Lithium ‘stigma’ leading to wrong Tx protocols

Organisation: Position: Deadline Date: Location:

LithiumWEBThose with bipolar disorder should take lithium to help control their condition, despite its reputation for dulling the senses, concludes first study comparing the side-effects of the four main mood-stabilising drugs that the UK’s National Health Service (NHS) prescribes.

Researchers claim that although the drug does carry some health risks, its overall effectiveness, especially its ability to reduce self-harm and suicide, mean it should be much more widely used.

The Guardian reports that the findings are contained in the first study comparing the side-effects of the four main mood-stabilising drugs the UK’s National Health Service (NHS) prescribes. They have prompted calls for a rethink about attitudes towards lithium, given that only an estimated 10% of those with bipolar disorder use it, mainly because patients fear it will cause loss of personality, weight gain and other problems.

The lead author behind the research is quoted in the report as saying that widespread “lithium stigma” among patients is leading to them receiving the wrong treatment and ending up admitted to hospital unnecessarily because their condition is not as well controlled as it could be.

“Lithium is a drug with a bad reputation. It is seen by patients, and some psychiatrists, as a dangerous drug. People rightly have suspicions about it. Patients say that the downsides include emotional numbing – feeling that you aren’t connected with your feelings – as well as tremors,” said Dr Joseph Hayes, a psychiatrist at University College London (UCL) in the report.

But lithium’s reputation is largely misplaced and based on the experiences of patients from the 1960s to the 1980s who were given too large a dose of the drug, he added. The new research found that the side-effects of the mood-stabilising alternatives used by most patients are either the same as or worse than lithium, Hayes said.

The report says the paper, co-written by Hayes and four colleagues from UCL and Oxford University, concluded that: “Lithium remains an important treatment for individuals with bipolar disorder.” It accepts that “there is clear evidence that its use is associated with a number of adverse events.” However, it adds: “These risks need to be offset with the potentially superior effectiveness and anti-suicidal benefits of the drug compared to other treatment options.”

The report says the researchers studied a nationally representative sample of 6,671 patients across the UK who were treated for bipolar disorder between 1995 and 2013. Of those, 2,148 had taken lithium, 1,670 had used valproate, 1,477 had been on olanzapine and 1,376 had taken quetiapine. They experienced side-effects including chronic kidney disease, thyroid disease, weight gain and high blood pressure.

The researchers’ analysis bore out one of the two main criticisms of lithium, but found the other to be baseless, the report says. They found that patients on lithium had a higher risk of suffering kidney function problems and developing hypothyroidism or hyperthyroidism and also hypercalcemia. However, none of the drugs caused more severe kidney problems.

Meanwhile, lithium patients were less likely to put on weight than patients on the other drugs. While 15%-20% of those on the three other drugs were more likely to gain more than 15% of their body weight, just 10% of those on lithium put on the same amount of extra pounds. Those on olanzapine added the most weight and experienced high blood pressure as a result.

However, the report says the study adds: “These risks need to be offset with the potentially superior effectiveness and anti-suicidal benefits of the drug compared to other treatment options.”

The researchers studied a nationally representative sample of 6,671 patients across the UK who were treated for bipolar disorder between 1995 and 2013. Of those, 2,148 had taken lithium, 1,670 had used valproate, 1,477 had been on olanzapine and 1,376 had taken quetiapine. They experienced side-effects including chronic kidney disease, thyroid disease, weight gain and high blood pressure.

The researchers’ analysis bore out one of the two main criticisms of lithium, but found the other to be baseless. They found that patients on lithium had a higher risk of suffering kidney function problems and developing hypothyroidism or hyperthyroidism and also hypercalcemia. However, none of the drugs caused more severe kidney problems.

Meanwhile, lithium patients were less likely to put on weight than patients on the other drugs. While 15%-20% of those on the three other drugs were more likely to gain more than 15% of their body weight, just 10% of those on lithium put on the same amount of extra pounds. Those on olanzapine added the most weight and experienced high blood pressure as a result.

The report says separate research has shown that patients on the other three medications are 40% more likely to harm themselves than those on lithium. Bipolar disorder carries one of the highest rates of suicide of any mental illness, alongside schizophrenia and alcohol and drug addiction.

The very limited use of lithium is despite the National Institute for Health and Care Excellence (Nice) advising in 2014 that it should be the standard treatment for bipolar disorder, which is also known as manic depression and is characterised by manic highs and bouts of depression. That superseded its previous view, outlined in 2006, that any of the four drugs were useful first lines of treatment for the condition, which affects about one in 100 people.

“Lithium stigma, which includes some people in the psychiatric community, leads to people using drugs that are less effective [than lithium]. To me as a doctor that’s a big worry because my main aim is to help people to be well and if you aren’t doing that with the best available evidence then you are failing patients,” said Hayes in the report.

“I think that many patients are missing out quite commonly on the best available treatment. That means that people end up in hospital more often than they need to and end up achieving less in their lives than they could do if they were on lithium. The high suicide rate with bipolar disorder should encourage greater use of lithium. There should be more sensible use of it.”

Abstract
Background: There is limited, poorly characterized information about adverse events occurring during maintenance treatment of bipolar disorder. We aimed to determine adverse event rates during treatment with lithium, valproate, olanzapine, and quetiapine.
Methods and Findings: We conducted a propensity score adjusted cohort study using nationally representative United Kingdom electronic health records from January 1, 1995, until December 31, 2013. We included patients who had a diagnosis of bipolar disorder and were prescribed lithium (n = 2148), valproate (n = 1670), olanzapine (n = 1477), or quetiapine (n = 1376) as maintenance mood stabilizer treatment. Adverse outcomes were chronic kidney disease, thyroid disease, hypercalcemia, weight gain, hypertension, type 2 diabetes mellitus, cardiovascular disease, and hepatotoxicity. The propensity score included important demographic, physical health, and mental health predictors of drug treatment allocation. The median duration of drug treatment was 1.48 y (interquartile range 0.64–3.43). Compared to patients prescribed lithium, those taking valproate, olanzapine, and quetiapine had reduced rates of chronic kidney disease stage 3 or more severe, following adjustment for propensity score, age, and calendar year, and accounting for clustering by primary care practice (valproate hazard ratio [HR] 0.56; 95% confidence interval [CI] 0.45–0.69; p < 0.001, olanzapine HR 0.57; 95% CI 0.45–0.71; p < 0.001, quetiapine HR 0.62; 95% CI 0.47–0.80; p < 0.001). Hypothyroidism was reduced in those taking valproate (HR 0.60; 95% CI 0.40–0.89; p = 0.012) and olanzapine (HR 0.48; 95% CI 0.29–0.77; p = 0.003), compared to those taking lithium. Rates of new onset hyperthyroidism (valproate HR 0.24; 95% CI 0.09–0.61; p = 0.003, olanzapine HR 0.31; 95% CI 0.13–0.73; p = 0.007) and hypercalcemia (valproate HR 0.25; 95% CI 0.10–0.60; p = 0.002, olanzapine HR 0.32; 95% CI 0.14–0.76; p = 0.008, quetiapine HR 0.23; 95% CI 0.07–0.73; p = 0.013) were also reduced relative to lithium. However, rates of greater than 15% weight gain on valproate, olanzapine, and quetiapine were higher (valproate HR 1.62; 95% CI 1.31–2.01; p < 0.001, olanzapine HR 1.84; 95% CI 1.47–2.30; p < 0.001, quetiapine HR 1.67; 95% CI 1.24–2.20; p < 0.001) than in individuals prescribed lithium, as were rates of hypertension in the olanzapine treated group (HR 1.41, 95% CI 1.06–1.87; p = 0.017). We found no significant difference in rates of chronic kidney disease stage 4 or more severe, type 2 diabetes mellitus, cardiovascular disease, or hepatotoxicity. Despite estimates being robust following sensitivity analyses, limitations include the potential for residual confounding and ascertainment bias and an inability to examine dosage effects.
Conclusions: Lithium use is associated with more renal and endocrine adverse events but less weight gain than commonly used alternative mood stabilizers. Risks need to be offset with the effectiveness and anti-suicidal benefits of lithium and the potential metabolic side effects of alternative treatment options.

Authors
Joseph F Hayes, Louise Marston, Kate Walters, John R Geddes, Michael King, David PJ Osborn

Full report in The Guardian
PLOS Medicine abstract


Receive Medical Brief's free weekly e-newsletter



Related Posts

Thank you for subscribing to MedicalBrief


MedicalBrief is Africa’s premier medical news and research weekly newsletter. MedicalBrief is published every Thursday and delivered free of charge by email to over 33 000 health professionals.

Please consider completing the form below. The information you supply is optional and will only be used to compile a demographic profile of our subscribers. Your personal details will never be shared with a third party.


Thank you for taking the time to complete the form.