Trinity College Dublin: Researchers investigate the role of ketamine in the treatment of depression

Researchers from Trinity and St Patrick’s Mental Health Services are trialing a new treatment option (ketamine) for people who are experiencing severe depression.

Led by Declan McLoughlin, Research Professor of Psychiatry at Trinity, and Consultant Psychiatrist at St Patrick’s Mental Health Services, the team will investigate the role of ketamine in improving outcomes for people receiving inpatient treatment for depression.

The randomised, controlled trial, entitled Ketamine as an Adjunctive Therapy for Major Depression (2) [KARMA-Dep-2], will mark the first clinical trial to be sponsored by Trinity, and is a definitive pragmatic trial informed by a previous smaller feasibility pilot trial. It will investigate the impact that a low dose of ketamine as an add-on treatment could have on people with severe depression. The trial is funded by the Health Research Board.

Depression has been recognised by the World Health Organisation as the leading cause of disability globally. In Ireland, over 200,000 people experience a depressive episode each year with approximately 6,000 requiring acute care.

Neurotransmitters are chemical messengers in our bodies that play important roles in our moods, behaviours and functionality. Though there has been intense research in this area to date, pharmacological treatments for depression that target monoamine neurotransmitters, for example serotonin, dopamine and noradrenaline, have remained mostly unchanged over the past 60 years.

While these treatments work effectively for many, research supports the need for novel and faster-acting treatments. Studies show that for patients with severe depression, only 30% achieve a reduction in symptoms after their first treatment for the condition with a type of antidepressant medication called a serotonin reuptake inhibitor. A further 30% of patients are resistant to this type of treatment. Moreover, these treatments can take many weeks to see the full benefit.

Ketamine is a type of drug called a dissociative anaesthetic, which means that a person who takes it feels disconnected or detached from themselves and the environment around them. It is routinely used in anaesthetic practice. However, when used in low doses that do not induce anaesthesia it has antidepressant effects.

Ketamine works differently to widely used antidepressants and may change dysfunctional brain cell pathways and connections, a process called neuroplasticity. Its effects come about by the way it acts on the signals of a particular chemical messenger, glutamate, in the brain. Crucially, and in comparison to current treatments, ketamine has a rapid-onset antidepressant effect with symptoms improving within one-hour of single infusions and peak benefits after 24-hours.

Declan McLoughlin, Research Professor of Psychiatry at Trinity College Dublin and Consultant Psychiatrist at St Patrick’s Mental Health Services, said:

“Years of research has shown that ketamine can be a powerful and quick acting antidepressant. In the KARMA-Dep-2 trial, we aim to see whether it’s possible to harness the powerful antidepressant action of ketamine as part of routine care for hospital inpatients experiencing severe depression. This has never been done in Ireland before on a scale this size.”

The research aims to test the hypothesis or possibility that repeated ketamine infusions (twice-weekly, maximum 8 infusions) as an add-on to current inpatient care will improve depression outcomes.

A secondary hypothesis, in collaboration with research at Queen’s University Belfast led by Prof Ciaran O’Neill, predicts that ketamine treatment could lead to a reduction in healthcare costs, and an improved quality of life for those living with the condition. Statistical support to the trial is being provided by Prof Ricardo Segurado at University College Dublin.

Professor McLoughlin added:

“Depression is the most common reason in the EU for long-term sick leave and disability. According to the World Health Organisation, it is the leading cause of disability worldwide. It is therefore a public health priority to not only recognise and treat depression, but to do so in a more time-effective manner than traditional antidepressants have achieved to date.”

The results of KARMA-Dep-2 should be able to be applied to people with depression who are hospitalised in industrialised nations but may be applicable more internationally and to patients with severe depression in general.

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