Anxiety disorders frequently co-occur in individuals with a diagnosis of bipolar disorder (Merikanges et al, 2007). Those with additional anxiety disorder comorbidities are associated with an increased risk of relapse, more severe depressive episodes and increased rates of substance abuse and suicide attempts.

More broadly individuals with additional anxiety disorders also experience diminished quality of life and this often continues to cause functional impairment (Simon et al, 2004).

The authors of this new systematic review and meta-analysis sought to establish the prevalence of anxiety disorders in individuals with bipolar disorder and to compare the rates of prevalence against a control group and individuals with a diagnosis of bipolar I and bipolar II.

Methods

• Authors searched two online databases (Web of Knowledge, Medline)
• Studies were included if they reported original data about lifetime prevalence DSM-III or DSM-IV anxiety disorders in adults with bipolar disorder
• Diagnosis was required to have been validated by a diagnostic interview
• Studies in any language were included
• Studies were excluded if they contained data with discrepancies that could not be resolved by contacting the study authors
• Studies were included if they reported the lifetime prevalence of at least one anxiety disorder
• Authors also contacted authors of identified articles for additional information
• Prevalence of anxiety disorders between bipolar I and bipolar II were compared.

Results

Characteristics

• 40 studies were eligible and included data from 14,914 individuals
• 29 studies analysed clinical samples, 7 studies analysed community samples from the general population, 4 studies had analysed a mixed sample including clinical and community samples
• 13 studies provided data about the lifetime prevalence of anxiety for people with a diagnosis of bipolar I and bipolar II
• Prevalence was also reviewed for those with a diagnosis of bipolar disorder and those without.

Main findings

• Rates of lifetime prevalence ranged from 8% to 88%
• Any lifetime anxiety disorders were identified in 45% (95% CI: 40.0 to 50.6%) of individuals with a diagnosis of bipolar disorder
• The most common lifetime anxiety disorders identified in individuals with bipolar were:
  • Generalised Anxiety Disorder (GAD): 20% (95% CI: 0.147 to 0.262)
  • Social phobia: 20% (95% CI: 0.150 to 0.248)
  • Panic disorder: 19% (95% CI: 0.147 to 0.262)
  • Post-traumatic stress disorder (PTSD): 17% (95% CI: 0.128 to 0.217)
  • Specific phobia: 10% (95% CI: 0.080 to 0.136)
  • Obsessive compulsive disorder (OCD): 10% (95% CI: 0.086 to 0.126)

• The lifetime prevalence of specific anxiety disorders did not differ between people with a diagnosis of bipolar I or bipolar II
• When compared against those without a diagnosis of bipolar disorder, those with bipolar were:
  • 7 times more likely to have a lifetime diagnosis of OCD
  • nearly 6 times more likely to have a diagnosis of panic disorder
  • 6 times more likely to have diagnosis of PTSD
  • nearly 5 times more likely have a diagnosis of GAD or social phobia
  • nearly 3 times more likely to have a diagnosis of a specific phobia
• There was no difference between the prevalence of agoraphobia between those with a diagnosis of bipolar disorder and those without
• Potential sources of heterogeneity were investigated. Authors noted no significant differences between the lifetime rates of anxiety disorders between clinical and community samples (b-0.10 [95% CI -0.24 to 0.03]; p=0.121, R²=4.24%), or area of recruitment (b 0.06 [95%CI -0.07 to 0.18]
• There was also no effect of interviewer’s profession, age of participants, mean age of participants or proportion of female participants
• The authors also conducted analysis to assess the bias of small studies which showed that there was no small study bias present (bias- 118.0 [95% CI -572.7 to 336.7]; p=0.579.

Conclusions

• There is a 45% lifetime prevalence of anxiety disorders in individuals with a diagnosis of bipolar disorder
• Anxiety disorders are three times more common in individuals with a diagnosis of bipolar disorder in comparison with the general population
• Previous studies have indicated that individuals with bipolar disorder and co-morbid anxiety disorders have a worse prognosis than those without anxiety
• The authors considered four possible explanations of the increased prevalence of comorbid anxiety disorders:
  • The increase prevalence might partly represent anxiety associated with depression
  • Those with a diagnosis of bipolar disorder are more likely to be exposed to childhood trauma and stressful life events in adulthood
  • Low self-esteem may be a common factor in contributing to increased anxiety disorder in individuals with bipolar disorder
  • Anxiety disorders are more common in the biological relatives of individuals with a diagnosis of bipolar disorder and may be a manifestation of common genetic susceptibility
• The assessment and treatment of those with a diagnosis of bipolar disorder for other anxiety disorders is important and should be a part of routine practice. As comorbidity increases, the likelihood and degree of adverse outcomes also increases.

Discussion

The review attempts to establish the prevalence of anxiety disorders in individuals with bipolar disorder. The authors approached the study in a clear and systematic manner with transparent reporting of the review process and funding sources. In addition the authors conducted several analyses of possible sources of bias and controlled for the effect of small studies.

The review highlights that individuals with a diagnosis of bipolar disorder are three times more likely to have a diagnosable anxiety disorder.

Limitations

The major limitations of the study are that only two electronic resources were included. Searching more widely may have led to further eligible studies being included in the meta-analysis, which arguably would have added to the power of the authors’ conclusions. Also the impact of the DSM-5 was not assessed as both OCD and PTSD have been removed from the anxiety disorders, although the authors do address this in the review.

Clinical implications

The interesting clinical implications are that a large number of individuals with a diagnosis of bipolar disorder may benefit from discrete treatments focusing on addressing anxiety disorders specifically. This has implications for clinical provision as this need often goes unaddressed and this should become a target for intervention with effective evidence-based treatments such as cognitive-behavioural therapy.

The review also suggested that the assessment and treatment for anxiety disorders where individuals have a bipolar diagnosis should be routine and may improve clinical outcomes and functioning. However to establish this, high quality research trials are required as currently this area is significantly under-researched.

Links

Primary paper

Pavlova B, Perlis RH, Alda M, Uher R. (2015) Lifetime prevalence of anxiety disorders in people with bipolar disorder: a systematic review and meta-analysis. The Lancet Psychiatry, Volume 2, Issue 8, Pages 710-717. [Abstract]

Other references

Merikanges, Akiskal, Angst et al. (2007) Lifetime and 12-month prevalence of bipolar spectrum disorders in the National Comorbidity Survey replication. Archives of General Psychiatry, 64, 543-52.

Simon, Otto, Wisbuewski et al. (2004) Anxiety disorder comorbidity in bipolar patients: data from the first 500 participants in the Systematic Treatment Enhancement Program for bipolar disorder in the US population (PDF). Journal of Psychiatric Research, 46, 865-872.