Opioid abuse affects about 0.4% of the world’s population in the age range of 15–64 years
]. Many of them are dependent on opioids and fail to complete opioid withdrawal. Standard treatment for these individuals is opioid substitution treatment (OST), also known as opioid maintenance treatment. However, opioid-dependence is often complicated with psychiatric comorbidity. In epidemiological studies, the joint lifetime prevalence of opioid dependence and non-substance-use psychiatric disorders has ranged from almost 50% up to 90%, while the current prevalence of mood, anxiety, or personality disorders is also high
]. Consequently, polypharmacy with psychoactive medication is a common practice in OST
]. While several studies have examined the cognitive performance differences between buprenorphine- vs. methadone-treated opioid-dependent patients
], few studies have examined the possible role of other psychoactive medications on the cognitive functioning of these patients. Thus, the results of current studies may not be fully appropriate for multidrug-treated patients. However, studies concentrating on this patient group would be important because opioid-dependent patients who are treated with multiple drugs tend to have lower quality of life than those who only use an opioid agonist drug
]. A recent study concerning cannabis-dependent individuals found that even relatively subtle cognitive deficits that were seen in test performance can be verified by those who know the affected individual well
]. Furthermore, at least for BZDs, even prescription drug use has been shown to be associated with serious health and safety risks
]. Thus, if a drug treatment variable is negatively associated with cognitive performance in OST patients this may have practical relevance.
Earlier we have reported that opioid-dependent patients treated with buprenorphine/naloxone along with BZDs do not show attention deficit as measured by reaction time tasks, but their working memory and verbal memory performance is worse than that of healthy controls, at least for the first six months in treatment
]. Patients treated with methadone along with BZDs show deficits in attention, working memory, and verbal memory. In our later study, OST drug group membership (buprenorphine vs. methadone) correlated significantly with attention performance and improvement in the Letter-Number Sequencing. Recent high-frequency substance abuse was associated with poor performance in working memory. Although the effects of the other two highest correlates were controlled for, many other variables could not be taken into account.
Our major aim in the current study was to examine the predictive power of drug treatment variables on specific cognitive performance measures in a naturalistic sample of multidrug-treated opioid-dependent patients. There is some evidence that short-term use of high dose methadone and BZD diazepam affects negatively on simple reaction times in opioid-dependent patients, but in buprenorphine patients only high diazepam dose affects negatively on reaction times
]. Therefore, we hypothesized that in buprenorphine patients, BZD treatment (use vs. non-use or dose) but not buprenorphine treatment variables (dose) would be negatively associated with attention performance; while in methadone patients both methadone and BZD treatment variables would affect negatively on attention performance as measured by reaction times. There is preliminary evidence that buprenorphine may preserve working memory performance better than methadone
]. Thus, we hypothesized that having buprenorphine as the OST drug would predict good working memory performance among opioid-dependent patients. It has been shown that long-term use of BZD drugs is associated with a wide range of cognitive deficits
]. Sedative and anticholinergic effects have been reported for various psychiatric drugs
]. Consequently, patients treated with several psychoactive drugs typically perform worse in cognitive tests than patients treated with a single drug
]. We therefore hypothesized that being on a BZD drug or on a high number of prescribed psychoactive drugs (other than opioid or BZD) would predict poor cognitive performance in all measures among opioid-dependent patients treated with buprenorphine or methadone.