Influence of inpatient withdrawal treatment on drug safety in alcohol use disorders – a quasi-experimental pre-post study | BMC Psychiatry

The present study examined the influence of inpatient withdrawal treatment on the prevalence probability and characteristics of pAMIs and pDDIs in general in patients treated for AUD over a period of one year in the addiction ward of a university hospital in Germany. Two different tools were used to detect potential drug interactions, namely the Drugs.com classification for pAMIs and the interaction program AiDclinic^® for the detection of pDDIs. To our knowledge, this is the first study to apply the Drugs.com classification to patients with AUD and examine the impact of inpatient withdrawal treatment on the risk of pAMIs.

Our study population differed from previous studies in terms of age, gender, and comorbidity profiles [19,20,21]. The average age of our study population was 47 years and the most common psychiatric diagnosis, other than alcohol use disorder, was depression. Previous studies have examined the prevalence and characteristics of pAMIs in the general population [14, 17]. These studies consistently show that a significant proportion of people are prescribed medications that may interact with alcohol [14, 17]. The prevalence of such prescriptions varies greatly, ranging from 13 to 42%, which is likely due to different study designs and settings [14, 17]. The most commonly prescribed medications associated with pAMIs include benzodiazepines, antipsychotics, and medications used to treat cardiovascular disease [14, 17].

Many studies have examined the characteristics of pAMIs in geriatric populations [22,23,24,25]. A systematic review by Holton et al. reported that 21–35% of older adults may be affected by pAMIs [20]. Furthermore, Schröder et al. (2024) identified potentially significant interactions between alcohol and prescribed medications in over 80% of a cohort of geriatric inpatients with AUD [21].

In the present study, inpatient withdrawal treatment appeared to increase the risk of patients experiencing at least one pAMI.

For severe pAMI, the most commonly prescribed medications before withdrawal treatment in our population were buprenorphine, gabapentin, and metformin. After withdrawal treatment, buprenorphine, gabapentin, and metformin were the most commonly prescribed medications. Opioid prescriptions are common in patients with AUD, often as medication for a co-existing opioid use disorder or for analgesia [26]. In our study, 11.5% of patients had opioid use disorder. Jobski et al. (2015) reported common pharmacokinetic interactions between orally administered opioids and alcohol, leading to a significant increase in ADR incidence, highlighting the clinical relevance of this combination [27]. Taking gabapentin with alcohol appears to increase the risk of tachycardia [28]. In addition, prescribing biguanides such as metformin in patients with AUD significantly increases the risk of potentially fatal lactic acidosis and is therefore contraindicated [29, 30].

For moderate pAMIs, ramipril, insulin, and levetiracetam were the most commonly prescribed medications before withdrawal treatment. After withdrawal treatment, ramipril, mirtazapine, and insulin were the most commonly prescribed medications. Alcohol consumption can acutely lower blood pressure and, when combined with antihypertensive medications such as ramipril, increases the risk of hypotension, which can lead to serious falls [31]. Hypoglycemia is not uncommon in patients with AUD who are treated with insulin due to poor nutritional status or impaired liver function, so any prescription of glucose-lowering medications should be carefully considered [32]. Patients with AUD are at increased risk of withdrawal seizures. However, long-term prescription of antiepileptic drugs without a formal epilepsy diagnosis should be critically evaluated due to the lack of regulatory approval [33]. In particular, levetiracetam, although commonly prescribed, is not suitable for long-term treatment of AUD because it may increase alcohol consumption [34]. The frequent prescription of mirtazapine after withdrawal treatment may be due to the many psychiatric comorbidities in this population. Mirtazapine, a sedating antidepressant, has side effects that are increased by alcohol, although the exact mechanisms are still poorly understood [35].

For mild interactions before withdrawal, quetiapine and abacavir were the most commonly prescribed medications. After withdrawal, the prescriptions remained the same: quetiapine and abacavir. The sedative effects of quetiapine may produce synergistic effects when taken with alcohol [36]. Abacavir is metabolized by alcohol dehydrogenase, resulting in reduced formation and elimination of its metabolites in patients with hepatic impairment. Therefore, it is contraindicated in patients with moderate to severe hepatic impairment, which is common in patients with AUD [37, 38].

The results of our study suggest that a significant proportion of medications prescribed to patients with AUD should be critically evaluated. Although the Drugs.com classification system was not specifically designed for patients with AUD, it may be a valuable tool for improving medication safety in this population. Using Drugs.com's classification criteria can provide a comprehensive evaluation of prescribed medications for patients with AUD. This process requires a thorough analysis of the benefits and risks of each medication, as well as careful consideration of alternative pharmacological and non-pharmacological options.

Inpatient withdrawal treatment appeared to increase the risk of patients being affected by at least one pDDI (P21].

In our study, chlorthalidone + ramipril and ramipril + spironolactone were the most common serious pDDIs before withdrawal treatment. After hospitalization, ramipril + spironolactone and chlorthalidone + ramipril were the most common serious pDDIs. Despite the relative safety of many antihypertensive drugs, they still account for a significant number of DDIs and ADRs [39]. When combining spironolactone and ACE inhibitors, attention should be paid to the increased risk of hyperkalemia [40]. In patients with volume depletion, which is particularly common in alcohol dependent individuals, the use of thiazide(-like) diuretics such as chlorthalidone may worsen this condition [41]. When used concurrently with ACE inhibitors, this combination may result in an excessive fall in blood pressure and symptomatic hypotension [42].

In moderate pDDIs, the combination of acetylsalicylic acid + ramipril was the most commonly observed combination before withdrawal treatment. After hospitalization, this combination remained the most common moderate pDDI. There is evidence that acetylsalicylic acid reduces the improvement in glomerular filtration and renal plasma flow induced by ACE inhibitors and should therefore only be prescribed under close monitoring of renal function [43].

Levodopa + olanzapine was the only contraindicated combination prescribed both before and after withdrawal treatment. In patients with movement disorders treated with levodopa, olanzapine has such a negative effect on motor symptoms that its use is contraindicated [44].

In conclusion, our study found that after inpatient withdrawal treatment, a significantly higher proportion of patients with AUD were treated with medications that may interact with alcohol or other drugs. The use of drug assessment tools such as the Drugs.com classification and the AiDclinic^® The interaction program appears to be useful in clinical practice to improve medication safety in patients with AUD. A disadvantage of these medication assessment tools is that they are not specifically designed for patients with substance use disorders. The Drugs.com classification and the AiD are noteworthyclinic^® The interaction program does not suggest more suitable (non-)pharmacological alternatives.

One might question the choice of drugs examined in our study. The medications were taken from patient prescriptions before and after inpatient treatment. The therapeutic goal is to achieve alcohol abstinence after qualified withdrawal therapy, so that theoretically no interactions between alcohol and medication should occur after discharge from the hospital. Unfortunately, a relapse into alcohol consumption after release is not uncommon; Therefore, alcohol-drug interactions represent a relevant problem in clinical practice that should be appropriately addressed by healthcare providers [45].

Limitations of our study are the monocentric design and the setting in a highly specialized department of a university hospital; Therefore, our results may not be fully applicable to other healthcare settings. Furthermore, due to the design of our study, we were unable to investigate whether the pAMIs or pDDIs detected in our study population actually led to the occurrence of adverse events. Future research should focus on analyzing the true risk of adverse outcomes associated with pAMIs and pDDIs in patients with AUD. This will help healthcare professionals stratify patients with AUD according to their individual risk profile at the time of prescription.