Monday, January 23, 2017

Depressing - but there is hope

It is depressing to think about the fact that nearly 100 in the US and ten times as many across the world succumb to suicide every day. That is almost a person lost every minute, somewhere in the world. With nearly 10% of the US population suffering from depressive disorders, we may not be paying sufficient attention to a disease that kills silently. Nearly 10% of this cohort - almost 3 Million, suffer from Bipolar Depression, a condition that shows 20- 30 times higher probability of attempting suicide than the general population (1). This horrible disease sometimes leads to Acute Suicidal Ideation/Behavior (ASIB) - a condition that integrates suicidal thoughts with planning. And, it is growing at a 24% per year clip (from 1999-2014), especially among young adults.

The human brain, an evolutionary quirk, is a complex and fragile organ, prone to malfunctioning in many different ways. Initially designed to monitor and manage routine systems of the body, its massive excess capacity predictably led to thoughts and emotions, not typically seen in other biological entities. That was the beginning of trouble for the humans, as they struggled to understand and cope with the energy hog they carry on their shoulders. Primitive humans equated diseases of the brain to maligned acts of spirits and set out to ferret out the miscreants through unthinkable interventions. Ironically, the contemporary treatment regimen for ASIB is not substantially different, as patients are mostly locked in psychiatric hospitals, and receive electroconvulsive therapy (ECT). With no available medication for this indication, patients require many sessions of ECT, resulting in memory loss and confusion (1).

Large pharmaceutical companies have enjoyed a profitable franchise of Central Nervous System (CNS) treatments including SSRI/SNRI based antidepressants that carry an increasing risk of suicide. These widely available therapies are not effective in ASIB, a costly condition to treat as patients often progress to inpatient settings and ECT to tactically reduce the risk of catastrophic loss. The challenges to develop new medicines in neuroscience and particularly in psychiatry are very large, such that many big Pharmaceutical companies have abandoned psychiatry after their antidepressants became generic. However, ASIB appears to be a druggable target (1) as Bipolar Depression and in particular suicidal thoughts, may be modulated by the brain's NMDA receptor.

Treating this horrible disease with high risk of death with a medicine is potentially a great prospect for patients, but it will require investments and concerted efforts. Recent publications indicate that ketamine - an anesthetic, and potent NMDA blocker, reduces the impulse for suicide and for depression- which though related - seem not to be the same (1). However, its effect seems to be short lived, 4-7 days, and, it is administered through an iv infusion, making it important to find options that can extend its effect and allow patients to be treated on an outpatient basis once they are not a danger to themselves anymore.