Are we ignoring a powerful treatment for depression?

It might be worth revisiting lithium as a treatment for unipolar depression, a study suggests

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A Danish psychiatrist called Dr Mogens Schou became legendary when he put forward lithium as a treatment for bipolar disorder in the 1960s.

The drug reduced mortality by suicide by more than 60%.

Dr Schou’s research also showed lithium was an effective first-line therapy for major depression, but it was never widely adopted for this purpose.

Was this a mistake? A study from Finland published this month suggests it could be.

In the study, patients with unipolar depression taking lithium had a lower risk of readmission to hospital than patients taking other antidepressants and antipsychotics.

The effect size was large, with around a 50% lower risk of readmission in the cohort taking lithium alone.

The researchers looked at three decades worth of data, which included around 120,000 individuals admitted to hospital for depression.

Over the eight-year follow-up, around 40% of patients had at least one readmission to hospital for mental illness.

Lithium is rarely used as a first-line treatment for unipolar depression, although it is sometimes used to augment antidepressants in people who do not respond to other treatments, an Australian expert says.

“This study suggests maybe that is an error,” Professor Michael Berk, a psychiatrist at the University of Melbourne, said.

“Maybe we should be looking at more ready use of lithium in people with significant depressive illness.”

The researchers drew a similar conclusion, saying that lithium treatment should be considered for a wider population of severely depressed patients.

Currently, lithium is used as a first-line treatment for acute mania, often in combination with antipsychotics and benzodiazepines.

It was seldom prescribed for depression by the younger generation of clinicians who were more familiar with newer alternatives, said Professor Berk.

In addition, lithium is a complicated agent to prescribe as it has a narrow dose range, becoming toxic at higher levels. It is known to have significant side effects, including suppression of thyroid function, risk of renal dysfunction and weight gain.

Laboratory monitoring was needed to prevent severe adverse events in patients, the authors said.

“But this needs to be offset against other properties that lithium has,” Professor Berk said.

“Lithium probably has the most robust suicide-prevention effect of all the psychotropic drugs we’ve got. And suicide is a leading cause of death in people with these disorders.”

There is some evidence that lithium has benefits beyond its effects on mood. Several studies suggest that it might decrease the risk of dementia and cancer.

“Lithium probably has the most robust suicide-prevention effect of all the psychotropic drugs we’ve got.”

A “rather surprising and consistent finding” was that lithium monotherapy was more effective at keeping patients out of hospital than lithium taken in combination with antidepressants, the authors said.

But only about 2% of the study cohort was taking lithium (around 2000 patients), compared with around 80% that were taking other antidepressants.

The cohort taking lithium was likely to have a different pattern of illness to those taking antidepressants, Professor Berk said.

With this in mind, Professor Berk said the study did not demonstrate that lithium was the most effective drug for people with unipolar depression.

“But I think you can draw some meaningful conclusions out of the value of lithium and its ability to prevent depression and prevent readmission,” Professor Berk told The Medical Republic.

The Lancet Psychiatry 2017, online 1 June