.
It is well known that the goals for the treatment of substance use disorders include preventing harm associated with substance use, preventing withdrawal symptoms and reducing craving and compulsive substance use. In general, any suitable pharmacotherapeutic agent should be orally effective, and should have slow onset, long duration and slow termination of action [2]. The positive effects of this approach on patients’ health and delinquency (oral medication, longer half-life), have led to growing acceptance of the maintenance concept for opioid use disorders. In 2005, the World Health Organization (WHO) included methadone and buprenorphine in the list of essential medicines [3] for the maintenance treatment of opioid addiction, and later combined evidence-based recommendations for best practice in opioid maintenance treatment, with a range of recommended minimum requirements [4].
Continued clinical research has revealed that maintenance treatment possesses positive long-term effects. This is the case not only for methadone and buprenorphine, and recently morphine sulphate, but also in the latter case for diacetylmorphine, particularly for treatment-refractory heroin-dependent patients [5]. Maintenance treatment with methadone, buprenorphine and diacetylmorphine has now been integrated fully into the addiction treatment system in Switzerland (by public vote) and other European countries [6].
Why we do not try to substitute other agonists in patients with severe substance use disorders? This could be especially helpful in those substance use disorders where no evidence-based pharmacotherapeutic agents are available, for example, in stimulant use disorder [7]. It has been shown that methylphenidate, when used as a stimulant medication, might have potential as a treatment for cocaine addiction. However, current evidence for the use of methylphenidate in the treatment of cocaine abuse is still weak, especially as controlled studies have failed to find significant benefits in reducing cocaine use compared to placebo [8]. In contrast to methylphenidate, cocaine and other stimulants achieve their effects by affecting a variety of different neurotransmitters, including serotonin and noradrenaline. Thus, methylphenidate is similar to cocaine, but is not a real cocaine agonist.
Similar considerations apply to alcohol substitution. We wonder about the negative prospects in this area anticipated by Darke & Farrell [1]. Clearly, there is no direct alcohol agonist, probably because there is no single alcohol receptor and alcohol has a complex molecular mechanism of action, basically via different low-affinity biding sites. Interestingly, baclofen, which is viewed by some as a partial substitution for alcohol use disorder, acts as a gamma-aminobutyric acid class B (GABA-B) receptor agonist. Some studies gave only mixed results compared to placebo [9]. Recently, however, baclofen has shown longer abstinence duration in a randomized controlled trial [10].
The drug has already been introduced into clinical practice in France and can very well be viewed as a partial agonist for the effects of alcohol. To conclude, the agonist maintenance treatment may not be suitable for all drugs of abuse. A favourable agonist maintenance treatment requires good pharmacological potential, as well as suitable clinical and neurocognitive characteristics. Effective pharmacological agents should be combined with effective psychosocial and psychotherapeutic treatment options in order to improve the therapeutic outcome of our patients. In most cases, improvement means good quality of life, good psychosocial functioning and a reduction in substance use.
