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13 Feb 2021

Schiweck C et al. Neurosci Biobehav Rev 2021; 124: 100-123

There is a high degree of comorbidity between ADHD and bipolar disorder. The aim of this study was to perform a systematic review and meta-analysis of the available literature to determine the degree of comorbidity between ADHD and adult bipolar disorder.

To perform the systematic review, databases PubMed and World of Knowledge were used to search for relevant articles without year limitations prior to 14 October 2020.* For inclusion in the systematic review, studies must have used the International Classification of Diseases (ICD) or Diagnostic and Statistical Manual of Mental Disorders (DSM) for diagnosis of individuals with ADHD (before age 12 years and/or adulthood) and bipolar disorder (aged ≥15 years at the time of bipolar disorder assessment). To assess comorbidity of ADHD and bipolar disorder, a random-effects meta-analysis of proportions was performed. Comorbidity estimates were derived by pooling individual study prevalence with a pooled estimate for between study heterogeneity.

Overall, 71 studies involving 646,766 participants from 18 countries were included in the meta-analysis of ADHD and bipolar disorder comorbidity: 38 studies with 234,833 participants assessed comorbidity of bipolar disorder with ADHD; 35 studies with 411,933 participants assessed ADHD comorbidity with bipolar disorder; and two studies assessed both.

Out of the 38 studies assessing comorbidity of bipolar disorder with ADHD, 27 (n=221,443 participants) assessed lifetime comorbidity of the two disorders, which was determined to be 7.95% (95% confidence interval [CI] 5.31–11.06) once an influential outlier was excluded. The other 11 studies (n=13,322 participants) assessed current or 12-month comorbidity of bipolar disorder with ADHD, which was determined to be 2.98% (95% CI 1.02–5.91). There was substantial heterogeneity between studies for lifetime comorbidity (Q=5533.78; p<0.001; I²=100%) and for current comorbidity (Q=165.32; p<0.001; I²=94%). Of the 35 studies that assessed ADHD comorbidity with bipolar disorder, 23 studies (n=401,108 participants) assessed the lifetime diagnosis of ADHD and 12 studies (n=10,825 participants) assessed current or adult ADHD comorbidity with bipolar disorder. The percentage of participants with a lifetime diagnosis of ADHD with comorbid bipolar disorder was determined to be 16.0% (95% CI 11.19–21.48). Additionally, the comorbidity of current adult ADHD diagnosis with bipolar disorder was 19.37% (95% CI 12.23–27.70). Pooled comorbidity of any ADHD diagnosis in participants with bipolar disorder was 17.11% (95% CI 13.5–21.59); however, there was substantial heterogeneity between studies (Q=2374.36; p<0.001; I2=99.81%).

Out of the 71 studies, 14 studies compared the age of bipolar disorder onset between those with and without comorbid ADHD. Overall, all 14 studies reported a younger age at onset of bipolar disorder in individuals who had ADHD. In total, nine studies reported a significant difference in age at onset between participants with bipolar disorder and comorbid ADHD and those with bipolar disorder but without comorbid ADHD. The raw mean difference in age at onset comparing bipolar disorder only and bipolar disorder with comorbid ADHD in a random-effects model was estimated to be 3.96 years (95% CI 2.65–5.26; p<0.001). However, significant heterogeneity was observed (I2=64.98%; p=0.001).

There were several limitations to this systematic review and meta-analysis. Firstly, although the authors felt that a random-effects meta-analysis was the best choice for this study, it attributes a smaller weight to larger studies; therefore, comorbidity rates of ADHD in the bipolar disorder sample could have been over-estimated. Consequently, the reported heterogeneity for comorbidity rates likely does not reflect prevalence in the general population. However, these prevalence rates do give an indication of what may be expected in clinical samples if diagnostic interviews are used. Secondly, the article selection was restricted to five languages (Dutch, English, French, German or Spanish), which could have led to other relevant articles being excluded. Finally, data were insufficient to reliably estimate the effect of different versions within a diagnostic system (for example, between DSM-IV and DSM-5TM), which could have reduced heterogeneity.

To conclude, the study findings showed a co-occurrence of ADHD and bipolar disorder in adults was much higher than expected by chance. Substantial heterogeneity was present, which was in part explained by diagnostic system, geographical location and sample size, highlighting the importance of contextual factors. The authors proposed that the findings from this study suggest that clinicians should be aware of this diagnostic co-occurrence, which could have important implications for diagnostic specification of ADHD and potentially treatment.

Read more about comorbidity of ADHD and bipolar disorder here

 

*Search terms included: ‘ADHD’ OR ‘attention deficit’ OR ‘hyperactive*’ OR ‘hyperkinetic’ AND ‘Bipolar Disorder’ OR ‘bipolar*’ OR ‘manic’ OR ‘mania*’; or, ‘comorbidity’ AND ‘ADHD’ or ‘comorbidity’ AND ‘Bipolar Disorder’ OR ‘bipolar*’ OR ‘manic’ OR ‘mania*’. The ‘NOT’ connection was used to exclude articles that mentioned ‘mouse’ OR ‘rat’ OR ‘animal’ OR ‘zebrafish’
Sources of heterogeneity included: continuous variables, diagnostic quality variables, diagnostic status, diagnostic system, geographic location and population

Schiweck C, Arteaga-Henriquez G, Aichholzer M, et al. Comorbidity of ADHD and adult bipolar disorder: a systematic review and meta-analysis. Neurosci Biobehav Rev 2021. Epub ahead of print.

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