NHS England encourages integrated care boards (ICBs) to address inappropriate antidepressant prescribing and to consider commissioning services for patients wishing to reduce or stop prescribed medicines that can cause dependence and withdrawal.

In March 2023, NHS England published Optimising personalised care for adults prescribed medicines associated with dependence or withdrawal symptoms: Framework for action for ICBs and primary care. The framework includes actions, resources and case studies to help systems develop plans that can support people who are taking medicines associated with dependence and withdrawal symptoms. The framework is available at the following link:

https://www.england.nhs.uk/long-read/optimising-personalised-care-for-adults-prescribed-medicines-associated-with-dependence-or-withdrawal-symptoms/

ICBs are responsible for planning health services for their local population. This includes consideration of services for patients taking medicines associated with dependence and withdrawal symptoms based on local population needs.

An increasing number of non-pharmacological alternatives have become available on the National Health Service, including significant investment in NHS Talking Therapies for common conditions like anxiety and depression, with 1.26 million referrals starting a course of treatment in 2023/24. There has also been considerable investment in social prescribing, which can help people with mental health problems, and there are now over 3700 full-time equivalent trained social prescribing link workers, and over 2.5 million people have been referred to a social prescribing link worker.

Additionally, the National Institute for Health and Care Excellence has published guidelines, Medicines associated with dependence or withdrawal symptoms: safe prescribing and withdrawal management for adults, which is available at the following link:

https://www.nice.org.uk/guidance/NG215

The Medicines and Healthcare products Regulatory Agency is currently leading a project to improve the information supplied with dependency-forming medicines. The project aims to improve risk minimisation measures and better inform and educate healthcare professionals and patients about the risk of dependence, addiction, tolerance and withdrawal related to a wide range of medicines including antidepressants in the United Kingdom.

The following table shows the total number of items issued for mirtazapine, each year since 2014 to 2023:

Source: Data was provided by the NHS Business Services Authority, using the British National Formulary chemical substance mirtazapine

Note: Items have been dispensed, but not necessarily prescribed, in England.

The Medicines and Healthcare products Regulatory Agency (MHRA) is responsible for ensuring medicines, medical devices, and blood components for transfusion meet applicable standards of safety, quality, and efficacy. The MHRA rigorously assesses available data, including from the Yellow Card scheme, and seeks advice from their independent advisory committee, the Commission on Human Medicines, where appropriate to inform regulatory decisions.

The MHRA has received a total of 46 Yellow Card reports of sexual dysfunction related reactions suspected to be associated with mirtazapine, four of which include information that suggest the suspected adverse reactions persisted after mirtazapine was withdrawn. The following table shows the number of Yellow Card reports of suspected mirtazapine related sexual dysfunction, and reports of sexual dysfunction that persisted after the drug was withdrawn, each year from 2014 to 2024:

Source: data provided by the MHRA.

It is important to note that the inclusion of a particular report on the MHRA’s system does not necessarily mean that the adverse reactions reported have been caused by the suspect drug. Additionally, the number of reports received should not be used as a basis for determining the incidence of a reaction, as neither the total number of reactions occurring, nor the number of patients using the drug, is known.

The MHRA continuously monitors the safety of medicines on the United Kingdom’s market, including mirtazapine. Reports of suspected adverse reactions are reviewed weekly by a multidisciplinary team as part of the MHRA’s signal detection process. The term signal is used to define any suspected adverse reaction or potential safety concern that requires further evaluation.

Responsibility for adding a side effect to the product information leaflet sits with the MHRA. The product information for mirtazapine reflects the data currently available, and does not include sexual dysfunction as a possible side effect. However, data from Yellow Card reports and other sources such as published studies and periodic safety assessments are kept under continuous review by the MHRA. The marketing authorisation holder has recently submitted the latest periodic safety update report to the MHRA, and this will be carefully assessed. If there is sufficient evidence and associated data about the potential to experience sexual dysfunction as a side effect, the patient information for mirtazapine can be updated.

There are no current plans to make an assessment. Information on the safety of mirtazapine during pregnancy and while breast feeding is provided in the product information supplied with each pack of medicine.

While there is currently limited data on the use of mirtazapine in pregnant women, the data available do not indicate an increased risk of congenital malformations. Caution is advised when used during pregnancy, particularly as until or shortly before the birth, the baby should be monitored for any possible side effects relating to withdrawal or toxicity.

The product information also includes information about the potential risk of persistent pulmonary hypertension of the newborn, which is known to be associated with the use of some antidepressants with a similar mechanism of action as mirtazapine.

The safety of mirtazapine use in pregnancy is continually monitored and assessed through the periodic review of the latest available data from scientific studies and side effects reported through the Yellow Card Scheme. The product information is updated in response to these ongoing data assessments to reflect the most up to date advice for patients and prescribers.