Comorbidities: Alcohol with Polydrug Use

The most common comorbidity for people diagnosed with an alcohol use disorder is another substance use disorder; such disorders occur seven times more frequently in this population than in the general population. The most common comorbid substance disorders for people with alcohol dependence typically involve the use of other sedatives such as benzodiazepines, cannabis, opioids; also stimulants like nicotine and methamphetamine. Accordingly, people presenting with alcohol use disorders should be screened for other substance use disorders.  

Having more than one substance use disorder increases risk to the individual and presents challenges for the treating clinician. The substances of greatest clinical significance in combination with an alcohol use disorder include:  

    • Tobacco smoking with nicotine dependence 
    • Pharmaceutical medication use, including those with adverse sedative interaction with alcohol such as benzodiazepines, gabapentinoids and antipsychotics like quetiapine  
    • Illicit drugs, including stimulants (e.g. methamphetamine) 
    • Opioids including analgesics and opioid agonist therapy. 

The use of two or more substances known to have “abuse liability” concurrently with hazardous, harmful or dependent alcohol use (with reference to the International Classification of Diseases 11) is described herein as “alcohol and polydrug use”. It is important to recognise that most patterns of polydrug use involve alcohol and that there are various patterns of polydrug use, some involving episodic use of one or more other substances and others involving dependence on one or more than one substance. Most people with an alcohol use disorder combined with polydrug use have comorbid mental health problems, including background trauma-related disorders (e.g., PTSD) and disorders of personality (e.g. borderline and antisocial traits/cluster B group). Further, people with alcohol use disorder and polydrug use, often acquire medical complications because of their chronic, high dose, multiple substance exposure history. This can include smoking related diseases, cognitive injury from recurrent intoxication and/or overdose, liver disease, hypertension and cardiovascular disease from heavy alcohol and stimulant use. Hence, this is a complex population to manage in which both physical and mental comorbidity is commonly encountered along with polydrug use.  

The motivation for polydrug use may be to control the level and the duration of intoxication. Alcohol use disorder with polydrug use, as behaviour, appears directed towards achieving enhancement of desired drug effect by concurrent use of multiple drugs sharing similar effects (e.g. accumulating sedative interaction). In the presence of mental comorbidity, intoxication may diminish distressing emotional experiences as discussed further in Chapter 21. Another sometimes observed behaviour is some people’s use of drug combinations with dissimilar effects in order to facilitate continued use of one or more substances. For example, combining stimulants like amphetamines with heavy alcohol consumption may result in reduced sedation from increasing alcohol intoxication effects, and thereby facilitate more drinking. 

Another factor can be substitution of alcohol with another drug/s or vice versa, particularly when access to supply of one or other substances is variable. Finally, a second drug may be used to assist recovery from intoxication. For example, a sedative might be taken to suppress the unwanted persisting effects of a stimulant. Alcohol interactions with other drugs may be related to pharmacokinetic, pharmacodynamic and metabolic mechanisms. For example, in the presence of alcohol, cocaine is metabolised to cocaethylene, a long acting active metabolite that is thought to contribute both to intoxication and toxicity including cardiovascular injury. 

Why do people take multiple drugs?
To control the level and the duration of intoxication
To enhance the desired drug effect by using drugs with similar effects (alcohol + benzodiazepines)
To reduce desired drug effect by using drugs with dissimilar effects to facilitate continued use (e.g., alcohol + stimulants)
To substitute another drug when access to another is limited
To help recover from intoxication (e.g., alcohol to mask the effects of a stimulant)

There is evidence of an increasing prevalence of alcohol use disorder within the ageing population (particularly amongst the 50 – 65 year old or “Baby-Boomer” cohort). This age group are also more likely to have used illicit drugs in the past, in contrast with previous generations. Further, an older population are more likely to be prescribed medications and have a high prevalence of polypharmacy. Several medications prescribed for the treatment of alcohol use disorder, with or without concurrent polydrug use, carry risk for adverse interaction. These possible interactions include naltrexone with opioid analgesics, disulfiram with warfarin, phenytoin, amitriptyline etc., and baclofen with benzodiazepines (latter sometimes prescribed for outpatient withdrawal treatment); also the latter two medications pose risk for adverse sedative interaction with alcohol (i.e., should a lapse to drinking occur while on such prescribed medications). Therefore, the possibility for adverse drug-drug interaction always needs careful consideration in individuals with alcohol use disorder and polydrug use and/or while receiving polypharmacy.