Off-label use of dopamine agonists

Some dopamine agonists are prescribed off-label for conditions they are not formally licensed to treat - known as off-label prescribing. 

A licence is not a statement that a drug can only be used for one condition. Rather, it indicates the conditions for which regulators have formally reviewed evidence of safety and effectiveness. Doctors may legally prescribe medicines off-label when they believe it is clinically appropriate. However, off-label use may involve less regulatory scrutiny, less long-term experience, or less complete information about risks and benefits in that particular patient group. 

Pramipexole for depression and other mental health conditions

Pramipexole has been prescribed for treatment-resistant depression (TRD), bipolar depression, apathy, and other disorders involving motivation and reward processing. Recent clinical trials have increased interest in these uses, and some specialists now prescribe pramipexole as an add-on treatment for people whose depression has not responded adequately to standard therapies. 

Lessons from licensed use in Parkinson’s Disease and Restless Legs Syndrome

The severity and prevalence of psychiatric side effects of dopamine agonists, including impulse control disorders (ICDs), were significantly under-recognised for many years. Many affected individuals did not initially recognise the behavioural changes themselves, while shame, stigma and lack of awareness of the link to medication contributed to widespread under-reporting. 

If dopamine agonists are rolled out to new conditions and patient groups, it is vital these mistakes are not repeated.

It should also be noted that, for RLS and Parkinson’s Disease, several studies have identified a history of depression as a risk factor associated with an increased risk of impulse control disorders in patients taking dopamine agonists.

Added risks in treatment for psychiatric conditions

Prescription of dopamine agonists can involve complex trade-offs between physical health symptoms and mental health side effects. This becomes even more complicated when medication is used to treat changes in mood, motivation and behaviour, and some of its most serious adverse effects also involve changes in mood, motivation and behaviour.

Patients of all backgrounds and conditions have faced stigma and scepticism that impulsive behaviour is simply a result of poor choices or part of ‘who they are’, but these challenges may be even greater for patients being treated for mental health conditions.

That is because there is a greater risk that new or escalating changes in energy, impulsivity, risk-taking and behaviour will be attributed to the individual, their underlying mental health condition, recovery from depression, emerging bipolar symptoms, personality traits or life circumstances – rather than being recognised as medication-induced effects. This may delay recognition that the medication itself is contributing to the changes, potentially allowing harmful behaviours to escalate before appropriate action is taken.

This concern is particularly relevant because many of the behavioural changes associated with dopamine agonists overlap with symptoms and experiences already encountered in psychiatric settings. As a result, harmful behavioural side effects may be more difficult to recognise, report, investigate and correctly attribute to medication.

The licensed use of dopamine agonists has demonstrated that delayed recognition and inadequate awareness can have devastating personal, financial, psychological and relational consequences.

Clinical trials and routine practice should distinguish genuine improvement in depressive symptoms from dopamine agonist-induced behavioural activation or emerging impulse control disorders. Increased motivation, spending, sexual drive, confidence or goal-directed activity could superficially resemble clinical improvement unless behavioural adverse effects are actively sought using appropriate measures and collateral information where appropriate.

The need for greater scrutiny

The expansion of dopamine agonists into new uses should be accompanied by greater scrutiny, not less. Existing protections, monitoring and safeguarding for licensed conditions require significant improvement, and we eagerly await the outcome of the MHRA review, which DAAG has asked to contribute to.

Any expansion of dopamine agonist prescribing into mental health conditions would require particularly careful consideration of monitoring, patient information and safeguarding. We believe the MHRA review should extend beyond licensed indications and also consider the experiences of patients prescribed dopamine agonists off-label.