Intramuscular versus Intravenous Ketamine for the Management of Treatment-Resistant Depression and Suicidal Ideation
Cristina Albott of the University of Minnesota Medical School reported relatively similar efficacy of intramuscular versus intravenous ketamine for the management of treatment-resistant depression and suicidal ideation in outpatient settings.
“Intramuscular (IM) delivery represents an underexplored and promising route of administration given its high bioavailability and low cost….Sixty-six patients underwent a series of 7 to 9 IV (n=35) or IM (n=31) administrations of 0.5mg/kg ketamine during a 21-28 day period. Both IV and IM showed similar magnitudes of improvement in depression, but surprisingly only the IM route was associated in a significant improvement in suicidal ideation in a within subjects change.”
“No adverse events occurred throughout the treatment series for either administration route…. This clinical case series provides preliminary support for the effectiveness and safety of IM compared to IV ketamine in TRD. “
Depression and Suicidal Thoughts Linked to Brain Inflammation
A 2017 article by Sophie E. Holmes and colleagues in the journal Biological Psychiatry reports that people with major unipolar depression, especially those with suicidal thoughts, have higher levels of the inflammatory marker translocator protein than do healthy individuals.
The participants with depression and suicidal thinking had high levels of translocator protein in the anterior cingulate cortex, which suggests that inflammation is affecting microglia.
Many studies have found links between different indicators of inflammation and mood disorders, leading researchers to speculate whether targeting the immune system could be an effective way to treat mood disorders. Patients with high levels of inflammation often fail to respond to typical treatments for depression.
Some previous research has found evidence of microglial activation in the brains of people who died from suicide.
The small study by Holmes and colleagues used positron-emission tomography, or PET scans, to observe evidence of translocator protein levels in the brain in 14 medication-free participants in a major depressive episode and 13 healthy volunteers. Those with depression, and particularly those with suicidal thoughts, showed more evidence of neuroinflammation.
Very Low Doses of Opioid Buprenorphine May Reduce Suicidal Ideation
There is no perfect treatment to reduce the risk of suicide in someone who is considering it. Antidepressants can reduce suicidal ideation, but they take several weeks to start working. Intravenous ketamine is used at higher doses as an anesthetic, but in low doses works quickly to reduce suicidal thoughts. However, it requires repeated infusions to keep working. Researchers led by Yoram Yovell are exploring another option: ultra-low doses of the opioid buprenorphine.
In a study published in the American Journal of Psychiatry in 2015, Yovell and colleagues compared low-dose buprenorphine to placebo in 62 patients with no history of substance abuse who had been contemplating suicide for a week or more. Many had attempted suicide before, and more than half met the criteria for borderline personality disorder.
Buprenorphine was administered under the tongue, in doses of 0.1 mg once or twice a day. The researchers used these low doses to minimize the side effects of a drug that could potentially be addictive. Those randomized to receive buprenorphine saw greater reductions in suicidal ideation compared to those who received placebo, both after two weeks and after four weeks.
Use of antidepressants did not affect the likelihood that patients would respond to buprenorphine. The researchers suggest that buprenorphine specifically treats suicidal thoughts, rather than improving depression in general.
Patients with borderline personality disorder, who are often unresponsive to medication, also saw improvement in suicidal ideation after taking buprenorphine, suggesting that the opioid treated a particular symptom of their disorder—sensitivity to feelings of separation from the people with whom they are close.
Patients did not experience withdrawal when they discontinued buprenorphine. Side effects included fatigue, nausea, dry mouth, and constipation. Patients who started out taking 0.2 mg per day were much more likely to drop out than those who started at 0.1 mg per day.
There is another reason the researchers used very low doses. A potential benefit to ultra-low–dose buprenorphine is that even a week’s supply of the drug would not produce a dangerous overdose, so patients could potentially be prescribed a week’s worth of medication to take at home instead of in an inpatient setting.
Buprenorphine is not recommended for patients with a history of substance abuse. The study only explored short-term use of the drug, and replication studies are needed to clarify its effects.
