A Cure for the Holiday Blues?



PEOPLE SUFFERING FROM depression often struggle more over the holidays. If you’ve ever known someone with intractable depression or who has considered trying to commit suicide, you will understand the enthusiasm for a drug that can reduce this suffering and risk almost instantaneously –-compared to traditional anti-depressants, which can take up to eight weeks to work.

Ketamine is most commonly known as a horse tranquilizer or club drug, but few are aware of its near-miraculous potential for combating depression. Dr. Thomas Insel, past director of the National Institute of Mental Health (NIMH), called ketamine “the most important breakthrough in antidepressant treatment in decades.”

“We need suicide treatments so greatly in psychiatry,” NIMH researcher Elizabeth Ballard told WebMD. That ketamine reduces suicidal thoughts, independent of its effect on depression or anxiety, is important, said Ballard, because not all suicides can be traced to depression: some are related to post-traumatic stress disorder, borderline personality disorder or substance dependence. Ketamine offers the possibility of preventing suicide long enough for a person to get more in-depth treatment by providing a critical “window of relief,” according to the WebMD article.

The same “window of relief” can be important for depressive patients, even when long-term use isn’t possible because of ketamine’s side effects. Every year, some 14 million Americans have major depression; of those who seek treatment, up to 40 percent will not fully recover with standard antidepressants. Living with severe depression over time can cause irreversible damage to the cardiovascular system when fluctuating serotonin levels cause high levels of adrenaline to surge through the blood vessels.

In addition, depression appears to shrink the size of the hippocampus – involved in forming and storing long-term memories — based on worldwide studies of more than 1,700 people with major depression. In 65 percent of these, the hippocampus size was reduced, with more depressive episodes causing greater reduction in size.

Months or even mere days on the drug can offer such relief that patients break through “negative behaviors and thought loops that were previously inescapable,” according to the NIH-affiliated Ketamine Advocacy Network, which provides information on the drug along with a list of physicians and clinics offering ketamine treatment. (There appear to be none in the DMV, but a clinic is rumored to be opening in Towson in 2016.) Physicians most likely to provide ketamine treatments are anesthesiologists and pain management specialists or “pdocs.”

Ketamine belongs to a class of drugs known as dissociative anesthetics that includes phencyclidine (PCP) and nitrous oxide (laughing gas). These drugs can make a person feel detached from their surroundings and even immobilized, similar to the effect of heroin, and can cause hallucinations. Ketamine wears off in around an hour, but its use can lead to increased tolerance and addiction. Recreationally known as “special K,” ketamine has many risks, especially if mixed with alcohol, that include over-sedation and death; and it has been used as a date rape drug. Its rate of use is around .2 percent among ages 18 to 25.

For medical use, ketamine is usually given by injection in doses close to .1 gram — compared to quantities as high as one gram or more, usually snorted, for recreational use. Effects peak around one minute after injection. In a University of Oxford study, 28 treatment-resistant depressive patients received either three or six infusions of 80 milligrams (.12 grams) each over a three-week period. For one third of these, depression scores decreased by half by the third day after the last infusion, with benefits lasting between 25 days and eight months.

“Patients talked about how ‘the flow of their thinking seems suddenly freer,’” said Dr. Rupert McShane, lead investigator of the Oxford study. “For some, even a brief experience…helps them to realize that they can get better and this gives hope.”

Ketamine’s mechanism of action – blocking the pathway of the neurotransmitter glutamate, which is involved in memory and cognition – can allow it to work for people not helped by commonly used antidepressants, which affect the serotonin and noradrenaline pathways. Ketamine appears to combat depression by strengthening synaptic connections between brain cells that have been impaired by depression and stress.

Ketamine’s medical safety has been documented in its use for more than 20 years to treat both acute and chronic pain, particularly pain related to nerve damage. In clinical settings, other drugs such as benzodiazepines are often given to reduce the psychotropic effects.

Ketamine doesn’t work well for everyone and, because it can have unpleasant if short-lived side effects, many in the scientific community caution that more long-term research is needed before making it widely available. In addition, because ketamine has been in use for so long, pharmaceutical companies are unable to hope for big dividends from developing the drug and have so far been unwilling to fund studies on long-term ketamine use for depression. Instead, the hunt is underway for drugs similar to ketamine but different enough to be patented.

The Ketamine Advocacy Network aims to “overcome these obstacles [by spreading] awareness and acceptance of this powerful new weapon against depression, bipolar and PTSD.”

–Mary Carpenter

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