Introduction

• Major depressive disorder (MDD) and anxiety are some of the most common psychiatric disorders, with their effects and comorbidities having life-changing implications. Due to this, effective therapeutics are paramount in helping suffering individuals manage their symptoms and eventually take strides towards curing their illnesses.
• This report will focus on antidepressant and anxiolytic drug innovation, with an emphasis on promising drugs with novel mechanisms of action.
• To view additional details, please click the triangular bullet points to expand.

Glutamatergic agents

Ketamine

• Ketamine is better known as a general anaesthetic but, various preclinical studies have identified the drugs ability to reduce depressive symptoms with a single below-anaesthetic dose. These effects have been shown to take action within hours, rather than weeks or months seen with traditional antidepressants, and are relatively sustained for 7-14 days[1].
• Despite the drug being relatively safe and well-tolerated by participants in short term research settings, there are still questions about the long term side effects which make it difficult to identify the optimal dose for antidepressant treatment with ketamine.

To address these questions and identify an optimal dose for rapid antidepressant effects, a study NCT01920555 was completed in 2017 by Massachusetts General Hospital [2]. This trial showed promising short term antidepressant results for 0.5kg/mg and 1.0kg/mg ketamine doses.

NCT01920555

Trying to prolong ketamine’s antidepressant effects is currently being investigated throughly. Janssen R&D released results from a study NCT01627782 in 2016 investigating the effects of a twice- or thrice-weekly dosing regime of ketamine in producing sustained antidepressant effects in TRD patients[4].

The trial found that 0.5kg/mg doses could produce sustained antidepressant effects over 15 days which were not significantly different with either dosing regime highlighting the potential for the twice-a-week regime.

NCT01627782

Esketamine

Esketamine is a nasal spray with a similar mechanism of action to ketamine. It was developed by Johnson&Johnson to avoid the logistical challenges that come with an intravenously administered drug, such as the necessity of hospital visits.

• The drug was approved for adjunctive treatment of TRD with traditional antidepressants by the US Food and Drug Association (FDA) in 2019 [5]. The approval was gained largely due to esketamine’s rapid onset of action (hours) and various clinical studies.

Xenon Gas (NBTX-001)

• NBTX-001 is a drug developed by Nobilis therapeutics, the active constituent being Xenon gas which is also an approved anaesthetic like ketamine.

Promising early pieces of human data prompted a study NCT04432155, which is set to take place during 2021 and be completed by the 4th quarter of the year, for the study of Xenon inhalation as a treatment for panic disorders [7].