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Mental health conditions

Clear link between antidepressant use and bipolar risk shown in ‘real-world’ study

Study of 21,000 patients with unipolar depression shows SSRI and venlafaxine use are associated with a 35% increased risk of mania or bipolar disorder.

Use of antidepressants is associated with an increased risk of mania and bipolar disorder, according to researchers. Pictured, a person with depression.

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Clinicians should consider risk factors for mania or hypomania in people with depression, say researchers

Use of antidepressants is associated with an increased risk of mania and bipolar disorder and clinicians should consider risk factors for these conditions when treating people with depression, according to researchers writing in BMJ Open[1] on 15 December 2015.

Researchers from King’s College London and the South London and Maudsley NHS Foundation Trust analysed data from the electronic medical records of more than 21,000 patients to estimate the incidence of acute mania or hypomania in patients with unipolar depression (major depression).

The research team found a significant association between antidepressant therapy – particularly serotonin reuptake inhibitors (SSRIs) and the dual action antidepressant venlafaxine – and the development of mania or bipolar disorder.

Overall, the incidence rate of bipolar disorder or mania after an original diagnosis of unipolar depression was 10.9 per 1,000 person-years; with antidepressants this rose to 13.1-19.1 per 1,000 person-years. The risk of mania or bipolar disorder in people treated with SSRIs and venlafaxine rose by 34-35%.

Although the data show a clear link between antidepressant drugs and mania or bipolar disorder, they don’t indicate the reason for the association. “It is unclear whether antidepressants cause acute mania or hypomania in patients with unipolar depression or trigger the expression of an underlying bipolar disorder,” the researchers say.

But David Taylor, director of pharmacy and pathology at South London and Maudsley NHS Foundation Trust, who was not involved in the research, says a causal link is unlikely. “It is well known that bipolar disorder can initially present as recurrent depression. These episodes are often treated with antidepressants and so their prescription is simply a marker of prior depression,” Taylor says.

“It is also established that people diagnosed with unipolar depression have often experienced sub-syndromal hypomanic symptoms about which the prescriber is unaware. The possibility that antidepressants ‘convert’ unipolar depression into bipolar disorder is, in my view, very small,” he adds.

Earlier studies have identified links between antidepressants and bipolar disorder; the difference with this study is that it used ‘real-world’ data from medical records of people receiving secondary care for unipolar depression.

The researchers point out the need to consider risk factors for mania or hypomania in people with depression, and also the need to develop better ways to predict the consequences of these risk factors. Apart from antidepressant therapy, other risk factors for mania or hypomania in people receiving treatment for depression include a family history of bipolar disorder, a depressive episode with psychotic symptoms, young age at onset of depression and antidepressant resistance. Communicating the adverse events of therapeutics in bipolar disorder is important, they say.

“As the authors of this study have pointed out, no firm conclusions can be drawn about cause and effect,” says Brian Dow, director of external affairs at Rethink Mental Illness. “We do however want to see people with mental illness being made aware of the potential risks and side effects of medication, so that they can make an informed decision about their own treatment, and find what works for them.”

Citation: The Pharmaceutical Journal DOI: 10.1211/PJ.2015.20200354

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  • Use of antidepressants is associated with an increased risk of mania and bipolar disorder, according to researchers. Pictured, a person with depression.

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