EVIDENCE RELATING TO ADHD MEDICATIONS FROM PHARMACOEPIDEMIOLOGY STUDIES

Using population-based prescription databases, we conducted a comprehensive search without language constraints in PubMed and Embase for studies that looked into the relationship between ADHD drugs and behavioral or neuropsychiatric outcomes between January 1, 2008, and February 1, 2019. We combined phrases pertaining to ADHD, medicine, and data type. By adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement's standards, we were able to locate forty papers that met the criteria, covering ten distinct outcomes. We distinguished between short-term (like concurrent impacts) and long-term (like any prolonged or compounded effects) effects of medicine. Furthermore, we separated the results for the three main design/analytical approaches used to account for confounding: within-individual comparisons, propensity-score methods, and regression adjustment. Because within-individual comparisons are less influenced by unmeasured confounding, we summarized the results separately for those that used them.

Traumas and injuries

Eleven studies on traumas and injuries from Asia, North America, and Europe were found. Four of the six studies that looked at short-term impacts employed within-individual designs. Four investigations, three of which were within-individual studies, indicated a significant correlation between ADHD medication and a 9–32% lower risk of injury, with some evidence suggesting that the findings may vary by gender. Research examining stimulants and other ADHD drugs did not significantly differ from one another, and no studies examined the impact of non-stimulant medications in isolation.

Five out of the six studies that looked at the long-term impacts discovered a statistically significant negative correlation between the likelihood of injuries and taking an ADHD medication. A non-statistically significant negative correlation between medium or high and low treatment adherence was only found in one study. No within-individual design was employed.

Auto accidents

Two studies on auto accidents that we found both utilized within-individual designs, one from the US and one from Sweden. When assessing the short-term impacts, they found that male ADHD medication users had a 38–58% lower incidence of motor vehicle accidents. One study, however, found a non-statistically significant positive correlation in females, whereas the other found a comparable finding in females.

Additionally, a study employing a within-individual design discovered a correlation between the long-term use of ADHD drugs and a decreased incidence of motor vehicle accidents.

Instruction

We found seven studies from the US and Europe that looked at various elements of medicine use, such as when to take it, and how it affected test results, grades, and grade point average (GPA). Regarding immediate effects, two within-individual studies discovered a statistically significant correlation between ADHD medication and improved test scores and grades, while a third study discovered a non-significant mean difference between stimulant users who were currently taking them and those who had not.

Regarding long-term effects, one study discovered that those who started stimulant medication later than those who started earlier scored higher. Another study discovered that starting stimulant medication later than those who started earlier was linked to a higher risk of academic decline in mathematics but not in language arts. According to two studies, using ADHD medication consistently was linked to a higher GPA than receiving it inconsistently.

Criminal Activity

Two research on criminality were found. In one study, a within-individual design was used in Sweden. The study found no discernible difference between stimulants and atomoxetine, and that taking ADHD medicine was related with a 41% and 32% lower risk of crime in males and females, respectively. A long-term protective effect that was not statistically significant was also revealed by the study. The other study, which took place in Denmark, found that taking an ADHD medication was significantly linked to a lower chance of being found guilty and of going to jail.

Self-destruction

Five European and Asian studies that looked into self-harm, completed suicide, and suicide attempts were found. Two of the three studies that looked into short-term impacts used within-individual designs. Regardless of sex or medication type, none of these trials revealed evidence for an elevated risk of suicide episodes.

There was no proof of an elevated risk of suicidal episodes in any of the three long-term impact studies that looked into the matter. They all did not employ a within-individual design.

drug abuse disorders

Three studies on drug use disorder were found; two were conducted in Europe and one in the United States. According to two within-individual studies examining short-term effects, using ADHD medication was linked to a 27–35% lower risk of developing a drug use disorder.

Each of the three research looked into long-term impacts. A study that used a within-individual design discovered statistically significant negative correlations between the length of therapy and prior treatment. When comparing treatment to no treatment, the other two studies likewise found unfavorable relationships, though only one of them was statistically significant.

Depression

Two research on depression risk were found; one was conducted in Taiwan, and the other in Sweden. According to a study that used a within-individual design to examine short-term effects, using ADHD medication was linked to a 20% lower likelihood of unscheduled hospital visits because of depression.

Although neither study employed a within-individual design, they both examined the long-term impact of ADHD medication on depression and discovered a negative correlation.

Mania and bipolar illness

We found two studies, one from Taiwan and one from Sweden, on bipolar disorder/mania. The Swedish study was the only one to look at the short-term effects and the risk of mania among bipolar illness patients receiving stimulant medication using a within-individual approach. Within three months of starting medication, patients on methylphenidate monotherapy saw a higher incidence of manic episodes, according to the study. On the other hand, the rate of mania decreased in individuals on mood stabilizers after beginning methylphenidate.

The long-term effects of ADHD medication on mania and bipolar disorder (70) were examined in both investigations. The Swedish study discovered that the outcomes from 0–3 months were comparable to those from 3–6 months. According to a Taiwanese study, individuals who had taken methylphenidate for more than 365 days had a lower likelihood of receiving a bipolar disorder diagnosis than ADHD patients who had never used the medication. There was no statistically significant correlation seen between the short-term treatment and atomoxetine.

Insanity

Two studies on the likelihood of psychotic episodes were found. A Hong Kong study that used a within-individual design to examine short-term effects found no evidence linking stimulant use to psychotic episodes in people with a history of psychotic episodes.

The second study, conducted in Taiwan, looked at the long-term effects and discovered a positive correlation between stimulant usage and the likelihood of developing any psychotic disorders in people with ADHD, even if this correlation did not reach statistical significance when looking at schizophrenia as the primary outcome.

Convulsions

Five studies on seizures were found; two of them employed a within-individual design; four were from the US and one was from Sweden. Regardless of the kind of medicine, none of the five trials that looked at short-term effects showed any evidence of an elevated risk of seizures. Findings from within-individual studies point to a potential preventive short-term benefit of ADHD treatment for people with and without a history of seizures..

ESSENTIAL RESULTS AND LIMITATIONS

Within-individual designs have been used in an increasing number of pharmacoepidemiology research (18 of 26 studies) on short-term benefits and risk in order to account for confounding variables. Overall, the data point to a number of short-term advantages and few short-term hazards in terms of behavioral and neuropsychiatric outcomes. However, there is currently little evidence for a number of significant effects, necessitating replication. As a result, only injuries have been included in systematic reviews with enough data for meta-analyses of the short-term effects of ADHD medication, and these reviews have found that people with ADHD had a lower risk of injuries when using ADHD medication. Using the Newcastle-Ottawa Scale, the quality assessment of the included within-individual studies indicated good quality.Future within-individual research on the hazards and benefits of short-term interventions must take time-varying confounding limits into account. To be more precise, time-varying variables that influence people to begin or discontinue treatment may also alter their chance of certain outcomes, which would complicate within-individual relationships. Although they also depend on the assessment of time-varying confounders, a number of statistical techniques, including G estimation and the inverse probability of treatment weighting, have been proposed as suitable adjustments for time-varying confounding. Using negative controls to identify confounding bias is an alternate method. As a negative control, a medicine with prescription patterns comparable to the medication under study and no or very little causal impact on the result under study could be employed. SSRIs, for instance, have been utilized as a negative control in studies on ADHD drugs and auto accidents; however, due to the impact of SSRIs on the outcome, these studies would not be appropriate for studies on suicidality.

FINAL VERDICT

Existing pharmacoepidemiology research points to the short-term positive benefits of ADHD drugs on a number of behavioral and neuropsychiatric outcomes, as well as the absence of a higher risk of seizures or suicidality. Within-individual designs, also known as self-controlled designs, have been used in an increasing number of research to take indicator confounding into account. Additional noteworthy outcomes require replications. Less is known about the long-term impacts based on the pharmacoepidemiology investigations that have been conducted. When interpreting the findings of pharmacoepidemiology investigations, time-varying confounding and other constraints must be taken into account. It will be necessary to carefully balance the possible benefits of ADHD drugs against any potential drawbacks, such as side effects and social issues.