Links between aripiprazole and gambling disorder highlighted in new drug safety update

19th December 2023

Healthcare professionals prescribing aripiprazole for schizophrenia and bipolar disorder should be alert to the known risk of patients developing addictive gambling, according to a new drug safety update.

This reminder about aripiprazole from the Medicines and Healthcare products Regulatory Agency (MHRA) comes after a rise in the number of reports of gambling or gambling disorder it received in 2023.

Between 1 January and 31 August 2023, the MHRA’s Yellow Card scheme received 32 reports of gambling or gambling disorder where aripiprazole was suspected to be the cause.

In the last 14 years, there have been 69 reports, making the 2023 figures over 46% of the total.

The MHRA asked gambling clinics in March 2023 to report any suspected cases, which may account for some of the rise, it said.

The UK reports of this suspected addictive behaviour occurred in patients both with and without a history of problem gambling and most reported that the urges resolved on reducing the dose or stopping treatment with the drug.

The MHRA is advising patients to tell their doctor if they or their family and friends notice they are having unusual urges or cravings that they cannot resist, including behaviours such as addictive gambling, excessive eating or spending, or an abnormally high sex drive.

And it warned that patients should continue taking aripiprazole as advised, as stopping the drug without medical advice can be harmful.

Alison Cave, MHRA chief safety officer, said: ‘The number of reports for suspected gambling and other impulsive behaviours associated with aripiprazole are small in comparison to the frequency with which it is prescribed, but the consequences for any patient developing these conditions can be significant.

She also highlighted that ‘aripiprazole is an effective and acceptably safe drug for many people.’

Professor Henrietta Bowden-Jones, director of the National Problem Gambling Clinic, added: ‘Clinicians prescribing aripiprazole must commit to consistently alert patients about these potential risks, both during the initial prescription and follow-up reviews.’

This includes asking patients if they have a personal history of excessive gambling or any other impulsive behaviours before prescribing aripiprazole.

NHS England launches valproate decision support tools

26th May 2023

Decision support tools to help clinicians and patients decide whether or not valproate is the right option for them have been launched by NHS England.

In efforts to maintain patient safety and curb inappropriate prescribing of valproate during pregnancy, the tools are aimed at women, girls and anyone who could become pregnant, aged between 12 and 55, who are considering or taking valproate for epilepsy or bipolar disorder.

Developed in accordance with the NICE standards framework for shared decision-making support tools, the aim is to help patients understand the benefits and harms of taking valproate, and come to a decision based on what matters most to them.

NICE guidance states that the medication ‘must not be used in women and girls of childbearing potential (including young girls who are likely to need treatment into their childbearing years), unless other options are unsuitable and the pregnancy prevention programme is in place.’

Sodium valproate is prescribed as a treatment for epilepsy and bipolar disorder and can cause birth defects in around one in 10 babies born to those taking it while pregnant, as well as causing developmental problems in 30-40% of children whose mothers took the medicine while pregnant.

Updated valproate advice

The new tools come after the independent Commission on Human Medicines (CHM) advised in December that two specialists must independently consider that valproate is the only effective or tolerated treatment before a patient under the age of 55 can be initiated on the medication.

The Commission also advised that men under the age of 55 should also be offered the opportunity to have their treatment reviewed. The UK’s Medicines and Healthcare Regulatory Agency is set to release information about additional versions of the tools for men imminently.

According to NHS Digital, between April 2018 and September 2020, 180 females in England were prescribed valproate while pregnant. Some 47,532 females aged 0-54 were given one or more prescriptions for the drug over the reporting period, and 238 females stopped receiving prescriptions of valproate prior to their pregnancy.

A version of this story was originally published by our sister publication The Pharmacist.

Higher risk of osteoporosis in bipolar disorder reduced by lithium therapy

18th April 2022

The risk of developing osteoporosis is higher in people with bipolar disorder but this risk is reduced to some extent by lithium therapy

Bipolar disorder is associated with an increased risk of developing osteoporosis but this risk is lower among patients treated with lithium but not any of the other anti-psychotics. This was the finding of a retrospective analysis by a team from the Psychosis Research Unit, Aarhus University Hospital, Aarhus, Denmark.

Bipolar disorder (BD) is best described as a multicomponent illness involving episodes of severe mood disturbance, neuropsychological deficits, immunological and physiological changes, and disturbances in functioning.

According to the World Health Organization, BD affects about 45 million people worldwide. Osteoporosis is a disease of the bones and characterised by a reduction in bone mineral density and a decrease in bone mass or when the quality or structure of bone changes.

Having osteoporosis increases an individual’s risk of fractures and while there are several factors associated with an increased risk for developing the condition, one purported factor is bipolar disorder, though to date, the evidence is far from conclusive but suggestive. For example, one study identified how patients with BD had a lower bone mineral density (a risk factor for osteoporosis) when compared to an age and gender matched healthy control sample.

In addition, other studies have shown that BD is associated with an increased fracture risk. Lithium is an effective mood stabiliser that is used principally for the management of bipolar disorder and there is some evidence points to the fact that lithium use is associated with a significant decreased risk of fracture.

In an attempt to better comprehend both the relationship between BD and osteoporosis and the impact of lithium therapy, the Danish team turned to a national, longitudinal register. They first sought to compare the incidence of osteoporosis among those with BD in comparison to the general population and secondly, whether the usual treatments for BD including lithium and other anti-psychotics were protective. The primary outcome measure was osteoporosis and this was determined from both hospital diagnoses and prescribed treatments.

Bipolar disorder and osteoporosis risk

A total of 22,912 individuals with BD and a median age of 50.4 years (56.6% women) and 114,560 reference individuals (without BD) were followed over a median of 7.68 years. Among those with BD, 38.2% were prescribed lithium, 73.6% an anti-psychotic, 16.8% valproate and 33.1% lamotrigine.

During this follow-up period, patients with BD had a 14% higher risk of developing osteoporosis compared to the reference group (hazard ratio, HR = 1.14, 95% CI 1.08 – 1.20).

However, when the researchers compared those prescribed lithium to no lithium, there was a substantial decreased risk of developing osteoporosis in fully adjusted models (HR = 0.62, 95% CI 0.53 – 0.72. In contrast, there was no such significant associations for any of the other prescribed treatments.

The authors concluded that patients with BD have an elevated risk of osteoporosis and that treatment with lithium reduces this risk, suggesting that bone health should become a priority in the clinical management of these patients.

Citation
Köhler-Forsberg O et al. Association of Lithium Treatment With the Risk of Osteoporosis in Patients With Bipolar Disorder JAMA Psychiatry 2022